Hirsutism in women – literature review

Here some excerpts from the 2012 review of hirsutism in women in the journal American Family Physician:

Hirsutism is excess terminal hair that commonly appears in a male pattern in women.

Although hirsutism is generally associated with hyperandrogenemia, 50% of women with mild symptoms have normal androgen levels.

Causes of hirsutism

The most common cause of hirsutism is polycystic ovary syndrome (PCOS), which accounts for 3 out of every 4 cases.

Many medications can also cause hirsutism.

In patients whose hirsutism is not related to medication use, evaluation is focused on testing for endocrinopathies and neoplasms, such:

- polycystic ovary syndrome (PCOS)
- adrenal hyperplasia
- thyroid dysfunction
- Cushing syndrome
- androgen-secreting tumors

Symptoms of hirsutism

Symptoms and findings suggestive of neoplasm include rapid onset of symptoms, signs of virilization, and a palpable abdominal or pelvic mass.

Patients without these findings who have mild symptoms and normal menses can be treated empirically.

For patients with moderate or severe symptoms, an early morning total testosterone level should be obtained, and if elevated, it should be followed by a plasma free testosterone level.

A total testosterone level greater than 200 ng per dL (6.94 nmol per L) should prompt evaluation for an androgen-secreting tumor.

Diagnosis of hirsutism

Laboratory workup may include:

- early morning total testosterone level
- plasma free testosterone level
- thyroid function tests
- prolactin level
- 17-hydroxyprogesterone level
- corticotropin stimulation test

Treatment of hirsutism

Treatment includes hair removal and pharmacologic measures.

Shaving is effective but needs to be repeated often. Evidence for the effectiveness of electrolysis and laser therapy is limited.

Laser treatment does not result in complete, permanent hair reduction, but it is more effective than other methods such as shaving, waxing, and electrolysis. It produces hair reduction for up to 6 months. The effect is enhanced with multiple treatments.

In patients who are not planning a pregnancy, first-line pharmacologic treatment should include oral contraceptives. Topical agents, such as eflornithine, may also be used.

Treatment response should be monitored for at least six months before making adjustments.

References:

Hirsutism in women. Bode D, Seehusen DA, Baird D. Am Fam Physician. 2012 Feb 15;85(4):373-80.

Management of Hirsutism (Excess Hair)

Image source: Skin layers. Wikipedia, public domain.

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CW competition blog – Philip Ball

This is a guest post from one of our judges for the Chemistry World Science Communication Competition

 

Communicating science, like any kind of journalism, typically has a formula. There are good reasons for this. Readers need to be able to get to the news very quickly, often in the first sentence and usually at least in the first paragraph. They also need to be told what is really new – not generalities such as ‘Researchers have developed an amazing new material/drug/device’, but what really distinguishes the new work from what has gone before – and most of all, why they should care. In attempting to get this right, I always try to repeat to myself the mantra that I learnt from the veteran science writer Tim Radford: ‘No one has to read this stuff.’ The trick is to make them want to read: not with false promises, hype, or sensationalism, but with smart, concise, and perhaps witty writing.

OK, so much for the formula. Rules are, of course, there to be broken – but only if you have a very good reason to do so. A rigid adherence to tradition can be the death of good writing. I don’t advocate gimmicks for their own sake, but there are doubtless more valid ways to grab a reader’s attention than with a first sentence that basically tells the whole story. You might want to use the first paragraph to describe a compelling first-hand scene or encounter, or to pose a tantalising question. To my mind, the winners of this competition might simply do a great job with the standard ‘news story’ template, or might surprise us with a totally new approach. Don’t feel obliged to do either – just think about what will make the piece work.

Be wary of words that strain for effect. Readers won’t necessarily believe that what you’re describing is ‘amazing’, ‘revolutionary’ or ‘gob-smacking’ just because you say it is. Words like this have to earn their place, and usually there are better alternatives anyway. When the writing is good, it doesn’t need to be pumped up with adjectives on steroids; in fact, they usually detract. At the same time, be wary of falling into science-speak. It’s easy enough to avoid obvious jargon, harder to steer clear of scientists’ habitual turns of phrase, such as the passive voice or comments such as ‘The crystal structure showed that…’. When things get a bit technical, it’s often best not to try to explain everything – the trick may be to persuade the reader that they know, rather than reminding them of what they don’t.

Of course, there’s no substitute for a good story. These aren’t easy to find, so take your time. It could be something surprising, or important, or fun, or perhaps even shocking or disturbing. Whatever the case, you have to be clear what the story is, which means being able to express it in a sentence. You might not use that sentence, but you have to be able to write it. Now have fun!

Philip Ball is a science writer based in London, UK

 

Find out about the Chemistry World Science Communication Competition and submit your entry here.

 

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Rx Prescription Bottle Sticker Packs

$12.95 each at the Street Anatomy store!

Rx Prescription Bottle sticker packs available at the Street Anatomy store (2)

Rx Prescription Bottle sticker packs available at the Street Anatomy store (7)

Rx Prescription Bottle sticker packs available at the Street Anatomy store (2)

Rx Prescription Bottle sticker packs available at the Street Anatomy store (1)

Rx Prescription Bottle sticker packs available at the Street Anatomy store (2)
Photos by Vanessa Ruiz

Are you looking for more excitement in your life? Want to take more risks, but fear is holding you back?  Then talk to your doctor about a prescription for an Rx sticker pack.

  • 15–20 high quality hand cut stickers and 1 Rx pin per bottle
  • Stickers range in size from 1.5–3.5 inches
  • Vivid colors make these stickers stand out against almost any surface
  • Colors and sticker sizes vary from bottle to bottle
  • Created by street artists Rx, Kater, The Lost Cause, Twigs, Just1, Obit, Numbskull, Face, and more…
  • Only 50 prescriptions available
  • Refills encouraged!
  • $12.95 each at the Street Anatomy store

 

IMPORTANT SAFETY INFORMATION
May cause adrenaline rush, incarceration, and/or fine if taken on city streets.  Use caution when taking around street signs, newspaper boxes, dumpsters, and abandoned buildings.

