Nanoscopy for nanomedicine Institute for Bioengineering …

The main goal of our group is to use Super Resolution Microscopy (nanoscopy) to visualize and track in living cells and tissues self-assembled nanomaterials with therapeutic potential (nanomedicine).

TEM image of novel self-assembled nanofibers synthesized in the group.

The understanding of materials-cell interactions is the key towards the development of novel nanotechnology-based therapies for treatment of cancer and infectious diseases.Our group aims to use a multidisciplinary approach, at the interface of chemistry, physics and biology, to develop novel nanomaterials for the treatment of cancer and infectious diseases.

We aim at the development of novel nanocarriers for drug delivery based on self-assembly, i.e. able to build themselves. Molecular self-organization is ubiquitous in the biological world and represents for us a source of inspiration for the design of nanostructures with biomedical potential. In particular we focus on the development of self-assembled nanoparticles and nanofibers able to selectively target diseased cells and deliver locally therapeutic moieties such as drugs and genetic material (e.g. DNA, siRNA, mRNA).

A key point towards the development of novel nanotechnology-based therapies is the understanding of the behavior of nanomaterials in the complex biological environment. Here we use super resolution microscopy to track nanomaterials during their voyage in the biological environment and to visualize the interactions with blood components, immune system and target cells. We make use of a variety of super resolution techniques based on single molecule detection such a stochastic optical reconstruction microscopy (STORM), photoactivated localization microscopy (PALM), point accumulation for imaging in nanoscale topography (PAINT), and single particle tracking (SPT). These methods allow to achieve a resolution down to few nanometers and are therefore ideal to visualize nanosized synthetic objects in the biological environment. Super resolution microscopy provides a molecular picture of structure-activity relations and represent a guide towards the design of innovative materials for nanomedicine.

Eight IBECers were in the Netherlands on 13th and 14th September for the first ever IBEC-ICMS Symposium, NanoSens&Med.

Two IBEC groups have clubbed together to combine their expertise and reveal new knowledge that could advance the design of micro- and nanomotors for applications in health.

Three of IBECs women researchers have been successful in BISTs recent To the Mothers of Science call.

The Nanoscopy for Nanomedicine group has studied Single-Chain Polymeric Nanoparticles (SCPNs) mimicking enzymes as possible drug activators in biological environments, like the living cell.

An article by BIOCAT profiles the three winners in Catalonia of the last round of ERC Starting Grants, including IBECs Lorenzo Albertazzi.

A paper published in Small last month by Lorenzo Albertazzis group is featured in Advanced Science News, Wiley publishing companys in-house news website. This platform presents advances in various fields of research for a general audience.

The Nanoscopy for Nanomedicine junior group leader was successful in the European Research Councils 2017 call for Starting Grants, of which just 17 out of the total of 406 have been awarded to scientists working in Spain.

IBEC junior group leader Lorenzo Albertazzi is a contributor to the 2017 edition of ChemComm Emerging Investigators, which is published annually by the UKs Royal Society of Chemistry.

The AXA Research Fund, the international scientific philanthropy initiative of global insurer AXA, officially announced last week that it will devote 15.6m in 2016 to 44 new research projects with leading academic institutions in 16 countries.

New IBEC junior group leader Lorenzo Albertazzi and his former colleagues at the Eindhoven University of Technology, working together with industry partner Novartis, have made a leap in drug delivery vectors by developing a new type of carrier with some groundbreaking improvements.

Lorenzo Albertazzis research project funded by AXA, Novel approaches for Pandemic Virus Targeting Using Adaptive Polymers, is featured on the Granted Projects section of their website.

New IBEC junior group leader Lorenzo Albertazzi is profiled in El Mundos Personajes nicos section this week.

Dr Lorenzo Albertazzi, a nanoscientist whose research focuses on creating smart self-assembling materials for therapeutic applications, is joining IBEC this September.

(See full publication list in ORCID)

Liu, Yiliu, Pujals, Slvia, Stals, Patrick J. M., Paulhrl, Thomas, Presolski, Stanislav I., Meijer, E. W., Albertazzi, Lorenzo, Palmans, Anja R. A., (2018). Catalytically active single-chain polymeric nanoparticles: Exploring their functions in complex biological media Journal of the American Chemical Society 140, (9), 3423-3433

Dynamic single-chain polymeric nanoparticles (SCPNs) are intriguing, bioinspired architectures that result from the collapse or folding of an individual polymer chain into a nanometer-sized particle. Here we present a detailed biophysical study on the behavior of dynamic SCPNs in living cells and an evaluation of their catalytic functionality in such a complex medium. We first developed a number of delivery strategies that allowed the selective localization of SCPNs in different cellular compartments. Live/dead tests showed that the SCPNs were not toxic to cells while spectral imaging revealed that SCPNs provide a structural shielding and reduced the influence from the outer biological media. The ability of SCPNs to act as catalysts in biological media was first assessed by investigating their potential for reactive oxygen species generation. With porphyrins covalently attached to the SCPNs, singlet oxygen was generated upon irradiation with light, inducing spatially controlled cell death. In addition, Cu(I)- and Pd(II)-based SCPNs were prepared and these catalysts were screened in vitro and studied in cellular environments for the carbamate cleavage reaction of rhodamine-based substrates. This is a model reaction for the uncaging of bioactive compounds such as cytotoxic drugs for catalysis-based cancer therapy. We observed that the rate of the deprotection depends on both the organometallic catalysts and the nature of the protective group. The rate reduces from in vitro to the biological environment, indicating a strong influence of biomolecules on catalyst performance. The Cu(I)-based SCPNs in combination with the dimethylpropargyloxycarbonyl protective group showed the best performances both in vitro and in biological environment, making this group promising in biomedical applications.

Patio, Tania, Feiner-Gracia, Natalia, Arqu, Xavier, Miguel-Lpez, Albert, Jannasch, Anita, Stumpp, Tom, Schffer, Erik, Albertazzi, Lorenzo, Snchez, Samuel, (2018). Influence of enzyme quantity and distribution on the self-propulsion of non-Janus urease-powered micromotors Journal of the American Chemical Society 140, (25), 7896-7903

The use of enzyme catalysis to power micro- and nanomachines offers unique features such as biocompatibility, versatility, and fuel bioavailability. Yet, the key parameters underlying the motion behavior of enzyme-powered motors are not completely understood. Here, we investigate the role of enzyme distribution and quantity on the generation of active motion. Two different micromotor architectures based on either polystyrene (PS) or polystyrene coated with a rough silicon dioxide shell (PS@SiO2) were explored. A directional propulsion with higher speed was observed for PS@SiO2 motors when compared to their PS counterparts. We made use of stochastically optical reconstruction microscopy (STORM) to precisely detect single urease molecules conjugated to the micromotors surface with a high spatial resolution. An asymmetric distribution of enzymes around the micromotor surface was observed for both PS and PS@SiO2 architectures, indicating that the enzyme distribution was not the only parameter affecting the motion behavior. We quantified the number of enzymes present on the micromotor surface and observed a 10-fold increase in the number of urease molecules for PS@SiO2 motors compared to PS-based micromotors. To further investigate the number of enzymes required to generate a self-propulsion, PS@SiO2 particles were functionalized with varying amounts of urease molecules and the resulting speed and propulsive force were measured by optical tracking and optical tweezers, respectively. Surprisingly, both speed and force depended in a nonlinear fashion on the enzyme coverage. To break symmetry for active propulsion, we found that a certain threshold number of enzymes molecules per micromotor was necessary, indicating that activity may be due to a critical phenomenon. Taken together, these results provide new insights into the design features of micro/nanomotors to ensure an efficient development.

Delcanale, Pietro, Miret-Ontiveros, Bernat, Arista-Romero, Maria, Pujals, Silvia, Albertazzi, Lorenzo, (2018). Nanoscale mapping functional sites on nanoparticles by Points Accumulation for Imaging in Nanoscale Topography (PAINT) ACS Nano 12, (8), 7629-7637

The ability of nanoparticles to selectively recognize a molecular target constitutes the key toward nanomedicine applications such as drug delivery and diagnostics. The activity of such devices is mediated by the presence of multiple copies of functional molecules on the nanostructure surface. Therefore, understanding the number and the distribution of nanoparticle functional groups is of utmost importance for the rational design of effective materials. Analytical methods are available, but to obtain quantitative information at the level of single particles and single functional sites, i.e., going beyond the ensemble, remains highly challenging. Here we introduce the use of an optical nanoscopy technique, DNA points accumulation for imaging in nanoscale topography (DNA-PAINT), to address this issue. Combining subdiffraction spatial resolution with molecular selectivity and sensitivity, DNA-PAINT provides both geometrical and functional information at the level of a single nanostructure. We show how DNA-PAINT can be used to image and quantify relevant functional proteins such as antibodies and streptavidin on nanoparticles and microparticles with nanometric accuracy in 3D and multiple colors. The generality and the applicability of our method without the need for fluorescent labeling hold great promise for the robust quantitative nanocharacterization of functional nanomaterials.

Ardizzone, Antonio, Kurhuzenkau, Siarhei, Illa-Tuset, Slvia, Faraudo, Jordi, Bondar, Mykhailo, Hagan, David, Van Stryland, Eric W., Painelli, Anna, Sissa, Cristina, Feiner, Natalia, Albertazzi, Lorenzo, Veciana, Jaume, Ventosa, Nora, (2018). Nanostructuring lipophilic dyes in water using stable vesicles, quatsomes, as scaffolds and their use as probes for bioimaging Small , 14, (16), 1703851

Abstract A new kind of fluorescent organic nanoparticles (FONs) is obtained using quatsomes (QSs), a family of nanovesicles proposed as scaffolds for the nanostructuration of commercial lipophilic carbocyanines (1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI), 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indodicarbocyanine perchlorate (DiD), and 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indotricarbocyanine iodide (DiR)) in aqueous media. The obtained FONs, prepared by a CO2-based technology, show excellent colloidal- and photostability, outperforming other nanoformulations of the dyes, and improve the optical properties of the fluorophores in water. Molecular dynamics simulations provide an atomistic picture of the disposition of the dyes within the membrane. The potential of QSs for biological imaging is demonstrated by performing superresolution microscopy of the DiI-loaded vesicles in vitro and in cells. Therefore, fluorescent QSs constitute an appealing nanomaterial for bioimaging applications.

Krivitsky, Adva, Polyak, Dina, Scomparin, Anna, Eliyahu, Shay, Ofek, Paula, Tiram, Galia, Kalinski, Hagar, Avkin-Nachum, Sharon, Feiner Gracia, N., Albertazzi, Lorenzo, Satchi-Fainaro, Ronit, (2018). Amphiphilic poly()glutamate polymeric micelles for systemic administration of siRNA to tumors Nanomedicine: Nanotechnology, Biology, and Medicine , 14, (2), 303-315

RNAi therapeutics carried a great promise to the area of personalized medicine: the ability to target undruggable oncogenic pathways. Nevertheless, their efficient tumor targeting via systemic administration had not been resolved yet. Amphiphilic alkylated poly()glutamate amine (APA) can serve as a cationic carrier to the negatively-charged oligonucleotides. APA polymers complexed with siRNA to form round-shaped, homogenous and reproducible nano-sized polyplexes bearing ~50 nm size and slightly negative charge. In addition, APA:siRNA polyplexes were shown to be potent gene regulators in vitro. In light of these preferred physico-chemical characteristics, their performance as systemically-administered siRNA nanocarriers was investigated. Intravenously-injected APA:siRNA polyplexes accumulated selectively in tumors and did not accumulate in the lungs, heart, liver or spleen. Nevertheless, the polyplexes failed to induce specific mRNA degradation, hence neither reduction in tumor volume nor prolonged mice survival was seen.

Casellas, Nicolas M., Pujals, Slvia, Bochicchio, Davide, Pavan, Giovanni M., Torres, Toms, Albertazzi, Lorenzo, Garca-Iglesias, Miguel, (2018). From isodesmic to highly cooperative: Reverting the supramolecular polymerization mechanism in water by fine monomer design Chemical Communications 54, (33), 4112-4115

Two structurally-similar discotic molecules able to self-assemble in water, forming supramolecular fibers, are reported. While both self-assembled polymers are indistinguishable from a morphological point-of-view, a dramatic change in their polymerization mechanism is observed (i.e., one self-assemble via an isodesmic mechanism, while the other shows one of the highest cooperativity values).

van Elsland, Daphne M., Pujals, Slvia, Bakkum, Thomas, Bos, Erik, Oikonomeas-Koppasis, Nikolaos, Berlin, Ilana, Neefjes, Jacques, Meijer, Annemarie H., Koster, Abraham J., Albertazzi, Lorenzo, van Kasteren, Sander I., (2018). Ultrastructural imaging of salmonella-host interactions using super-resolution correlative light-electron microscopy of bioorthogonal pathogens ChemBioChem , 19, (16), 1766-1770

The imaging of intracellular pathogens inside host cells is complicated by the low resolution and sensitivity of fluorescence microscopy and by the lack of ultrastructural information to visualize the pathogens. Herein, we present a new method to visualize these pathogens during infection that circumvents these problems: by using a metabolic hijacking approach to bioorthogonally label the intracellular pathogen Salmonella Typhimurium and by using these bioorthogonal groups to introduce fluorophores compatible with stochastic optical reconstruction microscopy (STORM) and placing this in a correlative light electron microscopy (CLEM) workflow, the pathogen can be imaged within its host cell context Typhimurium with a resolution of 20nm. This STORM-CLEM approach thus presents a new approach to understand these pathogens during infection.

Oria, Roger, Wiegand, Tina, Escribano, Jorge, Elosegui-Artola, Alberto, Uriarte, Juan Jose, Moreno-Pulido, Cristian, Platzman, Ilia, Delcanale, Pietro, Albertazzi, Lorenzo, Navajas, Daniel, Trepat, Xavier, Garca-Aznar, Jos Manuel, Cavalcanti-Adam, Elisabetta Ada, Roca-Cusachs, Pere, (2017). Force loading explains spatial sensing of ligands by cells Nature 552, 219-224

Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts1,2. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrinligand bonds are separated by more than a few tens of nanometres3,4,5,6. It has thus been suggested that a crosslinking adaptor protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly3,7,8,9. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model10,11, in which individual integrinECM bondsthe molecular clutchesrespond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow speeds support our model. Our results provide a general framework for how cells sense spatial and physical information at the nanoscale, precisely tuning the range of conditions at which they form adhesions and activate transcriptional regulation.

