Readers Struggling with Rejection Will be Encouraged by Author’s Story of Healing – PR Web

Posted on August 1, 2020 by Prof Baldwin

...tells the authors story of finding the healing acceptance of God in a circumstance and location which otherwise screamed of failure and inadequacy.

CHANDLER, Ariz. (PRWEB) August 01, 2020

Brandon Johnsons book, The Heavy Heart And The Unexpected Place of Healing: Guernsey ($11.49, paperback, 9781631299520; $19.99, hardcover, 9781631299537; $5.99, ebook, 9781631299544), is available for purchase.

Sometimes in life, we find ourselves facing rejection. This can come from family members, friends, work, significant othersno matter the origin of the rejection, however, the end result stings, making us question our self-worth and if we will be able to find the acceptance we so desperately seek.

Author Brandon Johnson struggled with rejection throughout his life, which led to other struggles, but the rejections that devastated him actually eventually led to his healing. The Heavy Heart and the Unexpected Place of Healing: Guernsey by Brandon Johnson tells the authors story of finding the healing acceptance of God in a circumstance and location which otherwise screamed of failure and inadequacy.

By taking the reader on a journey through his time in the United States Air Force and his many experiences both domestic and abroad, Brandon explains how God met him in his darkest moments and restored him, even when he felt like hed gone past the point of no return.

Whoever reads this book will gain a new perspective on their life, said Johnson.

Brandon Johnson is originally from Tulsa, Oklahoma, a small but diverse community. He currently works at Whole Foods Market and enjoys teaching others the importance of living and eating a healthy lifestyle.

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Xulon Press, a division of Salem Media Group, is the worlds largest Christian self-publisher, with more than 12,000 titles published to date. The Heavy Heart And The Unexpected Place of Healing, Guernsey is available online through xulonpress.com/bookstore, amazon.com, and barnesandnoble.com.

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Development of a pH-responsive polymersome inducing endoplasmic reticulum stress and autophagy blockade – Science Advances

Posted on July 31, 2020 by Prof Baldwin

INTRODUCTION

The important role of autophagy in health and disease has received unprecedented attention (1). As an essential and conservative physiological catabolic process, autophagy is responsible for the removal of protein aggregates, damaged organelles, and foreign bodies that invade cells (2). The autophagy contents are sequestered by double-membraned compartments (autophagosomes). Subsequently, the autophagosomes are fused with lysosomes to form autolysosomes, which degrade and circulate to produce nutrients (amino acids, fatty acids, and nucleotides) to be supplied to cells, and this dynamic process is called autophagic flux (3, 4). The unhindered autophagic flux is of great notable for maintaining homeostasis and protecting cells from attacks (5). The autophagic level is characterized by the amount of autophagy markers (e.g., autophagosomes and autolysosomes) and autophagy protein markers [e.g., LC3 (microtubule-associated protein-1 light chain-3)]. The upstream initiation or downstream blocking of autophagic flux will lead to the increase in autophagy markers (6). Malignant tumors are at a relatively high autophagic level compared with normal tissues to satisfy their metabolic demands, evasion, and resistance and allow tumor growth, survival, and malignancy (7). The involvement of autophagy in the occurrence and development of tumors suggests the reliable prospect of autophagy manipulation as an interventional means for tumor therapy (8). Autophagic flux blockade can disrupt the metabolism cycle of cancer cells, thereby reducing their fitness (9). Hydroxychloroquine (HCQ) and chloroquine (CQ) are the only clinically available autophagic blocking agents and they have been proven to be effective adjuvants for chemotherapeutics to increase their antitumor effects (10). HCQ/CQ, as a lysosomal alkalizing agent, can diffuse into lysosomes, causing the lysosomal pH to rise and dysfunction so that the lysosomes no longer fuse with the autophagosome, thereby blocking autophagic flux (11). However, the use of HCQ/CQ as a monotherapy strategy to block autophagic flux displays limited antitumor activity in clinical treatment (12). However, when HCQ is combined with autophagic stimulus, it can significantly increase its antitumor effect and reduce its dosage (13).

Aberrant endoplasmic reticulum (ER) status triggers autophagy stimulation (14). The ER acts as a reservoir of calcium ions in cells and is responsible for the correct folding and secretion of proteins (15). The accumulation and aggregation of misfolded proteins cause ER stress, triggering unfolded protein response (UPR) to significantly increase the autophagic level to restore homeostasis (16). As an ER stress initiator, tunicamycin (Tuni) blocks N-glycosylation and causes ER stressinduced autophagy to increase the autophagic level through PERK [protein kinase RNAlike ER kinase]/Akt (protein kinase B)/mTOR (mammalian target of rapamycin) signaling pathways, which are also closely related to matrix metalloproteinase-2 (MMP-2) expression (17).

Therefore, the combined application of the autophagic flux blocker HCQ and the ER stress initiator Tuni could cause cancer cells to have a special autophagic stress, which can severely disrupt cell homeostasis and cause cell death, resulting in a better therapeutic effect for tumor treatment. However, for a systemic administration of HCQ and Tuni, challenges such as poor hydrophilicity, poor biodistribution profile, low tumor accumulation, and tumor acid microenvironment prevent the drugs from penetrating the cell membranes, further affecting the application of free drugs in vivo (18). Moreover, high-dose HCQ in clinical application can only produce a moderate blockage of autophagic flux due to its poor efficacy, thus producing capricious therapeutic effects (19). Thus, the drug nanocarrier is considered to solve the above problems (20), as it has the following features: co-encapsulating hydrophilic and hydrophobic drugs, accumulating in tumor tissues through an enhanced permeability and retention (EPR) effect (21), entering the cells through the lysosomal pathway, and stimulating drug release with environment-responsive signals (22).

In addition, metastatic tumors undergo local migration and invasion in the early stage of tumor metastasis, and the migration speed depends on the focal adhesions (FAs) turnover (23). FAs are transmembrane multiprotein complexes containing integrins, paxillin, talin, zyxin, etc. Both cell-cell and cellextracellular matrix (ECM) adhesions form a stable connection via FAs (24). The decomposition of FAs at the cell rear by autophagy is critical for the forward movement and successful migration/invasion of tumor cells (25). In addition, MMPs are also an important factor in the selective regulation of tumor microenvironment to promote tumor metastasis, and are considered to be an inducer of epithelial-mesenchymal transition (26). The ER stress induced by Tuni regulates the PERK/Akt signaling pathway and down-regulates the expression of MMP-2 (27). Both the inhibition of the FAs turnover and the down-regulation of the expression of MMP-2 will reduce tumor metastasis.

Accordingly, in this study, we develop a pH-responsive polymersome for codelivering HCQ and Tuni drugs to simultaneously induce ER stress and block autophagic flux for achieving the antitumor effect and inhibiting tumor metastasis. A dual drugloaded, pH-responsive polymersome, Tuni/HCQ@CS-PAE, was designed to achieve this objective. The amphiphilic polymer chondroitin sulfate (CS)poly(-amino ester) was used to fabricate this polymersome, and hydrophilic HCQ and hydrophobic Tuni were loaded into the inner cavity and outer shell, respectively. Poly(-amino esters) with acid-stimulated responses are a class of highly biocompatible polymers and are believed to satisfy the performance of drug delivery (28). Repeated tertiary amine groups on the poly(-amino esters) are protonated by acid stimulation, thereby converting the hydrophobicity of the segment, resulting in the dissociation of the nanostructure and drug release (29). Simultaneously, the protonation process produces a similar HCQ effect to deacidify the lysosomes, swelling and rupturing the lysosomes, which can help the drugs to escape from the lysosomes and block the autophagic flux together with HCQ (30). Polymersomes with both a hydrophilic inner cavity and a hydrophobic shell are considered promising drug delivery platforms (31). In this work, the hydrophilic CS component can mask the surface positive charges of poly(-amino ester), prolonging the blood circulation time of the polymersomes. These polymersomes reached tumor tissues through the EPR effect, overcoming the nonselective distribution of the Tuni and HCQ drugs in vivo, increasing intratumoral accumulation, entering cells by endocytosis, and remaining in the lysosomes. Because of the pH response of poly(-amino ester), the polymersomes dissociated and produced a similar alkalization effect in lysosomes with HCQ, destroying and rapidly escaping the lysosomes, releasing the drugs Tuni and HCQ. Under the dual action of poly(-amino ester) and HCQ, the lysosomes in the tumor cells were destroyed, resulting in the blockade of autophagic flux. Moreover, the released Tuni triggered ER stress, further regulating the PERK/Akt signaling pathway to enhance the autophagic level and down-regulate the MMP-2 expression. The tumor cells were simultaneously attacked by both the inducement of autophagy due to the ER stress and the blockade of autophagic flux due to lysosomal destruction, resulting in a special autophagic stress, which seriously damaged the cell homeostasis and caused cell death.

The synthetic routes of CS-poly(-amino ester) are shown in fig. S1. The chemical structures of the block copolymers were confirmed using Fourier transform infrared spectra and nuclear magnetic resonance (NMR) spectra (figs. S2 to S4). The number-average molecular weight of CS-poly(-amino ester) was obtained as 8044 g/mol through gel permeation chromatography. The dual drugloaded Tuni/HCQ@CS-PAE polymersome was prepared by dialysis. The encapsulation efficiency (EE) and encapsulation content (EC) of Tuni were 38.5 and 10.5%, while those of HCQ were 56.1 and 11.2%, respectively. The morphologies of the Tuni/HCQ@CS-PAE polymersomes were characterized using transmission electron microscopy (TEM). Apparent vesicle structures with a size of ~180 nm can be observed in Fig. 1A, and the shell thickness of the vesicle in the enlarged image is ~30 nm. The average hydrodynamic size of the Tuni/HCQ@CS-PAE polymersomes was 230.0 9.3 nm, as measured using dynamic light scattering (DLS), with a polydispersity index of 0.156. The potential was 17.2 mV (Fig. 1B), and the negative charge indicated that it is suitable for drug carriers because it cannot be prematurely cleared in the blood circulation (32). The investigation of stability suggested that the polymersomes showed no significant changes (P > 0.05) in particle size when they were placed in phosphate-buffered saline (PBS) buffer and 10% fetal bovine serum (FBS) for 48 hours at 37C (fig. S5), indicating their potential for application in vivo. The pH response of the Tuni/HCQ@CS-PAE polymersomes was evaluated in a lysosomal acidic environment, and the CS-poly(-amino ester) was assayed to determine its pKa (where Ka is the acid dissociation constant) via acid-base titration. The results showed that CS-poly(-amino ester) had a pKa value of 5.4 (Fig. 1C), which was close to the lysosomal acidity (pH = ~5.0) (33). The TEM image obtained after the Tuni/HCQ@CS-PAE polymersomes were stored at pH 5.0 for 4 hours showed that the polymersome structure disappeared (Fig. 1D), indicating that the pH response of CS-poly(-amino ester) successfully caused the dissociation of the polymersomes. The 1H-NMR spectrum of CS-poly(-amino ester) in deuterium chloride at pH 5.0 (fig. S6) showed that the peak of poly(-amino ester) could be observed, indicating that it was hydrophilic at pH 5.0. DLS was further used to detect the pH response of the Tuni/HCQ@CS-PAE polymersomes. As shown in Fig. 1E, after the polymersomes were stored under the three acidic conditions of pH 7.4, pH 6.8, and pH 5.0 for 4 hours, the particle size distribution demonstrated that the polymersomes at both pH 7.4 and pH 6.8 (tumor ECM acidity) were stable; whereas at pH 5.0, the polymersome structure was destroyed, which is consistent with the TEM results. At pH 5.0, the potential of the Tuni/HCQ@CS-PAE polymersomes significantly shifted from 17.2 to 2.08 mV (Fig. 1F), indicating that the protonation of CS-poly(-amino ester) resulted in the capture of strong positive charges. The pH response of the polymersomes imparts them the ability to release drugs on-demand. As shown in Fig. 1 (G and H), the release of HCQ and Tuni at pH 6.8 was not significantly different (P > 0.05) from that at pH 7.4, suggesting that the polymersomes were stable in the tumor ECM and would not be released in advance. However, the 24-hour releases of HCQ and Tuni at pH 5.0 (lysosomal acidity) were 86.5 and 76.6%, respectively, which were 7.52 and 6.66 times the releases at pH 7.4, respectively. This result indicates that the Tuni/HCQ@CS-PAE polymersomes can rapidly release drugs in acidic lysosomes.

(A) TEM images of the Tuni/HCQ@CS-PAE polymersomes at pH 7.4. (B) Measurement results of the Tuni/HCQ@CS-PAE polymersomes by the Malvern laser particle size analyzer at pH 7.4. (C) Acid-base titration curve of CS-poly(-amino ester). (D) TEM images of Tuni/HCQ@CS-PAE at pH 5.0. (E) Hydrodynamic particle size distribution of the Tuni/HCQ@CS-PAE polymersomes at pH 7.4, pH 6.8, and pH 5.0. (F) potential of the Tuni/HCQ@CS-PAE polymersomes at pH 7.4, pH 6.8, and pH 5.0. (G) Release profiles of HCQ from the Tuni/HCQ@CS-PAE polymersomes. (H) Release profiles of Tuni from the Tuni/HCQ@CS-PAE polymersomes.

Before applying the polymersomes to cells and animals, both mouse breast cancer cells (4T1) and human umbilical vein endothelial cells (HUVECs) were used to evaluate the cytocompatibility of the polymersome delivery system. The blank material CS-PAE polymersomes exhibited good cytocompatibility at a concentration of 20 to 400 g/ml (cell viability over 85%, Alamar Blue assay; fig. S7, A and B). Only a small amount of red spots (representing dead cells) was observed in the fluorescence image of cells, with a polymersome concentration of up to 400 g/ml (live-dead cell staining; fig. S7C), also confirming the low cytotoxicity of the polymersomes.

The endocytic pathway of polymersomes was further examined in vitro. Fluorescein isothiocyanate (FITC)labeled (green) polymersomes were cocultured with adherent 4T1 cells, and the locations of the polymersomes in the cells and lysosomes labeled by LysoTracker Red DND-99 (red) were observed using fluorescence microscopy at 1 hour (fig. S8A) and 4 hours (fig. S8C), respectively. A large amount of yellow fluorescence in the cells was observed at 1 hour, which was the result of the overlap between green fluorescence and red fluorescence, suggesting that the polymersomes were in the lysosomes. At 4 hours, the yellow fluorescent signal decreased and the separated green and red fluorescent signals increased, indicating that the polymersomes were separated from the lysosomes. The figures (fig. S8, B and D) show the corresponding fluorescence intensity profiles of the white arrow regions in fig. S8 (A and C) obtained using ImagePro Plus, respectively. It can be observed that there was a large overlap between the two fluorescent signals at 1 hour, and their Pearsons correlation coefficient was calculated to be 0.88, indicating that the polymersomes and the lysosomes were strongly colocalized at 1 hour. At 4 hours, the Pearsons correlation coefficient was reduced to 0.04 according to fig. S8D, indicating that the polymersomes successfully escaped from the lysosomes. This result indicates that the polymersomes were endocytosed into the cells by the lysosomal pathway and could successfully escape the lysosomes at 4 hours in vitro.

The damage to the lysosomes by poly(-amino ester) and HCQ was marked by an increase in the lysosomal pH value. The LysoSensor Green-189 can monitor the acidity of the lysosomes, and its fluorescence reaches the highest value in normal lysosomes and decreases with increasing pH value. As shown in fig. S8E, it was observed via fluorescence microscopy that the green fluorescence in the HCQ, blank material CS-PAE polymersomes, and Tuni/HCQ@CS-PAE treatment groups was weakened to varying degrees. The results of the fluorescence-activated cell sorter (FACS) can be more intuitively observed (fig. S8F), and Tuni did not cause a change in the acidity of the lysosomes compared with that of untreated cells (control). Both the HCQ drug and CS-PAE polymersome had an alkalization ability for lysosomes, but HCQ performed better. This can be ascribed to the fact that CS-PAE polymersomes can only destroy lysosomes involved in endocytosis. The Tuni/HCQ@CS-PAE treatment group performed the best, and the median fluorescence intensity was only 14.3% of the control group, suggesting that the double action of HCQ and the polymersomes caused an increase in the intracellular lysosomal pH.