Manufactured by hand on the streets of Portland, Oregon by Rx.  Only available by prescription via Street Anatomy.

International shipping available.

 

 

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"Phantom Creep Theatre: Lon Chaney Shall Not Die," Tonight at The Coney Island Museum

At the Coney Island Museum in Brooklyn, the Phantom Creep Theater pays tribute to classic horror with its version of the spook show, a macabre entertainment popular in the early 20th century that weds Grand Guignol tradition with modern sideshow showmanship. Hosted by M.C.’s in the vein of late-night television horror hosts like Ghoulardi and Dr. Creep, the shows feature B movies, live music, old-hat magic and a total blackout in which a monster or phantom tears through the theater.
--"No Rest for the Wicked, Undead or Ghoulish," New York Times.
July 12, 2012

Tonight, at the Coney Island Museum, I hope to see you for "Phantom Creep Theatre: Lon Chaney Shall Not Die!",  an ode to the 1950s spook show organized in part by friend and Midnight Archive creator Ronni Thomas. The night's series of performances, screenings and hijinx will be dedicated to the memory and work of Lon Chaney Sr., patron saint of classic horror, and will feature a live theatrical recreation of the lost 1929 film "Thunder,"which included "insidious carnies, murderous dwarves, [and] ravenous gorillas on the loose" and reputedly killed "the man of a 1,000 faces." In fine spook show tradition, there will also be an attempt to make contact with the ghost of Mr. Chaney, a chance to meet the "Hypno Corpse," varied film screenings, live music, and many thrills and screams, all for only 10 dollars.

Full details follow; hope very much to see you there!

PHANTOM CREEP THEATRE: Lon Chaney Shall Not Die!
Location: The Coney Island Museum
Date: TONIGHT Saturday, July 21
Time: Doors 8:00, Event 8:30 PM
Admission: $10
Free Popcorn!

Set your faces to stun for THE UNHOLY THREE (1930), screened from a 16mm film print! This film includes insidious carnies, murderous dwarves, ravenous gorillas on the loose, Lon Chaney, Sr.'s only speaking role, and much, much more!

Experience a one time live theatrical recreation of the (lost) film that killed Lon Chaney, Sr.... THUNDER! No one has seen this gut wrenching, edge of your seat, golden era rail road drama, in over 80 years!! You can't see it anywhere, but the Phantom Creep Theatre stage!

These presentations and more are part of an entire evening celebrating the man of a 1,000 faces, the man who ceased to exist between pictures, the broken hearted clown who was born on April Fool's Day - Lon Chaney, Sr.!

Will you bear witness to COUNT MOLOCH and EK, as they attempt to make contact with the ghost of Lon Chaney, Sr., live on the Coney Island Museum stage?!?!

Entities known, and unknown, may leave the stage and roam the room in the dark. Will you be ripped from your seat, or frozen with fear to it?

"That's all there is to life: A little laugh, a little tear." - Lon Chaney, Sr.

Plus, the HYPNO CORPSE will shock and amaze you!

LIVE performances, FILM (not digital!) projections, LIVE music! ...ONLY ten bones?! YES! 

The team that ran the original Silver Scream Spook Show at Coney Island, reunite for the first time ever on the stage that started it all! NYC's 8mm Movie Matinee, along with Atlanta GA's Silver Scream Spook Show, and the internet's own Midnight Archive web series, are throwing a gala summer-long series!

A spook show collaboration of colossal proportions in Coney Island! Ghosts materialize before your eyes! Monsters summoned from beyond! Strange creatures reach out at you through the darkness!

Including, but not limited to:

Golden era monster movies presented from 16mm film prints!

Live morbid magicians conjuring spirits that may run out into the audience to shake and shock you to your very core!

Each month is a DIFFERENT theme with NEW films, NEW gags, and NEW live hijinks! Collect ALL the memories and experiences!

You can find out more, and get tickets, by clicking here; tickets can also be purchased at the door. You can read the entire New York Times article about the event by clicking here.

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"Dissection on Display: Cadavers, Anatomists and Public Spectacle" by Christine Quigley, Book Review by Bess Lovejoy

I am very excited to read the new and wonderful looking book Dissection on Display: Cadavers, Anatomists and Public Spectacle by Christine Quigley, who many of you might best know as editor of the wide-ranging blog Quigley's Cabinet. I have not yet had a chance to read the book, but we are all in luck, as friend of Morbid Anatomy Bess Lovejoy--author of the forthcoming Rest in Pieces: The Curious Fates of Famous Corpses--has kindly offered up a very detailed and thoughful review of the book special for the Morbid Anatomy blog.

Lovejoy's review follows; you can also find out more about the book--or purchase a copy of your very own--by clicking here.

Dissection on Display: Cadavers, Anatomists and Public Spectacle
By Christine Quigley
Mcfarland, February 24, 2012

Most of us have never seen a dead body, let alone witnessed the dissection of a cadaver. But for centuries in Europe, Britain, and America, public dissections were highly social occasions. In the candlelit, damask-draped anatomy theatre of 18th century Bologna, townspeople jostled medical students and high-ranking officials during a two-week-long dissection that took place as part of the annual carnival. In 16th century Britain, hundreds crowded around to watch the dissections of executed criminals. And in early 19th century America, the most fashionable strata of society (men and women alike) attended public dissections for a chance to “see and be seen.”