Duro-Castano, Aroa, Nebot, Vicent J., Nio-Pariente, Amaya, Armin, Ana, Arroyo-Crespo, Juan J., Paul, Alison, Feiner-Gracia, Natalia, Albertazzi, Lorenzo, Vicent, Mara J., (2017). Capturing extraordinary soft-assembled charge-like polypeptides as a strategy for nanocarrier design Advanced Materials , 29, (39), 1702888

The rational design of nanomedicines is a challenging task given the complex architectures required for the construction of nanosized carriers with embedded therapeutic properties and the complex interface of these materials with the biological environment. Herein, an unexpected charge-like attraction mechanism of self-assembly for star-shaped polyglutamates in nonsalty aqueous solutions is identified, which matches the ubiquitous ordinaryextraordinary phenomenon previously described by physicists. For the first time, a bottom-up methodology for the stabilization of these nanosized soft-assembled star-shaped polyglutamates is also described, enabling the translation of theoretical research into nanomaterials with applicability within the drug-delivery field. Covalent capture of these labile assemblies provides access to unprecedented architectures to be used as nanocarriers. The enhanced in vitro and in vivo properties of these novel nanoconstructs as drug-delivery systems highlight the potential of this approach for tumor-localized as well as lymphotropic delivery.

Keywords: Charge-like, Drug delivery, Polymer therapeutics, Polypeptides, Self-assembly

Labernadie, A., Kato, T., Brugus, A., Serra-Picamal, X., Derzsi, S., Arwert, E., Weston, A., Gonzlez-Tarrag, V., Elosegui-Artola, A., Albertazzi, L., Alcaraz, J., Roca-Cusachs, P., Sahai, E., Trepat, X., (2017). A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion Nature Cell Biology , 19, (3), 224-237

Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers -catenin recruitment and adhesion reinforcement dependent on -catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.

Feiner-Gracia, Natalia, Buzhor, Marina, Fuentes, Edgar, Pujals, S., Amir, Roey J., Albertazzi, Lorenzo, (2017). Micellar stability in biological media dictates internalization in living cells Journal of the American Chemical Society 139, (46), 16677-16687

The dynamic nature of polymeric assemblies makes their stability in biological media a crucial parameter for their potential use as drug delivery systems in vivo. Therefore, it is essential to study and understand the behavior of self-assembled nanocarriers under conditions that will be encountered in vivo such as extreme dilutions and interactions with blood proteins and cells. Herein, using a combination of fluorescence spectroscopy and microscopy, we studied four amphiphilic PEGdendron hybrids and their self-assembled micelles in order to determine their structurestability relations. The high molecular precision of the dendritic block enabled us to systematically tune the hydrophobicity and stability of the assembled micelles. Using micelles that change their fluorescent properties upon disassembly, we observed that serum proteins bind to and interact with the polymeric amphiphiles in both their assembled and monomeric states. These interactions strongly affected the stability and enzymatic degradation of the micelles. Finally, using spectrally resolved confocal imaging, we determined the relations between the stability of the polymeric assemblies in biological media and their cell entry. Our results highlight the important interplay between molecular structure, micellar stability, and cell internalization pathways, pinpointing the high sensitivity of stabilityactivity relations to minor structural changes and the crucial role that these relations play in designing effective polymeric nanostructures for biomedical applications.

Feiner-Gracia, Natalia, Beck, Michaela, Pujals, Slvia, Tosi, Sbastien, Mandal, Tamoghna, Buske, Christian, Linden, Mika, Albertazzi, Lorenzo, (2017). Super-resolution microscopy unveils dynamic heterogeneities in nanoparticle protein corona Small , 13, (41), 1701631

The adsorption of serum proteins, leading to the formation of a biomolecular corona, is a key determinant of the biological identity of nanoparticles in vivo. Therefore, gaining knowledge on the formation, composition, and temporal evolution of the corona is of utmost importance for the development of nanoparticle-based therapies. Here, it is shown that the use of super-resolution optical microscopy enables the imaging of the protein corona on mesoporous silica nanoparticles with single protein sensitivity. Particle-by-particle quantification reveals a significant heterogeneity in protein absorption under native conditions. Moreover, the diversity of the corona evolves over time depending on the surface chemistry and degradability of the particles. This paper investigates the consequences of protein adsorption for specific cell targeting by antibody-functionalized nanoparticles providing a detailed understanding of corona-activity relations. The methodology is widely applicable to a variety of nanostructures and complements the existing ensemble approaches for protein corona study.

Keywords: Heterogeneity, Mesoporous silica nanoparticles, Protein corona, Super-resolution imaging, Targeting

Van Onzen, A. H. A. M., Albertazzi, L., Schenning, A. P. H. J., Milroy, L. G., Brunsveld, L., (2017). Hydrophobicity determines the fate of self-assembled fluorescent nanoparticles in cells Chemical Communications 53, (10), 1626-1629

The fate of small molecule nanoparticles (SMNPs) composed of self-assembling intrinsically fluorescent -conjugated oligomers was studied in cells as a function of side-chain hydrophobicity. While the hydrophobic SMNPs remained intact upon cellular uptake, the more hydrophilic SMNPs disassembled and dispersed throughout the cytosol.

Pujals, S., Tao, K., Terradellas, A., Gazit, E., Albertazzi, L., (2017). Studying structure and dynamics of self-Assembled peptide nanostructures using fluorescence and super resolution microscopy Chemical Communications 53, (53), 7294-7297

Understanding the formation and properties of self-Assembled peptide nanostructures is the basis for the design of new architectures for various applications. Here we show the potential of fluorescence and super resolution imaging to unveil the structural and dynamic features of peptide nanofibers with high spatiotemporal resolution.

Caballero, David, Blackburn, Sophie M., de Pablo, Mar, Samitier, Josep, Albertazzi, Lorenzo, (2017). Tumour-vessel-on-a-chip models for drug delivery Lab on a Chip , 17, 3760-3771

Nanocarriers for drug delivery have great potential to revolutionize cancer treatment, due to their enhanced selectivity and efficacy. Despite this great promise, researchers have had limited success in the clinical translation of this approach. One of the main causes of these difficulties is that standard in vitro models, typically used to understand nanocarriers' behaviour and screen their efficiency, do not provide the complexity typically encountered in living systems. In contrast, in vivo models, despite being highly physiological, display serious bottlenecks which threaten the relevancy of the obtained data. Microfluidics and nanofabrication can dramatically contribute to solving this issue, providing 3D high-throughput models with improved resemblance to in vivo systems. In particular, microfluidic models of tumour blood vessels can be used to better elucidate how new nanocarriers behave in the microcirculation of healthy and cancerous tissues. Several key steps of the drug delivery process such as extravasation, immune response and endothelial targeting happen under flow in capillaries and can be accurately modelled using microfluidics. In this review, we will present how tumour-vessel-on-a-chip systems can be used to investigate targeted drug delivery and which key factors need to be considered for the rational design of these materials. Future applications of this approach and its role in driving forward the next generation of targeted drug delivery methods will be discussed.

Bakker, Maarten H., Lee, Cameron C., Meijer, E. W., Dankers, Patricia Y. W., Albertazzi, Lorenzo, (2016). Multicomponent supramolecular polymers as a modular platform for intracellular delivery ACS Nano 10, (2), 1845-1852

Supramolecular polymers are an emerging family of nanosized structures with potential use in materials chemistry and medicine. Surprisingly, application of supramolecular polymers in the field of drug delivery has received only limited attention. Here, we explore the potential of PEGylated 1,3,5-benzenetricarboxamide (BTA) supramolecular polymers for intracellular delivery. Exploiting the unique modular approach of supramolecular chemistry, we can coassemble neutral and cationic BTAs and control the overall properties of the polymer by simple monomer mixing. Moreover, this platform offers a versatile approach toward functionalization. The core can be efficiently loaded with a hydrophobic guest molecule, while the exterior can be electrostatically complexed with siRNA. It is demonstrated that both compounds can be delivered in living cells, and that they can be combined to enable a dual delivery strategy. These results show the advantages of employing a modular system and pave the way for application of supramolecular polymers in intracellular delivery.

Beun, L. H., Albertazzi, L., Van Der Zwaag, D., De Vries, R., Cohen Stuart, M. A., (2016). Unidirectional living growth of self-assembled protein nanofibrils revealed by super-resolution microscopy ACS Nano 10, (5), 4973-4980

Protein-based nanofibrils are emerging as a promising class of materials that provide unique properties for applications such as biomedical and food engineering. Here, we use atomic force microscopy and stochastic optical reconstruction microscopy imaging to elucidate the growth dynamics, exchange kinetics, and polymerization mechanism for fibrils composed of a de novo designed recombinant triblock protein polymer. This macromolecule features a silk-inspired self-assembling central block composed of GAGAGAGH repeats, which are known to fold into a roll with turns at each histidine and, once folded, to stack, forming a long, ribbon-like structure. We find several properties that allow the growth of patterned protein nanofibrils: the self-assembly takes place on only one side of the growing fibrils by the essentially irreversible addition of protein polymer subunits, and these fibril ends remain reactive indefinitely in the absence of monomer ("living ends"). Exploiting these characteristics, we can grow stable diblock protein nanofibrils by the sequential addition of differently labeled proteins. We establish control over the block length ratio by simply varying monomer feed conditions. Our results demonstrate the use of engineered protein polymers in creating precisely patterned protein nanofibrils and open perspectives for the hierarchical self-assembly of functional biomaterials.

Keywords: Nanofibrils, Protein polymers, Self-assembly, STORM microscopy

Garzoni, M., Baker, M. B., Leenders, C. M. A., Voets, I. K., Albertazzi, L., Palmans, A. R. A., Meijer, E. W., Pavan, G. M., (2016). Effect of H-bonding on order amplification in the growth of a supramolecular polymer in water Journal of the American Chemical Society 138, (42), 13985-13995

While a great deal of knowledge on the roles of hydrogen bonding and hydrophobicity in proteins has resulted in the creation of rationally designed and functional peptidic structures, the roles of these forces on purely synthetic supramolecular architectures in water have proven difficult to ascertain. Focusing on a 1,3,5-benzenetricarboxamide (BTA)-based supramolecular polymer, we have designed a molecular modeling strategy to dissect the energetic contributions involved in the self-assembly (electrostatic, hydrophobic, etc.) upon growth of both ordered BTA stacks and random BTA aggregates. Utilizing this set of simulations, we have unraveled the cooperative mechanism for polymer growth, where a critical size must be reached in the aggregates before emergence and amplification of order into the experimentally observed fibers. Furthermore, we have found that the formation of ordered fibers is favored over disordered aggregates solely on the basis of electrostatic interactions. Detailed analysis of the simulation data suggests that H-bonding is a major source of this stabilization energy. Experimental and computational comparison with a newly synthesized 1,3,5-benzenetricarboxyester (BTE) derivative, lacking the ability to form the H-bonding network, demonstrated that this BTE variant is also capable of fiber formation, albeit at a reduced persistence length. This work provides unambiguous evidence for the key 1D driving force of hydrogen bonding in enhancing the persistency of monomer stacking and amplifying the level of order into the growing supramolecular polymer in water. Our computational approach provides an important relationship directly linking the structure of the monomer to the structure and properties of the supramolecular polymer.

Aloi, Antonio, Vargas Jentzsch, Andreas, Vilanova, Neus, Albertazzi, Lorenzo, Meijer, E. W., Voets, Ilja K., (2016). Imaging nanostructures by single-molecule localization microscopy in organic solvents Journal of the American Chemical Society 138, (9), 2953-2956

The introduction of super-resolution fluorescence microscopy (SRM) opened an unprecedented vista into nanoscopic length scales, unveiling a new degree of complexity in biological systems in aqueous environments. Regrettably, supramolecular chemistry and material science benefited far less from these recent developments. Here we expand the scope of SRM to photoactivated localization microscopy (PALM) imaging of synthetic nanostructures that are highly dynamic in organic solvents. Furthermore, we characterize the photophysical properties of commonly used photoactivatable dyes in a wide range of solvents, which is made possible by the addition of a tiny amount of an alcohol. As proof-of-principle, we use PALM to image silica beads with radii close to Abbes diffraction limit. Individual nanoparticles are readily identified and reliably sized in multicolor mixtures of large and small beads. We further use SRM to visualize nm-thin yet m-long dynamic, supramolecular polymers, which are among the most challenging molecular systems to image.

da Silva, Ricardo M. P., van der Zwaag, Daan, Albertazzi, Lorenzo, Lee, Sungsoo S., Meijer, E. W., Stupp, Samuel I., (2016). Super-resolution microscopy reveals structural diversity in molecular exchange among peptide amphiphile nanofibres Nature Communications 7, 11561

The dynamic behaviour of supramolecular systems is an important dimension of their potential functions. Here, we report on the use of stochastic optical reconstruction microscopy to study the molecular exchange of peptide amphiphile nanofibres, supramolecular systems known to have important biomedical functions. Solutions of nanofibres labelled with different dyes (Cy3 and Cy5) were mixed, and the distribution of dyes inserting into initially single-colour nanofibres was quantified using correlative image analysis. Our observations are consistent with an exchange mechanism involving monomers or small clusters of molecules inserting randomly into a fibre. Different exchange rates are observed within the same fibre, suggesting that local cohesive structures exist on the basis of [beta]-sheet discontinuous domains. The results reported here show that peptide amphiphile supramolecular systems can be dynamic and that their intermolecular interactions affect exchange patterns. This information can be used to generate useful aggregate morphologies for improved biomedical function.

DeKoker, Stefaan, Cui, Jiwei, Vanparijs, Nane, Albertazzi, Lorenzo, Grooten, Johan, Caruso, Frank, DeGeest, Bruno G., (2016). Engineering polymer hydrogel nanoparticles for lymph node-targeted delivery Angewandte Chemie - International Edition , 55, (4), 1334-1339

The induction of antigen-specific adaptive immunity exclusively occurs in lymphoid organs. As a consequence, the efficacy by which vaccines reach these tissues strongly affects the efficacy of the vaccine. Here, we report the design of polymer hydrogel nanoparticles that efficiently target multiple immune cell subsets in the draining lymph nodes. Nanoparticles are fabricated by infiltrating mesoporous silica particles (ca. 200nm) with poly(methacrylic acid) followed by disulfide-based crosslinking and template removal. PEGylation of these nanoparticles does not affect their cellular association invitro, but dramatically improves their lymphatic drainage invivo. The functional relevance of these observations is further illustrated by the increased priming of antigen-specific Tcells. Our findings highlight the potential of engineered hydrogel nanoparticles for the lymphatic delivery of antigens and immune-modulating compounds.