The relationship between various treatments and autophagy was further examined in vitro. Acridine orange (AO) is an acid-sensitive dye that stains the acidic organelles, including autophagosomes and autolysosomes in the cells red, whereas the DNA and cytoplasm in cells are green. Accordingly, the ratio of red to green signals can be used to evaluate the autophagic level (34). As shown in Fig. 2A, the number of red spots (observed via fluorescence microscopy) is positively correlated with the autophagic level. The red/green ratio calculated using FACS determines the autophagic level in each treatment group (Fig. 2B). The red/green ratios of the treatment groups increased compared with those of the untreated cells (control). The red/green ratio of the Tuni/HCQ@CS-PAE treatment group was approximately 68.0% higher than that of the Tuni/HCQ treatment group and was 1.91 and 2.21 times those of Tuni@CS-PAE and HCQ@CS-PAE, respectively. The red/green ratios of Tuni@CS-PAE and HCQ@CS-PAE also increased by 83.3 and 58.3%, respectively, compared with that of the blank material CS-PAE polymersomes. The red/green ratio of the CS-PAE polymersomes treatment group was also significantly increased by 71.4% compared with that of the control group. The results suggest that both Tuni and HCQ can cause an accumulation of acidic organelles, in addition to CS-PAE polymersomes. Unfortunately, the AO cannot distinguish whether the acidic organelles are autophagosomes or autolysosomes.

(A) Fluorescence images and (B) FACS analysis of AO-stained 4T1 cells after incubation with different treatments for 24 hours; ***P < 0.001. (C) Fluorescence images of mCherry-GFP-LC3 4T1 cells after incubation with different treatments for 48 hours. (D) Quantification of the number of LC3 puncta per cell (autophagosomes, yellow puncta; autolysosomes, red puncta). (E) TEM images of cells treated with saline or Tuni/HCQ@CS-PAE polymersomes (N, nucleus; green arrow, autophagosomes; red arrow, autolysosomes).

To track the autophagic flux, mCherrygreen fluorescent protein (GFP)LC3 adenovirustransfected cells were used. When autophagy occurs, a recognized autophagy marker, LC3, aggregates in both the inner and outer membranes of the autophagosomes. The LC3 in the transfected cells simultaneously expresses red fluorescence (mCherry) and green fluorescence (GFP). Thus, it will be observed in the form of yellow puncta in the autophagosomes. When the autophagosomes and lysosomes eventually fuse to form the autolysosomes, GFP is quenched by lysosomal acidity and only exhibits red puncta. Thus, the yellow and red puncta represent the autophagosomes and autolysosomes in the autophagic flux, respectively (Fig. 2C). The LC3 puncta statistic is shown in Fig. 2D. Comparing the LC3 puncta distribution of the Tuni@CS-PAE treatment group with that of the HCQ@CS-PAE treatment group, the former has more red puncta, indicating that the autophagic flux had entered the final stage, and the autolysosome had been formed. The large yellow puncta of the latter indicate that the autophagic flux mainly remained in the autophagosome stage, suggesting that HCQ@CS-PAE destroyed the lysosomes and prevented the autophagosomes from merging with the lysosomes. In contrast to CS-PAE polymersomes, Tuni@CS-PAE increased the autophagosome puncta and autolysosome puncta, indicating that it effectively increased the autophagic level in the cells. Compared with CS-PAE polymersomes, HCQ@CS-PAE showed a significant increase in the autophagosomes, but there was a decrease in the autolysosomes, which proved that HCQ@CS-PAE has a stronger ability to destroy the lysosomes and block the autophagic flux at the autophagosome stage. The autophagic level of the Tuni/HCQ@CS-PAE treatment group was greatly improved compared with that of Tuni/HCQ, whereas the number of autolysosomes was reduced. This result indicated that the dual drugloaded, pH-responsive polymersomes could increase the autophagic level and block the autophagic flux more evidently than free drugs.

From the TEM images (Fig. 2E), it can be observed that abundant autophagosomes (green arrows) and a few autolysosomes (red arrows) accumulated in the Tuni/HCQ@CS-PAE treatment group, in contrast to the control group (saline treatment). The increase in the autophagosomes and autolysosomes showed that the autophagic level of the Tuni/HCQ@CS-PAE treatment group was significantly enhanced. Furthermore, the amount of autophagosomes was significantly more than the amount of autolysosomes, indicating that the autophagic flux was blocked during the fusion process of the autophagosomes and the lysosomes.

The ability of the polymersomes to resist tumor metastasis was examined. A wound-healing assay (Fig. 3A) and the transwell invasion assay (Fig. 3B) were used to assess the cell migration and invasion in each group of treatments in vitro. The migration area (calculated by ImageJ) in the wound-healing assay is shown in Fig. 3C. The migration area of the Tuni/HCQ@CS-PAE treatment group is only 21.1% (P < 0.001) and 38.4% (P < 0.001) of those of Tuni@CS-PAE and HCQ@CS-PAE, respectively. Matrigel matrix (simulated ECM) was coated in the transwell upper chamber as an in vitro test tool for cell invasion. As shown in Fig. 3D, the number of cells (crystal violet staining) that arrived at the back of the polycarbonate membrane was counted as a quantitative index of invasive ability. The number of invasive cells in the Tuni/HCQ@CS-PAE treatment group was only 6.7% of that in the untreated group, 8.7% of that in the Tuni@CS-PAE treatment group, and 19.3% of that in the HCQ@CS-PAE treatment group. The above results show that the drug delivery system can effectively inhibit cell migration and invasion in vitro. Furthermore, Tuni@CS-PAE has a certain effect in inhibiting cell migration and invasion, but this effect is weaker than that of HCQ@CS-PAE.

(A) Typical images of wound-healing assay. (B) Cell invasion with the transwell assay (bottom). (C) Migration area of the wound-healing assay. (D) Number of invaded cells by the transwell assay. All data are represented as the means SD from three independent experiments; ***P < 0.001.

The in vitro cell viability of different treatment groups was firstly investigated. As shown in fig. S9A, the decrease in cell viability was positively correlated with increased autophagic level and autophagic flux blockade. On the basis of the concentration of fig. S9B, the median effect plots (fig. S9, C and D) of Tuni/HCQ and Tuni/HCQ@CS-PAE can be calculated to obtain their half maximal inhibitory concentration (IC50) values. According to the calculation method in the Supplementary Materials, the IC50 value of the Tuni/HCQ@CS-PAE treatment group is 8.2 M, which is 27.7% lower than that of the Tuni/HCQ treatment group.

The antitumor effect of the pH-responsive polymersome codelivering HCQ and Tuni drugs was further evaluated using the orthotopic luciferase genetransfected 4T1 (4T1-Luc) tumorbearing BALB/c mice. The treatment schedule is shown in Fig. 4A. After 7 days of orthotopic 4T1-Luc tumor implantation, the mice were randomly divided into six groups, and the drugs or drug-loaded polymersomes were administered intravenously at 0, 3, 6, and 9 days. The IVIS imaging system was used to monitor the bioluminescence signals of the tumors at days 0 and 30 (Fig. 4B). Ex vivo tumors were photographed on day 30 (Fig. 4C), and tumor volume was measured once in 3 days (Fig. 4D) and ex vivo tumors weighed on day 30 (Fig. 4E). Tumor growth inhibition (TGI; Fig. 4F) was calculated by tumor weight. The results indicated that three of the 4T1 tumors in the Tuni/HCQ@CS-PAE treatment group had successfully ablated, and the tumor weight was only 9.6% (P < 0.001) and 4.6% (P < 0.001) of those treated with Tuni@CS-PAE and HCQ@CS-PAE, respectively, whereas the TGI was as high as 97.5%. This proves that Tuni/HCQ@CS-PAE has an excellent antitumor effect. The body weight of the mice was monitored every 3 days (Fig. 4G), and it showed no difference in each treatment group on day 30 (P > 0.05), indicating the safety of the polymersome delivery system and the potential for application in vivo. Hematoxylin and eosin (H&E) staining of the main organs (heart, liver, spleen, and kidney) (fig. S10) also revealed no significant morphological changes in all the treatment groups.

(A) Treatment schedule for 4T1 breast tumor in BALB/c mice. (B) Bioluminescence images of 4T1-Luc tumorbearing BALB/c mice were taken on days 0 and 30 after various treatments. (C) Photographs of the tumors removed from the mice in the different treatment groups at the end of the experiment. (D) Tumor volume growth curves of the different treatment groups. (E) Weight of isolated tumors in the different treatment groups. (F) Tumor growth inhibition (TGI) after the different treatments. (G) Body weight changes of mice in the different treatment groups. (H) Hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) analysis of tumor sections after the different treatments. All statistical data are presented as means SD. (n = 5; #P > 0.05; ***P < 0.001). [Photo credit for (B), (C), and (H): Funeng Xu, Southwest Jiaotong University].

H&E staining, terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick end labeling (TUNEL), and immunohistochemical (IHC) analyses (Ki67) were used to characterize the antitumor effects further (Fig. 4H). The H&E staining sections of the Tuni/HCQ@CS-PAE treatment group showed nuclear shrinkage and fragmentation, and the cell contour disappeared. Its TUNEL-positive signal (characterized apoptosis, brown) was the largest, and its Ki67-positive signal (characterized proliferation, brown) was the smallest. These results suggest that the lysosomal pH-responsive polymersomes entrapped with Tuni and HCQ can achieve excellent antitumor effects in tumor-bearing mouse models, demonstrating the success of autophagy regulation in antitumor applications.

The mouse 4T1 tumor is a metastatic tumor, corresponding mainly to lung and bone metastasis (35). The lung of the mouse was excised on day 30, and the lung metastasis of the tumor was observed using the bioluminescence images (Fig. 5A). There was no bioluminescence signal in the Tuni/HCQ@CS-PAE treatment group, indicating that there was no lung metastasis. Moreover, the pulmonary nodules are visualized using a Bouins fixative in Fig. 5B, which also supports this conclusion. The table summarizes the number of metastasis nodes (NOMN) (Fig. 5C), and the lung nodules are categorized by diameter: less than 0.5 mm, 0.5 to 1 mm, 1 to 2 mm, and greater than 2 mm, weighted 1 to 4 in turn. Because of the effective treatment of orthotopic tumors and the effective regulation of autophagy, Tuni/HCQ@CS-PAE has an excellent antimetastatic ability. The results of NOMN are shown in Fig. 5D. The average NOMN of the HCQ@CS-PAE treatment group was 52.89% that of the Tuni@CS-PAE treatment group and 22.49% that of the CS-PAE polymersomes treatment group. This indicates that both HCQ@CS-PAE and Tuni@CS-PAE can inhibit tumor metastasis to a certain extent, but the former performed better than the latter, which is also consistent with the results of in vitro antimetastasis evaluation. The H&E staining of the lungs can also demonstrate the antimetastatic effect (Fig. 5E). The red circle framed the foreign tissues of the lungs, and the foreign tissues were observed to be tumor tissues by comparison with the H&E staining of the tumors. No tumor tissue was observed in the H&E sections of the Tuni/HCQ@CS-PAE treatment group, and the area of the tumor tissue was significantly reduced in the Tuni@CS-PAE and HCQ@CS-PAE treatment groups compared with that in the saline group, which is consistent with the lung metastasis results of Fig. 5 (A and B).

(A) Bioluminescence images of tumor lung metastases in each treatment group in vitro. (B) Photographs of lung tissues; tumor metastasis was visualized by Bouins fixative, and metastatic nodules were white (represented by red arrows). (C and D) Counting the number of lung metastasis nodules, measurement of the diameter of metastatic tumors, and performing classification and counting. Number of metastasis nodes (NOMN) = I 1 + II 2 + III 3 + IV 4 (according to the diameter of the lung nodules for class 4: I < 0.5 mm, 0.5 mm II < 1 mm, 1 mm III 2 mm, and IV > 2 mm). (E) H&E staining of lung tissue after the various treatments. The red circle marks the metastatic tumor tissue. [Photo credit for (A), (B), and (E): Funeng Xu, Southwest Jiaotong University].

The dual drugloaded, pH-responsive polymersomes (Tuni/HCQ@CS-PAE) have made breakthroughs in the antitumor effect and metastasis inhibition effects in tumor-bearing mice. Western blot (WB) and IHC were further used to explore the mechanism of action of Tuni/HCQ@CS-PAE. ER stress and autophagy are closely related (Fig. 6A). It has been reported that the ER stress enhances the autophagic level by negatively regulating the Akt/mTOR pathway (36). In addition, the expression of MMP-2 is down-regulated by the down-regulation of Akt expression. Therefore, it can be concluded that the Tuni/HCQ@CS-PAE polymersome has two important functions in vivo: increasing autophagic levels and decreasing the MMP-2 expression and blocking the autophagic flow at the autophagosome stage by preventing the fusion of the autophagosomes and the lysosomes.

(A) Schematic diagram of Tuni causing ER stress, promoting autophagy, and reducing MMP-2 expression via signaling pathways in vivo. (B) WB analysis of key proteins of ER stress and downstream pathway protein of 4T1 tumor in BALB/c mice. (C) Relative expression level of key proteins in (B); ***P < 0.001 compared with control. (D) Expression of LC3 and p62 lanes of 4T1 tumor in BALB/c mice via WB. (E) Quantification of the ratio of LC3-II to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and p62 to GAPDH expression using ImageJ software. (F) IHC pictures of talin-1, paxillin, and MMP-2 in 4T1 tumorbearing BALB/c mice.

Under normal physiological conditions, GRP78/BiP (78-kDa glucose-regulated protein/immunoglobulin heavy chainbinding protein) acts as an ER chaperone and binds to ER receptors, which is in an inactive state. However, under ER stress, GRP78/BiP dissociates from ER receptors to activate and trigger UPR (37). The dissociation of GRP78/BiP from PERK (ER transmembrane receptor) triggers kinase dimerization and autophosphorylation to generate activated PERK (p-PERK) (38). Therefore, the expression of GRP78/BiP and p-PERK can be used as an indicator of ER stress. The expression of GRP78/BiP and p-PERK of the Tuni/HCQ@CS-PAE treatment group was significantly increased by 59.7% (P < 0.001) and 87.0% (P < 0.001), respectively, compared with that of the control group (Fig. 6, B and C). It indicated that Tuni/HCQ@CS-PAE can strongly trigger ER stress. The expressions of GRP78/BiP and p-PERK of the Tuni/HCQ treatment group were only 71.7% (P < 0.001) and 70.9% (P < 0.001), respectively, of that of the Tuni/HCQ@CS-PAE treatment group, suggesting that the polymersome system is more efficient than the free drugs at the same dose. The occurrence of ER stress triggered a series of downstream signaling pathways. The expressions of p-Akt and p-mTOR proteins in the Tuni/HCQ@CS-PAE treatment group were reduced by 80.0% (P < 0.001) and 67.2% (P < 0.001), respectively, compared to the control group, suggesting that the increase in the upstream event down-regulates Akt and mTOR activity. The expression of MMP-2 was significantly decreased in the Tuni/HCQ@CS-PAE and Tuni@CS-PAE treatment groups, which were only 32.8 and 41.0% of that of the control group, respectively, which was consistent with the trend of p-Akt expression.

When the autophagy occurs, LC3-I, which is in the cytoplasm of cells, is modified and processed to form LC3-II and expressed on the autophagosome membrane. The expression of p62 (sequestosome-1) as an autophagy substrate can characterize the smoothness of the autophagic flux. When the autophagic level is increased and the autophagic flux is smooth, the expression of LC3-II is increased and the expression of p62 is decreased; however, when the autophagy level is increased and the autophagic flux is blocked, the expression of both LC3-II and p62 is increased (39, 40). As shown in Fig. 6 (D and E), the expression of LC3-II and p62 was up-regulated in all the treatment groups compared with that in the control group, suggesting that the autophagic level of each treatment group was increased, and the autophagic flux was blocked to some extent. The highest expression of LC3-II was observed for Tuni/HCQ@CS-PAE and Tuni@CS-PAE, which was consistent with the results of down-regulation of p-mTOR. The expression of LC3-II of HCQ@CS-PAE was also significantly improved, indicating that, when autophagic flux was blocked by lysosomal destruction, the overall autophagic level of the cells also increased, and the autophagic flux mainly remained in the autophagosome stage. The expression of p62 was the highest in the Tuni/HCQ@CS-PAE and HCQ@CS-PAE treatment groups, i.e., 4.67 (P < 0.001) and 4.13 (P < 0.001) times that of the control group, respectively, suggesting that substrate degradation in the autophagosomes was largely blocked.