In her new book, Dissection on Display: Cadavers, Anatomists and Public Spectacle, scholar, author, and blogger Christine Quigley traces the hidden history of anatomists who perform for the public. Not all of the men she profiles are known just for their dissections: some, like 17th and 18th century Europeans Frederik Ruysch and Honoré Fragonard, did the dirty work in private, then displayed the exquisitely-crafted results to the public in the form of art and illustration. Many of the names Quigley profiles will be familiar to Morbid Anatomy readers, though others -- like Thomas “Mummy” Pettigrew, the 19th century London antiquarian who unrolled mummies to entertain his guests – may be fresh discoveries.

Using a series of thematically-grouped vignettes, Quigley explores anatomists as demonstrators, educators, collectors, showmen, and more. Some of the book’s most intriguing passages deal with the lessons that public dissections were supposed to impart: not just about the workings of the body, but the workings of God, and of justice. Even more than a chance to gain medical wisdom, public dissections were often promoted as an opportunity to witness the glory of God in the functioning of a corpse’s entrails. Sometimes they were also seen as a chance to exult in the final stage of  punishment meted out to a criminal. The mutilation of the corpse was thought to deny the deceased a chance at Resurrection -- thus condemning him or her both in life and afterlife.

Quigley also touches on the racial and sexual undertones that have long troubled the study of anatomy. One of the book’s most disturbing sections profiles French naturalist and zoologist Georges Cuvier and his quest to uncover (literally) the mysteries that lay between the legs of Saartjie Bjartmaan, also known as the “Hottentot Venus.” Bjartmaan – a young Khoisan woman from South Africa -- entertained audiences in early 19th century London and Paris with the enormous size of her buttocks. Some whispered that Bjartmaan was also blessed with a similarly enormous labia minora, and like other scientists of the time, Cuvier was fascinated by such rumors. After Bjartmaan’s death, he detailed her dissection in a medical journal and preserved both her brain and genitals in greenish glass bottles outside his office. Thus the last shred of modesty that Bjartmaan had protected in life was unceremoniously stripped from her in death, in a way that calls to mind the brutally frank autopsy reports of modern dead celebrities.

Today, human dissection is usually hidden from the public. This cloaking began in the 19th century, when, as Quigley writes, “The anatomists withdrew behind the doors of educational institutions, and the townspeople were not invited to join them.” These days dissections occur exclusively in a medical or forensic context, and the only corpses we see are on television. No longer is the public treated to theatrical displays of their own inner-workings, as they were in the days when Andreas Vesalius kept Renaissance audiences glued to their seats.

But there have been exceptions. In 2002, the controversial Gunter von Hagens – he of the plastinated corpses and Body Worlds exhibits – staged a ticketed dissection of the body of a 72-year-old man in London. The event drew considerable attention, and Hagens faced the threat of arrest even while wielding the scalpel. Yet the room was packed, proving that our appetites for dissection haven’t waned. Quigley includes an excellent photograph of the event, notable not for the pale cadaver about to be sliced apart, but for the front row of the audience, their faces horrified, bemused, and fascinated in turn. One woman crosses her hands over her chest in protection, clutching her check and beginning to grimace. Next to her, an older gentleman folds his wrists behind his elbows and leans back as if to say “show me what you got.” Von Hagens himself is at the forefront of the image, clad in a black fedora -- his nod to Rembrandt’s “The Anatomy Lesson of Dr. Nicolaes Tulp,” which hangs on the wall above him.

In fact, Quigley takes pains to show us how conscious Von Hagens – the most famous modern anatomist -- is of his historical lineage. (Many of his most famous pieces, such as his flayed horse and rider, quote directly from the work of earlier anatomists such as Fragonard.) This is where the book shines: Quigley has stitched together a family tree of public anatomists who contributed to our understanding of the body, but whose work often remains hidden like the organs beneath our skin. Dissection on Display is recommended reading for anyone with a healthy sense of curiosity, morbid or otherwise, about what used to happen when we were allowed to watch.

The writer of this post, Bess Lovejoy, is a writer, editor, and researcher based in Seattle. Her book Rest in Pieces: The Curious Fates of Famous Corpsesis coming out March 2013. You can find out more about her at her website besslovejoy.com." To find out more--or to purchase a copy of this book--click here.

Image: The Anatomy lesson of Dr Nicolaes Tulp, Remrandt van Rijn, 1632; found on Wikipedia. According to Quigley, the dissection was performed in Leiden’s anatomical theatre, and included an audience of townspeople that were left out of the painting. Instead, Rembrandt was paid to include surgeons who may or may not have actually been there.

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"Dissection as Studio Practice with Real Anatomical Specimens," Class with Laura Splan, Observatory, Next Monday, July 23

I am very excited about "Dissection as Studio Practice," a class taking place next Monday, July 23, at Observatory. Taught by artist Laura Splan, the class will begin with an illustrated survey of the use of notions of "dissection" in contemporary art practice; these principles will then be applied to in-class projects which include the dissection of your very own anatomical specimens (i.e. frog, sheep brain, cow eye). This class is open to all expernience levels, and participants are invited to bring additional materials, objects and artifacts that will inspire their “dissective” inclinations.

We had a wonderful time in the last iteration of this class, as you can see from the photos above. Full description of the class follows. Class size is limited; if interested, be sure to RSVP via email to morbidanatomy[at]gmail.com. You can see more of Laura Splan's work by clicking here. Hope very much to see you there!

