Monthly Archives: August 2012

Quay Brothers Retrospective in New York City! "On Deciphering the Pharmacist’s Prescription for Lip-Reading Puppets," Museum of Modern Art, NYC

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I just had the honor to view the beautifully installed and revelatory Quay Brothers retrospective "On Deciphering the Pharmacist's Prescription for Lip-Reading Puppets" at the Museum of Modern Art in New York. I have long been a fan of the Quay's work, and still, this exhibition had much to astonish, delight and surprise, situating the Quay's work within the larger context of an avant-garde tradition, and revealing the Quay's oeuvre to be much broader and richer than expected. Surprises and highlights included pen and ink drawings evoking a slightly less whimsical Edward Gorey, a mini-exhibition of the of the kind of Polish theater posters from the 1960s which inspired much of their work, and paintings by a scientific illustrator who mentored them in high school. Also of special interest, at least to me, was a collection of 8 mm Eastern European travel films which The Quay's collected as inspiration for their work; these grainy and blurred snatches of dark and forgotten streets, shop windows with wax mannequin heads, and church interior possess much of the atmosphere, mystery, and powerful detail evident the Quay's best works; they serve as both an excellent introduction to the exhibition and an illuminating key to their film work.

If you are able to visit the exhibition--which I very highly recommend!--make very sure not to miss the bottom floor portion of the exhibit, where you will find a collection of The Quay Brother's dioramic film decors installed in what feels like a furtive peepshow, a sort of perverse and surrealistic Musée Mécanique. Here you can immerse yourself in the tiny and exquisite sets from such films as Street of Crocodiles; Le Bourgeois Gentilhomme; The Piano Tuner of Earthquakes; and The Cabinet of Jan Svankmajer; their wealth of detail rewards a careful and slow eye. Also, make sure to set some time aside to watch the films, many of which play in mini-theatres set up within the exhibition; the ballet piece The Sandman was an especial revelation to this viewer; dance and the Quays go surprisingly well together.

As we see in this exhibition, the through line of The Quay's long and storied careers--which has spanned drawing, painting, film, animation, theater and graphic design, and dioramic "film decors"-- is a sense of mysterious and compelling atmosphere created by an exacting and exquisite attention to detail: the craquelure of antique objects, a perfectly fractured piece of glass, the patina of caked on dirt, the hand-rendered imperfection of calligraphic script, the artful use of shadow, and, above all, a wonderful wit and humor that counterbalances the unapologetic inscrutability of the work. Do not miss this exhibition! You will never look at the work of the Quay Brothers the same way again. In a good way!

The exhibition will be on view at New York Museum of Modern Art from August 12–January 7.You can find out about the exhibition here. Also, the museum will be hosting a series of screenings of Quay Brothers films running the duration of the exhibition; you can find out more about that here.

All above images were taken in the exhibition.

Source:
http://morbidanatomy.blogspot.com/feeds/posts/default?alt=rss

"Objectify This: Female Anatomy Dissected and Displayed," Exhibition Curated by Street Anatomy’s Vanessa Ruiz, September 7-29, Chicago

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Just received notice of the very exciting looking exhibition "Objectify This: Female Anatomy Dissected" curated by Vanessa Ruiz, founder of the wonderful Street Anatomy Blog; images from the show above, and full info follows:

'OBJECTIFY THIS: Female Anatomy Dissected and Displayed', a group exhibition of paintings and illustrations featuring the underlying anatomy of the female body.

September 7th – September 29th
Design Cloud Gallery
118 N. Peoria St. 2N, Chicago, IL

Opening event Friday, September 7th, 6–10p.m. with burlesque performances by Chicago's Vaudezilla troupe.

Throughout time, female anatomical illustration has evoked a multitude of feelings beyond simple academic representation. It's one of the reasons why the male form has been the exemplum of the human body throughout time, with the female being illustrated only as the variation in terms of reproductive organs and surface anatomy. This gallery show seeks to portray females only in relation to other females. It will compel viewers to question the objectivity surrounding ‘female anatomy’ and define—or re-define—their own perceptions through the art, perspectives, literature, and live burlesque performances.

Featured artists: Fernando Vicente, Jason Levesque, Cake, Michael Reedy, Emily Evans, Danny Quirk, Pole Ka, Tristan des Limbes, Amylin Loglisci.

You can find out more by clicking here.

Images, Top to bottom (click on images to see larger version):

  1. "American Housewife" by Fernando Vicente
  2. "Anatomical Meluxine" by Jason Levesque, 2012
  3. "Christina" by Danny Quirk, 2010

Source:
http://morbidanatomy.blogspot.com/feeds/posts/default?alt=rss

On The Curious Victorian Phenomenon of Exactingly Produced Miniature Butcher Shops, Collector’s Weekly, 2012

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PETA would never approve: This grisly 1840 doll-sized butcher shop with miniature animal carcasses and a floor covered in sawdust and blood would be shockingly graphic to our modern sensibilities. After all, here in the 21st century, we like to remain cheerfully oblivious about where our meat products come from.

But in Victorian times, such detailed model butcher shops were not uncommon, says Sarah Louise Wood, a curator at the Museum of Childhood at the Victoria and Albert Museum in London. The real question is: Why exactly do such things exist?
--Baby’s First Butcher Shop, Circa 1900, Collector's Weekly, Lisa Hix

Find out more by about this forgotten art by reading the entirety of "Baby’s First Butcher Shop, Circa 1900"  on the Collector's Weekly website by clicking here.

All images drawn from the Collector's Weekly website. You can see larger copies by clicking on images, and find out more by clicking here.

Source:
http://morbidanatomy.blogspot.com/feeds/posts/default?alt=rss

India’s Pharma FDI Mess…

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A note: "Apothecurry" - a blog with a very creative and meaningful name is my favorite blog to get some nifty scoops  on the status of the Indian pharma industry, and I suppose what the Indian Government is doing to it...