Talin-1 and paxillin are the constituent proteins of the FAs. The turnover of FAs is the basis of cell movement. The blockade of the autophagic flux leads to the failure of FAs degradation, which reduces the ability of cell movement. As shown in Fig. 6F, the IHC sections of Tuni/HCQ@CS-PAE and HCQ@CS-PAE showed the largest amounts of talin-1 and paxillin, indicating that the blockade of autophagic flux can significantly prevent FAs turnover. In the IHC section analysis of MMP-2, the expression of MMP-2 of the Tuni/HCQ@CS-PAE and Tuni@CS-PAE treatment groups was significantly inhibited, and the results were also consistent with the WB test in Fig. 6B, indicating that the MMP-2 expression was closely related to the ER stress induced by Tuni. It is suggested that based on the results of in vitro and in vivo antimetastasis experiments, it is known that HCQ@CS-PAE has stronger antimetastatic ability than Tuni@CS-PAE, also suggesting that the reduction in FAs turnover by autophagy affects tumor metastasis more than the decrease in the MMP-2 expression. Thus, Tuni/HCQ@CS-PAE achieved a considerable tumor-metastasis inhibition effect under the combined effect of down-regulation of MMP-2 expression and inhibition of FAs turnover.

CS was acetylated to increase its solubility in dimethyl sulfoxide (DMSO). Briefly, CS (1.0 g) was added to a round-bottom flask containing formamide (50.0 ml). The system was heated to 80C to promote dissolution and then cooled to room temperature. Pyridine (557.0 l) and acetic anhydride (500.0 l) were added to the round-bottom flask and magnetically stirred at room temperature for 12 hours. The reaction solution was dialyzed and lyophilized to obtain acetylated CS (Ac-CS; 0.91 g), which was stored for later use.

Ac-CS (0.41 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.16 g), and N-hydroxysuccinimide (0.04 g) were dissolved in reverse osmosis (RO) water. Triethylamine (0.08 g) was added to this mixture, and magnetic stirring was performed to activate the carboxyl group in an ice bath. Subsequently, 1,6-hexanediamine (0.63 g) was added, and the mixture was stirred at room temperature for 24 hours. The product Had-Ac-CS (0.49 g) was obtained via the dialysis and lyophilization of the reaction solution.

CS-poly(-amino ester) was prepared via the Michael addition reaction. Had-Ac-CS (0.37 g), Hexane-1,6-dioldiacrylate (HDDA) (0.5 g), and 3-dibutylamino-1-propylamine (DBPA) (0.37 g) were dissolved in 15 ml of DMSO, and the round-bottom flask was purged with N2. The mixture was stirred at 50C for 5 days. CS-poly(-amino ester) (1.1 g) was obtained via the dialysis and lyophilization of the reaction solution.

Dialysis was used to prepare the dual drugloaded polymersomes. First, 20.0 mg of CS-poly(-amino ester) and 7.0 mg of Tuni were codissolved in a beaker containing 5.0 ml of DMSO. Then, 5.0 ml of RO water containing 5.1 mg of HCQ was added dropwise under high-speed stirring, and the system was continuously stirred for 20 min. The system was transferred to a dialysis bag (molecular weight cutoff, 3500) for 48 hours and then lyophilized for the next experiment. EE and EC were calculated by Eqs. 1 and 2, respectivelyEE(%)=Weight of the drug in polymersomesWeight of the drug in feed100(1)EC(%)=Weight of the drug in polymersomesWeight of drug-loaded polymersomes100(2)

CS-poly(-amino ester) was placed in deionized water, and HCl solution was added until it was completely dissolved. Then, 1 to 5 l of 0.1 M NaOH solution was added dropwise, and the pH was measured after each addition. The pKa of the polymer is the pH at which it is half ionized.

The pH response of polymersomes was characterized by DLS, TEM, and 1H-NMR, respectively. The polymersomes were placed at pH 5.0, pH 6.8, and pH 7.4, respectively. After 4 hours, DLS was used to measure the particle size distribution and potential. Samples at pH 5.0 were also used for TEM and 1H-NMR detection.

The release of Tuni and HCQ in Tuni/HCQ@CS-PAE was investigated under three acidity conditions of pH 7.4, pH 6.8, and pH 5.0 at 37C. The release solution was taken 1 ml each time at the planned time point, and the same volume of fresh medium was added. The release solution was treated and analyzed by high-performance liquid chromatography.

Size changes of Tuni/HCQ@CS-PAE polymersomes after incubation in PBS or in cell culture medium [containing 10% FBS (v/v)] were monitored by DLS. The polymersome concentration was 1 mg ml1, and the experimental conditions were 37C.

Alamar Blue assay and live-dead staining were used to determine the cytocompatibility of blank polymersomes. In Alamar Blue assay detection, 1 104 cells per well of 4T1 and HUVECs were seeded in 48-well plates. After 24 hours of culture, polymersomes with 20 to 400 g/ml were added to each well. After 48 hours, the culture medium was removed, and 300 l of Alamar Blue solution [10% Alamar Blue, 80% media 199 (Gibco), and 10% FBS, (v/v)] was added for a further 3-hour incubation. They were then transferred to 96-well plates and detected by automated microplate spectrophotometer. For live-dead staining, 2 104 cells per well of 4T1 and HUVECs were seeded in 24-well plates. The cells were stained by 2 mM calcein acetoxymethylester for 10 min and propidium iodide for 5 min after 48 hours incubation, with different concentrations of polymersomes. Live cells were stained green, and dead cells were stained red when visualized by fluorescence microscopy.

4T1 cells were cultured in confocal dishes for 12 hours in Dulbeccos modified Eagles medium with 10% FBS. FITC-labeled polymersomes were added to two sets of confocal dishes, and then the medium was discarded at 1 and 4 hours, respectively. Cells were washed three times with PBS before staining, and then lysosomes were labeled with the LysoTracker Red DND-99. The fluorescence signal was observed by fluorescence microscopy.

Adherent 4T1 cells were treated with saline, Tuni, HCQ, CS-PAE, and Tuni/HCQ@CS-PAE for 12 hours, and stained with the acid-sensitive dye LysoSensor Green-189. The fluorescence intensity of each group was measured by fluorescence microscope and FACS.

The adherent 4T1 cells were treated with saline, CS-PAE, Tuni/HCQ, Tuni@CS-PAE, HCQ@CS-PAE, and Tuni/HCQ@CS-PAE, respectively. After 24 hours, the cells were stained with AO (1 l) for 15 min and detected by fluorescence microscopy and FACS, respectively.

4T1 cells were inoculated with 5 105 per well in confocal dishes before infection. The density of cells before virus transfection reached 50%, and the amount of virus mother liquor added to the plate was plaque-forming units = cell number multiplicity of infection (MOI). MOI was 20, 24 hours after infection; 2 ml of fresh medium was added to each well to replace the virus-containing medium.

4T1 cells were seeded in culture flasks at a density of 1 106 cells/ml for 18 hours. Then, saline and Tuni/HCQ@CS-PAE were added for 48 hours, respectively. Cells were digested, collected by centrifugation, and then fixed overnight in 2.5% glutaraldehyde. Samples were prepared according to TEM standard procedures and photographed.

Alamar Blue assay was used to assess the in vitro cytotoxicity. 4T1 cells were seeded in 48-well plates at a density of 2 104 cells per well. After the cells were cultured for 24 hours, various preparations were added to the well plates for 48 hours. After the incubation, 300 l of Alamar Blue solution was added for further 3 hours, and then the Alamar Blue solution was transferred to a 96-well plate, and the absorbance was measured with an automated microplate spectrophotometer. The median effect plot was a straight line fit with X = log(D) versus Y = log[fa/(1 fa)] (41). The theoretical IC50 value is the drug concentration corresponding to the x axis intercept of the median effect plot.

4T1 cells were seeded in six-well plates. When the cell confluence reached 100%, scratches were made with a 200-l pipette tip, and cells were washed three times with PBS to remove the delineated cells. The treatments were added to each group. Various therapeutic agents were added to the treated six-well plates and cultured for 36 hours in serum-free medium. The entire process was monitored with a microscope, and the healing area was calculated by ImageJ.

One hundred microliters of the diluted Matrigel was added vertically in the center of the transwell upper chamber and incubated at 37C for 4 hours to form a gel. Six hundred microliters of 10% serum medium was added to the lower chamber, and 100 l of the cell suspension was added to the upper chamber, and incubation was continued for 24 hours. The transwell chamber was removed, fixed in methanol for 30 min, stained with 0.1% crystal violet for 20 min, and the uninjured cells in the upper layer were gently wiped off with a cotton swab, and the count was observed with a microscope.

4T1-Luc cells were injected into the mouse mammary fat pad to establish an orthotopic breast cancer model. The animal experiments were approved by the Institutional Animal Care and Use Committee of Sichuan University and carried out in compliance with its guidelines. When the tumor volume of the mouse reached approximately 35 mm3, it was defined as 0 day of treatment, and the mice were randomly divided into six groups of five mice each. Each group was administered through the tail vein at 0, 3, 6, and 9 days of treatment [Tuni (7.5 mg/kg)]. Tumor volumes were calculated using the following equation: V = 0.5 A B2 (A refers to tumor length, and B refers to the tumor width). TGI was calculated using the following equation: TGI (%) = 100 (mean tumor weight of saline group mean tumor weight of experimental group)/mean tumor weight of saline group.

4T1 tumorbearing BALB/c mice were sacrificed, and the heart, liver, spleen, lung, kidney, and tumor tissues were excised, fixed with 10% formalin, dehydrated with gradient ethanol, and embedded in paraffin block. After denitrification with xylene, 4-m-thick tissue sections were stained with H&E, or for TUNEL detection, or for IHC staining with rabbit antiKi-67 polyclonal antibody and lastly observed with an optical microscope.

The potential association of ER stress with autophagy and antimetastatic mechanisms were analyzed by WB and immunohistochemistry. BIP/GRP78, PERK, Akt, mTOR, LC3, and p62 were used for WB analysis to explore the ER stressautophagy signaling pathway based on relative expression levels. MMP-2, talin, and paxillin were used as indicators of antimetastasis to analyze changes in their expression through WB and immunohistochemistry.

SPSS software was used for the statistical data analysis. Data were presented as means SD. One-way analysis of variance (ANOVA) was performed to determine statistical significance of the data. The differences were considered significant for #P > 0.05, *P < 0.05, **P < 0.01, and ***P < 0.001.

Acknowledgments: We thank the Analytical and Testing Center of the Southwest Jiaotong University. Funding: This work was partially supported by the China National Funds for Distinguished Young Scientists (51725303), the National Natural Science Foundation of China (21574105), and the Sichuan Province Youth Science and Technology Innovation Team (2016TD0026). Author contributions: F.X., Y.W., and S.Z. designed research; F.X., X.L., and X.H. performed research; F.X. and J.P. analyzed data; and F.X. and S.Z. wrote the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Aytu BioScience Announces Regulatory Approval of ZolpiMist(R) by Australian Therapeutic Goods Administration – Yahoo Finance

Posted on July 31, 2020 by Prof Baldwin

Aytu BioScience's Sublicensee SUDA Pharmaceuticals Secures TGA Approval, Enabling Near-Term Commercialization of ZolpiMist

ENGLEWOOD, CO / ACCESSWIRE / July 30, 2020 / Aytu BioScience, Inc. (NASDAQ:AYTU), a specialty pharmaceutical company (the "Company") focused on commercializing novel products that address significant patient needs, today announced the approval of ZolpiMist (zolpidem tartrate oral spray) by the Therapeutic Goods Administration (TGA) in Australia. This approval, which was secured by the Company's ZolpiMist sublicensee SUDA Pharmaceuticals Ltd ("SUDA"), enables near-term commercialization of ZolpiMist in Australia. SUDA (ASX:SUD) is a publicly-listed drug delivery company focused on oro-mucosal administration and is headquartered in Perth, Western Australia.

With this approval by Australia's TGA, ZolpiMist will be included on the Australian Register of Therapeutic Goods and can now be commercialized and supplied within Australia. Further, this approval will assist SUDA's current ZolpiMist sublicensees, Teva Pharmaceuticals, Mitsubishi Tanabe Pharma Singapore and MTP Korea, in their submissions in their respective territories.

On March 9, 2010 Aytu BioScience announced a global distribution agreement for ZolpiMist with SUDA whereby the Company assumed a milestone and royalty-based licensing agreement with SUDA. As specified in the companies' global licensing agreement, SUDA will pay Aytu a portion of each upfront and milestone payment received from sublicensees, and Aytu will receive ongoing royalty payments on sales generated by SUDA's sublicensees as ZolpiMist is launched in each territory.

Josh Disbrow, Chief Executive Officer of Aytu BioScience, stated, "We congratulate the SUDA team for obtaining TGA approval for ZolpiMist and look forward to SUDA and their partners moving ZolpiMist closer to commercialization in Australia and elsewhere. This is an exciting time for SUDA and represents an important milestone for Aytu as we move closer to realizing ex-US licensing revenue for ZolpiMist."

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Dr. Michael Baker, Chief Executive Officer and Managing Director of SUDA, commented, "The TGA submission was a combined effort by SUDA's technical team as well as our regulatory consultant, Pharma To Market. Obtaining the approval indicates the calibre of our staff and is also a key benefit to our partners for ZolpiMist. We are delighted by the outcome and look forward to seeing the commencement of commercial sales in the foreseeable future."

The global sleep aid market is currently estimated at almost $50 billion in annual revenue, and annual revenue is estimated to reach nearly $80 billion in 2022.

About Aytu BioScience, Inc.Aytu BioScience is a commercial-stage specialty pharmaceutical company focused on commercializing novel products that address significant patient needs. The company currently markets a portfolio of prescription products addressing large primary care and pediatric markets. The primary care portfolio includes (i) Natesto, the only FDA-approved nasal formulation of testosterone for men with hypogonadism (low testosterone, or "Low T"), (ii) ZolpiMist, the only FDA-approved oral spray prescription sleep aid, and (iii) Tuzistra XR, the only FDA-approved 12-hour codeine-based antitussive syrup. The pediatric portfolio includes (i) AcipHex Sprinkle, a granule formulation of rabeprazole sodium, a commonly prescribed proton pump inhibitor; (ii) Cefaclor, a second-generation cephalosporin antibiotic suspension; (iii) Karbinal ER, an extended-release carbinoxamine (antihistamine) suspension indicated to treat numerous allergic conditions; and (iv) Poly-Vi-Flor and Tri-Vi-Flor, two complementary prescription fluoride-based supplement product lines containing combinations of fluoride and vitamins in various for infants and children with fluoride deficiency. Aytu also distributes a COVID-19 IgG/IgM rapid test. This coronavirus test is a solid phase immunochromatographic assay used in the rapid, qualitative and differential detection of IgG and IgM antibodies to the 2019 Novel Coronavirus in human whole blood, serum or plasma.

Aytu also operates a subsidiary focused on consumer health, Innovus Pharmaceuticals, Inc. ("Innovus"), a specialty pharmaceutical company commercializing, licensing and developing safe and effective consumer healthcare products designed to improve men's and women's health and vitality. Innovus commercializes over thirty-five consumer health products competing in large healthcare categories including diabetes, men's health, sexual wellness and respiratory health. The Innovus product portfolio is commercialized through direct-to-consumer marketing channels utilizing the company's proprietary Beyond Human marketing and sales platform.

Aytu's strategy is to continue building its portfolio of revenue-generating Rx and consumer health products, leveraging its focused commercial team and expertise to build leading brands within large therapeutic markets. For more information visit aytubio.com and visit innovuspharma.com to learn about the company's consumer healthcare products.