Keywords: Dendritic cells, Disulfides, Hydrogels, Nanoparticles, Vaccines

Li, Hui, Fierens, Kaat, Zhang, Zhiyue, Vanparijs, Nane, Schuijs, Martijn J., Van Steendam, Katleen, Feiner Gracia, Natlia, De Rycke, Riet, De Beer, Thomas, De Beuckelaer, Ans, De Koker, Stefaan, Deforce, Dieter, Albertazzi, Lorenzo, Grooten, Johan, Lambrecht, Bart N., De Geest, Bruno G., (2016). Spontaneous protein adsorption on graphene oxide nanosheets allowing efficient intracellular vaccine protein delivery ACS Applied Materials & Interfaces , 8, (2), 1147-1155

Nanomaterials hold potential of altering the interaction between therapeutic molecules and target cells or tissues. High aspect ratio nanomaterials in particular have been reported to possess unprecedented properties and are intensively investigated for their interaction with biological systems. Graphene oxide (GOx) is a water-soluble graphene derivative that combines high aspect ratio dimension with functional groups that can be exploited for bioconjugation. Here, we demonstrate that GOx nanosheets can spontaneously adsorb proteins by a combination of interactions. This property is then explored for intracellular protein vaccine delivery, in view of the potential of GOx nanosheets to destabilize lipid membranes such as those of intracellular vesicles. Using a series of in vitro experiments, we show that GOx nanosheet adsorbed proteins are efficiently internalized by dendritic cells (DCs: the most potent class of antigen presenting cells of the immune system) and promote antigen cross-presentation to CD8 T cells. The latter is a hallmark in the induction of potent cellular antigen-specific immune responses against intracellular pathogens and cancer.Nanomaterials hold potential of altering the interaction between therapeutic molecules and target cells or tissues. High aspect ratio nanomaterials in particular have been reported to possess unprecedented properties and are intensively investigated for their interaction with biological systems. Graphene oxide (GOx) is a water-soluble graphene derivative that combines high aspect ratio dimension with functional groups that can be exploited for bioconjugation. Here, we demonstrate that GOx nanosheets can spontaneously adsorb proteins by a combination of interactions. This property is then explored for intracellular protein vaccine delivery, in view of the potential of GOx nanosheets to destabilize lipid membranes such as those of intracellular vesicles. Using a series of in vitro experiments, we show that GOx nanosheet adsorbed proteins are efficiently internalized by dendritic cells (DCs: the most potent class of antigen presenting cells of the immune system) and promote antigen cross-presentation to CD8 T cells. The latter is a hallmark in the induction of potent cellular antigen-specific immune responses against intracellular pathogens and cancer.

van der Zwaag, Daan, Vanparijs, Nane, Wijnands, Sjors, De Rycke, Riet, De Geest, Bruno G., Albertazzi, Lorenzo, (2016). Super resolution imaging of nanoparticles cellular uptake and trafficking ACS Applied Materials & Interfaces , 8, (10), 6391-6399

Understanding the interaction between synthetic nanostructures and living cells is of crucial importance for the development of nanotechnology-based intracellular delivery systems. Fluorescence microscopy is one of the most widespread tools owing to its ability to image multiple colors in native conditions. However, due to the limited resolution, it is unsuitable to address individual diffraction-limited objects. Here we introduce a combination of super-resolution microscopy and single-molecule data analysis to unveil the behavior of nanoparticles during their entry into mammalian cells. Two-color Stochastic Optical Reconstruction Microscopy (STORM) addresses the size and positioning of nanoparticles inside cells and probes their interaction with the cellular machineries at nanoscale resolution. Moreover, we develop image analysis tools to extract quantitative information about internalized particles from STORM images. To demonstrate the potential of our methodology, we extract previously inaccessible information by the direct visualization of the nanoparticle uptake mechanism and the intracellular tracking of nanoparticulate model antigens by dendritic cells. Finally, a direct comparison between STORM, confocal microscopy, and electron microscopy is presented, showing that STORM can provide novel and complementary information on nanoparticle cellular uptake.Understanding the interaction between synthetic nanostructures and living cells is of crucial importance for the development of nanotechnology-based intracellular delivery systems. Fluorescence microscopy is one of the most widespread tools owing to its ability to image multiple colors in native conditions. However, due to the limited resolution, it is unsuitable to address individual diffraction-limited objects. Here we introduce a combination of super-resolution microscopy and single-molecule data analysis to unveil the behavior of nanoparticles during their entry into mammalian cells. Two-color Stochastic Optical Reconstruction Microscopy (STORM) addresses the size and positioning of nanoparticles inside cells and probes their interaction with the cellular machineries at nanoscale resolution. Moreover, we develop image analysis tools to extract quantitative information about internalized particles from STORM images. To demonstrate the potential of our methodology, we extract previously inaccessible information by the direct visualization of the nanoparticle uptake mechanism and the intracellular tracking of nanoparticulate model antigens by dendritic cells. Finally, a direct comparison between STORM, confocal microscopy, and electron microscopy is presented, showing that STORM can provide novel and complementary information on nanoparticle cellular uptake.

Beuwer, Michael A., Knopper, M. F., Albertazzi, Lorenzo, van der Zwaag, Daan, Ellenbroek, Wouter G., Meijer, E. W., Prins, Menno W. J., Zijlstra, Peter, (2016). Mechanical properties of single supramolecular polymers from correlative AFM and fluorescence microscopy Polymer Chemistry , 7, (47), 7260-7268

We characterize the structure and mechanical properties of 1,3,5-benzenetricarboxamide (BTA) supramolecular polymers using correlative AFM and fluorescence imaging. AFM allows for nanoscale structural investigation but we found that statistical analysis is difficult because these structures are easily disrupted by the AFM tip. We therefore correlate AFM and fluorescence microscopy to couple nanoscale morphological information to far-field optical images. A fraction of the immobilized polymers are in a clustered or entangled state, which we identify based on diffraction limited fluorescence images. We find that clustered and entangled polymers exhibit a significantly longer persistence length that is broader distributed than single unentangled polymers. By comparison with numerical simulations we find significant heterogeneity in the persistence length of single unentangled polymers, which we attribute to polymer-substrate interactions and the presence of structural diversity within the polymer.

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Nanoscopy for nanomedicine Institute for Bioengineering ...

A New Generation of Transhumanists Is Emerging | HuffPost

A new generation of transhumanists is emerging. You can feel it in handshakes at transhumanist meet-ups. You can see it when checking in to transhumanist groups in social media. You can read it in the hundreds of transhumanist-themed blogs. This is not the same bunch of older, mostly male academics that have slowly moved the movement forward during the last few decades. This is a dynamic group of younger people from varying backgrounds: Asians, Blacks, Middle Easterners, Caucasians, and Latinos. Many are females, some are LGBT, and others have disabilities. Many are atheist, while others are spiritual or even formally religious. Their politics run the gamut, from liberals to conservatives to anarchists. Their professions vary widely, from artists to physical laborers to programmers. Whatever their background, preferences, or professions, they have recently tripled the population of transhumanists in just the last 12 months.

"Three years ago, we had only around 400 members, but today we have over 10,000 members," says Amanda Stoel, co-founder and chief administrator of Facebook group Singularity Network, one of the largest of hundreds of transhumanist-themed groups on the web.

Transhumanism is becoming so popular that even the comic strip Dilbert, which appears online and in 2000 newspapers, recently made jokes about it.

Despite its growing popularity, many people around the world still don't know what "transhuman" means. Transhuman literally means beyond human. Transhumanists consist of life extensionists, techno-optimists, Singularitarians, biohackers, roboticists, AI proponents, and futurists who embrace radical science and technology to improve the human condition. The most important aim for many transhumanists is to overcome human mortality, a goal some believe is achievable by 2045.

Transhumanism has been around for nearly 30 years and was first heavily influenced by science fiction. Today, transhumanism is increasingly being influenced by actual science and technological innovation, much of it being created by people under the age of 40. It's also become a very international movement, with many formal groups in dozens of countries.

Despite the movement's growth, its potential is being challenged by some older transhumanists who snub the younger generation and their ideas. These old-school futurists dismiss activist philosophies and radicalism, and even prefer some younger writers and speakers not have their voices heard. Additionally, transhumanism's Wikipedia page -- the most viewed online document of the movement -- is protected by a vigilant posse, deleting additions or changes that don't support a bland academic view of transhumanism.

Inevitably, this Wikipedia page misses the vibrancy and happenings of the burgeoning movement. The real status and information of transhumanism and its philosophies can be found in public transhumanist gatherings and festivities, in popular student groups like the Stanford University Transhumanist Association, and in social media where tens of thousands of scientists and technologists hang out and discuss the transhuman future.

Jet-setting personality Maria Konovalenko, a 29-year-old Russian molecular biophysicist whose public demonstrations supporting radical life extension have made international news, is a prime example.

"We must do more for transhumanism and life extension," says Konovalenko, who serves as vice president of Moscow-based Science for Life Extension Foundation. "This is our lives and our futures we're talking about. To sit back and and just watch the 21st Century roll by will not accomplish our goals. We must take our message to the people in the streets and strive to make real change."

Transhumanist celebrities like Konovalenko are changing the way the movement gets its message across to the public. Gauging by the rapidly increasing number of transhumanists, it's working.

A primary goal of many transhumanists is to convince the public that embracing radical technology and science is in the species' best interest. In a mostly religious world where much of society still believes in heavenly afterlives, some people are skeptical about whether significantly extending human lifespans is philosophically and morally correct. Transhumanists believe the more people that support transhumanism, the more private and government resources will end up in the hands of organizations and companies that aim to improve human lives and bring mortality to an end.

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A New Generation of Transhumanists Is Emerging | HuffPost

Transhumanism | Future | FANDOM powered by Wikia

Transhumanism (sometimes abbreviated >H or H+) is an international intellectual and cultural movement supporting the use of new sciences and technologies to enhance human cognitive and physical abilities and ameliorate what it regards as undesirable and unnecessary aspects of the human condition, such as disease, aging, and death. Transhumanist thinkers study the possibilities and consequences of developing and using human enhancement techniques and other emerging technologies for these purposes. Possible dangers, as well as benefits, of powerful new technologies that might radically change the conditions of human life are also of concern to the transhumanist movement.

Although the first known use of the term "transhumanism" dates from 1957, the contemporary meaning is a product of the 1980s, when a group of scientists, artists, and futurists based in the United States began to organize what has since grown into the transhumanist movement. Transhumanist thinkers postulate that human beings will eventually be transformed into beings with such greatly expanded abilities as to merit the label "posthuman".

The transhumanist vision of a profoundly transformed future humanity has attracted many supporters as well as critics from a wide range of perspectives. Transhumanism has been described by a proponent as the "movement that epitomizes the most daring, courageous, imaginative, and idealistic aspirations of humanity," while according to a prominent critic, it is the world's most dangerous idea.

In his 2005 article A History of Transhumanist Thought, philosopher Nick Bostrom locates transhumanism's roots in Renaissance humanism and the Enlightenment. The Marquis de Condorcet, an eighteenth century French philosopher, is the first thinker whom he identifies as speculating about the use of medical science to extend the human life span. In the twentieth century, a direct and influential precursor to transhumanist concepts was J.B.S. Haldane's 1923 essay Daedalus: Science and the Future, which predicted that great benefits would come from applications of genetics and other advanced sciences to human biology.

Biologist Julian Huxley, brother of author Aldous Huxley (a childhood friend of Haldane's), appears to have been the first to use the actual word "transhumanism". Writing in 1957, he defined transhumanism as "man remaining man, but transcending himself, by realizing new possibilities of and for his human nature". This definition differs substantially from the one commonly in use since the 1980s.

The coalescence of an identifiable transhumanist movement began in the last decades of the twentieth century. In 1966, FM-2030 (formerly F.M. Esfandiary), a futurist who taught "new concepts of the Human" at The New School for Social Research in New York City, began to identify people who adopt technologies, lifestyles and world views transitional to "posthumanity" as "transhuman" (short for "transitory human"). In 1972, Robert Ettinger contributed to the popularization of the concept of "transhumanity" in his book Man into Superman. FM-2030 published the Upwingers Manifesto in 1973 to stimulate transhumanly conscious activism.

The first self-described transhumanists met formally in the early 1980s at the University of California, Los Angeles, which became the main center of transhumanist thought. Here, FM-2030 lectured on his "third way" futurist ideology. At the EZTV Media venue frequented by transhumanists and other futurists, Natasha Vita-More presented Breaking Away, her 1980 experimental film with the theme of humans breaking away from their biological limitations and the earth's gravity as they head into space. FM-2030 and Vita-More soon began holding gatherings for transhumanists in Los Angeles, which included students from FM-2030's courses and audiences from Vita-More's artistic productions. In 1982, Vita-More authored the Transhumanist Arts Statement, and, six years later, produced the cable TV show TransCentury Update on transhumanity, a program which reached over 100,000 viewers.

In 1988, philosopher Max More founded the Extropy Institute and was the main contributor to a formal transhumanist doctrine, which took the form of the Principles of Extropy in 1990.[ In 1990, he laid the foundation of modern transhumanism by giving it a new definition:

"Transhumanism is a class of philosophies that seek to guide us towards a posthuman condition. Transhumanism shares many elements of humanism, including a respect for reason and science, a commitment to progress, and a valuing of human (or transhuman) existence in this life. [] Transhumanism differs from humanism in recognizing and anticipating the radical alterations in the nature and possibilities of our lives resulting from various sciences and technologies []." In 1998, philosophers Nick Bostrom and David Pearce founded the World Transhumanist Association (WTA), an organization with a liberal democratic perspective. In 1999, the WTA drafted and adopted The Transhumanist Declaration. The Transhumanist FAQ, prepared by the WTA, gave two formal definitions for transhumanism:

The intellectual and cultural movement that affirms the possibility and desirability of fundamentally improving the human condition through applied reason, especially by developing and making widely available technologies to eliminate aging and to greatly enhance human intellectual, physical, and psychological capacities. The study of the ramifications, promises, and potential dangers of technologies that will enable us to overcome fundamental human limitations, and the related study of the ethical matters involved in developing and using such technologies. A number of similar definitions have been collected by Anders Sandberg, an academic with a high profile in the transhumanist movement.

In 2006, the board of directors of the Extropy Institute made a decision to cease operations of the organization, stating that its mission was "essentially completed". This left the World Transhumanist Association as the leading international transhumanist organization.

For a list of notable individuals who have identified themselves, or been identified by others, as advocates of transhumanism, see the list of transhumanists.

While many transhumanist theorists and advocates seek to apply reason, science and technology for the purposes of reducing poverty, disease, disability and malnutrition around the globe, transhumanism is distinctive in its particular focus on the applications of technologies to the improvement of human bodies at the individual level. Many transhumanists actively assess the potential for future technologies and innovative social systems to improve the quality of all life, while seeking to make the material reality of the human condition fulfill the promise of legal and political equality by eliminating congenital mental and physical barriers.

Transhumanist philosophers argue that there not only exists an ethical imperative for humans to strive for progress and improvement of the human condition but that it is possible and desirable for humanity to enter a post-Darwinian phase of existence, in which humans are in control of their own evolution. In such a phase, natural evolution would be replaced with deliberate change. To this end, transhumanists engage in interdisciplinary approaches to understanding and evaluating possibilities for overcoming biological limitations. They draw on futures studies and various fields or subfields of science, philosophy, economics, history, and sociology. Unlike philosophers, social critics and activists who place a moral value on preservation of natural systems, transhumanists see the very concept of the "natural" as an obstacle to progress. In keeping with this, many prominent transhumanist advocates refer to transhumanism's critics on the political right and left jointly as "bioconservatives" or "bioluddites", the latter term alluding to the nineteenth century anti-industrialisation social movement that opposed the replacement of manual labor by machines.