You can find the blog linked at the end of  the post.

The question everyone wants to ask: Why is the Indian Government f*ing up the pharma industry?

Among other things they have done:

1. They forced Bayer to license a Cancer drug in a very ambiguous manner. Bayer is no saint, the proposed drug cost and their stance is a direct evidence of either greed or self-loathing inanity - hard to say.

2. They have made a pledge to provide free drugs to India's teeming millions without a proper plan or even the semblance of one...

3. Now, they have threatened Foreign Direct Investments, and, according to Apothecurry, in quite a disparate manner.

Bringing the License Raj back:

Well, not the TBBT Raj, but the much maligned "License Raj", the practice of requiring companies to obtain licenses and burying them in reams of paperwork, promoting corruption, stifling even a whiff of innovation and essentially choking an industry.

Apparently, various arms of the Indian Government have their own plans to stuff their hand in the cookie jar. First apparently the Commerce Ministry wants every foreign investor to go through an intermediary agency called the Foreign Investment Promotion Board (FIPB).

A group of folks from various ministries, on the other hand have suggested that this hell befall only those foreign investors that dare seek more than 49% of a local pharma company. Either way, this is not good news for the Indian pharma industry.

Pharmaceutical Xenophobia

As with everything else, independent India simply misunderstood and maligned Gandhi's "Swadesi" exhortation. Untimely as his death would have ever been, were he to live today, he would pooh-pooh the anti-foreigner sentiment being used to gain popularity and votes while burying real issues.

You would think in a failing economy, the Indian Government, led by none other than Manmohan Singh, famous for bailing India out of the License Raj would not even think of suggesting protectionism.

However, like any other Government, they would like to blame their failings on someone else and thus would have you believe that India's impoverished healthcare system is a consequence of unscrupulous FDI. They may be unscrupulous, yes, but the bulk of the problem, all the way from apathy to lack of vision and corruption rests solely with India.

Whither India?

Someone should tell Sonia Gandhi, Manmohan Singh and their bandwagon of daylight dreamers that the Indian economy is not on a bed of roses. Rather than ease restrictions and make it easy for investor money to flow, the Indian Government is looking to take the country back and plunge it into the same darkness as the energy grids.

If they worry foreign investors would get carried away, they should put forth legal barriers, not imbue some Russian-Venezuelan axis of Xenophobic Hell on Earth.

If this continues, we will see that India's healthcare reach suffers worse than ever, drugs get pulled off the market, or never get into the market and the industry will whither away with stiff external competition.

Reference:

http://apothecurry.wordpress.com/2012/08/08/fdi-in-pharma-another-punch/http://apothecurry.wordpress.com/2012/08/08/fdi-in-pharma-another-punch/

Source:
http://chaaraka.blogspot.com/feeds/posts/default

Hemicelluloses negatively affect lignocellulose crystallinity for high biomass digestibility under NaOH and H2SO4 pretreatments in Miscanthus

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Background:
Lignocellulose is the most abundant biomass on earth. However, biomass recalcitrance has become a major factor affecting biofuel production. Although cellulose crystallinity significantly influences biomass saccharification, little is known about the impact of three major wall polymers on cellulose crystallization. In this study, we selected six typical pairs of Miscanthus samples that presented different cell wall compositions, and then compared their cellulose crystallinity and biomass digestibility after various chemical pretreatments.
Results:
A Miscanthus sample with a high hemicelluloses level was determined to have a relatively low cellulose crystallinity index (CrI) and enhanced biomass digestibility at similar rates after pretreatments of NaOH and H2SO4 with three concentrations. By contrast, a Miscanthus sample with a high cellulose or lignin level showed increased CrI and low biomass saccharification, particularly after H2SO4 pretreatment. Correlation analysis revealed that the cellulose CrI negatively affected biomass digestion. Increased hemicelluloses level by 25% or decreased cellulose and lignin contents by 31% and 37% were also found to result in increased hexose yields by 1.3-times to 2.2-times released from enzymatic hydrolysis after NaOH or H2SO4 pretreatments. The findings indicated that hemicelluloses were the dominant and positive factor, whereas cellulose and lignin had synergistic and negative effects on biomass digestibility.
Conclusions:
Using six pairs of Miscanthus samples with different cell wall compositions, hemicelluloses were revealed to be the dominant factor that positively determined biomass digestibility after pretreatments with NaOH or H2SO4 by negatively affecting cellulose crystallinity. The results suggested potential approaches to the genetic modifications of bioenergy crops.Source:
http://www.biotechnologyforbiofuels.com/rss/

Torque measurements reveal large process differences between materials during high solid enzymatic hydrolysis of pretreated lignocellulose