About SUDA Pharmaceuticals Ltd SUDA Pharmaceuticals Ltd (ASX:SUD) is a drug delivery company focused on oro-mucosal administration, headquartered in Perth, Western Australia. The Company is developing low-risk oral sprays using its OroMist technology to reformulate existing pharmaceuticals. The many potential benefits of administering drugs through the oral mucosa (i.e.: cheeks, tongue, gums and palate) include ease of use, lower dosage, reduced side effects and faster response time. SUDA's product pipeline includes ZolpiMist, a first-in-class oral spray of zolpidem for insomnia. ZolpiMist is marketed in the USA and SUDA has rights to the product outside of the US and Canada. Other products in development include oral sprays for the treatment of: migraine headache; chemotherapy-induced nausea and vomiting; erectile dysfunction; pulmonary hypertension; epileptic seizures and pre-procedural anxiety and cancer. For more information, visit http://www.sudapharma.com

Forward-Looking StatementThis press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, or the Exchange Act. All statements other than statements of historical facts contained in this presentation, are forward-looking statements. Forward-looking statements are generally written in the future tense and/or are preceded by words such as ''may,'' ''will,'' ''should,'' ''forecast,'' ''could,'' ''expect,'' ''suggest,'' ''believe,'' ''estimate,'' ''continue,'' ''anticipate,'' ''intend,'' ''plan,'' or similar words, or the negatives of such terms or other variations on such terms or comparable terminology. These statements are just predictions and are subject to risks and uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, among others: market and other conditions, the regulatory and commercial risks associated with introducing the COVID-19 rapid test, the effectiveness of the COVID-19 rapid rest, market acceptance of the National Cancer Institute or other independently conducted studies' testing results, the regulatory, clinical, and commercial risks associated with the investigational Healight device, effects of the business combination of Aytu and the Commercial Portfolio and the merger ("Merger") with Innovus Pharmaceuticals, including the combined company's future financial condition, results of operations, strategy and plans, the ability of the combined company to realize anticipated synergies in the timeframe expected or at all, changes in capital markets and the ability of the combined company to finance operations in the manner expected, the diversion of management time on Merger-related issues and integration of the Commercial Portfolio, the ultimate timing, outcome and results of integrating the operations the Commercial Portfolio and Innovus with Aytu's existing operations, risks relating to gaining market acceptance of our products, including the risks associated with ZolpiMist's commercial success in Australia and elsewhere, obtaining or maintaining reimbursement by third-party payors for our prescription products, the potential future commercialization of our product candidates, the anticipated start dates, durations and completion dates, as well as the potential future results, of our ongoing and future clinical trials, the anticipated designs of our future clinical trials, anticipated future regulatory submissions and events, our anticipated future cash position and future events under our current and potential future collaboration. We also refer you to the risks described in ''Risk Factors'' in Part I, Item 1A of the company's Annual Report on Form 10-K and in the other reports and documents we file with the Securities and Exchange Commission from time to time.

Contact for Investors:James CarbonaraHayden IR(646) 755-7412james@haydenir.com

SOURCE: Aytu BioScience, Inc.

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Aytu BioScience Announces Regulatory Approval of ZolpiMist(R) by Australian Therapeutic Goods Administration - Yahoo Finance

Whatcom Family YMCA Announces that the Lynden YMCA Will Not Reopen – whatcomtalk.com

Posted on July 31, 2020 by Prof Baldwin

Submitted by Whatcom Family YMCA

For 40 years, the Lynden YMCA has taught children to swim, developed youth sports skills and teamwork, improved the health and well-being of the community, and built a place of acceptance and fellowship. Though the YMCA remains committed to healthy living, youth development, and social responsibility throughout Whatcom County during these unprecedented times and beyond, the Y has determined it is not financially viable or prudent to reopen the Lynden location for the foreseeable future.

Over the past few years, due to the rising costs of operating the pool and building, this facility has run at a deficit.Unfortunately, the economic impact from the COVID-19 pandemic has made these losses insurmountable, at least until the pandemic has passed.

It is with profound sadness we announce that we are not able to reopen the Lynden YMCA at this time, said Bill Ziels, CEO of the Whatcom Family YMCA. We respect the City of Lyndens desire to reopen the site and understand they may explore leasing the building to other operators. We sincerely hope a solution is found that will enable the facility to reopen and serve the community.

While the Y will not be able to provide a central location in Lynden currently, they are exploring ways to offer programs and services when COVID restrictions are fully lifted.

We know the Y is needed now more than ever to help our communities endure and recover from this crisis. The Y is more than just a placewe are a movement, said Ziels. We greatly appreciate the help and support we have received from the City of Lynden, and we value our long-term relationship.

The YMCA has been a part of the Whatcom community for over a century andis grateful for support during this critical period. Today, they continue to provide vital services such as much-needed childcare and youth enrichment, food delivery to those in need throughout the county, in-person and virtual healthy living classes, and more.

To learn more about the Y, please visit whatcomymca.org.

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Whatcom Family YMCA Announces that the Lynden YMCA Will Not Reopen - whatcomtalk.com

Weight Loss Tips That Work – Anti Aging News

Posted on July 31, 2020 by Prof Baldwin

Any one who has ever tried to drop some unwanted weight over the years has probably tried and heard of countless tips and strange weight loss advice from drinking celery juice to replacing meals with so-called weight loss cookies, and most often these pointers are promoted by those without any actual health expertise.

It is true that there are pages and pages full of misguided weight loss advice out there that one really should avoid, but there are also a ton of legitimate tips that are science backed and expert approved suggestions such as picking a time to exercise and sticking with it as a study published in the journal Obesity found that exercising at a certain time every day consistently may help successful weight loss.

Another helpful tip is to choose nuts over heavily processed snacks as a report published in BMJ Nutrition, Prevention & Health found that eating up to one ounce of nuts each day is linked with less weight gain and lower odds of obesity.

JAMA Internal Medicine published a report suggesting that a weight loss counselor may be helpful in helping to trim waistlines, showing that those with type 2 diabetes utilizing such counseling sessions with group medical visits helped them to lose weight and lower their blood sugar levels.

Losing weight can be challenging and even though it may be daunting every effort made is worth the benefits when it comes to improving health. The Journal of the National Cancer Institute published a study showing that overweight women who lost weight after turning 50 years old lowered their risks of developing breast cancer.

Diabetic Medicine published a report suggesting that it may be possible to potentially put type 2 diabetes into remission, finding that among those with type 2 diabetes losing 10% or more of their body weight within the first 5 years of diagnosis was associated with better odds of putting the disease into remission. Additionally, according to the American Heart Association carrying extra weight increases the odds of heart disease and stroke.

Whether you only have a few pounds to drop or a lot to lose experts can offer science backed tips and pointers to effectively help you on your weight loss journey such as eating slowly, portion control, keeping a food diary, totally body movement, keeping a gratitude journal, meal prep, getting enough sleep, not skipping meals, staying hydrated, cutting calories, eating more whole foods, avoiding sweetened beverages, removing unhealthy food from your home, and eating breakfast among others.

Janet Zinn, a licensed clinical social worker and psychotherapist says: I have my clients learn how to choose foods they like, really taste each morsel going into their mouths, and chew deliberately. I advise them to chew slowly, swallow only when the food is all chewed up, and repeat. It takes time to know we're full. Eating slowly allows us to not only enjoy our food more, but gives us better cues of satiety.

Christine King, the founder and CEO of the health and wellness company YourBestFit suggests that if You bite it, you write it! Thats my rule, and numerous studies have shown the effectiveness of food journaling for weight loss. One of my clients went out of town for one week. She stopped journaling and gained 13 pounds. I promise that keeping a food journal helps!

Exercise anything that moves.Thats my mantra and I started this after I broke my back and was paralyzed from the waist down. Do it in bed, while seated, standing, or walking. Just move. People have a misconception that five minutes doesnt make a difference, but every minute makes a difference. (And research published in January 2014 in the journal Progress in Cardiovascular Diseases showed that physical activity is critical when it comes to actually keeping lost weight off.) King

Lauren Manganiello, RD, a nutrition counselor and fitness coach suggests that Our eating habits are usually connected to our emotions whether we realize it or not. When we're stressed, we tend to reach for sweets. I tell clients that by keeping a daily journal of things you're grateful for, youre better able to cope with the stress by acknowledging it rather than reaching for dessert.

According to Angela Lemond, RDN, a registered dietitian nutritionist: A lack of sleep increases your hunger hormone ghrelin and decreases your satisfaction hormone, leptin, which can contribute to weight gain. When we are sleep deprived, we crave more salty and sweet foods. Why? Because anytime you feel more intense hunger, your cravings for higher energy aka higher calorie foods intensify. We also know that the way we think and process our emotions is affected by inadequate sleep, so its easy to connect this with an impaired ability to make sound choices in many areas of life, including with food. If we flip the coin, we can safely assume that when we are well rested, we will make better choices. When it comes to eating, that would mean that we would eat when we are truly hungry, and eat just until satisfied. Our hormones are also going to be better balanced because our bodies got the time needed to sleep, repair, and refresh.

Dont skip meals. You may think that this is helping you to burn calories, but you may be damaging your metabolism. The proper way to skip a meal is to begin an intermittent fasting schedule, but skipping a meal and intermittent fasting are not the same thing. In general forgoing eating can have negative consequences for the body, while intermittent fasting helps to get cravings under control and is a scheduled mindful eating practice. Intermittent fasting may not be best for everyone. When a person skips a meal they tend to overeat at some point to make up for it. When you split up your meals to be consumed throughout the day, the body will use the nutrients from the food more efficiently. Most experts agree that you should be eating three balanced meals a day and a healthy snack.

Megan Casper, RDN, a nutrition counselor and the founder and CEO of Nourished Bite points out that: Research has found that people who drank two glasses of water before a meal lost more weight than people who didnt drink water before meals and they kept it off. This simple tip works in two ways. Thirst can mask itself as hunger, causing you to eat more. And water makes you feel fuller, causing you to eat less during a meal.

According to the USDA ChooseMyPlate.gov half of your plate at any given meal should be nutrient dense fruits/veggies. Perhaps aim to make a balanced plate consisting of half vegetables, a quarter whole grains, and a quarter lean protein. Additionally, the Cleveland Clinic suggests not to eat until you are full rather to the 80% point to help tame overeating. There is no need to be part of the finish the plate club, instead pack any extra food away. This is good advice for over eaters who are just learning how to fill their stomach without going overboard, aiming for 80% is a good gauge to help with this as it instructs you to stop eating when you are beginning to feel slightly full. Slowing down helps with overeating because it takes around 20 minutes for the stomach to digest food.

Theres a strong relationship between sugar-sweetened beverages and weight gain in adults. If you regularly have a sip of something sweet, consider this: Research has shown that reducing intake of sugar-sweetened beverages can result in meaningful weight loss, even if it's the only change you make. Replacing a 20-ounce soda with sparkling water every day would save more than 20,000 calories over a few months, which could translate into more than five pounds of weight loss! Brittany Markides, RDN, the founder of Choose Food in Austin, Texas.

Meals consumed away from home tend to be higher in calories and lower in nutrients. A study published in the Journal of the Academy of Nutrition and Dietetics found that the average restaurant entre contains over 1,000 calories, and an entire days worth of sodium and fat. When dining out to save on those calories, try splitting the entre or asking to substit
ute extra green veggies or a salad for the starchy potato or rice.

When looking for a snack and in doubt, reach for a low calorie, fiber rich and nutrient dense vegetable or fruit. You can even make fruits/veggies the star of your meal, for example rather than a main dish of pasta, lessen the pasta amount and add in some broccoli, cauliflower, and zucchini, with some small amount of chicken, garlic and lemon zest. Try considering a few squares of organic dark chocolate with an orange for a sweet dessert. This way you can still enjoy a small amount of pasta and a sweet treat while still being satisfied without depriving yourself.

Most people eat with their eyes and like to see that full plate; using smaller plates, bowls, and cups will reduce the amount of food you consume, while at the same time allowing yourself to fill your dish up and keep you from feeling deprived. For example, an observational study showed that people who used a 9-inch plate versus a 10- or 12-inch plate ate up to 22 percent less. Size matters, research consistently shows that people will consume more food when they are offered larger portions, according to the Mayo Clinic. There are many apps that offer visual cues that can help you to gauge what a portion size is to help you get a better handle on what you are eating.

Don't feel like you need to overhaul your entire life starting immediately. Assess where you are currently and then figure out where youd like to be in the future. A great starting point for mostly sedentary people is to get a step counter and see how much you walk on a normal day. Then set a step goal slightly higher than the norm and strive for that, working your way up slowly to a goal of 10,000 steps per day. Esther Avant, an ACE-certified personal trainer in Kapolei, Hawaii.

Try to avoid if not eliminate highly processed foods from your diet. That does not mean your meals will now be bland, healthy whole food options are far from being boring. There are many exciting colours from the rainbow and flavours to experiment with that come in a variety of textures and tastes ranging from naturally sweet to savory which can easily be enhanced with a wide selection of herbs and spices.

At some point in your weight loss journey you may experience some setbacks, but please keep in mind that this is not failure. Rather think of these minor speed bumps as an opportunity to learn and grow from. Pick yourself up and start over. The only true failure is if you give up.

So you say that you cant exercise for very long. That will change, your endurance, coordination and flexibility will gradually improve. You say its taking too long. Well unfortunately, there is no magic pill, you will need to work for it, and it may take some time. Stick to the healthy lifestyle path to achieve your goals. Most importantly remember that you are well worth every effort and the benefits that you will experience with improved health. You CAN do it!

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Weight Loss Tips That Work - Anti Aging News

Pulmonary, Cardiac Function in BPD Rat Model Improved by Added Klotho – Pulmonary Hypertension News

Posted on July 31, 2020 by Prof Baldwin

Preterm babies with the lung condition bronchopulmonary dysplasia (BPD) a risk factor for the development of pulmonary hypertension (PH) have lower levels of the anti-aging-associated protein Klotho, a study shows.

The results support the potential for Klotho as a biomarker for BPD. Moreover, early Klotho protein supplementation in a rat model of neonatal BPD reduced pulmonary vascular remodeling the key structural alteration in PH and improved both pulmonary and cardiac function.

The study, Soluble Klotho, a biomarker and therapeutic strategy to reduce bronchopulmonary dysplasia and pulmonary hypertension in preterm infants, was published in the journal Nature Scientific Reports.

BPDaffects premature babies and is characterized by damage to the airway passages, or bronchi. Preterm infants with BPD often have delayed growth and, in the most severe cases, develop PH and heart problems.

The lung condition is known to increase the risk of infant mortality, and BPD survivors often experience cardiovascular complications in adulthood. Estimates from the National Institute of Child Health and Human Development, for the years between 2003 and 2007, indicate that BPD incidence was 42% in infants with less than 29 weeks gestational age.

Theklothogene was identified as an anti-aging gene. It codes for the klotho protein that exists in several forms, including as a protein membrane and as a soluble form in the blood.

Mice engineered to lack the klotho gene show signs of premature aging, accompanied by spontaneous pulmonary fibrosis or scarring, emphysema a lung disease that causes shortness of breath and vascular impairment. In turn, above-normal levels of klotho protected animals from cardio-pulmonary injuries andextended their life span.

The role of Klotho in neonatal disease is poorly understood. Previous studies suggested that environmental factors like intra-amniotic infection and smoking during pregnancy are associated with reduced maternal levels of the protein. Pre-eclampsia and having babies who are small for their gestational age also are complications linked to lower levels of Klotho in the blood.

Now, researchers at the University of Miami Miller School of Medicine investigated whether lower Klotho levels in preterm infants are associated with an increased risk for BPDPH. The team also tested whether early protein supplementation could halt lung damage.

First, the levels of Klotho protein were measured in the cord blood of 40 infants. Among these babies, 11 had BPD and 14 had BPD-PH. The remaining 15 infants (controls) had neither BPD nor BPDPH.

Compared with the control group, the infants with BPD or BPD-PH had significantly lower Klotho levels a mean 1,306 picograms per milliliter (pg/mL) in the BPD group and a mean 1,529 pg/mL in those with BPD-PH compared with a mean 2,726 pg/ml in the control group.

The team also measured Klotho levels in a rodent BPD-PH model. In this model, neonatal rat pups were exposed to high levels of oxygen (85%) for different time periods three, five, 14 and 21 days. The animals developed similar symptoms to human newborns with BPD-PH.

A prolonged exposure to high levels of oxygen (14 to 21 days) led to a significant reduction in Klotho, both at the gene and protein levels. Blood sampling at day 14 and 21 confirmed the lower levels in the BPD-PH model rats compared with rats exposed to normal oxygen.

Next, the researchers tested whether early supplementation with Klotho had an impact on rat lung development. Rat pups either exposed to normal room air or to 85% oxygen were randomly assigned to receive injections of lab-made Klotho or a placebo. The injections were given every other day.

The results showed that these injections improved vascular development in the lungs of rats exposed to high oxygen levels.