Converging Technologies, a 2002 report exploring the potential for synergy among nano-, bio-, informational and cognitive technologies (NBIC) for enhancing human performance.While some transhumanists take a relatively abstract and theoretical approach to the perceived benefits of emerging technologies, others have offered specific proposals for modifications to the human body, including inheritable ones. Transhumanists are often concerned with methods of enhancing the human nervous system. Though some propose modification of the peripheral nervous system, the brain is considered the common denominator of personhood and is thus a primary focus of transhumanist ambitions. More generally, transhumanists support the convergence of emerging technologies such as nanotechnology, biotechnology, information technology and cognitive science (NBIC), and hypothetical future technologies such as simulated reality, artificial intelligence, mind uploading, and cryonics. Transhumanists believe that humans can and should use these technologies to become more than human. Transhumanists therefore support the recognition or protection of cognitive liberty, morphological freedom and procreative liberty as civil liberties, so as to guarantee individuals the choice of enhancing themselves and progressively become posthuman, which they see as the next significant evolutionary steps for the human species. Some speculate that human enhancement techniques and other emerging technologies may facilitate such a transformation by the midpoint of the twenty first century.

A 2002 report, Converging Technologies for Improving Human Performance, commissioned by the U.S. National Science Foundation and Department of Commerce, contains descriptions and commentaries on the state of NBIC science and technology by major contributors to these fields. The report discusses potential uses of these technologies in implementing transhumanist goals of enhanced performance and health, and ongoing work on planned applications of human enhancement technologies in the military and in the rationalization of the human-machine interface in industry.

Some theorists, such as Raymond Kurzweil, believe that the pace of technological evolution is accelerating and that the next fifty years may yield not only radical technological advances but possibly a technological singularity, which may fundamentally change the nature of human beings. Transhumanists who foresee this massive technological change generally maintain that it is desirable. However, they also explore the possible dangers of extremely rapid technological change, and frequently propose options for ensuring that advanced technology is used responsibly. For example, Bostrom has written extensively on existential risks to humanity's future welfare, including risks that could be created by emerging technologies.

On a more practical level, as proponents of personal development and body modification, transhumanists tend to use existing technologies and techniques that supposedly improve cognitive and physical performance, while engaging in routines and lifestyles designed to improve health and longevity. Depending on their age, some transhumanists express concern that they will not live to reap the benefits of future technologies. However, many have a great interest in life extension practices, and funding research in cryonics in order to make the latter a viable option of last resort rather than remaining an unproven method. Regional and global transhumanist networks and communities with a range of objectives exist to provide support and forums for discussion and collaborative projects.

There is a variety of opinion within transhumanist thought. Many of the leading transhumanist thinkers hold complex and subtle views that are under constant revision and development. Some distinctive currents of transhumanism are identified and listed here in alphabetical order:

Although some transhumanists report a very strong sense of spirituality, they are for the most part secular. In fact, many transhumanists are either agnostics or atheists. A minority, however, follow liberal forms of Eastern philosophical traditions or, as with Mormon transhumanists, have merged their beliefs with established religions.

Despite the prevailing secular attitude, some transhumanists pursue hopes traditionally espoused by religions, such as immortality albeit a physical one. Several belief systems, termed new religious movements, originating in the late twentieth century, share with transhumanism the goals of transcending the human condition by applying technology to the alteration of the body (Ralism) and mind (Scientology). While most thinkers associated with the transhumanist movement focus on the practical goals of using technology to help achieve longer and healthier lives, some speculate that future understanding of neurotheology will enable humans to achieve control of altered states of consciousness and thus "spiritual" experiences. A continuing dialogue between transhumanism and faith was the focus of an academic seminar held at the University of Toronto in 2004.

The majority of transhumanists are materialists who do not believe in a transcendent human soul. Transhumanist personhood theory also argues against the unique identification of moral actors and subjects with biological humans, judging as speciesist the exclusion of nonhuman and part-human animals, and sophisticated machines, from ethical consideration. Many believe in the compatibility of human minds with computer hardware, with the theoretical implication that human consciousness may someday be transferred to alternative media.

One extreme formulation of this idea is Frank Tipler's proposal of the Omega Point. Drawing upon ideas in physics, computer science and physical cosmology, Tipler advanced the notion that the collapse of the Universe billions of years hence could create the conditions for the perpetuation of humanity as a simulation within a megacomputer. Cosmologist George Ellis has called Tipler's book "a masterpiece of pseudoscience", and Michael Shermer devoted a chapter of Why People Believe Weird Things to enumerating perceived flaws in Tipler's thesis.

For more details on this topic, see Transhumanism in fiction. Transhumanist themes have become increasingly prominent in various literary forms during the period in which the movement itself has emerged. Contemporary science fiction often contains positive renditions of technologically enhanced human life, set in utopian (especially techno-utopian) societies. However, science fiction's depictions of technologically enhanced humans or other posthuman beings frequently come with a cautionary twist. The more pessimistic scenarios include many horrific or dystopian tales of human bioengineering gone wrong.

The cyberpunk genre, exemplified by William Gibson's Neuromancer (1984) and Bruce Sterling's Schismatrix (1985), has particularly been concerned with the modification of human bodies. Other novels dealing with transhumanist themes that have stimulated broad discussion of these issues include Blood Music (1985) by Greg Bear, The Xenogenesis Trilogy (19871989) by Octavia Butler; the "Culture" novels (19872000) of Iain Banks; The Beggar's Trilogy (199094) by Nancy Kress; much of Greg Egan's work since the early 1990s, such as Permutation City (1994) and Diaspora (1997); The Bohr Maker (1995) by Linda Nagata; Extensa (2002) and Perfekcyjna niedoskonao (2003) by Jacek Dukaj; Oryx and Crake (2003) by Margaret Atwood; Altered Carbon by Richard Morgan (2002); and The Possibility of an Island (Eng. trans. 2006) by Michel Houellebecq.

Fictional transhumanist scenarios have also become popular in other media during the late twentieth and early twenty first centuries. Such treatments are found in films (Star Trek: The Motion Picture, 1979; Blade Runner, 1982; Gattaca, 1997), television series (the Ancients of Stargate SG-1, the Borg of Star Trek, the Nietzscheans of Andromeda), manga and anime (Ghost in the Shell), role-playing games (Transhuman Space) and computer games (Deus Ex, Half-Life 2, Command & Conquer). The fictional universe of the table top war game Warhammer 40,000 also makes use of genetic and cybernetic augmentation. Human characters of the Imperium often employ cybernetic devices, while the Space Marines are indeed posthuman. Many of these works are considered part of the cyberpunk genre or its postcyberpunk offshoot.

In addition to the work of Natasha Vita-More, mentioned above, transhumanism has been represented in the visual and performing arts by Carnal Art, a form of sculpture originated by the French artist Orlan that uses the body as its medium and plastic surgery as its method. The American performer Michael Jackson used technologies such as plastic surgery, skin-lightening drugs and hyperbaric oxygen treatment over the course of his career, with the effect of transforming his artistic persona so as to blur identifiers of gender, race and age. The work of the Australian artist Stelarc centers on the alteration of his body by robotic prostheses and tissue engineering. Other artists whose work coincided with the emergence and flourishing of transhumanism and who explored themes related to the transformation of the body are the Yugoslavian performance artist Marina Abramovic and the American media artist Matthew Barney. A 2005 show, Becoming Animal, at the Massachusetts Museum of Contemporary Art, presented exhibits by twelve artists whose work concerns the effects of technology in erasing boundaries between the human and non-human.

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GHRP-2 / GHRP-6 / Sermorelin Acetate Injection (Blend …

ALERT: GHRP 2 and GHRP 6 have been placed on the FDA category 3 list and cannot be compounded. Should this change in the future, an alert will be emailed to our clients and updated on this page!

SermorelinAcetate is prescribed for the stimulation of the pituitary gland and increase the natural production of growth hormone (HGH), within the limits of endocrine system capacity.

The dosage presentation available for GHRP-2 / GHRP-6 / Sermorelin Acetate is an Injection Solution. Absolute Pharmacys injection solutions are combined under the strict standards of USP 797 for the sterile composition of each batch. Our quality assurance process ensures the uniformity of each compound dispensed.

GHRP-2 is a peptide that is only a member of the large family of peptide growth factors and is very similar in structure and function to GHRP-6.

Both act by stimulating the pituitary gland which causes an increased release of GH. GHRP-2 is used for a variety of medical problems such as low GH production and natural weight gain promoting abnormally thin individuals.

GHRP-2 has been extensively studied for its utility and action as growth hormone secretagogue (GHS), meaning it stimulates the secretion of growth hormone. This is a hexapeptide with potent properties. GHRP-2 is basically a sterile white lyophilized powder. It is considered to be the most potent classes in the GHRP family.

This peptide has been shown to be useful in adults and can be given through the oral, intravenous and intranasal route. GHRPs is not simply substituted for GHRH, instead, GHRP-6 is an artificial activator of a receptor called Secretagogues newly discovered receptor (GHS-R).

While both peptides of the amino acid release GH, there is a noticeable difference in GHRP-6, this speeds up digestion taking into account a larger consumption of food. It is worth adding that this particular peptide is a first generation GHRP. Get the absolute most value from GH releases.

While GHRH stimulates adenylate cyclase activity and increases cAMP production (21), synthetic GHs do not bind to the pituitary receptor for GHRH (22), generating depolarization and inhibition of potassium channels in somatotropic cells, activating the Protein kinase C and increasing the hydrolysis of phosphatidylinositol (7,9,21,22).

Recently, the existence of a specific high-affinity binding site in pituitary membranes has been shown to mediate the activity of these secretagogues. Accordingly, the receptor mediating the GH-secreting activities of GHRP-6, L-692,429 and L-163,191 (MK-0677) is bound to a G protein. In addition, the same authors indicate that they have characterized A similar receptor in hypothalamic membranes.

It is a hormonal peptide treatment known as a secretagogue that induces the secretion of human growth hormone. For this reason, Sermorelin is known as a growth hormone releasing agent.

Sermorelin Acetate (also known as GRF 1-29) is an analog of growth hormone releasing hormone (GHRH). GHRH is produced in the brain (in the hypothalamus) and is subsequently transported through the bloodstream into the pituitary gland where its role is to stimulate and release growth hormone (GH).

Sermorelin (GRF 1-29) has a short molecule, comprising 29 amino acids (for example, for comparison the HGH molecule is substantially larger comprising 191 amino acids). The Sermorelin GRF 1-29 sequence is a part of the endogenous human GHRH and is currently considered as the short synthetic peptide which possesses the full range of GHRH activity.

Sermorelin is often used as an effective anti-aging therapy product in men, usually in relation to testosterone. Sermorelin can be considered as an excellent alternative to recombinant growth hormone (rhGH), especially in people looking for similar hormones with anti-aging effects for achieving anti-aging goals. Sermorelin is so safe that in the USA. It is prescribed for children as a treatment for growth hormone deficiency or for patients who need to lose weight quickly and efficiently.

Sermorelin stimulates the patients own pituitary gland by binding to specific receptors that increase the production and secretion of endogenous or own HGH from the body. Because Sermorelin increases the natural endogenous hormones by stimulating the pituitary gland is considered as an excellent treatment.

Sermorelin stimulates your pituitary gland to make HGH more natural. Your pituitary gland will only produce what you need and no more. Its secretory effects are regulated by the pituitary gland through the negative feedback loop and the release of somatostatin so as to avoid the side effects of too much endogenous HGH.

Cell and tissue exposure to HGH released by the pituitary under the influence of Sermorelin is a natural physiological response to doses administered mimicking normal human physiology. By stimulating the pituitary gland it retains more of the neuroendocrine hormone growth hormone and loop feedback that deteriorates over time due to the aging process.

The pituitary stimulation resulting from Sermorelin injections helps mitigate the endocrine deficiency that occurs during the aging composition of the juvenile body and physiology. GH peptide therapy provides patients with all the benefits of HGH replacement therapy.

It is used in adults who take hormone replacement therapy for human growth hormone. A patient can take GH peptides alone or together with injections of human growth hormone to enhance the effects of bio-identical therapy.

Make sure your doctor knows if you are pregnant or breastfeeding. Your doctor will need to know if you have diabetes, hypothyroidism, or a history of problems with your blood sugar.

The presence of other medical problems may affect the use of this medication. Be sure to tell your doctor if you have any other medical problems such as interactions with drugs or other interactions.

In case you miss a dose, take it as soon as you notice it. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take extra doses to make up for a forgotten dose.

If you are losing your doses regularly, it is recommended to set an alarm or ask a family member to remind you. Please consult your doctor to discuss changes to the dosing schedule or a new schedule to compensate for missed doses if you have missed many doses recently.

In all studies, it has been observed that Sermorelin does not modify uterine activity, nor does it present sensitization phenomena on this organ. All studies show that it shows no mutagenic activity.

Chest tightness or fast heart rate.Fainting or fainting.Redness, pain, blisters, or rash at the injection site.

It should be kept refrigerated at 2C to 8C. During the period of conservation there are no qualitative or quantitative changes of the active principle, so its pharmacological action remains unchanged.

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GHRP-2 / GHRP-6 / Sermorelin Acetate Injection (Blend ...

Bioidentical Hormone Replacement Therapy | Menopause …

RejuvinAge, a Virginia Beach Bioidentical Hormone Replacement Center, focuses on Individualizing Hormone Therapy for Women and Men. RejuvinAge specializes in Hormone Replacement for approved indications of Menopause for women and Low Testosterone Replacement Therapy for men.

Women and men are very comfortable and confident in our boutique setting for hormone replacement. Programs are individualized; one size does not fit all. Every program is physician managed; appointments are always on time with our hormone replacement doctor, Jennifer Krup, M.D. Personalized care is our focus; we recognize the importance of one on one attention.

Focusing on menopause for women, Dr. Krup encourages every woman to embrace this phase of their life.Understanding BHRT empowers women with the knowledge to make the right decisions and successfully manage menopausal symptoms. Understanding appropriate dosages, appropriate routes of administration and the appropriate length of treatment for each woman keeps RejuvinAge in the forefront

Offering Low T options for men, Dr. Krup will help determine ifTestosterone Replacement Therapyis right for you. Making the right choice for TRT is an important decision for men today.

The RejuvinAge approach to Bio Identical Hormone Replacement for women and men is based on sound medicine. Hormone optimization takes patience, compliance, great communication and a partnership with you. Our Virginia Beach Hormone Replacement center is easily accessible to the surrounding cities of Norfolk, Chesapeake, Hampton Newport News, Williamsburg and beyond. Make your appointment today-meet Dr. Krup in her Virginia BeachBio-Identical Hormone Center.

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Bioidentical Hormone Replacement Therapy | Menopause ...

Top 5 Companion Supplements for Hormone Balance – EVEXIAS …

Men and women alike struggle with hormonal imbalance, and these imbalances can have serious impacts on our mental, physical, and emotional state. Our hormones are powerful; theyre chemical messengers can control our appetite, weight, and mood, among other things.