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Background:
A common trend in the research on 2nd generation bioethanol is the focus on intensifying the process and increasing the concentration of water insoluble solids (WIS) throughout the process. However, increasing the WIS content is not without problems. For example, the viscosity of pretreated lignocellulosic materials is known to increase drastically with increasing WIS content. Further, at elevated viscosities, problems arise related to poor mixing of the material, such as poor distribution of the enzymes and/or difficulties with temperature and pH control, which results in possible yield reduction. Achieving good mixing is unfortunately not without cost, since the power requirements needed to operate the impeller at high viscosities can be substantial. This highly important scale-up problem can easily be overlooked.
Results:
In this work, we monitor the impeller torque (and hence power input) in a stirred tank reactor throughout high solid enzymatic hydrolysis (< 20% WIS) of steam-pretreated Arundo donax and spruce. Two different process modes were evaluated, where either the impeller speed or the impeller power input was kept constant. Results from hydrolysis experiments at a fixed impeller speed of 10 rpm show that a very rapid decrease in impeller torque is experienced during hydrolysis of pretreated arundo (i.e. it loses its fiber network strength), whereas the fiber strength is retained for a longer time within the spruce material. This translates into a relatively low, rather WIS independent, energy input for arundo whereas the stirring power demand for spruce is substantially larger and quite WIS dependent. By operating the impeller at a constant power input (instead of a constant impeller speed) it is shown that power input greatly affects the glucose yield of pretreated spruce whereas the hydrolysis of arundo seems unaffected.
Conclusions:
The results clearly highlight the large differences between the arundo and spruce materials, both in terms of needed energy input, and glucose yields. The impact of power input on glucose yield is furthermore shown to vary significantly between the materials, with spruce being very affected while arundo is not. These findings emphasize the need for substrate specific process solutions, where a short pre-hydrolysis (or viscosity reduction) might be favorable for arundo whereas fed-batch might be a better solution for spruce.
Results:
In this work, we monitor the impeller torque (and hence power input) in a stirred tank reactor throughout high solid enzymatic hydrolysis (< 20% WIS) of steam-pretreated Arundo donax and spruce. Results from hydrolysis experiments at a stirrer speed of 10 rpm show that a very rapid decrease in impeller torque is experienced during hydrolysis of pretreated arundo (i.e. it loses its fiber network strength), whereas the fiber strength is retained for a longer time within the spruce material. This translates into a relatively low, rather WIS independent, energy input for arundo whereas the stirring power demand for spruce is substantially larger and quite WIS dependent. By operating the impeller at a constant power input (instead of a constant impeller speed) it is shown that power input greatly affects the hydrolysis yield of pretreated spruce whereas the hydrolysis of arundo seems unaffected.
Conclusions:
The results clearly highlight the large differences between the two materials, both in terms of needed energy input, and hydrolysis yields. The impact of power input is furthermore shown to vary significantly between the materials, with spruce being very affected while arundo is not. These findings emphasize the need for substrate specific process solutions, where a short pre-hydrolysis (or viscosity reduction) might be favorable for arundo whereas fed-batch might be a better solution for spruce.Source:
http://www.biotechnologyforbiofuels.com/rss/

Everyone At Risk From Mad Cow Disease

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By John von Radowitz, Science Correspondent, PA News

No one is immune to the human form of mad cow disease, variant CJD, new research suggests today.

Some people whose genetic make-up normally acts as a barrier against infection may ultimately develop a different and so-far unrecognised type of disease, it is claimed.

Scientists have shown that individuals with a pair of genes known as MM about a third of the population acquire vCJD relatively easily.

No one with a different paring, VV, has been known to suffer the disease.

Then in August it emerged that a patient from a mixed MV genetic group had been infected with vCJD from contaminated blood, without showing any symptoms. Just over half the population has the MV pairing.

The news sparked fears of a mad cow disease timebomb in the population, with thousands of people unwittingly carrying the brain disease on a long incubation fuse. Read more…

Source:
http://feeds.feedburner.com/integratedmedicine

Assisted reproductive technology in Europe, 2008: results generated from European registers by ESHRE

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BACKGROUND

This 12th European IVF-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2008.

METHODS

From 36 countries (3 more compared with 2007), 1051 clinics reported 532 260 treatment cycles including: IVF (124 539), ICSI (280 552), frozen embryo replacements (FER, 97 120), egg donation (ED, 13 609), in vitro maturation (IVM, 562), preimplantation genetic diagnosis/screening (PGD/PGS, 2875) and frozen oocyte replacements (FOR, 4080). Overall, this represents a 7.9% increase in the activity since 2007, which is mainly related to an increase in cycles from almost all registers and only partially to the new countries entering EIM (Estonia, Kazakhstan, Moldova and Romania, 5480 cycles in total). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 27 and 21 countries, respectively. A total of 144 509 IUI-H (+1.5%) and 24 960 IUI-D (–4.3%) cycles were included.

RESULTS

In 19 countries where all clinics reported to the ART register, a total of 350 143 ART cycles were performed in a population of 369.8 million, corresponding to 947 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.5 and 32.5%, respectively, and for ICSI the corresponding rates were 28.7 and 31.9%. In FER cycles, the pregnancy rate per thawing was 19.3%. The delivery rate after IUI was 9.1% for IUI-H and 13.8% for IUI-D. In IVF and ICSI cycles, one, two, three and four or more embryos were transferred in 22.4, 53.2, 22.3 and 2.1%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 78.3, 20.7 and 1.0%, respectively, resulting in a total multiple delivery rate of 21.7%, compared with 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.7% (13.4% twins and 0.3% triplets). In women undergoing IUI, twin and triplet deliveries occurred in 10.6% and 0.7% with IUI-H and in 9.4 and 0.3% with IUI-D, respectively.

CONCLUSIONS

In comparison with previous years, there was an increase in the reported number of ART cycles in Europe. For the first time in 5 years, the pregnancy rates failed to show a year-on-year increase. Compared with 2007, the number of transfers of multiple embryos (3+) and a multiple delivery rate showed a marginal decline.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Cryptorchidism-induced CFTR down-regulation results in disruption of testicular tight junctions through up-regulation of NF-{kappa}B/COX-2/PGE2

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STUDY QUESTION

Does elevated temperature-induced cystic fibrosis transmembrane conductance regulator (CFTR) down-regulation in Sertoli cells in cryptorchid testis disrupt testicular tight junctions (TJs) through the nuclear factor kappa B (NF-B)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway?

SUMMARY ANSWER

Our results suggest that CFTR may be involved in regulating testicular TJs and the blood-testis barrier (BTB) through its negative regulation of the NF-B/COX-2/PGE2 pathway in Sertoli cells, a defect of which may result in the spermatogenesis defect in cryptorchidism.