The scientists next sought to demonstrate that this improvement was due to a direct effect of the protein on pulmonary vasculature. They treated with Klotho human pulmonary artery endothelial cells exposed to high oxygen. Endothelial cells compose the lining of blood vessels and are affected by BPD.

Treatment with Klotho increased the cells viability and the number of capillaries these cells formed, in contrast with non-treated cells exposed to high oxygen.

Using the rodent model, the researchers also found that Klotho supplementation lessened the effects of PH. It also reduced the hearts right ventricular enlargement, which is a characteristic of PH.

Vascular remodeling defined by an increased percentage of muscle cells in vessels and greater wall thickness also was reduced with early administration of Klotho. Tests of cardiac function revealed that the protein supplement improved the hearts left ventricle function, namely its ejection fraction, or how much blood the hearts left ventricle pumps out with each contraction.

Moreover, Klotho had a positive effect on lung development, especially in the alveoli, which are the air sacs found at the end of the respiratory tree of the lungs. Compared with high-oxygen-exposed rats given a placebo, the Klotho group showed improved alveolar structure.

At the molecular level, Klotho supplementation was found to decrease oxidative stress in newborn rats exposed to high oxygen. Oxidative stress caused by an imbalance between the bodys production of potentially harmful reactive oxygen species and its ability to contain them is associated with increased cellular damage and death.

The researchers also observed that rats exposed to high oxygen and treated with the protein had a slight better survival (69%) compared with the placebo group (44%).

Overall, the results show that early administration of soluble Klotho improves lung vascular development, attenuates PH, and reduces myocardial dysfunction, the team wrote.

Our findings suggest that Klotho deficiency is a potential mediator and biomarker for BPD and PH risk and early interventions, which augment Klotho levels, may be an effective strategy to improve cardiopulmonary outcomes in preterm infants, the team added.

Further research is needed to evaluate the effects of Klotho on other developing organ systems, the investigators said.

This will be crucial to translate the findings of our studies to the bedside, they wrote.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

Total Posts: 329

Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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July: bat1k-study | News and features – University of Bristol

Posted on July 31, 2020 by Prof Baldwin

For the first time, the raw genetic material that codes for bats unique adaptations and superpowers such as the ability to fly, to use sound to move effortlessly in complete darkness, to survive and tolerate deadly diseases, to resist ageing and cancer - has been fully revealed by an international research team including scientists at Bristol. The findings are published in Nature.

In order to uncover bats unique traits,theBat1Kconsortium led by researchers at University College Dublin, the Max Planck Institutes of Molecular Cell Biology and Genetics (Dresden), and the Max Planck Institute for Psycholinguistics (Nijmegen),generated and analysed six highly accurate bat genomes that are ten times more complete than any bat genome published to date.

To generate these exquisite bat genomes, the team used the newest technologies to sequence the bats DNA, and generated new methods to assemble these pieces into the correct order and to identify the genes present.

Emma Teeling, University College Dublin, Co-Founding Director of Bat1K and Senior Author, said: Given these exquisite bat genomes, we can now better understand how bats tolerate viruses, slow down ageing, and have evolved flight and echolocation. These genomes are the tools needed to identify the genetic solutions evolved in bats that ultimately could be harnessed to alleviate human ageing and disease."

Eugene Myers, Director of Max Planck Institute of Molecular Cell Biology and Genetics, and the Center for Systems Biology, Dresden, Germany, and the studys Senior Author, added: Using the latest DNA sequencing technologies and new computing methods for such data, we have 96-99 per cent of each bat genome in chromosome level reconstructions - an unprecedented quality akin to for example the current human genome reference which is the result of over a decade of intensive "finishing" efforts. As such, these bat genomes provide a superb foundation for experimentation and evolutionary studies of bats fascinating abilities and physiological properties.

The team compared these bat genomes against 42 other mammals to address the unresolved question of where bats are located within the mammalian tree of life. Using novel phylogenetic methods and comprehensive molecular data sets, the team found the strongest support for bats being most closely related to a group called Ferreuungulata that consists of carnivores (which includes dogs, cats and seals, among other species), pangolins, whales and ungulates (hooved mammals).

To uncover genomic changes that contribute to the unique adaptations found in bats, the team systematically searched for gene differences between bats and other mammals, identifying regions of the genome that have evolved differently in bats and the loss and gain of genes that may drive bats unique traits.

Michael Hiller, Max Planck Research Group Leader, Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Max Planck Institute for the Physics of Complex Systems, and the Center for Systems Biology, Dresden, Senior Author, added: Our genome scans revealed changes in hearing genes that may contribute to echolocation, which bats use to hunt and navigate in complete darkness. Furthermore, we found expansions of anti-viral genes, unique selection on immune genes, and loss of genes involved in inflammation in bats. These changes may contribute to bats exceptional immunity and points to their tolerance of coronaviruses.

The team also found evidence that bats ability to tolerate viruses is reflected in their genomes. The exquisite genomes revealed fossilised viruses, evidence of surviving past viral infections, and showed that bat genomes contained a higher diversity than other species providing a genomic record of historical tolerance to viral infection.

Professor Gareth Jones from Bristols School of Biological Sciences, who contributed to the study,said: It has been 20 years since the first human genome was sequenced, and today we can obtain almost complete gene annotations for the genomes of wild mammals to better understand their adaptations and evolution. Analysis of the genomes helped resolve the phylogenetic position of bats in the mammal tree (basal in a lineage that includes carnivores, pangolins, hoofed mammals, pangolins and cetaceans), and supported the hypothesis that laryngeal echolocation is an ancestral trait in all bats. Moreover, the bat genomes revealed the incorporation of diverse fossilised viral genomes and selection on immunity-related genes that may contribute to bats exceptional immunity.

"One of the genomes we have been studying, to help us understand ageing in bats is from the greater horseshoe bat, which have exceptional longevity for their body size. For example, a six gram Brandtsbat can live for around 41 years. We plan to now use the genome to investigate epigenetic changes during ageing, and how these changes cause some animals to age biologically faster than expected for their chronological ages."

Given the quality of the bat genomes the team uniquely identified and experimentally validated several non-coding regulatory regions that may govern bats key evolutionary innovations.

Sonja Vernes, Co-Founding Director Bat 1K, Max Planck Institute for Psycholinguistics, Nijmegen, Senior Author, said: Having such complete genomes allowed us to identify regulatory regions that control gene expression that are unique to bats. Importantly we were able to validate unique bat microRNAs in the lab to show their consequences for gene regulation. In the future we can use these genomes to understand how regulatory regions and epigenomics contributed to the extraordinary adaptations we see in bats.

This is just a beginning. The remaining ~1,400 living bat species exhibit an incredible diversity in ecology, longevity, sensory perception and immunology, and numerous questions still remain regarding the genomic basis of these spectacular features. Bat1K will answer these questions as more and more exquisite bat genomes are sequenced, further uncovering the genetic basis of bats rare and wonderful superpowers.

The study was funded in part by the Max Planck Society, the European Research Council, the Irish Research Council, the Human Frontier Science Program, and the United States National Science Foundation.

Paper

'Six reference-quality genomes reveal evolution of bat adaptations' by Jebb et al. is published in Nature.

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July: bat1k-study | News and features - University of Bristol

Woman accused of causing more than $2K in damage in Milford garden – MetroWest Daily News

Posted on July 31, 2020 by Prof Baldwin

The garden contained native plants and seeds from Brazil, which one of the owners told police were expensive to buy and import.

MILFORD A Fall River woman is accused of destroying a garden valued at more than $2,000 while her mother stood by with a knife and hammer.

(The victim) stated that Ms. De Mirandas mother . was standing in front of her daughter holding a hammer and a knife, the arrest report reads, and appeared to be guarding Ms. De Miranda in case someone tried to stop her from destroying (the) garden.

Mariana De Miranda, 19, of 215 Thomas St., Apt. 2, Fall River, was arrested Thursday evening and charged with wanton destruction of property worth over $1,200, and unlicensed operation of a motor vehicle.

Officers on Thursday evening found a garden in Prospect Heights in disarray, with plants uprooted and thrown about, a punctured garden hose and several stakes pulled from the ground. The owners of the garden were very distraught and crying upon police arrival, police said.

The garden contained native plants and seeds from Brazil, which one of the owners told police were expensive to buy and import.

An itemized list in the police report includes tomato seeds valued at $125; jilo, a type of Brazilian eggplant, seeds valued at $150; and hot peppers valued at $100, among several others. The list also included $1,050 of fertilizer, a $73 garden hose and $96 in plant food and fertilizer.

Owners also told police that De Miranda had driven her car into the backyard and tried to run them over when she left.

De Miranda refused to tell police much, according to the arrest report. She was stopped driving a car a street over from Prospect Heights, and did not have a valid drivers license, police said.

The report said the mother had not yet been identified.

Owners told police they argued with De Miranda and her mother, whom they said were neighbors, and that tensions had escalated in recent days.

(The owner) stated that she likes to live a healthy lifestyle which (includes) organic gardening and working out, the report read. (The owner) states that Ms. De Miranda and her mother are jealous of her and make fun of her because she has a big garden.

De Miranda is listed as having a Fall River address, but the owner of the garden identified her as her neighbor. When questioned by police, De Miranda said she lived in Fall River but that her mother lived in Prospect Heights.

Alison Bosma can be reached at 508-634-7582 or abosma@wickedlocal.com. Find her on Twitter at @AlisonBosma.

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Respect the elderly – Philstar.com

Posted on July 31, 2020 by Prof Baldwin

During the PRE-COVID days, economists in some regions of the world worry about declining birth rates and aging population. You can credit this to the fast pace of life for declining birth rates and better nutrition, medical breakthroughs, exercise, and healthy living for aging.

One of the most exciting future predictions came from futurist Peter Diamandis. Diamandis is a Greek-American engineer, physician, and entrepreneur best known for being the founder and chairman of the X Prize Foundation. I have read his books and attended a talk he gave in New York in a business leadership conference some years ago. The book that launched him to fame is entitled: Abundance: The Future is Better Than You Think.

One of the concepts that excite the readers deal with his presentation ofDavid Gobel and popularized by Ray Kurzweil and Aubrey de Grey. Their fearless futuristic prediction is called: Longevity escape velocity, or actuarial escape velocity.

According to this concept, an indefinite lifespan can be achieved when medical and technological improvements add years to lifespan faster than the passage of time. In simple terms, humanity continues to discover new ways of extending life at a pace that doesnt allow death to catch up. In laymans terms, senior citizens will live longer, and life longevity will extend beyond human imagination.

We are nearing longevity escape velocity where science can extend your life for more than a year for every year you are alive, says the title of one article hailing the concept. Ray Kurzweil claims it will happen by 2022. Scientists believe genetic engineering, or the discovery of anti-aging drugs, could extend human lifefar beyond its natural course. The same Aubrey de Grey thinks there is no reason humans cannot livefor at least 1,000 years.

But then COVID-19 happens. As a person gets older, the risk for severe illness from COVID-19 increases. Many health experts have explained it in many news programs that people in their 50s are at higher risk for severe illness than people in their 40s. Similarly, people in their 60s or 70s are, in general, at higher risk for severe illness than people in their 50s. The highest risk for severe illness from COVID-19 is among those aged 85 or older. Other factors can increase the risk of severe illness, for instance, havingunderlying medical conditions.

Why do I have this funny feeling that the virus will take lives, and a significant chunk of them would belong to the older generation as is now reflected in the numbers of casualties presented in the news daily? It is as if Generation Z will grow up to a world with a relatively smaller aging population.

Today when I see a lot of young people speak, react, and treat their parents or older people, I wince. There is so much disrespect and too much of an obnoxious attitude there. Helmut Schmidt says: I remembered the youth movement in 1968. It started on American university campuses as a protest against the Vietnam war, then came to Paris, Frankfurt and Berlin. Within a year, you had an uprising of youth against their elders. This is not a good thing.

I guess I behaved the same way when I was young, dumb, and foolish, thinking that I knew it all and that older people are just irrelevant and obsolete. And now thinking back, yes, I was young, dumb, and stupid to have behaved that way. But it was then when there was no COVID-19 around taking the lives of the elderly. This Virus has reminded us that life is short and fickle. And that we need to value love, respect, compassion, and care for each other.

To the young, love your parents and respect your elders. Sometimes kids are growing up so fast they have forgotten the fact that their parents are growing old faster. And you never know how much time you have left to be with them.Scriptures even remind us with this warning: Never speak harshly to an older man, but appeal to him respectfully as you would to your father.(Timothy 5:1-3).

And here is the most practical reason why the young should respect and admire their elders.

They made it through school without cut-copy-paste,GoogleorWikipedia.

(Connect with Francis Kong at http://www.facebook.com/franciskong2. Or listen to Business Matters Monday to Friday 8:00 a.m. and 6:30 p.m. over 98.7 DZFE-FM The Masters Touch, the classical music station.)

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How AI is uncovering the ‘dark matter of nutrition’ – World Economic Forum

Posted on July 31, 2020 by Prof Baldwin

The COVID-19 pandemic didnt just transform how we work and communicate. It also accelerated the need for more proactive health measures for chronic health problems tied to diet. Such problems have emerged as a top risk factor for coronavirus and people with poor metabolic health accounted for half of COVID-19 hospitalizations in some regions around the world. The resulting high numbers led the authors of a report in The Lancet to issue a call for more resources to tackle metabolic health to avoid needless deaths.

Thankfully, new tools have been developed to offer comprehensive understanding of nutrition. This expertise and technology wont just help us tackle metabolic health it could help us finally fully realize the power of plants to improve health and wellness outcomes.

The first global pandemic in more than 100 years, COVID-19 has spread throughout the world at an unprecedented speed. At the time of writing, 4.5 million cases have been confirmed and more than 300,000 people have died due to the virus.

As countries seek to recover, some of the more long-term economic, business, environmental, societal and technological challenges and opportunities are just beginning to become visible.

To help all stakeholders communities, governments, businesses and individuals understand the emerging risks and follow-on effects generated by the impact of the coronavirus pandemic, the World Economic Forum, in collaboration with Marsh and McLennan and Zurich Insurance Group, has launched its COVID-19 Risks Outlook: A Preliminary Mapping and its Implications - a companion for decision-makers, building on the Forums annual Global Risks Report.

The report reveals that the economic impact of COVID-19 is dominating companies risks perceptions.

Companies are invited to join the Forums work to help manage the identified emerging risks of COVID-19 across industries to shape a better future. Read the full COVID-19 Risks Outlook: A Preliminary Mapping and its Implications report here, and our impact story with further information.

We know that plants are critical for health, but do not fully understand why. Humans have not mapped the breadth of what plants offer, nor have we pinpointed the specific biological mechanisms of action triggered in our bodies when we eat them. This knowledge gap exists at the molecular level, with a need to understand how phytonutrients tiny plant molecules with anti-inflammatory, cardioprotective and neuroprotective properties work in our bodies. In fact, the scientific community refers to the vast world of phytonutrients as the dark matter of nutrition because less than 1% of these molecules have been catalogued to date. The opportunity to learn more about phytonutrients and further tangibly connect their impact to health is massive.

Technologies, such as Artificial Intelligence, are helping researchers learn more about the biological connections between plants and humans. For instance, Brightseed has created a powerful artificial intelligence called Forager, which coupled with advanced metabolomics instrumentation, systematically identifies unknown plant compounds and predicts their likely roles in human health. Thus far, the technology has predicted beneficial phytonutrients for many important health conditions.

Recently, in collaboration with leading biomedical researchers, Brightseed discovered a powerful phytonutrient with the potential to improve metabolic health. This phytonutrient helps restore proper function of a central metabolic regulator, including maintaining healthy lipid and sugar levels in the bloodstream and key organs such as the liver, whose function is impaired by a poor diet. Brightseed will start clinical studies on this phytonutrient before the end of this year.

The impact of this discovery could be wide reaching and have profound implications for more than two billion people worldwide at elevated risk of chronic metabolic diseases. Elevated levels of fat in the liver (which are directly caused by chronic overeating) afflict between 25% and 30% of the global population. These individuals with fatty liver disease are 57% more likely to die prematurely and much more like to develop other debilitating metabolic diseases, including diabetes. The discovery of this phytonutrient is a glimpse into the positive change deeper nutritional understanding could bring.

Just as 1918 pandemic led to creation of the modern medicine industry, we now are at a similar tipping point with nutrition, on the precipice of developing a much more complete understanding of how plants are connected to human health.