If you think you may be struggling with hormonal imbalance, check out our symptom checklist for men and women. Once we identify your imbalance, we can create a customized treatment plan for you, and part of the treatment plan may involve natural supplements.

At EVEXIAS Medical Centers, we use a safe, all-natural, and effective hormone treatment known as BHRT Pellet Therapy; you can read more about it here.

To offer patients a complete solution and long-lasting treatment, we often suggest certain supplements to complement the natural pellet therapy. Today well go over 5 of these companion supplements and what you can get from them.

Diindolylmethane (DIM) is a natural plant nutrient that comes from cruciferous plants (like broccoli or cabbage). Both women and men may benefit from DIM as it supports estrogen metabolization and frees testosterone from binding agents in the blood.

DIM may be prescribed to enhance hormone optimization and to promote breast, uterine, cervical and prostate health. DIM may also reignite sex drive, decrease body fat and alleviate premenstrual and menopausal symptoms.

Methyl B-Complex is made up of eight B vitamins, along with essential support nutrients. The formulation helps support the brain, nervous system, and cardiovascular system and may be prescribed to improve memory, mental health, and energy levels. This supplement is essential in hormone optimization treatment and toxins from the body.

Essential for managing a vast number of diseases and conditions and also plays a crucial role in the production of thyroid hormone and receptor activity of other hormones. This powerful nutrient supports hormone optimization while also aiding patients with blood sugar issues and cancer of the:

Mega Probiotic

ND is a dairy-free probiotic formulation composed of several all-natural strains of beneficial microorganisms. Along with probiotics, the formulation includes soluble fiber and a pre-biotic.

Your body uses mega Probiotic-ND to maintain gut health and helps ensure hormones like cortisol (the stress hormone), and neurotransmitters like serotonin (the happiness chemical) are working in harmony to help you experience more energy.

Omega 3 HP-D is a high-potency supplement that combines high yield with omega 3 essential fatty acids EPA and DHA along with 1,000 IU of Vitamin D3. Hormones need Omega 3 fatty acids to build themselves, and they can also help transport hormones throughout the body by improving blood flow. Also, theyre anti-inflammatory and can help deal with certain symptoms.

You can read more about these five supplements and more here. When beginning your journey to wellness, one of the EVEXIAS team members will review your history, your goals, and much more to provide you with the most efficient hormone optimization treatment possible.

To schedule your completely confidential consultation, get in touch with us!

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Top 5 Companion Supplements for Hormone Balance

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When you come to EVEXIAS youll get a completely integral treatment that utilizes various resources to help you reach your wellness goals. Learn about 5 supplements we recommend for hormone optimization.

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International Journal of Nanomedicine | Call For Papers …

About JournalEditorsPublishing Fees Peer Reviewers Articles Open Outlook: Nanomedicine Aims and ScopeCall For PapersInterview: Dr Webster

The International Journal of Nanomedicine is indexed online:

Journal Impact Factor:4.370 (5 year impact 5.154)

What is the advantage to you of publishing in the International Journal of Nanomedicine?

To recover our editorial and production costs and continue to provide our content at no cost to readers we charge authors or their institution a publication processing fee.

PubMed CentralThe International Journal of Nanomedicine is indexed on PubMed Central and MedLine (title abbreviation: Int J Nanomedicine). All published papers in this journal are submitted to PubMed for indexing straight away.

Become a Favored Author and receive real benefitsIf you haven't already joined the Dove Press Favored Author ProgramI would encourage you to do so. Why? To receive real benefits like fast-tracking and a personal co-ordinatorfor your paper,as well as a discount on the publication processing fee. Click here to go through to the Favored Author signup page, you'll just need to supply the working title of your next paper and when you intend to submit by.

Yours sincerelyDr Thomas J WebsterEditor-in-ChiefInternational Journal of Nanomedicine

Email: Editor-in-Chief

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International Journal of Nanomedicine | Call For Papers ...

What Are the Side Effects of Testosterone Replacement …

Disclaimer: This information isnt a substitute for professional medical advice, diagnosis, or treatment. You should never rely upon this article for specific medical advice. If you have any questions or concerns, please talk to your doctor.

Testosterone replacement therapy (TRT) is a common way to increase testosterone and treat the symptoms of low testosterone. But one of the most common sideeffects of testosterone replacement therapy is low sperm count. A risk of TRT is that artificially high testosterone levels can trick your brain into stopping LH and FSH production. And when you stop making FSH, you stop making sperm.

Testosterone production is a feedback loop.When your brain senses low testosterone levels in your blood, it ramps up testosterone production in the testicles by releasing two hormones:

When you add external testosterone (from replacement therapy), your brain stops producing LH and FSH because it thinks you dont need anymore. But FSH is directly responsible for sperm production in the testicles.Decreased FSH levels together with already low natural levels of testosterone can decrease your sperm count. A lot. In fact, men using Testosterone replacement therapy can have a sperm count of zero.

Low testosterone production in the testicles means low sperm count. But too much testosterone can mean the same thing. Many of the side effects of low testosteronelike acne and mood shiftsare reversible. But TRT can have long-term effects on your sperm count and fertility. Talk to a doctor to find out if testosterone replacement therapy is right for you. Then work to find the right dose to make sure your testosterone levels stay within normal levels to reduce your risk of side effects.

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Yudkowsky – Simplified Humanism

Frank Sulloway once said: Ninety-nine per cent of what Darwinian theory says about human behavior is so obviously true that we dont give Darwin credit for it. Ironically, psychoanalysis has it over Darwinism precisely because its predictions are so outlandish and its explanations are so counterintuitive that we think, Is that really true? How radical! Freuds ideas are so intriguing that people are willing to pay for them, while one of the great disadvantages of Darwinism is that we feel we know it already, because, in a sense, we do.

Suppose you find an unconscious six-year-old girl lying on the train tracks of an active railroad. What, morally speaking, ought you to do in this situation? Would it be better to leave her there to get run over, or to try to save her? How about if a 45-year-old man has a debilitating but nonfatal illness that will severely reduce his quality of life is it better to cure him, or not cure him?

Oh, and by the way: This is not a trick question.

I answer that I would save them if I had the power to do so both the six-year-old on the train tracks, and the sick 45-year-old. The obvious answer isnt always the best choice, but sometimes it is.

I wont be lauded as a brilliant ethicist for my judgments in these two ethical dilemmas. My answers are not surprising enough that people would pay me for them. If you go around proclaiming What does two plus two equal? Four! you will not gain a reputation as a deep thinker. But it is still the correct answer.

If a young child falls on the train tracks, it is good to save them, and if a 45-year-old suffers from a debilitating disease, it is good to cure them. If you have a logical turn of mind, you are bound to ask whether this is a special case of a general ethical principle which says Life is good, death is bad; health is good, sickness is bad. If so and here we enter into controversial territory we can follow this general principle to a surprising new conclusion: If a 95-year-old is threatened by death from old age, it would be good to drag them from those train tracks, if possible. And if a 120-year-old is starting to feel slightly sickly, it would be good to restore them to full vigor, if possible. With current technology it is not possible. But if the technology became available in some future year given sufficiently advanced medical nanotechnology, or such other contrivances as future minds may devise would you judge it a good thing, to save that life, and stay that debility?

The important thing to remember, which I think all too many people forget, is that it is not a trick question.

Transhumanism is simpler requires fewer bits to specify because it has no special cases. If you believe professional bioethicists (people who get paid to explain ethical judgments) then the rule Life is good, death is bad; health is good, sickness is bad holds only until some critical age, and then flips polarity. Why should it flip? Why not just keep on with life-is-good? It would seem that it is good to save a six-year-old girl, but bad to extend the life and health of a 150-year-old. Then at what exact age does the term in the utility function go from positive to negative? Why?

As far as a transhumanist is concerned, if you see someone in danger of dying, you should save them; if you can improve someones health, you should. There, youre done. No special cases. You dont have to ask anyones age.

You also dont ask whether the remedy will involve only primitive technologies (like a stretcher to lift the six-year-old off the railroad tracks); or technologies invented less than a hundred years ago (like penicillin) which nonetheless seem ordinary because they were around when you were a kid; or technologies that seem scary and sexy and futuristic (like gene therapy) because they were invented after you turned 18; or technologies that seem absurd and implausible and sacrilegious (like nanotech) because they havent been invented yet. Your ethical dilemma report form doesnt have a line where you write down the invention year of the technology. Can you save lives? Yes? Okay, go ahead. There, youre done.

Suppose a boy of 9 years, who has tested at IQ 120 on the Wechsler-Bellvue, is threatened by a lead-heavy environment or a brain disease which will, if unchecked, gradually reduce his IQ to 110. I reply that it is a good thing to save him from this threat. If you have a logical turn of mind, you are bound to ask whether this is a special case of a general ethical principle saying that intelligence is precious. Now the boys sister, as it happens, currently has an IQ of 110. If the technology were available to gradually raise her IQ to 120, without negative side effects, would you judge it good to do so?

Well, of course. Why not? Its not a trick question. Either its better to have an IQ of 110 than 120, in which case we should strive to decrease IQs of 120 to 110. Or its better to have an IQ of 120 than 110, in which case we should raise the sisters IQ if possible. As far as I can see, the obvious answer is the correct one.

But you ask where does it end? It may seem well and good to talk about extending life and health out to 150 years but what about 200 years, or 300 years, or 500 years, or more? What about when in the course of properly integrating all these new life experiences and expanding ones mind accordingly over time the equivalent of IQ must go to 140, or 180, or beyond human ranges?

Where does it end? It doesnt. Why should it? Life is good, health is good, beauty and happiness and fun and laughter and challenge and learning are good. This does not change for arbitrarily large amounts of life and beauty. If there were an upper bound, it would be a special case, and that would be inelegant.

Ultimate physical limits may or may not permit a lifespan of at least length X for some X just as the medical technology of a particular century may or may not permit it. But physical limitations are questions of simple fact, to be settled strictly by experiment. Transhumanism, as a moral philosophy, deals only with the question of whether a healthy lifespan of length X is desirable if it is physically possible. Transhumanism answers yes for all X. Because, you see, its not a trick question.

So that is transhumanism loving life without special exceptions and without upper bound.

Can transhumanism really be that simple? Doesnt that make the philosophy trivial, if it has no extra ingredients, just common sense? Yes, in the same way that the scientific method is nothing but common sense.

Then why have a complicated special name like transhumanism ? For the same reason that scientific method or secular humanism have complicated special names. If you take common sense and rigorously apply it, through multiple inferential steps, to areas outside everyday experience, successfully avoiding many possible distractions and tempting mistakes along the way, then it often ends up as a minority position and people give it a special name.

But a moral philosophy should not have special ingredients. The purpose of a moral philosophy is not to look delightfully strange and counterintuitive, or to provide employment to bioethicists. The purpose is to guide our choices toward life, health, beauty, happiness, fun, laughter, challenge, and learning. If the judgments are simple, that is no black mark against them morality doesnt always have to be complicated.

There is nothing in transhumanism but the same common sense that underlies standard humanism, rigorously applied to cases outside our modern-day experience. A million-year lifespan? If its possible, why not? The prospect may seem very foreign and strange, relative to our current everyday experience. It may create a sensation of future shock. And yet is life a bad thing?

Could the moral question really be just that simple?

Yes.

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Yudkowsky - Simplified Humanism

Testosterone Replacement Therapy – Renue Health

Testosterone is a hormone that is present in both men and women. Testosterone is the androgenic hormone primarily responsible for normal growth and development of male sex and reproductive organs, including the penis, testicles, scrotum, prostate, and seminal vesicles. It facilitates the development of secondary male sex characteristics such as musculature, bone mass, fat distribution, hair patterns, laryngeal enlargement, and vocal chord thickening. Additionally, normal testosterone levels maintain energy level, healthy mood, fertility, and sexual desire.

The number of men diagnosed with hypogonadism, commonly referred to as Low T has grown dramatically in recent years due to an increasing awareness of the importance of hormones in a mans health and well being. Research shows that about 1 out of 4 men over the age of 30 may have low testosterone. Circulating testosterone levels decline progressively with age, starting in the second and third decade of life. Testing for testosterone deficiency requires a comprehensive understanding of the intricacies of hormone balance before one makes a commitment to what may be lifelong therapy.

Low Libido

Gaining fat around the middle

If you have any of these common symptoms, it is recommended you have a proper and thorough set of labs drawnto help determine if you havehypogonadism.

Testosterone replacement therapy is essential for men with hypogonadism. In these men, full replacement of testosterone is necessary. The amount of total testosterone in men can range from 300 to 1100 ng/ml, while the range for free testosterone is 50 to 250 ng/ml. It is more accurate to utilize free testosterone levels instead of total T levels.

Because the range is so broad, testosterone optimization must be individualized. In general, Dr. Rob aims to provide the lowest dose of testosterone that relieves symptoms and causes the man to be in the optimized zone. All while monitoring testosterone and its by-products for any potential unwanted side effects. There are several delivery method options and Dr. Rob presents the pros and cons of each before a mutually agreed upon delivery method is instituted.

It is also important to note that men should not be started on testosterone replacement without a careful endocrine evaluation to determine the cause of the low testosterone. Serious conditions including pituitary tumors can present with low testosterone.

Women have testosterone too

Men have 10 to 20 times higher levels of testosterone than women. Nonetheless, even this small amount of testosterone in women is important for maintaining sexual function, and healthy bladder and vaginal function.

When used in small physiologic doses with monitoring of testosterone blood levels, testosterone in women is well tolerated. High doses must be avoided as they can cause facial hair, loss of scalp hair, deepening of voice, and acne. Just like men, womenshould not be started on testosterone replacement without a careful endocrine evaluation to determine if it will provide a health benefit.

ReNue Healthis located conveniently in Springboro, Ohio with easy access from Dayton International Airport, Cincinnati International Airport or the adjacent Wright Brothers Private Airport (MGY) for those travelling by private aviation.Click here for directions and contact information.

Only one visit is necessary to perform a comprehensive history, interview, and education. Follow up evaluations, adjustments and balancing of hormones are done by phone or written communications and a return visit to Dr. Rob is not necessary. Ongoing testing and adjustment is mandatory and performed through a laboratory convenient to your home.

Its that nagging feeling that something does not feel quite right and you cant put your finger on it. Youre a busy person and your own health is the last thing you have time to think about, but think again!

To learn how the ReNue Health Opportunity may help restore your youth and vitality, simply call937-350-5527or visit us online atwww.renuehealth.com

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Testosterone Replacement Therapy - Renue Health

Low T Symptoms | Low Testosterone | Signs of Low T

Simply put, testosterone is the most important male sex hormone. It is secreted by the testicles and adrenal glands and is directly responsible for sperm production and sex drive. Testosterone also plays a role in developing secondary sexual characteristics that men experience through puberty while also contributing to the muscle mass, strength, bone density, and maturation. Testosterone naturally decreases as men age, but when it dips too low it can result in other issues. Fortunately, there is an easy way to combat low testosterone symptoms, and that's through the quality hormone replacement pelleting procedures that BioTE offers. We are dedicated to helping our male patients deal with hormone deficiency.