Lecture and Studio Art and Dissection Class with artist Laura Splan
Date: Monday, July 23
Time: 7-10 PM
Fee: $75
*** Class size is limited to 16; please RSVP to morbidanatomy[at]gmail.com

This class is part of the
Morbid Anatomy Art Academy

This class will survey the use of dissection in contemporary art practice through an illustrated lecture, specimen dissections, and studio time for individual and collaborative projects. We will examine the conceptual and cultural significance of cutting, excavating, disassembling, labeling, observing and displaying “bodies.” The lecture will present a brief history of dissection as well as work by contemporary artists exploring imagery, tropes and methods of dissection. The collaborative and individual art projects will be fun and lively hands on explorations of the meaning of dissection in a work of art. Each student will receive a complete specimen dissection kit (i.e. frog, sheep brain, cow eye) to create a self-directed dissection project with. Participants should bring additional materials, objects and artifacts that will inspire their “dissective” inclinations. Additional supplies will be provided by the instructor to stimulate your creativity. No prior art training is required. Everyone is welcome.

Laura Splanis a Brooklyn based visual artist. Her mixed media work explores historical and cultural ambivalence towards the human body. She was a Visiting Lecturer at Stanford University where she taught “Art and Biology”. She has been a Visiting Artist at the New York Academy of Sciences, California College of Art, San Francisco Art Institute, Maryland Institute College of Art, and Cal Arts. Her artwork was recently commissioned by the CDC Foundation. She curates the visual portal DomesticatedViscera.com. Images of her artwork can be found on her website: LauraSplan.com. You can find out more here. Feel free to contact Laura through her website with any questions about the class by clicking here. You can see photos from the last class by clicking here.

You can find out more here, and RSVP with an email to morbidanatomy[at]gmail.com.

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Integrated analysis of hydrothermal flowthroughpretreatment

Background:
The impact of hydrothermal flowthrough (FT) pretreatment severity on pretreatment and solubilization performance metrics was evaluated for three milled feedstocks (corn stover, bagasse, and poplar) and two conversion systems (simultaneous saccharification and fermentation using yeast and fungal cellulase, and fermentation by Clostridium thermocellum).
Results:
Compared to batch pretreatment, FT pretreatment consistently resulted in higher xylan recovery, higher removal of non-carbohydrate components and higher glucan solubilization by simultaneous saccharification and fermentation (SSF). Xylan recovery was above 90% for FT pretreatment below 4.1 severity but decreased at higher severities, particularly for bagasse. Removal of non-carbohydrate components during FT pretreatment increased from 65% at low severity to 80% at high severity for corn stover, and from 40% to 70% for bagasse and poplar.Solids obtained by FT pretreatment were amenable to high conversion for all of the feedstocks and conversion systems examined. The optimal time and temperature for FT pretreatment on poplar were found to be 16 minutes and 210 oC. At these conditions, SSF glucan conversion was about 85%, 94% of the xylan was removed, and 62% of the non carbohydrate mass was solubilized.Solubilization of FT-pretreated poplar was compared for C. thermocellum fermentation (10% inoculum), and for yeast-fungal cellulase SSF (5% inoculum, cellulase loading of 5 and 10 FPU/g glucan supplemented with beta-glucosidase at 15 and 30 U/g glucan). Under the conditions tested, which featured low solids concentration, C. thermocellum fermentation achieved faster rates and more complete conversion of FT-pretreated poplar than did SSF. Compared to SSF, solubilization by C. thermocellum was 30% higher after 4 days, and was over twice as fast on ball-milled FT-pretreated poplar.
Conclusions:
Xylan removal trends were similar between feedstocks whereas glucan conversion trends were significantly different, suggesting that factors in addition to xylan removal impact amenability of glucan to enzymatic attack. Corn stover exhibited higher hydrolysis yields than bagasse or poplar, which could be due to higher removal of non-carbohydrate components. Xylan in bagasse is more easily degraded than xylan in corn stover and poplar. Conversion of FT-pretreated substrates at low concentration was faster and more complete for C.thermocellum than for SSF.Source:
http://www.biotechnologyforbiofuels.com/rss/

Biodiesel biorefinery: opportunities and challenges for microbial production of fuels and chemicals from glycerol waste

The considerable increase in biodiesel production worldwide in the last 5 years resulted in astoichiometric increased coproduction of crude glycerol. As an excess of crude glycerol hasbeen produced, its value on market was reduced and it is becoming a "waste-stream" insteadof a valuable "coproduct". The development of biorefineries, i.e. production of chemicals andpower integrated with conversion processes of biomass into biofuels, has been singled out asa way to achieve economically viable production chains, valorize residues and coproducts,and reduce industrial waste disposal. In this sense, several alternatives aimed at the use ofcrude glycerol to produce fuels and chemicals by microbial fermentation have beenevaluated. This review summarizes different strategies employed to produce biofuels andchemicals (1,3-propanediol, 2,3-butanediol, ethanol, n-butanol, organic acids, polyols andothers) by microbial fermentation of glycerol. Initially, the industrial use of each chemical isbriefly presented; then we systematically summarize and discuss the different strategies toproduce each chemical, including selection and genetic engineering of producers, andoptimization of process conditions to improve yield and productivity. Finally, the impact ofthe developments obtained until now are placed in perspective and opportunities andchallenges for using crude glycerol to the development of biodiesel-based biorefineries areconsidered. In conclusion, the microbial fermentation of glycerol represents a remarkablealternative to add value to the biodiesel production chain helping the development ofbiorefineries, which will allow this biofuel to be more competitive.Source:
http://www.biotechnologyforbiofuels.com/rss/

Expression of fatty acid and lipid biosynthetic genes in developing endosperm of Jatropha curcas