WHAT IS KNOWN ALREADY

Cryptorchidism, or undescended testes, is known to result in defective spermatogenesis. Although an elevated testicular temperature is regarded as an important factor affecting spermatogenesis in cryptorchidism, the exact mechanism remains elusive. It is known that the expression of functional CFTR is temperature sensitive. Our previous study has demonstrated that CFTR negatively regulates NF-B/COX-2/PGE2 in bronchial epithelial cells. Disruption of TJs by COX-2/PGE2 has been found in tumour cells.

STUDY DESIGN AND METHODS

Expression of CFTR, NF-B, COX-2 and TJ proteins was examined in the testes of a surgical-induced cryptorchidism mouse model and a testicular hyperthermia mouse model, as well as in control or CFTR-inhibited/knocked down primary rat Sertoli cells. PGE2 production was measured by ELISA. Sertoli cell barrier function was determined by transepethelial resistance (TER) measurements in rat Sertoli cell primary cultures. BTB integrity in the cryptorchidism model was monitored by examining tracker dye injected into seminiferous tubules.

MAIN RESULTS

Down-regulation of CFTR accompanied by activation of NF-B, up-regulation of COX-2 and down-regulation of TJ proteins, including ZO-1 and occludin, was observed in a cryptorchidism mouse model. BTB leakage revealed impaired BTB integrity in cryptorchid testes, confirming the destruction of TJs. The inverse correlation of CFTR and COX-2 was further confirmed in a mouse testis hyperthermia model and CFTR knockout mouse model. Culturing primary Sertoli cells at 37°C, which mimics the pathological condition of cryptorchidism, led to a significant decrease in CFTR and increase in COX-2 expression and PGE2 production compared with the culture at the physiological 32°C. Inhibition or knockdown of CFTR led to increased COX-2 but decreased ZO-1 and occludin expression in Sertoli cells, which could be mimicked by PGE2, but reversed by NF-B or COX-2 inhibitor, suggesting that the regulation of TJs by CFTR is mediated by a NF-B/COX-2/PGE2 pathway. Inhibition of CFTR or administration of PGE2 significantly decreased Sertoli cell TER.

LIMITATIONS

This study has tested only the CFTR/NF-B/COX-2/PGE2 pathway in mouse testes in vivo and in rat Sertoli cells in vitro, and thus, it has some limitations. Further investigations in other species, especially humans, are needed.

WIDER IMPLICATIONS OF THE FINDINGS

Our study may shed more light on one of the aspects of the complicated underlying mechanisms of defective spermatogenesis induced by cryptorchidism.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported by the National Basic Research Program of China (2012 CB944900), Natural Sciences Foundation of China (30870933), Li Ka Shing Institute of Health Sciences, the Focused Investment Scheme of the Chinese University of Hong Kong and Morningside Foundation. The authors declare no conflict of interest.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Trophoblast cells induce a tolerogenic profile in dendritic cells

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BACKGROUND

Dendritic cells (DCs), which are biased toward a tolerogenic profile, play a pivotal role in tissue-remodeling processes and angiogenesis at the maternal–fetal interface. Here, we analyzed the effect of trophoblast cells on the functional profile of DCs to gain insight on the tolerogenic mechanisms underlying the human placental–maternal dialog at early stages of gestation.

METHODS

DCs were differentiated from peripheral blood monocytes obtained from fertile women (n = 21), in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor during 5 days in culture. Then, DCs were cultured with trophoblast cells (Swan-71 cell line obtained from normal cytotrophoblast, at 7 weeks) for 24 h and for an additional 24 h in the absence or presence of lipopolysaccharide (LPS) from Escherichia coli. DCs were recovered and used for flow cytometry, enzyme-linked immunosorbent assay, RT–PCR and suppression and migration assays.

RESULTS

Trophoblast cells significantly prevented the increase in CD83 expression induced by LPS without affecting the expression of CD86, CD40 and human leukocyte antigen-DR (P < 0.05). Trophoblast cells signifinatly decreased the production of IL-12p70 and tumor necrosis factor-α, while it increased the production of IL-10 (P < 0.05). No changes were observed in the production of IL-6 and monocyte chemotactic protein-1. The culture of DCs with trophoblast cells, also suppressed the stimulation of the allogeneic response triggered by LPS (P < 0.05). Conditioned DCs were able to increase the frequency of CD4 + CD25 + Foxp3 cells and this effect was accompanied by an increase in indoleamine 2, 3-dioxygenase expression in DCs (P < 0.05).

CONCLUSIONS

The interaction of DCs with trophoblast cells promotes the differentiation of DCs into cells with a predominantly tolerogenic profile that could contribute to a tolerogenic microenvironment at the maternal–fetal interface.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Prospective assessment of fetal-maternal cell transfer in miscarriage and pregnancy termination

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BACKGROUND

Fetal cells (microchimerism) are acquired by women during pregnancy. Fetal microchimerism persists decades later and includes cells with pluripotent capacity. Persistent microchimerism has the capacity for both beneficial and detrimental maternal health consequences. Both miscarriage and termination of pregnancy can result in fetal microchimerism. We sought to determine whether cellular fetal microchimerism is acquired during management of pregnancy loss and further explored factors that could influence fetal cell transfer, including viability of fetal tissue, surgical versus medical management and gestational age.

METHODS

Pregnant women (n= 150 samples from 75 women) with singleton pregnancies undergoing a TOP (n= 63) or treatment for embryonic or fetal demise (miscarriage, n= 12) were enrolled. Mononuclear cells were isolated from blood samples drawn before, and 30 min after, treatment. Fetal cellular microchimerism concentrations were determined using quantitative PCR for a Y chromosome-specific sequence, expressed as genome equivalents of fetal DNA per 100 000 maternal cell equivalents (gEq/105). Detection rate ratios were determined according to clinical characteristics.