In addition to the weak bones and increased risks of cardiovascular issues, low testosterone greatly affects your quality of life. If you've ever wondered what causes low-T, it's essentially broken down into two categories: primary hypogonadism and secondary hypogonadism. Primary hypogonadism occurs when the testicles are injured and have not descended, or if one suffers from Klinefelter syndrome. Secondary hypogonadism is from pituitary disorders, medications, type 2 diabetes, and aging. Some of the symptoms of low-T in men include depression, a decreased sex drive, and feeling weak. All of those low-T symptoms can change the way you live your life, and you shouldn't have to settle. BioTE can help you take your life back.

Here are some symptoms of low-T in men:

If you've experienced any of these symptoms and are concerned about low testosterone, the medical professionals at BioTE are ready to help.

You don't have to accept living with low testosterone. If you are experiencing symptoms of low-T, it's important to find a doctor that can help you improve. We at BioTE have created a way to assist you. Pellet therapy is an easy way to correct male hormone deficiency and has been proven to reduce other unseen risks of low hormones.

If you have any questions about pellet therapy or are wondering what BioTE can do for your low testosterone symptoms, please contact one of the many professionals at BioTE. We are here to help you take your life back from low testosterone.

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Low T Symptoms | Low Testosterone | Signs of Low T

Living a Healthy Lifestyle Student Health and Wellness Services

Nutrition and Food

Eat enough every day not eating enough tells your body to conserve calories and energy, and so the next time you eat more of the energy will be retained rather than being properly used.Hydrate Dehydration makes you feel tired. Caffeine and alcohol are very dehydrating. Balance caffeine or alcohol consumption with non-caffeinated, non-alcoholic fluids.Sleep Sleep deprivation increases appetite (and often body weight) and decreases brain function. So proper sleep helps your energy, weight maintenance and your ability to think and concentrate.Exercise Try to exercise at least 30 minutes a day, three times a week it can even be split up into 10 minute walks. The effects of brief physical exertion last much longer than those of caffeine, and exercise decreases stress rather than increasing it! Finding a physical activity that you really like to do will make exercise more fun and something to look forward to as well as help to keep you healthy throughout life. So try something new or something that has always appealed to you.

If we all looked the same the world would be a very boring place.

Genes (not jeans) have a lot to do with body shape there is no right weight for someone of a certain height. If you are eating and acting healthily, your weight is probably fine.Shaped like a pear? Fat around the hips, butt, and thighs is usually estrogen dependent, meaning that it doesnt go away through exercise and healthy nutrition. Torso fat, on the other hand, is associated with poor health.Repeated dieting can actually lower metabolism and thus make your body retain more of what you put into it. Increasing exercise while not giving your body more food to compensate can also increase body fat storage. Dieting also increases heart disease risk, when compared to simply gaining a little weight. If you really need to lose weight, the most effective way is to increase exercise and cutting only a little food, while concentrating on fruits, veggies, and high fiber foods.

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Living a Healthy Lifestyle Student Health and Wellness Services

10 Crucial Steps To Living A Healthy Lifestyle

If youve been reading us for some time now, you probably know that there is not only one right way to improve your life, there are in fact more ways to live a healthy lifestyle, which will probably result in changing many things about yourself.

Living full time (as we want to call it) can be very hard nowadays. Especially if you want to live a healthy lifestyle.Work, money, society It seems like everything is taking its turn, not allowing us to fully enjoy life.

But why do I correlate enjoying life with living a healthy lifestyle? Well simple, you see, if one is healthy in every sense of the word, its hard not to enjoy life. And living like that makes you enjoy it even more.

But how can one achieve that?

How to change your lifestyle to match that description? How can you have a lifestyle that is healthy, fulfilled, interesting and enjoyable?

Well, just keep reading:

Not only did we mention this before, but we also did a whole article on how much exercising is important if you want to move your life forward, and make room for some improvement. The truth, simple as it is, is that adding exercise to your life on daily basis is one of the best ways to promote a healthy lifestyle in general. The health related benefits are huge, as is the step you are taking towards self-improvement.

Here is the post that goes more deeply in this matter:

Giving the roller coaster of a schedule that many people are having today, probably the one that sent you here at the first place, we must come to realize just how much important sleep is to all of us. Many studies conducted on couple of the best universities around the world suggest that every individual needs from seven to eight hours a sleep during the night.

And this is the important part- during the night! You see, sleeping in a period in which the body isnt designed to sleep, is equally bad as sleeping less hours. By ruining this schedule, the body endocrine system is not producing melatonin (the hormone which is responsible for making us sleepy) in the right amounts, or shuts production completely.

Here is a post dedicated about why sleeping is so much important, the importance of a good sleeping schedule, the benefits of waking up early and what to do in order to make the most out of it:

This is one of the cornerstones, truly a foundation upon which one healthy lifestyle is build. And make no mistakes, it will change everything for better once you implement the healthy diet into your everyday life. Not only you will be healthy, but you will also have tons and tons of other benefits as well.

Here are some helpful articles we wrote about healthy diet a while ago:

Time = life, therefore, waste your time and waste your life, or master your time and master your life. Alan Lakein

Time management is a process, chain of techniques if you will, that not only make sure that we are on our best when it comes to spending our time, but also gives us the opportunity to know we are doing the best we can, and taking all we can actually take. It can also be a pretty good tool in the battle against stress.

You should only take a look at somebody who is successful in life and is truly enjoying it. The first picture you will get is of a person who is determined in what he is going after, and most of all a person who knows how to get organized, probably possess an effective time management skills and knows what to do in order to achieve his dream.

No man is an island. Youve heard that before, dont you? Well, it turns out that its not only true but its also necessary if you like to live healthy.

You probably assumed by now that we are not only talking about physical health, but rather about health as a whole. Meaning psychological health, health of the spirit as well as of the body. And being social creatures, we humans make everything with tilting toward this fact over and over again.

The way weve built society, the way we try to find new ways for us to correspond, interact Thats really in our nature, and by acknowledging that we must try to be as much social as we can. Forget about everyone that you are not quite fond of, and devote yourself on people you find spending time with enjoyable and relaxing.

Whether this may be your friend, family, significant other Doesnt matter really. What matters is that you go and spend as much time as you can with them.

Now many of you are confused as for why this is listed as one of the steps to living a healthy lifestyle. Fair enough, Ill give you an explanation.

Being curious and wanting to learn everything about everything makes you younger in a way. It makes your spirit remain like it was when you were just a child. It leads towards intellectual growth, and makes you engage yourself further on in using your brain as much as you can.

Just by reading this, you are proving that you are in fact curious person. And what is the result? Well, you are improved in a way or at least heading towards there.

You see, we said that health doesnt necessarily apply just to the body. You must also nurture your brain, your intellect. That is achieved by reading, asking questions, doing some games like puzzles and crosswords, challenge yourself to think deeply about something, have a profound discourse with someone that challenges you. Staying healthy is a wide concept, and this is one of its fundamentals.

An obvious way to fully live a life while enjoying it. Do you smile a lot? Or just from time to time? Or maybe youve forgot how is like to hear yourself giggling about something?

It is our aptitude for humor, our innate characteristics, which make us so fond of it. It is one of the first things a baby does while learning this world, a sign, a symptom of happiness and health if you will. Learning how to put a smile on your face is worth more than learning anything else in life.

Your outlook of life can affect you more than you think. It is about how you perceive things that surround you. Your interpretation of them is what defines them as being one way or another. It defines your perception upon this world as a whole, shapes your experiences even on a daily basis.

Give your undivided attention to people that have positive outlooks on life, and try to figure out how you can change your way of seeing things. Being positive helped many people in life. I once read a book by Bear Grylls in which he explains how being positive changed his life completely, and allowed him to be where he is today.

Another thing closely connected to living a healthy lifestyle when it comes to spirituality and psychological health is having a place or a thing that you really enjoy, and is just for you. Having a hobby is one of the steps to live a healthy life.

Whether this is reading, working in your garden, playing some sport, writing or playing some instrument, it doesnt really matter.

The thing is that you must hold up to this and try to enjoy it more often. For example, I play on my violin from time to time and enjoy practicing pieces from Bach, Sarassate, Mozart and many others. Find your passion about something, and hold up to it for dear life.

As for the last one, it is essential that you reminisce things now and then, and do a check. What am I talking about? Well for starters, you should schedule a visit to the doctors at least twice a year, and do some basic tests. That way you always have the upper hand in case something comes down the way. Checking things out from time to time is one of the steps to living a healthy lifestyle.

Visit a therapist or find some other ways to win the battle with the stress, or just try and take some time for you to realize in which aspect of life you are heading in opposite direction. Doing this you will never feel like there is something that you are not doing right when it comes to your health in general, and you will be more on top of things.

These are some of the ways that are proven to make your life better and h
ealthier in more than one way, and in turn make you enjoy a more fulfilled, healthier life. No matter which one you choose to start with, they will all allow you to make a great change towards better, and you will immediately feel the results .

Can you add more to this? Do you know some other ways of living a healthy lifestyle?

Image: FreeDigitalPhotos.net

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10 Crucial Steps To Living A Healthy Lifestyle

U.S. Transhumanist Party PUTTING SCIENCE, HEALTH …

Ojochogwu Abdul

Part 1 | Part 2 | Part 3 | Part 4 | Part 5

Part 5:Belief in Progress vs. Rational Uncertainty

The Enlightenment, with its confident efforts to fashion a science of man, was archetypal of the belief and quest that humankind will eventually achieve lasting peace and happiness. In what some interpret as a reformulation of Christianitys teleological salvation history in which the People of God will be redeemed at the end of days and with the Kingdom of Heaven established on Earth, most Enlightenment thinkers believed in the inevitability of human political and technological progress, secularizing the Christian conception of history and eschatology into a conviction that humanity would, using a system of thought built on reason and science, be able to continually improve itself. As portrayed by Carl Becker in his 1933 book The Heavenly City of the Eighteenth-Century Philosophers, the philosophies demolished the Heavenly City of St. Augustine only to rebuild it with more up-to-date materials. Whether this Enlightenment humanist view of progress amounted merely to a recapitulation of the Christian teleological vision of history, or if Enlightenment beliefs in continual, linear political, intellectual, and material improvement reflected, asJames Hughesposits, a clear difference from the dominant Christian historical narrative in which little would change until the End Times and Christs return, the notion, in any case, of a collective progress towards a definitive end-point was one that remained unsupported by the scientific worldview. The scientific worldview, as Hughes reminds us in the opening paragraph of this essay within his series, does not support historical inevitability, only uncertainty. We may annihilate ourselves or regress, he says, and Even the normative judgment of what progress is, and whether we have made any, is open to empirical skepticism.

Hereby, we are introduced to a conflict that exists, at least since after the Enlightenment, between a view of progressive optimism and that of radical uncertainty. Building on the Enlightenments faith in the inevitability of political and scientific progress, the idea of an end-point, salvation moment for humankind fuelled all the great Enlightenment ideologies that followed, flowing down, as Hughes traces, through Comtes positivism and Marxist theories of historical determinism to neoconservative triumphalism about the end of history in democratic capitalism. Communists envisaged that end-point as a post-capitalist utopia that would finally resolve the class struggle which they conceived as the true engine of history. This vision also contained the 20th-century project to build the Soviet Man, one of extra-human capacities, for as Trotsky had predicted, after the Revolution, the average human type will rise to the heights of an Aristotle, a Goethe, or a Marx. And above this ridge new peaks will rise, whereas for 20th-century free-market liberals, this End of History had arrived with the final triumph of liberal democracy, with the entire world bound to be swept in its course. Events though, especially so far in the 21st century, appear to prove this view wrong.

This belief moreover, as Hughes would convincingly argue, in the historical inevitability of progress has also always been locked in conflict with the rationalist, scientific observation that humanity could regress or disappear altogether. Enlightenment pessimism, or at least realism, has, over the centuries, proven a stubborn resistance and constraint of Enlightenment optimism. Hughes, citing Henry Vyberg, reminds us that there were, after all, even French Enlightenment thinkers within that same era who rejected the belief in linear historical progress, but proposed historical cycles or even decadence instead. That aside, contemporary commentators like John Gray would even argue that the efforts themselves of the Enlightenment on the quest for progress unfortunately issued in, for example, the racist pseudo-science of Voltaire and Hume, while all endeavours to establish the rule of reason have resulted in bloody fanaticisms, from Jacobinism to Bolshevism, which equaled the worst atrocities attributable to religious believers. Horrendous acts like racism and anti-Semitism, in the verdict of Gray: .are not incidental defects in Enlightenment thinking. They flow from some of the Enlightenments central beliefs.

Even Darwinisms theory of natural selection was, according to Hughes, suborned by the progressive optimistic thinking of the Enlightenment and its successors to the doctrine of inevitable progress, aided in part by Darwins own teleological interpretation. Problem, however, is that from the scientific worldview, there is no support for progress as to be found provided by the theory of natural selection, only that humanity, Hughes plainly states, like all creatures, is on a random walk through a mine field, that human intelligence is only an accident, and that we could easily go extinct as many species have done. Gray, for example, rebukes Darwin, who wrote: As natural selection works solely for the good of each being, all corporeal and mental endowments will tend to progress to perfection. Natural selection, however, does not work solely for the good of each being, a fact Darwin himself elsewhere acknowledged. Nonetheless, it has continually proven rather difficult for people to resist the impulse to identify evolution with progress, with an extended downside to this attitude being equally difficult to resist the temptation to apply evolution in the rationalization of views as dangerous as Social Darwinism and acts as horrible as eugenics.

Many skeptics therefore hold, rationally, that scientific utopias and promises to transform the human condition deserve the deepest suspicion. Reason is but a frail reed, all events of moral and political progress are and will always remain subject to reversal, and civilization could as well just collapse, eventually. Historical events and experiences have therefore caused faith in the inevitability of progress to wax and wane over time. Hughes notes that among several Millenarian movements and New Age beliefs, such faith could still be found that the world is headed for a millennial age, just as it exists in techno-optimist futurism. Nevertheless, he makes us see that since the rise and fall of fascism and communism, and the mounting evidence of the dangers and unintended consequences of technology, there are few groups that still hold fast to an Enlightenment belief in the inevitability of conjoined scientific and political progress. Within the transhumanist community, however, the possession of such faith in progress can still be found as held by many, albeit signifying a camp in the continuation therefore of the Enlightenment-bequeathed conflict as manifested between transhumanist optimism in contradiction with views of future uncertainty.