Background:
Temporal and spatial expression of fatty acid and lipid biosynthetic genes are associated with the accumulation of storage lipids in the seeds of oil plants. In jatropha (Jatropha curcas L.), a potential biofuel plant, the storage lipids are mainly synthesized and accumulated in the endosperm of seeds. Although the fatty acid and lipid biosynthetic genes in jatropha have been identified, the expression of these genes at different developing stages of endosperm has not been systemically investigated.
Results:
Transmission electron microscopy study revealed that the oil body formation in developing endosperm of jatropha seeds initially appeared at 28 days after fertilization (DAF), were actively developed at 42 DAF and reached to the maximum number and size at 56 DAF. Sixty-eight genes that encode enzymes, proteins or their subunits involved in fatty acid and lipid biosynthesis were identified from a normalized cDNA library of jatropha developing endosperm. Gene expression with quantitative reverse-transcription polymerase chain reaction analysis demonstrated that the 68 genes could be collectively grouped into five categories based on the patterns of relative expression of the genes during endosperm development. Category I has 47 genes and they displayed a bell-shaped expression pattern with the peak expression at 28 or 42 DAF, but low expression at 14 and 56 DAF. Category II contains 8 genes and expression of the 8 genes was constantly increased from 14 to 56 DAF. Category III comprises of 2 genes and both genes were constitutively expressed throughout endosperm development. Category IV has 9 genes and they showed a high expression at 14 and 28 DAF, but a decreased expression from 42 to 56 DAF. Category V consists of 2 genes and both genes showed a medium expression at 14 DAF, the lowest expression at 28 or 42 DAF, and the highest expression at 56 DAF. In addition, genes encoding enzymes or proteins with similar function were differentially expressed during endosperm development.
Conclusion:
The formation of oil bodies in jatropha endosperm is developmentally regulated. The expression of the majority of fatty acid and lipid biosynthetic genes is highly consistent with the development of oil bodies and endosperm in jatropha seeds, while the genes encoding enzymes with similar function may be differentially expressed during endosperm development. These results not only provide the initial information on spatial and temporal expression of fatty acid and lipid biosynthetic genes in jatropha developing endosperm, but are also valuable to identify the rate-limiting genes for storage lipid biosynthesis and accumulation during seed development.Source:
http://www.biotechnologyforbiofuels.com/rss/

Improved ethanol production by a xylose-fermenting recombinant yeast strain constructed through a modified genome shuffling method

Background:
Xylose is the second most abundant carbohydrate in the lignocellulosic biomass hydrolysate. The fermentation of xylose is essential for the bioconversion of lignocelluloses to fuels and chemicals. However the wild-type strains of Saccharomyces cerevisiae are unable to utilize xylose. Many efforts have been made to construct recombinant yeast strains to enhance xylose fermentation over the past few decades. Xylose fermentation remains challenging due to the complexity of lignocellulosic biomass hydrolysate. In this study, a modified genome shuffling method was developed to improve xylose fermentation by S. cerevisiae. Recombinant yeast strains were constructed by recursive DNA shuffling with the recombination of entire genome of P. stipitis with that of S. cerevisiae.
Results:
After two rounds of genome shuffling and screening, one potential recombinant yeast strain ScF2 was obtained. It was able to utilize high concentration of xylose (100 g/L to 250 g/L xylose) and produced ethanol. The recombinant yeast ScF2 produced ethanol more rapidly than the naturally occurring xylose-fermenting yeast, P. stipitis, with improved ethanol titre and much more enhanced xylose tolerance.
Conclusion:
The modified genome shuffling method developed in this study was more effective and easier to operate than the traditional protoplast fusion based method. Recombinant yeast strain ScF2 obtained in this was a promising candidate for industrial cellulosic ethanol production. In order to further enhance its xylose fermentation performance, ScF2 needs to be additionally improved by metabolic engineering and directed evolution.Source:
http://www.biotechnologyforbiofuels.com/rss/

Higher clusterin immunolabeling and sperm DNA damage levels in hypertensive men compared with controls

BACKGROUND

Clusterin, a heterodimeric glycoprotein found at several sites in the human male reproductive tract, could be a marker of morphologically abnormal spermatozoa, while TUNEL positivity indicates DNA fragmentation. Metabolic disorders such as diabetes mellitus and obesity may compromise sperm quality and fertility of men; however, little evidence specifically links hypertension with the impairment of male reproductive function.

METHODS

By flow cytometric, immunofluorescence (TUNEL assay and clusterin immunolabeling) and immunohistochemical (peroxidase-streptavidin method) analyses, we have compared both clusterin- and TUNEL labeling in ejaculated spermatozoa from healthy normotensive donors and hypertensive subjects with the purpose to reveal possible differences between the two conditions.

RESULTS

Data analysis from the normotensive (n = 25) and hypertensive subjects (n = 25) demonstrate a significant correlation between high levels of clusterin immunolabeling and the presence of sperm DNA damage, which is often associated with abnormal morphology. In the normotensive subjects, a low percentage (15.3 ± 4.5) of spermatozoa positive for high levels of clusterin was detected; however, this percentage significantly increased (30.9 ± 13.0) (P < 0.01) in hypertensive subjects. Standard semen evaluations does not reveal any significant differences between the two groups of subjects, except for a reduced forward motility and lower sperm vitality in the hypertensive subjects.

CONCLUSIONS

This pilot study strongly suggests a relationship between hypertension and markers indicative of poor sperm quality. In hypertensive subjects, high levels of clusterin immunolabeling identified a consistent fraction of ejaculated spermatozoa carrying both DNA fragmentation and strong morphological alterations, which was not correlated with age or with sperm cell mortality. The alternative possibility that sperm damage observed is due to adverse effects of anti-hypertensive drugs does not find support in the literature nor in the drug data sheets. The relationship observed between hypertension and human semen represents a novel and possibly relevant information to be considered in the study of male fertility.