RESULTS

Cellular fetal microchimerism was found more often in post- compared with pretreatment samples, 24 versus 5% (P= 0.004) and at higher concentrations, 0–36 versus 0–0.7 gEq/105 (P< 0.001). Likelihood of microchimerism was higher in surgical than medical management, detection rate ratio 24.7 (P= 0.02). The detection rate ratio for TOP versus miscarriage was 16.7 for known male fetuses (P= 0.02). Microchimerism did not vary with gestational age.

CONCLUSIONS

Significant fetal cell transfer occurs during miscarriage and TOP. Exploratory analyses support relationships between obstetric clinical factors and acquisition of fetal cellular microchimerism; however, our limited sample size precludes definitive analysis of these relationships, and confirmation is needed. In addition, the long-term persistence and potential consequences of fetal microchimerism on maternal health merit further investigation.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Unexplained first trimester recurrent pregnancy loss and low venous reserves

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BACKGROUND

More than half of recurrent pregnancy loss (RPL) remains unexplained. We hypothesized that women with a history of unexplained RPL (URPL) have low venous reserve.

METHODS

Case–control study in 12 women with a history of URPL, 11 healthy nulliparous controls and 12 primiparous controls with a history of uncomplicated pregnancy. To quantify venous reserve, we measured plasma volume (PV, ml/m2) and venous compliance in forearm and calf (VCarm, VCcalf, (ml/dl)/mmHg) during the follicular phase of the menstrual cycle. Mean arterial blood pressure (mmHg) was measured by oscillometry. Arterial demand was evaluated by cardiac index (CI, (l/min)/m2).

RESULTS

Baseline characteristics were comparable between groups. All groups had similar CI. Women with a history of RPL had 14% and 9% lower mean PV compared with nulliparous and primiparous controls (P < 0.01 and P = 0.04, respectively). In women with URPL, the mean VCarm was 25% and 32% lower compared with nulliparous and primiparous controls (P = 0.04 and P < 0.01, respectively), while the mean VCcalf was 29 and 22% lower compared with the two control groups (P < 0.01 and P = 0.03, respectively).

CONCLUSIONS

Women with URPL have lower venous reserves when compared with controls at comparable arterial demand. Interventions that increase venous reserve may improve pregnancy outcome.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

The influence of the type of embryo culture medium on neonatal birthweight after single embryo transfer in IVF

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STUDY QUESTION

Does the type of medium used to culture fresh and frozen–thawed embryos influence neonatal birthweight after single embryo transfer (SET) in IVF?

SUMMARY ANSWER

A comparison of two commercially available culture media showed no significant influence on mean birthweight and mean birthweight adjusted for gestational age, gender and parity (z-scores) of singletons born after a fresh or frozen–thawed SET. Furthermore, we show that embryo freezing and thawing cycles may lead to a significantly higher mean birthweight.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS

Animal studies have shown that culture media constituents are responsible for changes in birthweight of offspring. In human IVF, there is still little knowledge of the effect of medium type on birthweight. Until now, only a small number of commercially available culture media have been investigated (Vitrolife, Cook® Medical and IVF online medium). Our study adds new information: it has a larger population of singleton births compared with the previously published studies, it includes outcomes of other media types (HTF and Sage®), not previously analysed, and it includes data on frozen–thawed SETs.

DESIGN

This study was a retrospective analysis of birthweights of singleton newborns after fresh (Day 3) or frozen–thawed (Day 5) SET cycles, using embryos cultured in either of two different types of commercially available culture media, between 2008 and 2011.

PARTICIPANTS AND SETTING

Before January 2009, a single-step culture medium was used: human tubal fluid (HTF) with 4 mg/ml human serum albumin. From January 2009 onwards, a commercially available sequential medium was introduced: Sage®, Quinn's advantage protein plus medium. Singletons born after a fresh SET (99 embryos cultured in HTF and 259 in Sage®) and singletons born after a frozen–thawed SET (32 embryos cultured in HTF only, 41 in HTF and Sage® and 86 in Sage® only) were analysed. Only patients using autologous gametes without the use of a gestational carrier were considered. Also excluded were (vanishing) twins, triplets, babies with congenital or chromosomal abnormalities and babies born before 22 weeks of gestation.

MAIN RESULTS AND THE ROLE OF CHANCE

Analysis of 358 singletons born after a fresh SET and 159 singletons born after a frozen–thawed SET showed no significant difference between the HTF and Sage® groups in terms of birthweight. Gestational age, parity and gender of the baby were significantly related to birthweight in multiple linear regression analyses, and other possible confounding factors included maternal age, BMI and smoking, the number of blastomeres in the transferred embryo and the type of culture medium. Maternal age, BMI and smoking, gestational age at birth, gender of the baby and the percentage of firstborns did not differ significantly between the HTF and Sage® groups; however, among the fresh embryos, those cultured in Sage® had significantly more blastomeres at the time of embryo transfer compared with the embryos cultured in HTF. Birthweights adjusted for gestational age and gender or gestational age and parity (z-scores) were not significantly different between the HTF and Sage® groups for fresh or frozen–thawed SETs. Mean birthweight, as well as the mean birthweight among firstborns and the mean birthweights adjusted for gestational age and gender or parity (z-scores) were significantly higher in the cryopreservation group compared with the fresh embryo transfer group.

BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION

Our study is limited by its retrospective design and only two commercially available types of culture media were tested. More research is necessary to investigate the potential influence of culture media on gene expression.

GENERALIZABILITY TO OTHER POPULATIONS

Although our data do not indicate the major influences of the HTF and Sage® culture media on birthweight, our results cannot be extrapolated to other culture media types. Furthermore, there remains a potential influence of embryo culture environment on epigenetic variation not represented by birthweight differences but by more subtle features.