The first step is improving our foundational knowledge. In the U.S., there is a broad-based effort among leading academic, non-profit and industry stakeholders to create a National Institute of Nutrition (NIN) to accelerate nutrition science and uncover the role of human nutrition in improving public health and reducing disease. The NIN, similar to institutes that exist in other countries, can support and incentivize higher-quality, more rigorous nutrition research at the molecular level. This research will provide a stronger foundation for nutrition recommendations and guidelines, which is essential to developing consensus in both the scientific and consumer communities.

The second step is a mindset shift. Modern food and agricultural systems have largely focused on - and solved - the problem of food insufficiency. However, preventable diet-driven chronic diseases have emerged instead. We need to pivot from merely increasing the supply of food to leveraging technologies that can help improve the nutritional quality of what we consume.

"We need to pivot from merely increasing the supply of food to leveraging technologies that can help improve the nutritional quality of what we consume."

Healthier food options can be the center of a new proactive health industry and provide the food industry the opportunity to make important contributions to health and longevity, while benefiting economically from the capture of existing healthcare investment that currently is directed to treating chronic disease. Our current treatment-focused healthcare system is increasingly unaffordable and poorly suited to addressing the needs of individuals at heightened risk of developing chronic diseases that are largely preventable through lifestyle modifications, especially those related to diet.

No changes will be possible without forging new collaborations between public and private entities. Through cooperation we can develop more nutritious options and greatly influence policy change. Partnerships are also how well create a more nourished world and maximize our impact.

For the first time, we have the tools to explore the plant kingdom at the molecular level and answer questions such as How does what we eat really affect us? or How can food become medicine?

Technology is exponentially improving our understanding of how plants are connected to health. Together, we can goal shift the healthcare model from one squarely focused on treatment of disease to one that promotes health and natural resilience.

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How AI is uncovering the 'dark matter of nutrition' - World Economic Forum

How one company is using machine learning to remove bias from the hiring process – WRAL Tech Wire

Posted on July 31, 2020 by Prof Baldwin

Editors note: Stuart Nisbet is chief data scientist at Cadient Talent, a talent acquisition firm based in Raleigh.

RALEIGH At Cadient Talent, its a question that we wrestle with on a daily basis: How do we eliminate bias from the hiring process?

The only way to address a problem or bias is to acknowledge it head on, under the scrutiny of scientific examination. Through the application of machine learning, we are able to learn where we have erred in the past, allowing us to make less biased hiring decisions moving forward. When we uncover unconscious bias, or even conscious bias, and educate ourselves to do better based on unbiased machine learning we are able to take the first step toward correcting an identified problem.

Bias is defined as a prejudgment or a prejudice in favor of or against one thing, person, or group compared with another, usually in a way that is considered to be unfair. Think of bias as three sets of facts: The first is a set of objective facts that are universally accepted. The second is a set of facts that confirms beliefs, in line with what an individual believes to be true. Where bias enters the picture is in the intersection between the objective facts and the facts that confirm personal beliefs.

By selectively choosing the facts that confirm particular beliefs and focusing on the things that confirm those beliefs, bias enters. If we look at hiring from that perspective, and if our goal is to remove bias from the hiring process, then we need to remove the personal choice of which data points are included in the process. All data points that contribute to a positive choice (hire the applicant) or negative choice (decline the applicant) are included in the process and choosing the data points and their weights is done objectively through statistics, not subjectively through human choice.

How can computer algorithms help us do this? Our goal is to be able to augment the intelligence of humans, in particular by using the experiences and prior judgment in past hiring decisions, with an emphasis on those that resulted in good hiring decisions. Good hiring can be measured in a number of ways, that dont implement inappropriate bias, such as the longevity of employees. If a new hire does not remain on the job very long, then perhaps the recruiting effort was not done well, and, in hindsight, you would not have chosen that applicant. But, if you hire someone who is productive and stays for a long time, that person would be considered a good hire.

We want to remove bias when it is unintentional or has no bearing on whether an employee is going to be able to perform the job in a satisfactory manner. So, if a hiring managers entire responsibility is to apply their knowledge and experience to determine the best fit, why do we use machine learning to eliminate bias? Because, artificial intelligence only removes the bias towards non-work-related candidate attributes and augments decisions based on relevant work traits, where there is appropriate bias.

Our goal is then to make the hiring process as transparent as possible and consider all of the variables that are used in a hiring decision. Thats extremely complicated, if not impossible, if you have nothing but a human-based approach because the decision-making of a hiring manager is far more complex and less understood than those of a machine learning algorithm. So, we want to focus on the strength of simplicity in a machine learning algorithm; meaning we only want to look at variables, columns, and pieces of data in the algorithm that are pertinent to the hiring process and do not include any data points that are not relevant to performance.

Stuart Nisbet

An assessment result, for example, whether cognitive or personality-based, may be a very valid data point to consider if the traits being assessed are pertinent to the job. Work history and demonstrated achievement in similar roles may be very important to consider. The opposite is very clear, too. Gender, ethnicity, and age should have no legitimate bearing on someones job performance. This next point is critical. A hiring manager cannot meet an applicant in an interview and credibly say that they dont recognize the gender, ethnicity, or general age category of the person sitting across from them. No matter our intentions, this is incredibly hard to do. Conversely, it is the easiest task for an algorithm to perform.

If the algorithm is not provided gender, ethnicity, or age, there is no chance for those variables to be brought into the hiring decision. This involves bringing in the data that is germane, having a computer look at what hiring decisions have been made in the past that have resulted in high performing long-term employees, and then strengthening future decisions based on the past performance of good hiring management practices. This will ultimately remove the bias in hiring.

One of the things that deserves consideration is the idea of perpetuating past practices that could be biased. If all we are doing is hiring like we have hired in the past and there have been prejudicial or biased hiring practices, that could promote institutional bias. Through time, we have trained computers to do exactly what a biased manager would have done in the past. If the only data that is used (trained) for hiring is the same data that is selected by biases of the past, then it is difficult to train on data that is not biased. For example, if we identify gender as a bias in the hiring process, and we take the gender variable out of the algorithm, gender would not be considered. When we flag previous bias, we are able to minimize future bias.

We should unabashedly look at whether we are able to identify and learn from hiring practices that may have had bias in the past. This is one of the greatest strengths of applying very simple machine learning algorithms in the area of hourly hiring.

An aspect of the hiring process that opens up a lot of opportunities in the area of artificial intelligence and machine learning is implementing diversity.

Artificial intelligence can really differentiate itself here. Machine learning can make the very best hiring decisions based on the data that its given; if you have diversity goals and want hiring practices to encourage a diverse work population, it is very simple to choose the best candidates from whichever populations are important to corporate goals. This can be done transparently and simply. It doesnt prioritize one person over another. It allows the hiring of the very best candidates from each population that youre interested in representing the company.

Upon scrutiny and scientific examination, machine learning can be a very valuable tool for augmenting the hiring decisions managers make every day and help to understand when bias has entered into our decisions and yielded far less than our collective best.

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How one company is using machine learning to remove bias from the hiring process - WRAL Tech Wire

Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys – Science Advances

Posted on July 31, 2020 by Prof Baldwin

Cell-free DNA (cfDNA) released from damaged or dead cells combines with LL37 and is converted into an immune response activator to exacerbate psoriasis. Here, we show that cationic nanoparticles (cNPs) efficiently compete for DNA from the DNA-LL37 immunocomplex and inhibit DNA-LL37-induced cell activation. Using phenotypical images, psoriasis area and severity index scoring, histology, and immunohistochemical analysis, we demonstrate that topical application of cNPs on psoriasiform skin of a mouse model relieves psoriatic symptoms. It is noteworthy that the results were confirmed in a cynomolgus monkey model. Moreover, topically administrated cNPs showed low in vivo toxicity because of their retention in skin. Mechanistic analyses of cytokine expression in the psoriatic site, cfDNA levels in circulation and inflamed skin, skin permeation, and biodistribution of cNPs also matched the therapeutic outcomes. Therefore, we present a previously unidentified strategy of nanomedicine to treat skin inflammatory diseases, which demonstrates great potential for clinical application.

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Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys - Science Advances

Fresh, Fun and Fast: Summer Berry Good Eats – Redwood Falls Gazette

Posted on July 31, 2020 by Prof Baldwin

Summer is the best in the Midwest. Farmers markets are popping up all over the area with locally grown goodness. The summer is the perfect time to try new things,...

The post Fresh, Fun and Fast: Summer Berry Good Eats appeared first on Altru Blog.

Summer is the best in the Midwest. Farmers markets are popping up all over the area with locally grown goodness. The summer is the perfect time to try new things, especially new produce! As a registered dietitian nutritionist, I often dabble in the culinary arts. I love to try new recipes using produce grown in our family garden (on my father-in-law's farm land). He and I are pictured with our corn crop on July 4th.

Corn and peppers provide good sources of fiber. Fiber is helpful for lowering cholesterol and maintaining a healthy digestive tract. Tomatoes and peppers also pack in the vitamin C, an important antioxidant. Tomatoes also are excellent sources of potassium, vitamin C, vitamin A, vitamin K and manganese.

White plate with a serving of Black Bean Salad with cilantro garnish.

Here is a great option for fresh corn, tomatoes and peppers. Feel free to add any ingredients such as chopped green pepper to this mixture. It is great as a side dish for grilled chicken, tacos or as a salad topper. This year, I tried growing a few new things. Spinach was one that I had never grown, but knew I loved. Spinach is rich in many nutrients iron, folate, vitamin C. It has many uses such as sauting and adding to pasta dishes, in my favorite minestrone soup, and for salads. Salads can be boring and are often deemed 'rabbit food' (believe me the rabbits and deer do like my lettuce and spinach). Salads can be made into delicious culinary creations by simply mixing your favorite foods. When I have a salad, it better be fancy! In touring our garden, there are many things that would be delicious additions, including raspberries.

Fun fact: Did you know that raspberries contain 9 grams of fiber per cup? Amazingly, that is over 1/3 of your average daily requirement of 25-25 grams. Not only are they packed with fiber, the also contain valuable antioxidants such as vitamin C and phytochemicals such as quercetin and gallic acid which have been shown to be beneficial for heart health.

Other vegetables to add to a mix of spinach, lettuce and raspberries would be red onions, peppers, cabbage, broccoli, celery or roasted beets. Others include strawberries (in the summer), apples and pears (in the fall), are also amazing in a fancy salad! Aim for a rainbow of color. Other additions include: nuts, seeds, lean proteins such as chicken, fish, steak, beans or legumes, eggs, and even cooked whole grains including barley, quinoa or wild rice. Instead of a cream-based dressing, try a vinaigrette. Olive oil, a mono-unsaturated fat or the most heart healthy fat, is the perfect oil to use when making salad dressings.

Get out to the garden, the farm or the farmers market. Try new things! Fill half your plate with fruits and vegetables. This ensures low calorie, high volume, high nutrient foods help keep you satisfied and prevent disease.

Need more help navigating a healthy lifestyle? Make an appointment today for a free health and wellness consult through MyChart or call 701.732.7620, option 2.

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Fresh, Fun and Fast: Summer Berry Good Eats - Redwood Falls Gazette

How to live longer – the simple exercise you should do everyday to avoid an early death – Express

Posted on July 31, 2020 by Prof Baldwin

Maintaining a healthy lifestyle, including a well-rounded diet is crucial to prolonging your lifespan.

You could also boost your lifespan by doing regular exercise. Its the miracle cure weve all been waiting for, according to the NHS.

Making some small diet or lifestyle changes could help to increase your life expectancy and avoid an early death.

One of the easiest and best ways to improve your overall health, and to boost your longevity, is to walk fast every day, it's been claimed.

READ MORE: FREE Protect your Health magazine inside today's Daily Express

"I have found exercise to be a powerful performance-enhancer on a daily basis, and now I know how to exercise to increase healthy lifespan," he wrote on his blog.

"Walk fast for an hour every day - this doesnt need to happen all at once.

"For example, if the train station is a 15-minute walk away from your house, and you do that each way, thats 30 minutes right there. Then you could pick a coffee shop that is a 15-minute walk away from your office, and make a daily visit.

"On the weekend, walk everywhere, even faraway places do your best to leave your car in the garage or driveway all weekend long."

But, if you don't have the capacity to do a full hour of exercise every day, there are alternatives.

Just 15 minutes of exercise each day could provide you with some benefits.

For every extra 15 minutes of daily activity you do each day, your risk of premature death is lowered by around four percent, scientists have claimed.

It'll also add around three extra years to your life expectancy.

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How to live longer - the simple exercise you should do everyday to avoid an early death - Express

Schoolboy brothers use protein shakes and lift weights with bodybuilding parents – Metro.co.uk

Posted on July 31, 2020 by Prof Baldwin

Mother-of-four, Brandi Morrison, right, have trained her children how to lift weights to build muscle (Picture: Brandi Morrison/Metro.co.uk)

A bodybuilder mother lets her three year-old son lift weights and says pumping iron, clean-eating and protein shakes have given her other boys aged seven and 10 insane abs.

Fitness buff, Brandi Morrison, 33, lets her youngest son Ragnar, three lift dumbbells even though he is still a toddler. He can be seen confidently working with a dumbbell in a video Brandi shared with Metro.

She has also taught his older brother Preston, seven, and Cedrik, 10, how to bench press, dead lift and bicep curl during lockdown and says her young sons are thrilled with their newly-honed muscles.

The boys, from Peoria in Arizona, started pumping iron earlier this year to help them get bigger for football. They now workout with their bodybuilding parents at home almost every day. Stay-at-home mom Brandi also insists the children must eat a clean and healthy diet to help them get stronger and has admitted her four kids have never had a McDonalds. She also lets the older boys drink protein shakes to boost their fitness progress.

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Brandi, who is married to quality control officer, Rocky, 36, said: I make sure (Ragnar) uses a low weight, like 3lbs or 5lbs dumbbells. He does squats, squat jumps, push ups, pull ups and hell lift with weights a couple of times a month.

Its a lot more body weight stuff for him. He enjoys it and we show him the movements and correct him if its something that would hurt him, but typically hes amazing at picking up the movements.

When we ask him to show us his muscles he flexes and we compliment how big and strong hes getting. Hell say things like Yes I am with a big smile on his face.

I think his favorite part is when we use him as the weight. Like benching him, bicep curls, tricep extensions behind our head. Its us being all together and to him its a sure way of playing and having fun.

I dont anything wrong with it, we would never put our kids in harms way and if they didnt want to lift weights anymore then thats fine, but they want to and really enjoy it.

A lot of kids nowadays sit in front of the TV or on electronics and that does more harm than what weightlifting does for my kids. Nutrition is a big part of their lives too, they know that protein is good for their muscles and carbs are good for recovery, weve taught them you cant outwork a bad diet.

I dont think theyve ever had a McDonalds, we encourage healthy eating all the time. Sometimes after practice they will have protein shakes when I do, they are good for you.

Brandi and Rocky are both competitive powerlifters who usually train in a gym, but when the coronavirus lockdown led to public gyms shutting up for months on end, the couple decided to start working out at home instead. The lockdown also meant Preston and Cedrik could no longer attend football training for the teams they had only just joined.

As a fitness substitute, the brothers asked their parents if they could join in to help them bulk up and get stronger for when they are allowed to re-join their teammates on the football field. Over the last few months, since March, theyve become hooked on pumping iron and according to Brandi, have made some impressive gains.

They work out with their parents most days, and are even joined by their other brothers Rocky, eight and Ragnar, three, on the odd occasion, who also use low weights under supervision.

Brandi said: We are watching our kids enjoy fitness and we are proud of them, its amazing to see them develop. I dont force it on them at all, I just ask them if they want to join in when its time for me to work out.

I am being careful not to overwork them, but Preston and Cedrik have been doing it for so long now that they do all types of bodybuilding exercises. Only they do the more serious weightlifting exercises with us, they want to get bigger for football so asked if they could join in.

I think its really good for them, I dont think there is anything wrong with them wanting to lift weights and be healthy. I know some people dont agree with it but everyone brings their kids up in their own way.

We dont push them too hard and they do use low weights, but we have shown them how to do all of the main bodybuilding exercises. We do squats, dumbbell curls, lateral raises, bench press, shoulder press and deadlifts.

Preston can deadlift 65lbs now, its insane how well they are doing. Both of them are getting really strong and they have got insane ab muscles too.