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

Development of a novel synthetic oligopeptide for the detection of DNA damage in human spermatozoa

BACKGROUND

The integrity of DNA in spermatozoa is considered an additional parameter of semen quality and a potential fertility predictor. Significant progress has been made in recent years towards the development of reliable tests for sperm chromatin integrity and DNA damage assessment. However, most of the techniques available are labor intensive, require expensive instrumentation or utilize enzymes whose activity could be compromised by the highly condensed nature of sperm chromatin. In addition, all the methods currently available involve the destruction of the sperm tested; none is able to select intact spermatozoa that could then be used for fertilization. The aim of the present study was to create a peptide ligand-based stain, capable of binding specific DNA structures, thereby revealing the presence of DNA damage, preferably in living cells.

METHODS

The peptide was bioinformatically modelled on the critical region of the p53 protein associated with DNA binding and fluorescently labeled with a terminal rhodamine B dye. The ability of this 21 amino acid synthetic peptide (DW1) to detect DNA damage in intact and fixed human spermatozoa was assessed in detail. Human sperm samples (n = 20) were treated with reagents that induce single- and/or double-stranded DNA breaks. The effect of these treatments on peptide-labelling was measured and compared with results obtained using established tests for the evaluation of DNA damage, such as comet assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and sperm chromatin dispersion test.

RESULTS

The peptide had a high affinity for single-stranded DNA, and DNA lesions such as double- and single-stranded breaks. The proportion of spermatozoa with intense staining was found to be closely associated with the percentage of cells possessing DNA damage. The analysis of 10 sperm samples using DW1 staining and TUNEL technique showed a significant correlation between the extent of DNA fragmentation for the two methods (r = 0.892, Pearson's correlation, P< 0.05).

CONCLUSIONS

We have produced a novel peptide-based stain capable of detecting DNA damage in individual sperm cells. Evaluation of sperm DNA fragmentation using this peptide may be an inexpensive and easier to use alternative to the tests in current use. Additionally, although DW1 currently requires removal of the membrane using a detergent, further research may allow this approach to be applied to the selection of viable spermatozoa with intact DNA for use in ICSI and/or intra-cytoplasmic morphologically selected sperm injection.

Source:
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Is there an association between HOST grades and sperm quality?

BACKGROUND

Intracytoplasmic sperm injection (ICSI) is the primary treatment for male infertility. However for this procedure, with the exception of visual morphological selection, there is no standardization for sperm selection. Recently, the hypo-osmotic swelling test (HOST) has been proposed to potentially select sperm with intact membranes. The aim of this study is to evaluate the ability of this technique to select functional sperm in terms of apoptosis and morphology, as well as nuclear integrity.

METHODS

A total of 20 semen samples were randomly collected from men who attended the Andrology Unit of the Isfahan Fertility and Infertility Center. Semen samples were washed and exposed to hypotonic conditions, before being fixed and simultaneously assessed for membrane integrity as well as abnormal morphology, DNA fragmentation and protamine deficiency by using Papanicolaou, TUNEL and CMA3 staining techniques, respectively. The remaining semen samples were washed with calcium buffer and stained by Annexin V, then exposed to hypotonic conditions before being assessed for early apoptosis along with membrane integrity.

RESULTS

HOST grade ‘d’, followed by grade ‘c’, showed the highest percentages of healthy sperm, whereas sperm of HOST grade ‘g’ in which anomalies in terms of apoptosis, abnormal head morphology or nuclear immaturity or membrane damage, were most frequently observed in the samples assessed.

CONCLUSIONS

Integration of HOST into the sperm selection procedure may provide a valuable tool for selection of functional sperm required for ICSI. According to this study, insemination of HOST grade ‘g’ sperm should be avoided during ICSI.

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

Epidermal growth factor regulates connexin 43 in the human epididymis: role of gap junctions in azoospermia

BACKGROUND

Gap junctions (GJs) allow for direct communication between adjacent cells. They are composed of connexons consisting of transmembrane proteins, connexins (Cxs). The objectives of this study were to determine if GJ proteins GJA1 (Cx43), GJB1 (Cx32) and GJB2 (Cx26) are present in the epididymis of men with a normal epididymis, to assess whether or not Cx expression and localization are altered in azoospermic patients, and to determine if epidermal growth factor (EGF) regulates GJA1 expression.

METHODS

Epididymides were obtained from men with localized testis cancer with active spermatogenesis and histologically normal epididymal tubule (group 1), men with non-obstructive azoospermia secondary to Sertoli-cell only syndrome (group 2) and from azoospermic men with normal spermatogenesis and epididymal obstruction (group 3). Epididymides were subdivided into three segments: caput, corpus and cauda. Quantitative real-time RT–PCR was performed to assess GJA1, GJB1, GJB2 and EGF receptor (EGFR) mRNA levels in epididymides from patients from each group (all n= 3, except n= 1 for caput blockage). A human caput epididymal cell line was then used to determine the role of EGFR signaling on the regulation of human epididymal GJA1.

RESULTS

Real-time RT–PCR analysis revealed that GJA1, GJB1, GJB2 and EGFR were expressed along the human epididymis. In the cauda epididymidis of group 2 and 3 men, we observed a significant decrease in GJA1 (P= 0.0456 and P= 0.0465, respectively) and GJB1 (P= 0.0450 and P= 0.0497, respectively) mRNA levels when compared with group 1 men. We also observed a decrease in EGFR mRNA levels (P= 0.0358) in the cauda epididymidis of group 3 men when compared with group 1. Immunocytochemistry revealed that in the epididymis, GJA1 and EGFR were localized between basal and principal cells and between adjacent principal cells. In group 2 and 3 patients, however, we noted a dramatic increase in cytosolic immunostaining for both GJA1 and EGFR in both principal and basal cells. Using a human caput epididymal cell line derived from fertile men, we demonstrated that changes in GJA1 phosphorylation could be regulated by EGF (P= 0.015) and the extracellular regulated kinase 1/2 signaling pathway (P= 0.03). Furthermore, while the phosphoinositide-3-kinase (PI3K)/AKT signaling pathway did not alter GJA1 phosphorylation, treatment with PI3K/AKT inhibitor LY294002 significantly (P= 0.024) inhibited the EGF-stimulated increase in GJA1 total protein levels at 24 h. Immunolocalization indicated that loss of PI3K/AKT signaling was associated with increased cytosolic localization of Cx43 in this cell line.