STUDY FUNDING/COMPETING INTEREST(S)

No external funding was obtained for this study.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

ART culture conditions change the probability of mouse embryo gestation through defined cellular and molecular responses

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STUDY QUESTION

Do different human ART culture protocols prepare embryos differently for post-implantation development?

SUMMARY ANSWER

The type of ART culture protocol results in distinct cellular and molecular phenotypes in vitro at the blastocyst stage as well as subsequently during in vivo development.

WHAT IS KNOWN ALREADY

It has been reported that ART culture medium affects human development as measured by gestation rates and birthweights. However, due to individual variation across ART patients, it is not possible as yet to pinpoint a cause–effect relationship between choice of culture medium and developmental outcome.

STUDY DESIGN, SIZE, DURATION

In a prospective study, 13 human ART culture protocols were compared two at a time against in vivo and in vitro controls. Superovulated mouse oocytes were fertilized in vivo using outbred and inbred mating schemes. Zygotes were cultured in medium or in the oviduct and scored for developmental parameters 96h later. Blastocysts were either analyzed or transferred into fosters to measure implantation rates and fetal development. In total, 5735 fertilized mouse oocytes, 1732 blastocysts, 605 fetuses and 178 newborns were examined during the course of the study (December 2010–December 2011).

PARTICIPANTS/MATERIALS, SETTING, METHODS

Mice of the B6C3F1, C57Bl/6 and CD1 strains were used as oocyte donors, sperm donors and recipients for embryo transfer, respectively. In vivo fertilized B6C3F1 oocytes were allowed to cleave in 13 human ART culture protocols compared with mouse oviduct and optimized mouse medium (KSOM(aa)). Cell lineage composition of resultant blastocysts was analyzed by immunostaining and confocal microscopy (trophectoderm, Cdx2; primitive ectoderm, Nanog; primitive endoderm, Sox17), global gene expression by microarray analysis, and rates of development to midgestation and to term.

MAIN RESULTS AND THE ROLE OF CHANCE

Mouse zygotes show profound variation in blastocyst (49.9–91.9%) and fetal (15.7–62.0%) development rates across the 13 ART culture protocols tested (R2= 0.337). Two opposite protocols, human tubal fluid/multiblast (high fetal rate) and ISM1/ISM2 (low fetal rate), were analyzed in depth using outbred and inbred fertilization schemes. Resultant blastocysts show imbalances of cell lineage composition; culture medium-specific deviation of gene expression (38 genes, ≥4-fold) compared with the in vivo pattern; and produce different litter sizes (P ≤ 0.0076) after transfer into fosters. Confounding effects of subfertility, life style and genetic heterogeneity are reduced to a minimum in the mouse model compared with ART patients.

LIMITATIONS, REASONS FOR CAUTION

This is an animal model study. Mouse embryo responses to human ART media are not transferable 1-to-1 to human development due to structural and physiologic differences between oocytes of the two species.

WIDER IMPLICATIONS OF THE FINDINGS

Our data promote awareness that human ART culture media affect embryo development. Effects reported here in the mouse may apply also in human, because no ART medium presently available on the market has been optimized for human embryo development. The mouse embryo assay (MEA), which requires ART media to support at least 80% blastocyst formation, is in need of reform and should be extended to include post-implantation development.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported by the Deutsche Forschungsgemeinschaft (BO 2540/4-1 to M.B. and SCHL 394/9 to S.S.) and by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (no. 63-258 to S.L.G.). No competing interests.

TRIAL REGISTRATION NUMBER

Not applicable.

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http://humrep.oxfordjournals.org/rss/current.xml

A method for semi-automatic grading of human blastocyst microscope images

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BACKGROUND

The precise assessment of embryo viability is an extremely important factor for the optimization of IVF treatments. In order to assess embryo viability, several embryo scoring systems have been developed. However, they rely mostly on a subjective visual analysis of embryo morphological features and thus are subject to inter- and intra-observer variation. In this paper, we propose a method for image segmentation (the dividing of an image into its meaningful constituent regions) and classification of human blastocyst images with the aim of automating embryo grading.

METHODS

The delineation of the boundaries (segmentation) of the zona pellucida, trophectoderm (TE) and inner cell mass (ICM) were performed using advanced image analysis techniques (level set, phase congruency and fitting of ellipse methods). The fractal dimension and mean thickness of TE and ICM image texture descriptors (texture spectrum and grey-level run lengths) were calculated to characterize the main morphological features of the blastocyst with the aim of automatic grading using Support Vector Machine classifiers.

RESULTS

The fractal dimension calculated from the delineated TE boundary provided a good indication of cell number (presented a 0.81 Pearson correlation coefficient with the number of cells), a feature closely associated with blastocyst quality. The classifiers showed different accuracy levels for each grade. They presented accuracy ranges from 0.67 to 0.92 for the embryo development classification, 0.67–0.82 for the ICM classification and 0.53–0.92 for the TE classification. The value 0.92 was the highest accuracy achieved in the tests with 73 blastocysts.

CONCLUSIONS

Semi-automatic grading of human blastocysts by a computer is feasible and may offer a more precise comparison of embryos, reducing subjectivity and allowing embryos with apparently identical morphological scores to be distinguished.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

The impact of pronuclei morphology and dynamicity on live birth outcome after time-lapse culture

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STUDY QUESTION

Can the pronuclei (PN) morphology and the time of PN breakdown (PNB) predict the potential of embryos to result in live birth?

SUMMARY ANSWER

In comparison to embryos resulting in no live birth, PNB occurred significantly later in embryos resulting in live birth and never earlier than 20 h 45min. None of the tested scoring systems were shown to predict the live birth outcome in a time-lapse set-up.