Whilst light strength training can be good for a childs development, research by academic medial centre, Mayo Clinic, suggests that a high amount of bodybuilding or weightlifting can have a negative impact on a childs growth.

The site advises against children trying to build muscle mass because doing so can put too much strain on young muscles, tendons and areas of cartilage that havent yet turned to bone. Instead children should only take part in light resistance and controlled movements and doing so can have positive impacts on endurance, bone health and injury prevention.

Alongside daily workouts, Brandi has said she ensures all six members of the family eat a healthy diet day in and day out, with fast food and sugary snacks banned.

She said: We all eat super well, nutrition is such an important part of living a healthy lifestyle. We have taught them about what is good to eat and what is bad to eat and they know what foods help them get stronger.

We never buy cookies or chocolate treats and we never have fast food. Their grandma bought them doughnuts recently and they barely ate them because its not what theyre used to.

Childhood obesity is such a big problem and we dont want that for our kids.

I dont think anyone can say were doing anything wrong with the lifestyle our boys have, they are really healthy and are enjoying it, and as long as thats the case then they will keep on working hard.

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Schoolboy brothers use protein shakes and lift weights with bodybuilding parents - Metro.co.uk

Mixing Fun And Healthy Living: Why These Beverage Founders Bet On Premiumization – Forbes

Posted on July 31, 2020 by Prof Baldwin

Post by Cecilia F. Pineda

AVEC Co-Founders Dee Charlemagne (left) and Alex Doman (right) recognized trends in a traditional ... [+] industry and a void in the marketplace.

The Journey To Founding And Funding A Fresh Startup In A Traditional Industry

There was a time when ads claimed how delicious (and healthy) processed food like American cheese and Twinkies were. Chemical flavorings, colors, preservatives, and lots of sugar: These ingredients have now inspired whole movements and businesses whose aim is to eradicate them from our foods and beverages. As far as beverages go, for years people had been satisfied with mixing their whiskey with lemon-flavored soda or their rum with cola-flavored soda. Of course, there have been fancy mixers such as orgeat and falernum, but a visit to your local bar, restaurant, or club most often served guests cocktails with old-school mixers from a soda gun.

AVEC DRINKS Co-Founders Denetrias Dee Charlemagne and Alex Doman knew that they and their fellow consumers deserved a healthier, tastier mixer alternative and set out to develop one. They both saw how people would try to hack their way to a healthier drink by switching out sour mix for citrus, adding herbs, or even nut milks.

Healthy Trends And A Void In The Marketplace

After seeing these trends toward less processed and more indulgent food and drink with more natural, healthy, and interesting ingredientsand after rejecting some other less fun, less lucrative entrepreneurial ideas while still at Columbia Business School, both class of 2020Charlemagne and Doman also recognized the relative void in the premium mixer marketplace. They eventually agreed to collaborate to create AVEC, named after the French word for with. With the examples of successful premium natural beverages like Seedlip and Fever-Tree mixers, they established their line of premium all-natural carbonated mixers featuring low sugar and exotic flavors.

AVEC provides an innovative alternative featuring 5 flavors of all-natural, low sugar carbonated ... [+] premium mixers.

The Right Industry At The Right Time With The Right Team

Domans experience as a management consultant with a food & beverage or hospitality specialty (working with a range of businesses from S&P 500 stalwarts to new-born startups) along with Charlemagnes background in media and advertising (working at top firms like Ogilvy and Mather, WPP, and VICE Media building the brands of others) combine to form a diverse and complementary team that offers a fresh voice and an innovative product to a relatively stale, undiversified field. Although they just launched, the duos startup has already attracted the likes of Liquor, Trendhunter, Eater plus The New York Timess Florence Fabricant's Front Burner column. Doman states, The industry is crying out for a healthy alternative to sugar-filled mixers and tasteless soda water. Our five flavors use real juice, natural botanicals, and spices to create delicious mixers without all the sugar.

Although Charlemagne and Doman have yet to seek formal funding, Charlemagne does speculate about the eventual funding support for AVEC given the historical challenges. As she describes it, Im aware that there are only about 40 black female founders who have raised over $1 million in VC funding. I have met some of them and continue to be inspired by them as we build AVEC. Overall, Black founders have received about 1% of VC dollars, females founders 8%, and Black women founders .0006%.

Originally AVEC targeted raising a $1 million Pre-Seed with a big launch this summer. Due to Covid-19 and how it has affected deadlines worldwide, instead, they raised a Friends, Family, and Angels round. They launched softly while their customers have been meeting friends at virtual happy hours and quieter gatherings at home and now outside.

Bridging The American Divide

One woman whom Charlemagne finds particularly inspirational and fascinating to follow is fellow Columbia alumna Ursula Burns, MS 82SEAS ME, the former and first-ever Black and female CEO and chair of Xerox. She explains, As a Black woman who is a leader in her field, I know she had to work that much harder to get where she wanted to be, where she needed to be, to succeed and fulfill her potential. That motivates me in everything I do. Her story plus a class I took during my MBA program called Bridging the American Divide made me think differently about the kind of business leader I want to be. The class talks about the causes and consequences of the American divideand what the students as future business leaders might do to help bridge it.

Setting Goals For AVECs Future

We want to redefine the mixer category in the US around modern valueshigh quality, all-natural, low sugar, but also diverse teams and sustainable supply chains, Doman explains. He points out that the companys very name suggests and encourages the act of bringing people together, which in todays world is needed more than ever. Ultimately, AVECs founders know that when people convene to eat and drink together, they are creating moments where they can converse, connect, promote change, and drive empowerment.

AVEC with 6 Feet Apart Tables at White Horse Tavern "Drink Better. Mix AVEC."

Charlemagne adds, We want to promote living a balanced and healthy life while injecting a sense of fun in our brand and the way our products are consumed. Once we achieve that with the AVEC brand, there are several lifestyle directions we could pursue where we could continue to support diversity in taste and in communities.

When asked about what her idea of more immediate success would look like for AVEC, she envisions walking down the street and spotting people in restaurants, bars, and on terraces drinking an AVEC drink, with or without spirits. Based on their traction and the attention they have garnered so far, it looks like AVECs founders are on their way to making that first vision a reality.

S. Teresa Photography

Cecilia F. Pineda is Senior Associate Director at the Eugene Lang Entrepreneurship Center at Columbia Business School. For a while, her passion for food and beverage manifested in owning and managing restaurants/bars/catering companies, and marketing and distributing retail and wholesale food products.

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Mixing Fun And Healthy Living: Why These Beverage Founders Bet On Premiumization - Forbes

One 19th-century artist’s effort to grapple with tuberculosis resonates during COVID-19 – Reading Eagle

Posted on July 31, 2020 by Prof Baldwin

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

Elizabeth Lee, Dickinson College

(THE CONVERSATION) Like everyone else, artists have been challenged by new conditions and routines since the start of the COVID-19 pandemic. Many have had to adjust what they make as well as how and where they work, coming up with innovative ways to be productive in makeshift studios with limited supplies and in relative isolation.

One thing is certain, though: In response to daily headlines of devastating illness, suffering and death, the need for creative expression and meaningful reflection on loss remains essential.

For the past several years, Ive been researching the impact of disease on late 19th-century American artists. At the time, medical science was ill-equipped to manage rising rates of communicable disease, leaving art to help fill a need to comprehend and process illness.

One of the artists featured in my forthcoming book on art and disease is the painter Abbott Thayer, whose life and work underwent dramatic change following the death of his wife from tuberculosis. For the grieving painter, art functioned as a kind of medicine.

A romantic disease

In the late 18th century, tuberculosis started to be tinged with romanticism; it was thought of as an illness that could lead to elevated consciousness, creative insight and intellectual acuity. The poet John Keats and the pianist Frdric Chopin both died young from tuberculosis, cementing its reputation as an affliction of artists.

An early biographer of Robert Louis Stevenson argued that tuberculosis enhanced the writers talent, and in a sculptural relief depicting Stevenson during a stay in New York City, Augustus Saint-Gaudens portrays the bohemian writer with long hair and a cigarette in hand, looking alert and productive, despite being propped up by a stack of pillows in bed. As one critic observed, the relief captured Stevensons picturesque unfitness, as though illness heightened his allure.

If the effects of the disease were poorly understood, so too was the way in which it spread.

For hundreds of years, the cause of disease was believed to be miasmas, or foul-smelling air. Eventually, in the 1880s, medical science realized invisible microorganisms were the source of contagion, and that germs could be quietly passed from person to person. Unlike miasmas, which could be identified through smell, germs moved undetected through crowded cities. They were everywhere.

Pure air and healthy living

By the time the wife of painter Abbott Thayer succumbed to the disease in 1891, germ theory was widely accepted and would have been familiar to the artist, who was the son of a physician and public health expert. Fearing his three young children would be next, he sought out a healthy environment a place with plenty of fresh air and surrounded by nature, where the family could eat nutritious meals, roam freely outdoors and get plenty of rest.

The Thayers werent the only family looking for therapeutic settings. The 1870s marked the start of the sanatorium movement, in which individuals who had tuberculosis, or thought they might, were able to steel themselves against the illness in medically supervised, open-air compounds often near the mountains, desert or the sea. At the time, tuberculosis was the cause of roughly one in seven deaths in the U.S.

The life Thayer created for him and his children in Dublin, New Hampshire, was modeled on this type of facility. Their home, at the base of Mount Monadnock, gave the family ample opportunities to be immersed in fresh mountain air, which was then thought to be the purest type of air.

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On a typical day, Thayer spent his morning painting and then climbed Monadnock or took long trail walks with his family. These outdoor activities encouraged the kind of deep breathing believed to free toxins from contaminated lungs.

The Thayers also slept outdoors in individualized lean-tos a three-sided shelter that allowed them to breathe fresh air throughout the night. Thayer also invented a breath catcher a device worn around the nose and mouth, not unlike the protective masks of today which prevented the bodys noxious exhalations from freezing onto bedding at night, according to the thinking of the time. He also wore a special kind of wool underwear marketed for its protective qualities against disease in a further attempt to avoid germs.

Angels of vigor

While Thayer was working to protect the health of his family, his art underwent a shift.

Early in his career, Thayer mostly painted landscapes and portraits. But following the illness of his wife Kate, Thayer turned his own children Mary, Gerald and Gladys into the primary subjects of his work.

In the first of these, Angel, he painted his eldest child Mary as a heavenly creature, whose pale, chalky skin underscored by her white robe and wings conveys a fragility evoking the effects of tuberculosis.

The painting brings together the contradiction of a healthy daughter and sickly mother, collapsing the promise of wholesome youth and the fear of bodily disintegration.

In A Virgin of 189293, Thayer depicted all three children standing outside. The clouds, which emerge from Marys shoulders as wings, allude to Thayers earlier depiction of her in Angel and thus to her role as a stand-in for his late wife.

Given the way in which Kates illness focused the familys attention on nature and health, it seems significant, too, that the children, shown barefoot and windswept, walk vigorously and purposefully. Their classical clothing pays tribute to the ancient Greeks, celebrated in Thayers time for their commitment to physical fitness and outdoor living.

Immersed in a therapeutic environment while perhaps on one of their treks up Monadnock, Thayers children embody the life their father embraced. They become models of healthy outdoor living in an era of contagious disease.

The image may look antiquated, but it resonates today.

Both tuberculosis and COVID-19 target the lungs. Symptoms for both diseases include shortness of breath and coughing. There was no effective way to treat tuberculosis until the development of streptomycin in the 1940s, so prevention and perseverance during Thayers time as with COVID-19 often involved good hygiene and healthy living. Like Mary, Gerald and Gladys, we are still taking walks in nature in an effort to escape the psychological and physical limitations of quarantine.

Today, filling our lungs with fresh air remains a reassuring sign of health just as it did more than a century ago.

This article is republished from The Conversation under a Creative Commons license. Read the original article here: https://theconversation.com/one-19th-century-artists-effort-to-grapple-with-tuberculosis-resonates-during-covid-19-142343.

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One 19th-century artist's effort to grapple with tuberculosis resonates during COVID-19 - Reading Eagle

Weight Loss: These Metabolism Boosting Teas Can Help You Maintain A Healthy Weight – Doctor NDTV

Posted on July 31, 2020 by Prof Baldwin

Better metabolism can result in effective weight loss. Several diet and lifestyle changes can help boost metabolism. Here are some teas you must try.

A well balanced diet can help in maintaining a healthy weight

Metabolism plays an important role in weight management. It is a process by which your body converts the foods and drinks consumed into energy. Several factors can affect your metabolism. These may vary from diet to lifestyle. The better the metabolism the better is weight loss. When it comes to drinks, tea is one of the most common options to choose from. Many love to drink tea and are addicted to their daily cup. Here's a good news for all the tea lovers who are trying to lose weight. Several teas can help boost metabolism which can contribute to better weight management. Here are some teas you can try to boost your metabolism. Also, know other health benefits these can offer.

Green tea is loaded with several health benefits. It is commonly consumed for weight loss. Green tea is loaded with antioxidants. It also helps in boosting metabolism resulting in improved weight loss.

Drinking green tea can help in weight lossPhoto Credit: iStock

Ginger is a commonly used ingredient. It is commonly added to teas to enhance the taste. Ginger also offers immunity-boosting properties. Sipping ginger tea boosts metabolism and also helps in preventing sore throat.

Also read:6 Ways How Starting Your Day With Ginger Can Help You

Oolong tea is beneficial for your heart. Studies also suggest that oolong tea can also help reduce the risk of diabetes and improves brain function. This tea is also helpful in weight loss as it improves metabolism.

Also read:Weight Loss And Other Amazing Benefits Of Oolong Tea You Cannot Miss

Peppermint tea has a refreshing tea. Drinking this tea also helps ensure better sleep. It is also beneficial for your immune system. This tea is also beneficial for digestion. You can give a boost to your weight loss journey with this minty tea.

Several herbal teas can help boost metabolism that support the weight loss processPhoto Credit: iStock

Pu-erh tea may also help promote weight loss and boost metabolism. It can also help in improving cholesterol levels. If you have any pre-existing conditions consult an expert before adding it to your diet.

Also read:Try These Teas For Effective Weight Loss

Promoted

Do not overdose with these teas. You can consult your dietician to know the perfect fit in your diet. Also, discuss if you have any medical condition.

Disclaimer: This content including advice provides generic information only. It is in no way a substitute for qualified medical opinion. Always consult a specialist or your own doctor for more information. NDTV does not claim responsibility for this information.

DoctorNDTV is the one stop site for all your health needs providing the most credible health information, health news and tips with expert advice on healthy living, diet plans, informative videos etc. You can get the most relevant and accurate info you need about health problems like diabetes, cancer, pregnancy, HIV and AIDS, weight loss and many other lifestyle diseases. We have a panel of over 350 experts who help us develop content by giving their valuable inputs and bringing to us the latest in the world of healthcare.

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Weight Loss: These Metabolism Boosting Teas Can Help You Maintain A Healthy Weight - Doctor NDTV

Young Living Promotes Prasad Gankanda to EVP of Sales – The Herald Journal

Posted on July 31, 2020 by Prof Baldwin

LEHI, Utah, July 31, 2020 /PRNewswire/ -- Young Living, the world's leading provider of essential oils, today announced the promotion of Prasad Gankanda to executive vice president of global sales. As Prasad joins the executive leadership team, he will be responsible for global sales and expanding operations and maintaining Young Living's world class customer and business experience.

"As we lead our company through unprecedented times, Prasad has been instrumental in directing our sales team across the globe through the business challenges that come from a pandemic. He is an essential addition to our executive leadership team," said Jared Turner, president and COO of Young Living. "Prasad brings tremendous value to Young Living through his entrepreneurial spirit, using his creativity to help push everyone beyond their limits."

Prasad has over 10 years of experience in directing global business operations. Since joining Young Living in 2015, he has successfully expanded into new markets such as South Korea, South Africa, Brazil, Colombia, Costa Rica, and Macau, ensuring the standards of the company and delivering first-class services. He has brought high efficiency and productivity throughout his teams around the world.

Through Prasad's technical knowhow, he has improved inventory, enhanced delivery quality and implemented new operational enhancements. Just as Prasad has shown amazing leadership in operations, he has equally shown his skill over the past year leading global sales for all regions around the world. With Prasad's leadership, his team has quickly been able to pivot during this time, stabilize, and capitalize on growth. Prior to Young Living, Prasad held senior positions at MonaVie where he led engineering, manufacturing and supply chain.