As with several occasions in the past, humanity is, again, currently being spun yet another End of History narrative: one of a posthuman future. Yuval Harari, for instance, in Homo Deus argues that emerging technologies and new scientific discoveries are undermining the foundations of Enlightenment humanism, although as he proceeds with his presentation he also proves himself unable to avoid one of the defining tropes of Enlightenment humanist thinking, i.e., that deeply entrenched tendency to conceive human history in teleological terms: fundamentally as a matter of collective progress towards a definitive end-point. This time, though, our eras End of History glorious salvation moment is to be ushered in, not by a politico-economic system, but by a nascent techno-elite with a base in Silicon Valley, USA, a cluster steeped in a predominant tech-utopianism which has at its core the idea that the new technologies emerging there can steer humanity towards a definitive break-point in our history, the Singularity. Among believers in this coming Singularity, transhumanists, as it were, having inherited the tension between Enlightenment convictions in the inevitability of progress, and, in Hughes words, Enlightenments scientific, rational realism that human progress or even civilization may fail, now struggle with a renewed contradiction. And here the contrast as Hughes intends to portray gains sharpness, for as such, transhumanists today are torn between their Enlightenment faith in inevitable progress toward posthuman transcension and utopian Singularities on the one hand, and, on the other, their rational awareness of the possibility that each new technology may have as many risks as benefits and that humanity may not have a future.

The risks of new technologies, even if not necessarily one that threatens the survival of humanity as a species with extinction, may yet be of an undesirable impact on the mode and trajectory of our extant civilization. Henry Kissinger, in his 2018 article How the Enlightenment Ends, expressed his perception that technology, which is rooted in Enlightenment thought, is now superseding the very philosophy that is its fundamental principle. The universal values proposed by the Enlightenment philosophes, as Kissinger points out, could be spread worldwide only through modern technology, but at the same time, such technology has ended or accomplished the Enlightenment and is now going its own way, creating the need for a new guiding philosophy. Kissinger argues specifically that AI may spell the end of the Enlightenment itself, and issues grave warnings about the consequences of AI and the end of Enlightenment and human reasoning, this as a consequence of an AI-led technological revolution whose culmination may be a world relying on machines powered by data and algorithms and ungoverned by ethical or philosophical norms. By way of analogy to how the printing press allowed the Age of Reason to supplant the Age of Religion, he buttresses his proposal that the modern counterpart of this revolutionary process is the rise of intelligent AI that will supersede human ability and put an end to the Enlightenment. Kissinger further outlines his three areas of concern regarding the trajectory of artificial intelligence research: AI may achieve unintended results; in achieving intended goals, AI may change human thought processes and human values, and AI may reach intended goals, but be unable to explain the rationale for its conclusions. Kissingers thesis, of course, has not gone without both support and criticisms attracted from different quarters. Reacting to Kissinger, Yuk Hui, for example, in What Begins After the End of the Enlightenment? maintained that Kissinger is wrongthe Enlightenment has not ended. Rather, modern technologythe support structure of Enlightenment philosophyhas become its own philosophy, with the universalizing force of technology becoming itself the political project of the Enlightenment.

Transhumanists, as mentioned already, reflect the continuity of some of those contradictions between belief in progress and uncertainty about human future. Hughes shows us nonetheless that there are some interesting historical turns suggesting further directions that this mood has taken. In the 1990s, Hughes recalls, transhumanists were full of exuberant Enlightenment optimism about unending progress. As an example, Hughes cites Max Mores 1998 Extropian Principles which defined Perpetual Progress as the first precept of their brand of transhumanism. Over time, however, Hughes communicates how More himself has had cause to temper this optimism, stressing rather this driving principle as one of desirability and more a normative goal than a faith in historical inevitability. History, More would say in 2002, since the Enlightenment makes me wary of all arguments to inevitability

Rational uncertainty among transhumanists hence make many of them refrain from an argument for the inevitability of transhumanism as a matter of progress. Further, there are indeed several possible factors which could deter the transhumanist idea and drive for progress from translating to reality: A neo-Luddite revolution, a turn and rise in preference for rural life, mass disenchantment with technological addiction and increased option for digital detox, nostalgia, disillusionment with modern civilization and a return-to-innocence counter-cultural movement, neo-Romanticism, a pop-culture allure and longing for a Tolkien-esque world, cyclical thinking, conservatism, traditionalism, etc. The alternative, backlash, and antagonistic forces are myriad. Even within transhumanism, the anti-democratic and socially conservative Neoreactionary movement, with its rejection of the view that history shows inevitable progression towards greater liberty and enlightenment, is gradually (and rather disturbingly) growing a contingent. Hughes talks, as another point for rational uncertainty, about the three critiques: futurological, historical, and anthropological, of transhumanist and Enlightenment faith in progress that Phillipe Verdoux offers, and in which the anthropological argument holds that pre-moderns were probably as happy or happier than we moderns. After all, Rousseau, himself a French Enlightenment thinker, is generally seen as having believed in the superiority of the savage over the civilized. Perspectives like these could stir anti-modern, anti-progress sentiments in peoples hearts and minds.

Demonstrating still why transhumanists must not be obstinate over the idea of inevitability, Hughes refers to Greg Burchs 2001 work Progress, Counter-Progress, and Counter-Counter-Progress in which the latter expounded on the Enlightenment and transhumanist commitment to progress as to a political program, fully cognizant that there are many powerful enemies of progress and that victory was not inevitable. Moreover, the possible failure in realizing goals of progress might not even result from the actions of enemies in that antagonistic sense of the word, for there is also that likely scenario, as the 2006 movie Idiocracy depicts, of a future dystopian society based on dysgenics, one in which, going by expectations and trends of the 21st century, the most intelligent humans decrease in reproduction and eventually fail to have children while the least intelligent reproduce prolifically. As such, through the process of natural selection, generations are created that collectively become increasingly dumber and more virile with each passing century, leading to a future world plagued by anti-intellectualism, bereft of intellectual curiosity, social responsibility, coherence in notions of justice and human rights, and manifesting several other traits of degeneration in culture. This is yet a possibility for our future world.

So while for many extropians and transhumanists, nonetheless, perpetual progress was an unstoppable train, responding to which one either got on board for transcension or consigned oneself to the graveyard, other transhumanists, however, Hughes comments, especially in response to certain historical experiences (the 2000 dot-com crash, for example), have seen reason to increasingly temper their expectations about progress. In Hughess appraisal, while, therefore, some transhumanists still press for technological innovation on all fronts and oppose all regulation, others are focusing on reducing the civilization-ending potentials of asteroid strikes, genetic engineering, artificial intelligence and nanotechnology. Some realism hence need be in place to keep under constant check the excesses of contemporary secular technomillennialism as contained in some transhumanist strains.

Hughes presents Nick Bostroms 2001 essay Analyzing Human Extinction Scenarios and Related Hazards as one influential example of this anti-millennial realism, a text in which Bostrom, following his outline of scenarios that could either end the existence of the human species or have us evolve into dead-ends, then addressed not just how we can avoid extinction and ensure that there are descendants of humanity, but also how we can ensure that we will be proud to claim them. Subsequently, Bostrom has been able to produce work on catastrophic risk estimation at the Future of Humanity Institute at Oxford. Hughes seems to favour this approach, for he ensures to indicate that this has also been adopted as a programmatic focus for the Institute for Ethics and Emerging Technologies (IEET) which he directs, and as well for the transhumanist non-profit, the Lifeboat Foundation. Transhumanists who listen to Bostrom, as we could deduce from Hughes, are being urged to take a more critical approach concerning technological progress.

With the availability of this rather cautious attitude, a new tension, Hughes reports, now plays out between eschatological certainty and pessimistic risk assessment. This has taken place mainly concerning the debate over the Singularity. For the likes of Ray Kurzweil (2005), representing the camp of a rather technomillennial, eschatological certainty, his patterns of accelerating trendlines towards a utopian merger of enhanced humanity and godlike artificial intelligence is one of unstoppability, and this Kurzweil supports by referring to the steady exponential march of technological progress through (and despite) wars and depressions. Dystopian and apocalyptic predictions of how humanity might fare under superintelligent machines (extinction, inferiority, and the likes) are, in the assessment of Hughes, but minimally entertained by Kurzweil, since to the techno-prophet we are bound to eventually integrate with these machines into apotheosis.

The platform, IEET, thus has taken a responsibility of serving as a site for teasing out this tension between technoprogressive optimism of the will and pessimism of the intellect, as Hughes echoes Antonio Gramsci. On the one hand, Hughes explains, we have championed the possibility of, and evidence of, human progress. By adopting the term technoprogressivism as our outlook, we have placed ourselves on the side of Enlightenment political and technological progress.And yet on the other hand, he continues, we have promoted technoprogressivism precisely in order to critique uncritical techno-libertarian and futurist ideas about the inevitability of progress. We have consistently emphasized the negative effects that unregulated, unaccountable, and inequitably distributed technological development could have on society (one feels tempted to call out Landian accelerationism at this point). Technoprogressivism, the guiding philosophy of IEET, avails as a principle which insists that technological progress needs to be consistently conjoined with, and dependent on, political progress, whilst recognizing that neither are inevitable.

In charting the essay towards a close, Hughes mentions his and a number of IEET-led technoprogresive publications, among which we have Verdoux who, despite his futurological, historical, and anthropological critique of transhumanism, yet goes ahead to argue for transhumanism on moral grounds (free from the language of Marxisms historical inevitabilism or utopianism, and cautious of the tragic history of communism), and as a less dangerous course than any attempt at relinquishing technological development, but only after the naive faith in progress has been set aside. Unfortunately, however, the rational capitulationism to the transhumanist future that Verdoux offers, according to Hughes, is not something that stirs mens souls. Hughes hence, while admitting to our need to embrace these critical, pessimistic voices and perspectives, yet calls on us to likewise heed to the need to also re-discover our capacity for vision and hope. This need for optimism that humans can collectively exercise foresight and invention, and peacefully deliberate our way to a better future, rather than yielding to narratives that would lead us into the traps of utopian and apocalyptic fatalism, has been one of the motivations behind the creation of the technoprogressive brand. The brand, Hughes presents, has been of help in distinguishing necessarily Enlightenment optimism about the possibility of human political, technological and moral progress from millennialist techno-utopian inevitabilism.

Presumably, upon this technoprogressive philosophy, the new version of the Transhumanist Declaration, adopted by Humanity+ in 2009, indicated a shift from some of the language of the 1998 version, and conveyed a more reflective, critical, realistic, utilitarian, proceed with caution and act with wisdom tone with respect to the transhumanist vision for humanitys progress. This version of the declaration, though relatively sobered, remains equally inspiring nonetheless. Hughes closes the essay with a reminder on our need to stay aware of the diverse ways by which our indifferent universe threatens our existence, how our growing powers come with unintended consequences, and why applying mindfulness on our part in all actions remains the best approach for navigating our way towards progress in our radically uncertain future.

Conclusively, following Hughes objectives in this series, it can be suggested that more studies on the Enlightenment (European and global) are desirable especially for its potential to furnish us with richer understanding into a number of problems within contemporary transhumanism as sprouting from its roots deep in the Enlightenment. Interest and scholarship in Enlightenment studies, fortunately, seems to be experiencing some current revival, and even so with increasing diversity in perspective, thereby presenting transhumanism with a variety of paths through which to explore and gain context for connected issues. Seeking insight thence into some foundations of transhumanisms problems could take the path, among others: of an examination of internal contradictions within the Enlightenment, of the approach of Max Horkheimer and Theodor Adornos Dialectic of Enlightenment; of assessing opponents of the Enlightenment as found, for example, in Isaiah Berlins notion of Counter Enlightenment; of investigating a rather radical strain of the Enlightenment as presented in Jonathan Israels Radical Enlightenment, and as well in grappling with the nature of the relationships between transhumanism and other heirs both of the Enlightenment and the Counter-Enlightenment today. Again, and significantly, serious attention need be paid now and going forwards in jealously guarding transhumanism against ultimately falling into the hands of the Dark Enlightenment.

Ojochogwu Abdulis the founder of the Transhumanist Enlightenment Caf (TEC), is the co-founder of the Enlightenment Transhumanist Forum of Nigeria (H+ Nigeria), and currently serves as a Foreign Ambassador for the U.S. Transhumanist Party in Nigeria.

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U.S. Transhumanist Party PUTTING SCIENCE, HEALTH ...

Healthy lifestyle: 5 keys to a longer life – Harvard …

How is it that the United States spends the most money on healthcare, and yet still has the one of the lowest life expectancies of all developed nations? (To be specific: $9,400 per capita, 79 years, and 31st.)

Maybe those of us in healthcare have been looking at it all wrong, for too long.

Researchers from the Harvard T.H. Chan School of Public Health conducted a massive study of the impact of health habits on life expectancy, using data from the well-known Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). This means that they had data on a huge number of people over a very long period of time. The NHS included over 78,000 women and followed them from 1980 to 2014. The HPFS included over 40,000 men and followed them from 1986 to 2014. This is over 120,000 participants, 34 years of data for women, and 28 years of data for men.

The researchers looked at NHS and HPFS data on diet, physical activity, body weight, smoking, and alcohol consumption that had been collected from regularly administered, validated questionnaires.

These five areas were chosen because prior studies have shown them to have a large impact on risk of premature death. Here is how these healthy habits were defined and measured:

1. Healthy diet, which was calculated and rated based on the reported intake of healthy foods like vegetables, fruits, nuts, whole grains, healthy fats, and omega-3 fatty acids, and unhealthy foods like red and processed meats, sugar-sweetened beverages, trans fat, and sodium.

2. Healthy physical activity level, which was measured as at least 30 minutes per day of moderate to vigorous activity daily.

3. Healthy body weight, defined as a normal body mass index (BMI), which is between 18.5 and 24.9.

4. Smoking, well, there is no healthy amount of smoking. Healthy here meant never having smoked.

5. Moderate alcohol intake, which was measured as between 5 and 15 grams per day for women, and 5 to 30 grams per day for men. Generally, one drink contains about 14 grams of pure alcohol. Thats 12 ounces of regular beer, 5 ounces of wine, or 1.5 ounces of distilled spirits.

Researchers also looked at data on age, ethnicity, and medication use, as well as comparison data from the National Health and Nutrition Examination Surveys and the Centers for Disease Control and Preventions Wide-Ranging Online Data for Epidemiologic Research.

As it turns out, healthy habits make a big difference. According to this analysis, people who met criteria for all five habits enjoyed significantly, impressively longer lives than those who had none: 14 years for women and 12 years for men (if they had these habits at age 50). People who had none of these habits were far more likely to die prematurely from cancer or cardiovascular disease.

Study investigators also calculated life expectancy by how many of these five healthy habits people had. Just one healthy habit (and it didnt matter which one) just one extended life expectancy by two years in men and women. Not surprisingly, the more healthy habits people had, the longer their lifespan. This is one of those situations where I wish I could reprint their graphs for you, because theyre so cool. (But if youre very curious, the article is available online, and the graphs are on page 7. Check out Graph B, Estimated life expectancy at age 50 according to the number of low-risk factors.)