WHAT IS KNOWN ALREADY

The PN morphology is supported as a prominent embryo selection parameter in single light microscopy observations, although controversial results have been reported.

STUDY DESIGN, SIZE, DURATION

This was a prospective study of 159 embryos, all of which were later transferred. The PN morphology of 46 embryos which resulted in live birth was compared with that of 113 embryos which resulted in no live birth.

PARTICIPANTS, SETTING

From 1 March 2010 to 30 August 2011, 130 couples underwent fertility treatment by ICSI. Embryo culture was performed in a time-lapse set-up from fertilization to intrauterine transfer. PN morphological assessment was performed on every embryo replaced, using six different scoring systems at different times.

MAIN RESULTS AND THE ROLE OF CHANCE

No embryo with PNB earlier than 20 h 45 min resulted in live birth. All six PN assessment models showed no significant distribution of scores (P = NS) between the live birth and no live birth groups at 16 h post-fertilization (PF), 18 h PF and 40 min before PNB. The outcomes of assessments changed significantly (P < 0.001) over time and the time of PNB was found to be the optimal stage to evaluate the PN morphology.

LIMITATIONS, REASONS FOR CAUTION

The study includes only embryos reaching the 4-cell stage after ICSI, and transferred at 44 h PF.

WIDER IMPLICATIONS OF THE FINDINGS

The PN morphology changes over time, indicating that the single light microscopy observation approach is deficient in comparison to time-lapse. Although the assessment of the PN morphology does not improve embryo selection, the timing of PNB should be included in embryo selection parameters.

STUDY FUNDING/COMPETING INTEREST(S)

None.

TRIAL REGISTRATION NUMBER

Approval number from the National Ethical Committee of Medical Science of Denmark: SJ-250.

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http://humrep.oxfordjournals.org/rss/current.xml

Intrauterine contraception: incidence and factors associated with uterine perforation–a population-based study

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STUDY QUESTION

What are the incidence and factors associated with uterine perforation by modern copper intrauterine device (Cu-IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS)?

SUMMARY ANSWER

Perforation incidence was similar to that reported in prior studies and did not vary between Cu-IUD and LNG-IUS groups. Lactation, amenorrhoea and a post-partum period of <6 months were common.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS

The study supports findings in prior studies. The incidence rate was low and factors associated with uterine perforation were similar to those in earlier reports.

DESIGN AND DATA COLLECTION METHOD

This retrospective population-based registry study included 68 patients surgically treated for uterine perforation by an intrauterine device (IUD)/intrauterine system (IUS) at clinics in the Helsinki and Uusimaa hospital district.

PARTICIPANTS AND SETTING

Records of 108 patients with probable uterine perforation by an IUD/IUS were analysed, leaving 68 patients treated for uterine perforation.

RECRUITMENT/SAMPLING STRATEGY

Patients with diagnostic and surgical treatment codes indicating uterine perforation by an IUD/IUS between 1996 and 2009 were retrospectively selected from the Finnish National Hospital Register.

DATA ANALYSIS METHOD

Patients with Cu-IUDs (n = 17) and the LNG-IUS (n = 51) were analysed as one group and also compared using Mann–Whitney and chi-square tests. IUD/IUS sales numbers were used to calculate incidences.

MAIN FINDINGS

The overall incidence of perforation was 0.4/1000 sold devices, varying annually from 0 to 1.2/1000. The proportion of both sold and perforating LNG-IUSs increased during the study period, but perforation incidence was not affected. Demographic characteristics in the Cu-IUD and LNG-IUS groups were similar. More than half of the devices (55%) were inserted at <6 months post-partum. Breastfeeding at the time of insertion was common, comprising 32% of all patients. Moreover, of the breastfeeding women, 90% had delivered within 6 month prior to insertion.

IMPLICATIONS

The population-based study setting represents a good overview of patients experiencing uterine perforation with an IUD/IUS. As previously reported, the post-partum period, lactation and amenorrhoea may increase the risk of perforation.

BIAS, LIMITATIONS AND GENERALIZABILITY

As the study setting revealed only symptomatic patients or those attending regular follow-up, the true incidence might be somewhat higher. As there is no specific diagnostic code for uterine perforation or treatment, it is unlikely that all cases of uterine perforation can be identified in a retrospective study.

STUDY FUNDING/POTENTIAL COMPETING INTERESTS

Helsinki University Central Hospital research funds are acknowledged.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Ultrasound evaluation of uterine healing after laparoscopic intracapsular myomectomy: an observational study

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STUDY QUESTION

Can uterine scar healing after laparoscopic intracapsular myomectomy (LIM) be adequately monitored by traditional two-dimensional (2D) ultrasound (US) and Doppler velocimetry?

SUMMARY ANSWER

The myometrial area of the scar after LIM can be followed by 2D US and Doppler velocimetry.

WHAT IS KNOWN ALREADY

Apart from post-surgical adhesions, the main concern linked to laparoscopic myomectomy is the quality of healing of the myometrial incision: it has been suggested that US could be useful for assessing uterine scars after myomectomy. However, no diagnostic method has yet been widely accepted to assess the healing process.

STUDY DESIGN, SIZE, DURATION

A cohort prospective study (level of evidence II-2), run in University-affiliated hospitals: 149 women with symptomatic uterine fibroids (UFs) underwent LIM, between January 2007 and October 2011. During follow up 13 patients withdrew from the study.

PARTICIPANTS/MATERIALS, SETTING, METHODS

After LIM, all patients were followed by traditional 2D US scanning and Doppler velocimetry on Days: 0, 1, 7, 30 and 45. Authors evaluated: number, size and location of UFs, scar diameter and Doppler velocimetry and resistance index (RI) of the uterine arteries, at their ascending branch.