"I have always been impressed by the innovative spirit at Young Living and I have big visions for the future," said Gankanda. "In order to scale our high standards as we continue to build, I look forward to working closely with my teams to do their best work. I am passionate about advocating for our markets and members to make sure they have a voice within the company and that they have the tools they need to be successful. Our members are our number one asset."

To learn more about Young Living's global leadership team, visit YoungLiving.com.

About Young Living Essential Oils Young Living Essential Oils, LC, based in Lehi, Utah, is the world leader in essential oils, offering the highest quality oil-infused products available. Young Living takes its industry leadership seriously, setting the standard with its proprietary Seed to Seal quality commitment, which involves three critical pillars: Sourcing, Science, and Standards. These guiding principles help Young Living protect the planet and provide pure, authentic products that its members can feel confident about using and sharing with friends and family. Young Living's productswhich all come from corporate-owned farms, partner farms, and Seed to Seal-certified suppliersnot only support a healthy lifestyle but also provide opportunities for over 6 million global members to find a sense of purpose and whole-life wellness by aligning their work with their values and passions. For more information, visit YoungLiving.com, follow @youngliving on Instagram, or like us on Facebook.

Arizona’s major universities will reopen soon. Here’s what they plan – AZCentral

Posted on July 31, 2020 by Prof Baldwin

At Northern Arizona University, in-person courses will resume Aug. 31 with students alternating between remote and in-person classes as determined by theprofessor.(Photo: Northern Arizona University)

The spread of COVID-19 in Arizona is much wider than it was in March, when Arizona colleges shifted to online classes mid-semester to help curb the diseases spread.

But all intend to go back to school in person at some point in the coming months.

Arizonas COVID-19 situation started spiraling, making it a new hotspot and stretching hospital resources thin. In the past few weeks, Arizonas cases and hospitalizations have declined slightly, but arestill at very high levels.

Already, Grand Canyon University and Northern Arizona University have pushed back their in-person fall start dates to allow case numbers to decline. They will start the semester online, then move to in-person classes later.

Arizona State University, the University of Arizona and the Maricopa Community Colleges are starting their semesters in person, with offerings of online, in-person and hybrid courses.

All colleges will look different than they did last fall, before COVID-19 was widespread in the United States. Students and faculty can expect to see social distancing, masks, limited class sizes and extensive sanitizing of common areas.

These colleges face pressures of all kinds in decisions to reopen financial, educational, political and societal. Enrollment in some cases may be lower than expectations, crunching budgets. NAU and UA have had layoffs and planned furloughs in response to potential shortfalls.

Some students say they want to return to campus and that they learn better in person, while others have said theyre too concerned about safety measures to take classes in person. Faculty and staff, who are often older than traditional students and could have higher risk for complications if they contract the virus, have said theyre worried about safety as well.

Arizona colleges have worked on return-to-campus plans for months. Here are the basics of major colleges plans for fall classes.

ASU announced health guidance for the university in June, which includes mandatory face coverings on campus, daily health screenings and social distancing.(Photo: The Republic)

When do classes start: Aug. 20 is the first day of the fall semester. Fall break, which was originally scheduled for Oct. 12-13, was canceled to reduce travel risk, according to the university website.

Online or in person options:Classes will be taught in three waysin-person, ASU Sync and online.

University officials said the majority of all courses offered in the fallwill bea blend of in-person and ASU Sync, meaning students will alternate between attending class in-person and through a live lecture via Zoom.

About 2% of all fall courses, including labs, clinical experiencesand hands-on fine arts courses, that are not conducive to remote learning will be offered exclusively in-person. Courses with more than 100 students enrolled will only be offered via ASU Sync,the university said. As of Wednesday, that amounted tofewer than 4%of courses, they said.

What safety precautions are being taken:ASU announced health guidance for the university in June, which includes mandatory face coverings on campus, daily health screenings and social distancing. Face coverings are mandatory for all students, employees and visitors to the university in all indoor spaces and outdoor spaces where social distancing is not possible, such assidewalks, bike racks, parking garagesand public transportation, ASU officials said.

In addition to cleaning classrooms daily, hand sanitizer and disinfectant wipes will be available to students in classrooms. All on campus students, faculty and staff will receive a "Community of Carekit" with a thermometer and two face masks, the university said in its announcement of CARES Act funds distribution plans.

"Individuals or groups choosing to ignore the rules not only jeopardize their own health, but the health of others and will be subject to a range of appropriate disciplinary action under the Student Code of Conduct," the university said Wednesday."We need all members of the ASU community to do their part and adhere to public health guidelines in order to have a successful semester."

On-campus social gatherings that are not in compliance with health guidance for the fall semester are not allowed, the university said, adding that they also plan to take action against any off-campus social guidelines that are "purposefully designed to disregard public health protocols." It's a policy that has been in place at the university since before the COVID-19 pandemic, they said.

Testing plans:ASU offers a free saliva-based COVID-19 test to all students and employees. University officials said results are typically available in about 24 to 48 hours.

There is no limit currently as to the number of free tests a person can get, they said.

What's happening with dorms: About 15,000 students are currently signed up to live in on-campushousing, university officials said. It's a number they say is in line with previous years.

Early move-in for residential assistants and other arrangements will begin Aug. 1. Maricopa County-based students willbegin move-in the week following, on Aug. 5-9.

The university announced Thursday that all students living in university housing will need to test negative for COVID-19 with a PCR test prior to move-in. They are requiredto upload proof of the test via the ASU Services Patient Portal at least 48 hours prior to their scheduled move-in time, the university said. All other students are encouraged, but not required to get tested for COVID-19 before returningto campus.

Visitors will not be allowed in residence halls and both indoor and outdoor community spaces may be restricted depending on local conditions, ASU said.

On-campus dining will be takeout only with prepackaged, disposable utensils. Touchless payments, physical distancing in lines, Plexiglass barriers and extended hours will also be implemented in dining halls, according to the university website.

ASU also plans to maintain vacant rooms in residence halls for isolation. The university said they will communicate directly with students about isolation requirements, medical advice and information on their recent activities and contacts. The school will then check-in with students who have tested positive at leastdaily, they said.

What school leaders are saying:ASU President Michael Crow saiduniversity officials have worked around the clock to ensure all ASU campuses are prepared to transition into the upcoming academic year.

Crow cautioned that a "dramatic shift" in the virus could change operational plansand said university is prepared to "adapt and pivot," if needed.

"Campus life will look different in many ways and we will all need to make adjustments," Crow said last week. "But with the cooperation and care of every member of the ASU community, I am confident that we will have a successful fall semester."

When do classes start: Aug. 24, 2020 is the first day of the fall 2020 semester at University of Arizona. Though, UA President Robert Robbins said Thursday in a weekly reentry briefing that only about 5,000 students will attend in-person classes in the first week.

Robbins said the university plans a staged launch of in-person classes. In the first week of classes, he said only students in essential in-person classes, such as labs or fine arts courses, as well as classes scheduled to be held outdoors will start in-person instruction. All other classes will be online, he said.

The following week, in-person or flex in-person courses with 30 or fewer students will start in-person courses. Robbins said the university expects about 14,000 individuals to be on campus in week two.

All remaining in-person and flex in-person courses will start in-person instruction in the third week of the semester, he said.

All classes will end the semester online after Thanksgiving break, according to the university's website.

Online or in person options:The university plans to offer classes in four ways: in-person, flex in-person, live online and iCourse.About 50% of courses in each department are expected to be offered in-person, according to an university official.

Information about how each course will be offered is published online for students via their university web portal, they said.

Testing:Theuniversity is implementing a plan called Test, Trace, Treat,which details plans for COVID-19 testing, contract tracing and treatment.

Three different tests are available at UAto diagnose and track the virus: an antibody test, Polymerase Chain Reaction (PCR) test and an antigen test.The PCR test, which is the most accurate test for current presence of COVID-19, will be used for individuals showing symptoms of the virus. The antigen test, which also tests for current presence of COVID-19, will be used to test as many students, faculty and staff as possible when they return to campus. The antibody test is currently available for essential workers, but the university plans to have the test available to students and faculty soon, according to the university website.

What safety precautions are being taken:UA has multiple campus reentry working groups who have workedto develop a variety of safety precautions and procedures, according to the university website.

Face coverings are required on-campus in buildings and outdoor spaces where physical distancing is not possible, the university said. Modified traffic flows, one-way indoor pathways and a reduction of students in classrooms by at least 50% also were implemented to increase social distancing, they said.

The university has also engineered improved air filtration and increased fresh air ventilation in classroom, according to the website. All classrooms will be cleaned at least five days a week and disinfectant and hand sanitizer will be available throughout campus, they said.

University officials acknowledged at a June 16 campus reentry meeting thatthere were concerns voiced about students following necessary public health measures. They said student ambassadors from multiple health departments and programs at the university will lead efforts to educate, inform and encourage peers to follow guidelines.

What's happening with dorms:Move in will start Aug. 14 and last through Aug. 22, according to the university website.

UAPresident Robert C. Robbins said Thursdayabout 5,500 students are still planning to live on campus, about 1,100 fewer students than Robbins said had made deposits for university housing during a June 16 briefing.

The university announced Tuesday that students who have already paid their deposit have three options:living on campus for the full academic year, late arrival and canceling their housing application.Students also have the option to defer their enrollment, the school said.

All students who elect to live on campus are required to take a free, on-campus antigen test, which will be administered upon check-in. If a student tests negative, they will then be allowed to move-in to their dorm. Any student who tests positivewill go to an isolation dorm for a 10-day isolation, the university said.

What school leaders are saying: Robbins continued to emphasize Thursday thatthe university willto monitor public health conditions and adjust reentry plans, if necessary.

"We have a plan and we have confidence that our students, faculty and staff will carry it out," Robbins said in UA's weekly reentry meeting. "But if we see noncompliance or if the public health conditions require it, we will shut this down."

People who don'tfeel comfortable returning to campus will not be forced to do so, he added.

"There are some people who don't want to come back to campus and I understand that," Robbins said."We are not forcing anyone to come back on campus. If you choose to do it, we welcome you and these are the guidelines we will use going forward."

When do classes start: Aug. 12 online, Aug. 31 in person. Northern Arizona University originally planned to resume in person instruction on Aug. 12, but pushed back the start date in reaction to input from a range of stakeholders regarding the universitys reentry plans, according to the schools July 24 announcement.

Online or in person options: Remote delivery through NAUFlex, which features live online lectures through Zoom or Collaborate Ultra, will be the primary mode of instruction through Aug. 28, NAU said in theFriday announcement.

In-person courses will resume Aug. 31 with students alternating between attending class remotely via NAUFlex or in-person based on a schedule determined by theprofessor. Students who want to remain remote for the entire semester will need to submit a NAUFlex Full Remote Request form available on the universitys website by Aug. 3.

Some classes might have required in-person elements. Professors will decide how much in-person instruction is necessary for their classes, the university said.

What safety precautions are being taken: NAU is asking students to complete a daily self-screening checklist, answering questions about potential symptoms for COVID-19. Ifthey answer"yes" to any of the questions on the checklist, they are expected to stay home and attend class remotely.

The school also is asking students to wear a mask in buildings, physically distance, wash hands frequently and complete an online training about a safe return to campus.

Most public spaces will be disinfected at least daily, in accordance with the universitys updated cleaning procedures. Dining areas, for example, will be cleaned at least three times daily.

Testing plans:Campus Health is offering on-campus nasal swab COVID-19 tests, but they are only available to individuals who are symptomatic or who have potentially been exposed, according to the university website. Fees for the test are dependent on the individuals health care provider, NAU said.

The university announced Friday that all students should be tested for COVID-19 prior to arrival and all students who plan to live on-campus will be required to test negative prior to move-in.

Whats happening with dorms: The university pushed back move in dates after announcing the delay of in-person courses. The new move-in dates are Aug. 19 to Aug. 30.

Students will receive an email by July 29 to select a move-in appointment window. Prior to move in, students are required to prove that they tested negative for COVID-19 after July 24. They are then expected to quarantine from the day they test to the day they arrive on campus with a minimum of 10 days in between, according to the university website. The university says it is in the process of creating a portal to submit test results.

Students who plan to live in on-campus housing and who are unable to get tested for COVID-19 prior to move-in will need to quarantine in their residence hall upon arrival until they receive a negative test result.

NAU also is attempting to decrease density in on-campus housing. Triple rooms are no longer available. Most students will share a room with one other person.

What school leaders are saying: NAU President Rita Cheng in her July 24 update acknowledged some people might be disappointed in the adjustment of plans for the start of the fall semester, but emphasized that the health and safety of students, faculty, staff and the community is the universitys priority.

In these complex and challenging times, we are committed to our educational mission and we are prioritizing a healthy living and learning environment that will allow our students to realize their aspirations at NAU, Cheng said.

When do classes start: Sept. 8 online, Sept. 28 in person. Grand Canyon University originally planned to start classes on Aug. 24, but pushed their in-person start date back to give Arizona time to reduce its COVID-19 cases.

Online or in person options: Students will start courses Sept. 8 and spend the first three weeks of school online until transitioning to in-person classes. In-person classes will be a "physically distant blended model of instruction" until the end of the semester, Dec. 18, GCU said in mid-July.

Students cant start online then switch to in-person classes later in the semester, though. GCU said the face-to-face classes have a physical distancing requirement that decreases class sizes which cant be overridden.

GCU has a robust online class offering already because most of its students attend classes online regardless of the pandemic.

GCU is on pace to have its largest incoming class, with more than 8,000 students associated with the Phoenix campus newlystarting this fall and 24,000 overallstudents associated with the campus, GCU spokesman Bob Romantic said. Students have the choice to go to in-person classes, blended learning or online, he said. A few thousand of those traditional students may choose to go online-only for the fall semester, he said.

What safety precautions are being taken: GCU has had 11 work groups formulating its plans for the past few months, Romantic said.

The university is making its own personal protective equipment, including masks.

Cloth masks are required in classrooms, campus restaurants, indoor community spaces and outdoor settings where distancing of at least 6 feet isn't possible, Romantic said.

GCU expects dorms to be near capacity, so the campus hotel may operate as additional housing for those who become ill. The GCU Hotel closed on July 1 to the publicand has already been in use to house students who are required to quarantine when they arrive on campus, Romantic said.

Shared spaces and events will be scaled down or distanced, and class sizes will be reduced to allow for spacing.

In a typical semester, thousands of GCU students would attend a weekly chapel service in the GCU Arena. This semester, the service will be spread among four venues, Romantic said. Starting later also allows for more outside events since the weather is not as hot, he said.

Testing plans:The university canconduct 10,000 COVID-19 tests per month,Romantic said.

Students who are symptomatic or identified through contact tracing as a high-risk exposure to a positive case will be tested, Romantic said. Students can also voluntarily request a test. The university may do surveillance testing if theres a high concentration of positive cases in a particular area, like a dorm floor.

Once students arrive on campus, the university will be able to conduct diagnostic and antibody tests with quick turnaround times, Romantic said.

Whats happening with dorms: Dorms are expected to be near capacity. Move-in dateswill be during the week of Sept. 21 and by appointment.

Students will get an email by Aug. 5 telling them how to pick a move-in appointment. Once they arrive on campus, a group of two to three student leaders will show them their room and check them in. If they want, the leaders can help with unloading and bringing items to a students room.

Fall semester housing costs will be pro-rated to account for the later move-in date, GCU said. Students can also reduce their meal plans, if theyd like.

What school leaders are saying: In July updates to students, GCU said it was working to make sure students were safe, while balancing educational and financial considerations.

Pushing the in-person start date back made sense for those reasons, GCU said.

With the surge of positive coronavirus cases, hospitalizations and deaths in Arizona during the past 30 days, it is incumbent on the University to become part of the solution that puts our state in a better place, a July 22 update said. We also want to ensure our students have the best possible experience once they arrive on campus, and we think we can better accomplish that with the adjusted fall semester timeline. The modified dates will have a significant financial impact on GCU, but in times like these, everyone must make sacrifices for the greater good and the University must do its part.

Reach reporter Rachel Leingang by emailat rachel.leingang@gannett.com or by phone at 602-444-8157, or find her on Twitter and Facebook.Contact Grace Oldham atgrace.oldham@arizonarepublic.comor on Twitter at@grace_c_oldham.

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