This is huge. And, it confirms prior similar research a lot of prior similar research. A 2017 study using data from the Health and Retirement Study found that people 50 and older who were normal weight, had never smoked, and drank alcohol in moderation lived on average seven years longer. A 2012 mega-analysis of 15 international studies that included over 500,000 participants found that over half of premature deaths were due to unhealthy lifestyle factors such as poor diet, inactivity, obesity, excessive alcohol intake, and smoking. And the list of supporting research goes on.

As the authors of this study point out, in the US we tend to spend outlandishly on developing fancy drugs and other treatments for diseases, rather than on trying to prevent them. This is a big problem.

Experts have suggested that the best way to help people make healthy diet and lifestyle change is at the large-scale, population level, through public health efforts and policy changes. (Kind of like motorcycle helmets and seat belt legislation) We have made a little progress with tobacco and trans-fat legislation.

Theres a lot of pushback from big industry on that, of course. If we have guidelines and laws helping us to live healthier, big companies arent going to sell as much fast food, chips, and soda. And for companies hell-bent on making money at the cost of human life, well, that makes them very angry.

Follow me on Twitter @drmoniquetello

Impact of healthy lifestyle factors on life expectancies in the US population. Circulation, April 2018.

National Institute on Alcohol Abuse and Alcoholism, What is a standard drink?

The population health benefits of a healthy lifestyle: Life expectancy increased and onset of disability delayed. Health Affairs, August 2017.

The combined effects of healthy lifestyle behaviors on all-cause mortality: a systematic review and meta-analysis. Preventive Medicine, September 2012.

Changing minds about changing behavior. Lancet, January 2018.

The US Food and Drug Administration (FDA) Final Determination regarding Partially Hydrogenated Oils (trans fat)

The US Food and Drug Administration (FDA) Family Smoking Prevention and Tobacco Control Act- An Overview

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Healthy lifestyle: 5 keys to a longer life - Harvard ...

10 healthy lifestyle tips for adults: (EUFIC)

07 June 2017

For good health, we need more than 40 different nutrients, and no single food can supply them all. It is not about a single meal, it is about a balanced food choice over time that will make a difference!

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About half the calories in our diet should come from foods rich in carbohydrates, such as cereals, rice, pasta, potatoes, and bread. It is a good idea to include at least one of these at every meal. Wholegrain foods, like wholegrain bread, pasta, and cereals, will increase our fibre intake.

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Fats are important for good health and proper functioning of the body. However, too much of it can negatively affect our weight and cardiovascular health. Different kinds of fats have different health effects, and some of these tips could help us keep the balance right:

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Fruits and vegetables are among the most important foods for giving us enough vitamins, minerals and fibre. We should try to eat at least 5 servings a day. For example, a glass of fresh fruit juice at breakfast, perhaps an apple and a piece of watermelon as snacks, and a good portion of different vegetables at each meal.

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A high salt intake can result in high blood pressure, and increase the risk of cardiovascular disease. There are different ways to reduce salt in the diet:

Sugar provides sweetness and an attractive taste, but sugary foods and drinks arerich in energy, and are best enjoyed in moderation, as an occasional treat. We could use fruits instead, even to sweeten our foods and drinks.

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Eating a variety of foods, regularly, and in the right amounts is the best formula for a healthy diet.

Skipping meals, especially breakfast, can lead to out-of-control hunger, often resulting in helpless overeating. Snacking between meals can help control hunger, but snacking should not replace proper meals. For snacks, we could choose yoghurt, a handful of fresh or dried fruits or vegetables (like carrot sticks), unsalted nuts, or perhaps some bread with cheese.

Paying attention to portion size will help us not to consume too much calories, and will allow us to eat all the foods we enjoy, without having to eliminate any.

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Adults need to drink at least 1.5 litres of fluid a day! Or more if it's very hot or they are physically active. Water is the best source, of course, and we can use tap or mineral water, sparkling or non-sparkling, plain or flavoured. Fruit juices, tea, soft drinks, milk and other drinks, can all be okay - from time to time.

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The right weight for each us depends on factors like our gender, height, age, and genes. Being overweight increases the risks of a wide range of diseases, including diabetes, heart diseases, and cancer.

Excess body fat comes from eating more than we need. The extra calories can come from any caloric nutrient - protein, fat, carbohydrate, or alcohol, but fat is the most concentrated source of energy. Physical activity helps us spend the energy, and makes us feel good. The message is reasonably simple: if we are gaining weight, we need to eat less and be more active!

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Physical activity is important for people of all weight ranges and health conditions. It helps us burn off the extra calories, it is good for the heart and circulatory system, it maintains or increases our muscle mass, it helps us focus, and improves overall health well-being. We don't have to be top athletes to get on the move! 150 minutes per week of moderate physical activity is advised, and it can easily become part of our daily routine. We all could:

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Gradual changes in our lifestyle are easier to maintain than major changes introduced all at once. For three days, we could write down the foods and drinks we consume throughout the day, and make a note of the amount of movement we made. It wont be difficult to spot where we could improve:

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Hormone Optimization – Revive Therapy and Wellness

Bio-identical Hormone Replacement Therapy has numerous benefits for both women and men. Age-related hormone decline is one of the most common reasons for hormone imbalances; however, hormones may become imbalanced at any time due to stress, lack of sleep, poor lifestyle choices, and poor nutrition. In addition to preparing the bodys fight or flight responses, hormones are also important for regulating hunger and mood.

Because they are produced within our cells in small amounts, trace levels during replacement can have dramatic results.We know that a significant part of the aging process involves the diminished production of hormones, which begins in our early 30s and accelerates dramatically into our 50s and 60s. If left untreated, this can result in the development of chronic diseases.

With todays bio-identical hormone replacement therapy, restoring hormonal balance can not only relieve these symptoms, but modern research indicates that it can also slow down the aging process and, most importantly, prevent the occurrence of common diseases, such as cardiovascular disease, the number one killer of both men and women.

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Hormone Optimization - Revive Therapy and Wellness

Low T Treatment in Texas & Illinois | SynergenX Health …

Low T, which is a lower-than-normal level of the male hormone testosterone, can affect men in a variety of ways. It can also have a number of potential causes, including:

Really, age is the most common reason for Low T. Thats because most men begin to experience a decline in testosterone, albeit a gradual one, after age 30. Generally, testosterone levels peak during adolescence or early adulthood, and its pretty much all downhill from there. The older you become, the lower your T levels, and its faster for some men than for others.

Whatever the reason or reasons behind it, Low T can cause or contribute to a number of conditions that disrupt mens lives and can affect their productivity, relationships and sense of worth or self-identity. These include:

At SynergenX, we treat Low T with hormone replacement therapyand we do it differently. We tailor the treatment and dose to each mans individual needsas informed by lab tests. We also differ from the typical hormone treatment protocol by testing continually and varying the dose as your T levels rise and fall, because they do. By continually, actively monitoring patients and adjusting treatment, we minimize the risksand help most men achieve a marked, positive change and a reinvigorated life and sense of self.

While erectile dysfunction can be helped dramatically by hormone replacement, we also can help improve erectile function and sexual performance with BoostEREX. BoostEREX is a noninvasive, drug-free treatment that uses low-intensity shockwave pulses to treat EDs cause (unlike medicines like Viagra, which treat symptoms). In use in other countries for nearly a decade, penile shockwave therapy like BoostEREX has been proven by multiple studies to improve erectile function and sexual performance by eliminating micro-plaques, rejuvenating penile blood vessels, and releasing growth factors that help new blood vessels grow.

SynergenX also offers a tailored, effective weight management program to help men lose weight, keep it off for optimal health, and maximize the effects of their Low T treatment to both feel and look great. And speaking of looking your best, SynergenX offers aesthetic services designed to bring your appearance into harmony with how great you feel on the inside.

For more information about the conditions and symptoms SynergenX can help with, or to schedule an appointment for a FREE Low T test in McKinney, North Park, Woodlands, Kingwood, Vintage Park, Katy, Galleria, Burr Ridge, Sonterra San Antonio, Dallas, Houston, or Northwest San Antonio, call 877-915-2554 or use our easy online form.

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Low T Treatment in Texas & Illinois | SynergenX Health ...

The Lowdown on Low-T – Discover Health – Rush University …

If you bring up the topic of low testosterone (commonly known as low T), you'll likely hear a wide range of theories and opinions.

Some believe low T is just a natural part of aging for men and, therefore, does not require medical treatment. Others tout testosterone replacement therapy as a proverbial fountain of youth for men hoping to recapture the strength and stamina of their younger selves.

Like most controversial health issues, the truth about low T lies somewhere in the middle. While testosterone replacement therapy can make a dramatic difference in some men's lives, it's not for everyone.

"Almost every organ and tissue in a man's body has testosterone receptors," says Laurence Levine, MD, a urologist at Rush. "Testosterone plays a vital role in the proper functioning of your bones, muscles, brain, liver and everything in between."

In fact, testosterone is responsible for all of the following:

Due to the importance of testosterone in men's overall health, health care providers are increasingly recognizing low T (with varying degrees of severity) as more than just a fad. In fact, a recent study found that almost 40 percent of men over 45 years old had low testosterone.

Peaks and valleys are the norm when it comes to testosterone. Levels change several times a day; it's highest in the morning and lowest in the evening.

Throughout life, testosterone peaks in the early 30s and steadily declines with age. However, age is not the only culprit behind decreasing testosterone.

Other medical conditions that can cause low T include the following:

When low T occurs with or as the result of an existing medical condition, it can exacerbate symptoms of that condition and even accelerate disease progression.

Long-term, untreated low T can also increase the risk of age-related complications. "A man in his 50s with a long history of low T may have more rapid loss of muscle and bone. He also has a higher risk of developing dementia later in life," says Levine.

Men who have existing conditions that cause low T have been using testosterone therapy for years. Today, however, many men who do not have other medical problems are also using testosterone therapy in an attempt to feel younger, stronger and more vital.

As a result, much of the controversy surrounding low T and testosterone replacement therapy stems from determining who needs it and who doesn't.

"If you have some of the signs of low T, it does not necessarily mean your testosterone is low; and if your testosterone is low, it doesn't necessarily mean you'll have symptoms," Levine says. "To be a good candidate for treatment, you must have both low testosterone and symptoms."

Which symptoms should you watch for? According to Levine, these are the most common:

Some of these symptoms could mimic other conditions, such as depression or low thyroid function. Speak to your primary care physician or urologist to determine the cause of your symptoms, so you can make sure you get the right treatment.

Testosterone is tested with a simple blood test between 8 a.m. and 11 a.m. (when testosterone levels are highest). Normal levels fall between 300 and 1,000 ng/dL (nanograms per deciliter).

Here's what to do with your results:

"However, if I see a man who has no symptoms and his testosterone is at 150, I may recommend treatment because he could start to experience problems with cognition and frailty as he gets older," Levine says.

"The decision about whether to treat or watch and wait depends on each man's specific situation" he adds. "There's no one-size-fits-all. I always tailor the approach to the patient."

If you have low T and persistent symptoms, your doctor may recommend one of the following treatments:

"You may notice an improvement in energy and libido as quickly as a month into treatment. But typically it takes about three months of treatment to notice an obvious improvement in your symptoms," says Levine.

There are a number of concerns about the safety of testosterone replacement therapy. And most health care professionals agree more research is needed on the long-term effects of testosterone therapy.

But in the meantime, there have been some interesting findings in recent years:

However, Levine warns that testosterone can stimulate tumor growth in men who already have prostate cancer. Thus, men with existing prostate cancer will need regular monitoring with a prostate-specific antigen (PSA) test and a complete blood count every six months.

"Testosterone seems to actually have a beneficial effect on cardiovascular health," says Levine. "Studies show men with low T and heart disease who received testosterone replacement therapy had lower death rates than those who did not receive testosterone therapy."

If you have a heart condition, it is best to discuss your options with your cardiologist and men's health clinician.

"It is not a treatment for diabetes, but it can certainly help regulate glucose and metabolism," Levine says.

There are, however, some risks associated with long-term testosterone use, including the following:

Bottom line: Testosterone therapy may not be appropriate if you're just feeling a little more run down than usual. "Working closely with a trusted medical professional is the best way to determine if it is right for you," Levine says.

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The Lowdown on Low-T - Discover Health - Rush University ...

The Low T Scam? – Testosterone Centers of Texas – Low T …

With all of the press about the treatment of low testosterone and the role it plays in mens health, many are beginning to wonder, Is Low T a scam? The answer is, No, Low T is not a scam. Low testosterone levels can wreak havoc on a mans physical and emotional well-being. It can affect his relationships and can play a role in infertility if it is not properly treated by an experienced medical professional.

Once men with Low T are on the appropriatetestosterone replacement therapy, they can experience significant and sustainable results.

Low T refers to low testosterone levels, the medical condition is otherwise known ashypogonadism. Even a moderate dip in testosterone can have noticeable side effects. Some of the symptoms caused by low testosterone levels include:

The good news is that these symptoms can be improved once Low T is diagnosed and treated. Over time, low testosterone levels can lead to moreserious physical health problemssuch as heart disease, osteoporosis, and cognitive disorders.

So, is Low T a scam? No. It is a very real condition, experienced by millions of men across the country.

If you suffer fromone or more of the symptoms listed above, and suspect that Low T is the culprit,take our Low T Quiz. This will help to identify whether or not your symptoms indicate lower testosterone levels. If so, you can schedule an appointment to have your hormone levels tested. If it is determined that you do have Low T, we will discuss your options and help you to make the decision that is best for you.

Testosterone replacement therapyshould be specifically tailored to your specific response and your levels should becontinuously monitored to ensure you are getting the right dose. Never participate in testosterone replacement therapy without having your levels checked first. Once your therapy has begun, your hormone levels, as well as indicators of common side effects, should be monitored on a regular basis.

Decreasing levels of testosterone is a very normal biological process. In fact, most mens testosterone levels begin to decrease at a rate of about 1 percent each year after the age of 30. The problem is that environmental factors can also contribute to low testosterone, which is causing some mens testosterone levels to fall faster than normal, earlier than normal.

Pesticides. There are studies that have shown pesticides using the chemicalGlyphosate, one of the most common being Roundup, work as endocrine disrupters. Exposure to these pesticides and herbicides via ingestion or physical exposure can affect male testosterone levels as well as sperm counts.

Parabens. Take a look at your body washes, shampoos, and skin products and you may see some derivative of the word paraben. Parabens are also endocrine disrupters. They elevate estrogen levels while simultaneously decreasing testosterone levels. Look for products that are paraben-free before taking them off the shelf.

Stress and depression. In an era where people are always on the go, stress has become a state of being. Unfortunately, studies are showing that continued stress takes its toll on testosterone levels. The same is true for depression. If you are chronically stressed or prone to depression, you are more likely to suffer from Low T.

Be careful, there are plenty of companies out there that will take a real problem and exploit it to make a buck but does that mean that Low T a Scam? Definitely not! Do your homework, ask questions, and make sure you get the right answers!

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The Low T Scam? - Testosterone Centers of Texas - Low T ...