MAIN RESULTS AND THE ROLE OF CHANCE

The uterine examination showed a significant (P < 0.05) progressive reduction of uterine scar area from 78% of the previous UF location on the first day, to 19% on 30th day, and <4% on the 45th day. There was no correlation with the size of the fibroid or the relative reduction in the size of the scar, on both Days 1 and 45. There was a significant (P < 0.05) increase in the RI of the ipsilateral uterine arteries from 0.65 on the first post-operative day to 0.83 after 7 days followed by a decrease to 0.71 on the 30th and 0.61 on the 45th post-operative day.

LIMITATIONS, REASONS FOR CAUTION

This is a cohort investigation on a limited number of patients and it does not surgically compare LIM and ‘classic’ myomectomy in the scar US follow up.

WIDER IMPLICATIONS OF THE FINDINGS

LIM avoided intraoperative bleeding and excessive tissue damage, as post-operative US follow up showed, with just two intra-myometrial hematomas (1.5%). The 2D US and Doppler velocimetry, a non-invasive safe method to check the myometrium after LIM, can detect post-operative hematoma and disechogenic, heterogeneous or ill-defined scar area, all unfavorable signs for myometrial scarring. Moreover, Doppler transvaginal monitoring, evaluating the pulsatility index (PI) and RI of the uterine arteries at their ascending branch, could identify patients with altered PI and RI parameters, possible markers of impaired wound healing.

STUDY FUNDING/COMPETING INTEREST(S)

None.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

The sonographic prediction of invasive carcinoma in unilocular-solid ovarian cysts in premenopausal patients: a pilot study

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BACKGROUND

Unilocular-solid ovarian cysts are a rare but challenging pathology in young women, with a desire to spare their fertility. In these cases, the risks of borderline and invasive disease are around 10 and 20%, respectively. No ultrasound rule has yet demonstrated the ability to discriminate with high accuracy, a borderline tumor from a benign tumor or ‘invasive tumor’. The aim of this study was to assess the predictive performance of different ultrasound parameters in differentiating benign and borderline tumors versus invasive malignant tumors in premenopausal patients with unilocular-solid ovarian masses.

METHODS

Women aged ≤50 years with unilocular-solid adnexal masses with a maximum diameter ≤10 cm, undergoing surgery in our department within 3 months from ultrasound examination, were included in this retrospective study. A standardized ultrasound examination technique and predefined definitions of ultrasound characteristics were used. The results of ultrasound examination using gray scale and color Doppler were compared with the histological examination of the respective surgical specimens.

RESULTS

The study included 51 patients. On histological examination, 36 (70%) lesions were classified as benign, 10 (20%) as borderline ovarian tumors and 5 (10%) as invasively malignant tumors. In receiver-operating characteristic curve analysis, the best cut-off for the largest solid component with regard to discriminating non-invasive (benign or borderline) from invasive tumors was 14 mm. A largest solid component >14 mm, the presence of papillation blood flow and the combination of the two parameters provided a sensitivity of 100% and a specificity of 63, 63 and 80%, respectively.

CONCLUSIONS

Transvaginal ultrasound examination seems to be able to discriminate between invasive and non-invasive tumors in the premenopausal patients with unilocular-solid adnexal masses. Because of the retrospective nature of the study, further prospective clinical trials are needed to confirm the accuracy of the selected sonographic parameters in discriminating the invasive and non-invasive adnexal tumors.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Influence of controlled ovarian hyperstimulation on uterine peristalsis in infertile women

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STUDY QUESTION

Is there a difference in the characteristics of uterine peristalsis in natural and controlled ovarian hyperstimulation (COH) cycles?

SUMMARY ANSWER

COH significantly changed the uterine peristaltic pattern.

WHAT IS KNOWN ALREADY

In natural menstrual cycles, the periodic changes of uterine peristalsis are closely related to the reproductive process.

STUDY DESIGN, SIZE, DURATION

This is a prospective cohort study with a total of 64 subjects involved. The study was performed between May 2011 and August 2011.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Sixty-four infertile women with regular, ovulatory menstrual cycles underwent follicular tracking in one natural cycle and after ovarian stimulation (GnRH-agonist down-regulation) in the subsequent cycle (COH). Three time points were studied in both cycles: at LH surge/HCG plus 1 day, ovulation/oocyte retrieval and 2 days after ovulation/retrieval. The study was performed in an IVF center of the university-affiliated Xiangya hospital.

MAIN RESULTS AND THE ROLE OF CHANCE

Uterine peristaltic wave frequency was 1.31 times higher in the COH than in the natural cycle (P< 0.01). At all three time points in the COH cycle, waves moving from the cervix to fundus dominated, comprising 80–90% of the wave types observed, while ‘no activity’ was more frequently observed in the natural cycle. The wave frequency was positively correlated with the level of serum estradiol (E2) (r= 0.30; P< 0.01) and negatively correlated with the progesterone level (r= –0.48; P< 0.01) for the physiological range of steroid levels. No correlation was found between the wave frequency and supraphysiological concentrations of E2 or progesterone.

LIMITATIONS, REASONS FOR CAUTION

The two observers were not independent and this was a limitation of the study. Quantitative measurements of wave amplitude in the different cycles should be compared in future research.

WIDER IMPLICATIONS OF THE FINDINGS

Uterine peristalsis was much higher in the COH cycle than in the natural cycle. The endometrial movements did not weaken to the natural level before embryo transfer, even with high levels of progesterone. The wave frequency was positively correlated with serum E2 level and negatively correlated with that of progesterone within the physiological range. No correlation was found between the wave frequency and supraphysiological concentrations of E2 and progesterone.

STUDY FUNDING/COMPETING INTEREST(S)

The authors declare that they have no study funding or competing interests in this study.

Source:
http://humrep.oxfordjournals.org/rss/current.xml