CONCLUSIONS

Together, these data suggest that in azoospermic men decreased expression of EGFR may be responsible for decreasing GJA1 levels and increasing its cytosolic localization via the PI3K/AKT signaling pathway.

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Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage

BACKGROUND

We previously found that a normal karyotype in a previous miscarriage is a predictor of subsequent miscarriage. However, the prevalence of recurrent miscarriage caused by an abnormal embryonic karyotype has not yet been reported, since embryonic karyotype is not typically analyzed during conventional examinations.

METHODS

A total of 482 patients who underwent both embryonic karyotype determination and conventional examinations for recurrent miscarriage were enrolled in this study. The distribution of the causes and the live birth rate for each cause were examined.

RESULTS

The total percentage of subjects in whom conventional causes of recurrent miscarriage could be detected was 29.5%. The prevalence of the abnormal embryonic karyotype was 41.1% in the subjects in whom no conventional causes of miscarriage could be identified. The prevalence of recurrent miscarriage of truly unexplained cause, that is, of subjects without conventional causes in whom the embryonic karyotype was ascertained to be normal, was 24.5%. Among the patients in whom the first determination revealed an abnormal embryonic karyotype, 76.2% (32/42) showed an abnormal embryonic karyotype in the repeat determination as well. The cumulative live birth rate (71.9%) in women with recurrent miscarriages caused by the abnormal embryonic karyotype was significantly higher than that (44.7%) in women with recurrent miscarriages associated with the embryonal euploidy.

CONCLUSION

An abnormal embryonic karyotype was found to represent the commonest cause of recurrent miscarriage, and the percentage of cases with recurrent miscarriage of truly unexplained cause was limited to 24.5%.The two groups should be distinguished for both clinical and research purposes.

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Day 3 embryo selection by metabolomic profiling of culture medium with near-infrared spectroscopy as an adjunct to morphology: a randomized controlled trial

STUDY QUESTION

Is the selection of a single Day 3 embryo by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology able to improve live birth rates in IVF, compared with embryo selection by morphology alone?

SUMMARY ANSWER

The live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryos were selected by morphology alone.

WHAT IS KNOWN ALREADY

The elevated incidence of pregnancy and neonatal problems associated with a high-twinning rate after IVF can only be successfully reduced by the transfer of one embryo. Current embryo assessment methods are unable to accurately predict the reproductive potential of an individual embryo. Today, a number of techniques are said to be more accurate at selecting the best embryo. One of these new technologies is metabolomic profiling of spent embryo culture media with the use of NIR spectroscopy.

STUDY DESIGN, SIZE AND DURATION

A double-blind, randomized controlled trial was conducted between 2009 and 2011, and included 417 couples undergoing IVF with a single embryo transfer. Randomization was performed centrally just before Ovum Pick-Up (OPU), using a computerized randomization program. Both patient and physician were unaware of the treatment allocation. To ensure blinding, the allocations were placed in consecutively numbered, opaque envelopes. Patients were randomized (1:1) into either the control group (embryo selection by morphology only) or the treatment group (embryo selection by morphology plus NIR spectroscopy of embryo culture medium).

PARTICIPANTS/MATERIALS, SETTING AND METHODS

At OPU, 208 patients were randomized to the morphology only group and 209 patients were randomized to the morphology plus viability score group. On Day 3, 163 patients in the control group and 146 patients in the treatment group met the inclusion criteria. The study was conducted in an academic hospital with IVF laboratory and three non-academic hospitals.

MAIN RESULTS AND THE ROLE OF CHANCE

Patient demographics and baseline characteristics were distributed equally over the two groups, except for embryo fragmentation, which was significantly higher in the treatment group. In the intention to treat analysis, the live birth rates were 31.7 and 26.8% for the control group and the treatment group, respectively (relative risk 0.84; 95% confidence interval 0.63–1.14, P = 0.27). In the per protocol analysis, the live birth rates were 31.3 and 29.5% for the control group and the treatment group, respectively (relative risk 0.94; 95% confidence interval 0.67–1.32, P = 0.73). For the treatment group, the embryological technician's independent choice (by morphology) of which embryo to transfer was recorded 138 times. In 75.4% (104 of 138) of the transfers, the embryo with the best morphology did not have the highest viability score. The live birth rate of these 104 transferred embryos was 30.8%.

LIMITATIONS, REASONS FOR CAUTION

A possible limitation of our study is the pre-selection of all embryos by morphology and dividing the cohort of available embryos into two groups: good quality embryos and poor quality embryos. As a consequence, we have probably selected for a better prognosis patient group.

WIDER IMPLICATIONS OF THE FINDINGS

To avoid the use of incompetent embryo selection tools at the expense of the patient, an evidence-based proof of clinical usefulness is essential before the implementation of new diagnostic tools in IVF laboratories.

TRIAL REGISTRATION NUMBERS

Dutch Trial Registry, registry number NTR1178.

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Trends and factors associated with the Day 5 embryo transfer, assisted reproductive technology surveillance, USA, 2001-2009

STUDY QUESTION

What characteristics are associated with a Day 5 embryo transfer?

SUMMARY ANSWER

The use of the Day 5 embryo transfer has increased over time, with clinicians allowing women with typically ‘poorer’ prognostic characteristics to undergo a Day 5 embryo transfer. The mean number of embryos per Day 5 transfer decreased from 2001 to 2009, although the prevalence of the Day 5 single embryo transfer remains low and the rate of multiple births remains substantial.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS

Day 5 embryo transfer may reduce the rate of multiple gestation pregnancy. US trends over time in the prevalence of the Day 5 transfer, changes in characteristics of patients receiving Day 5 transfer, and number of embryos transferred are unknown.

DESIGN

We used 2001–2009 US National assisted reproductive technology (ART) Surveillance System (NASS) data on 620 295 fresh IVF cycles derived from autologous oocytes with a Day 3 or 5 embryo transfer. Trends in the mean number of embryos transferred from 2001 to 2009 were assessed by the day of transfer. For 349 947 cycles from clinics performing both Days 3 and 5 embryo transfers, multivariable logistic regression was used to determine the characteristics associated with the Day 5 embryo transfer. We also compared the characteristics of the Day 5 embryo cycles in 2001 and 2009.

MAIN RESULTS AND THE ROLE OF CHANCE

Overall, the proportion of ART cycles using the Day 5 embryo transfer increased from 12% in 2001 to 36% in 2009 (P< 0.0001), while the mean number of embryos transferred decreased from 2.4 to 2.1 (P< 0.0001). Among Day 5 transfers, the rate of the single embryo transfer tripled from 4.5% in 2001 to 14.8% in 2009 (P< 0.0001); and the rate of multiple births decreased from 44.8 to 41.1% (P< 0.0001). In cycles initiated after 2001, maternal age <35 years, no prior ART cycles, ≥1 prior pregnancies, baseline follicle stimulating hormone <10 international units and ≥10 oocytes retrieved were associated with the Day 5 embryo transfer. Compared with 2001, in 2009, a broader range of candidates received the Day 5 transfer.

BIAS

Women undergoing multiple ART cycles over time are not linked.

CONFOUNDING FACTORS AND OTHER REASONS FOR CAUTION

We ran multivariable logistic regression to lessen the effects of the confounding factors. Cycle cancelation rates by the day of embryo transfer are unknown.

GENERALIZABILITY TO OTHER POPULATIONS

Generalizable to ART clinics included in NASS.

STUDY FUNDING/COMPETING INTERESTS

This study was funded by the Centres for Disease Control. The authors have no competing interests to declare.

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Body mass index and central adiposity are associated with sperm quality in men of subfertile couples

BACKGROUND

The incidence of overweight and obesity in men of reproductive ages is rising, which may affect fertility. Therefore, this study aims to assess the associations between BMI, central adiposity and sperm parameters in men of subfertile couples.

METHODS

Ejaculate volume (ml), sperm concentration (millions per ml), percentage of progressive motile and immotile spermatozoa and total motile sperm count (millions) were measured in 450 men of subfertile couples visiting a tertiary outpatient clinic for reproductive treatment and preconception counseling.

RESULTS

Overweight was negatively associated with the percentage of progressive motility type A [β –0.32 (SE 0.2), P = 0.036] and positively associated with the percentage of immotility type C [β 0.21 (SE 0.07), P = 0.002]. Obesity was negatively associated with ejaculate volume [β –0.23 (SE 0.1), P = 0.02], sperm concentration [β –0.77 (SE 0.3), P = 0.006] and total motile sperm count [β –0.91 (SE 0.3), P = 0.007]. Waist circumference ≥102 cm, a measure for central adiposity, was inversely associated with sperm concentration [β –0.69 (SE 0.2), P = 0.001] and total motile sperm count [β –0.62 (SE 0.3), P = 0.02]. All associations remained significant after adjustment for age, ethnicity, active and passive smoking, alcohol and medication use and folate status.

CONCLUSIONS

This study shows that in particular, sperm concentration and total motile sperm count in men of subfertile couples are detrimentally affected by a high BMI and central adiposity. The effect of weight loss on sperm quality and fertility needs further investigation.

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

Inhibition of glycogen synthase kinase-3 promotes efficient derivation of pluripotent stem cells from neonatal mouse testis

BACKGROUND

Several studies have demonstrated the derivation of multi- or pluripotent stem cells from testicular cells of both newborn and adult mice by a spontaneous conversion process, when these cells are cultured in vitro for an extended time. To obtain a better and robust derivation, we have attempted to identify small molecules (SMs) that induce reprogramming of testicular cells in culture into germline-derived pluripotent stem cells (gPSCs).

METHODS

We tested several SMs based on previous reports that have shown enhancement of establishment of induced pluripotent stem cells or embryonic stem cells (ESCs) on mouse NMRI (outbred strain) and C57BL/6 (inbred strain) testicular cells. After appearance of ESC-like colonies at Day 6, they were passaged on mitotically arrested mouse embryonic fibroblasts in mouse ESC medium in the absence or presence of SMs up to Day 14. The generated cells were characterized using a variety of experimental approaches.

RESULTS

The application of several SMs involved in pluripotent reprogramming led to the discovery that CHIR99021 (CHIR), a glycogen synthase kinase-3 (GSK-3) inhibitor, promotes efficient derivation of gPSCs from neonatal mouse NMRI and C57BL/6 testes. The pluripotency of the generated cell lines has been confirmed by in vitro spontaneous and direct differentiation toward cardiac and neural lineages, and formation of chimeras after injection of gPSCs into blastocysts. We have shown that the generated gPSCs could be maintained and expanded under chemically defined serum and feeder-free conditions by inhibition of both the extracellular signal-regulated kinases (Erk1/2) and GSK-3.

CONCLUSIONS

To our knowledge, this is the first report of a simple and efficient protocol to reprogram gPSCs from testicular cells solely by inhibition of GSK-3 in two strains of mice with different genetic backgrounds. Additionally, this brings us closer to eliminating the need for genetic modification in pluripotent reprogramming. Future studies will determine whether the inhibition of GSK-3 could affect the generation of naïve gPSCs lines in other mammals.

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