Growing teeth from urine-harvested stem cells.


Chinese scientists develop a method for growing new teeth from stem cells generated from urine.

People lose teeth for all sorts of reasons, whether it’s through neglect, age, or sports injuries. A team of Chinese scientists from the Guangzhou Institute of Biomedicine and Health is working on an unusual way to replace those missing chompers.

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The researchers derived stem cells from urine as a starting point. The experiment involved combining those stem cells with material from mice. Implanting it back into mice resulted in the growth of what looks like little teeth.

“The tooth-like structure contained dental pulp, dentin, enamel space, and enamel organ,” the researchers reported.

If you’re a fan of science paper titles, this is a good one: “Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells.” The research was published in Cell Regeneration.

teeth2

The results are rudimentary at this point. The harvested teeth are not as strong as regular teeth, but the scientists are hopeful that the work could one day lead to “the final dream of total regeneration of human teeth for clinical therapy.”

It’s conceivable people in the future could receive implants that allow them to grow new teeth. There just might be some concern over using urine to get there.

Source: Annals of Improbable Research

 

 

 

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Smart Metal Artifact Reduction (MAR).


Exceptional image quality brings treatment plans clearly into focus.

 

double-hip-replacement-before-clinical

Source: gehealthcare.com

Radioactive seed localization for non-palpable breast cancer.


Radioactive seed localization (RSL) is an alternative to wire localization for guiding surgical excision of non-palpable breast cancer. This review provides an overview of the available evidence on the accuracy of RSL in patients undergoing breast-conserving surgery.

METHODS: PubMed, Embase and the Cochrane Library were searched systematically in January 2012 for studies that addressed localization of non-palpable breast cancer using an iodine-125-labelled seed. Studies were deemed eligible if they reported on the proportion of patients with tumour-positive margins after RSL, the proportion of patients needing re-excision after RSL, and procedural complications.
RESULTS: Six studies reported data on RSL in 1611 patients with non-palpable breast lesions. Overall complete resection rates ranged from 73 to 96.7 per cent. Three studies included over 300 patients, and complete resection rates in these studies varied between 89.5 and 96.7 per cent. The risk of seed migration and failure of seed placement ranged from 0 to 0.6 per cent and 0 to 7.2 per cent respectively.
CONCLUSION: Available scientific evidence suggests that RSL is a safe and accurate technique for localization of non-palpable breast lesions.

Source: British journal Of Surgery

 

Topiramate for the prophylaxis of episodic migraine in adults. .


 Some antiepileptic drugs but not others are useful in clinical practice for the prophylaxis of migraine. This might be explained by the variety of actions of these drugs in the central nervous system. The present review is part of an update of a Cochrane review first published in 2004, and previously updated (conclusions not changed) in 2007.

OBJECTIVES: To describe and assess the evidence from controlled trials on the efficacy and tolerability of topiramate for preventing migraine attacks in adult patients with episodic migraine. SEARCH
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2012, Issue 12), PubMed/MEDLINE (1966 to 15 January 2013), MEDLINE In-Process (current week, 15 January 2013), and EMBASE (1974 to 15 January 2013) and handsearched Headache and Cephalalgia through January 2013.
SELECTION CRITERIA: Studies were required to be prospective, controlled trials of topiramate taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. For headache frequency data, we calculated mean differences (MDs) between topiramate and comparator (placebo, active control, or topiramate in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with >/= 50% reduction in headache frequency), we calculated odds ratios (ORs) and, in select cases, risk ratios (RRs); we also calculated numbers needed to treat (NNTs). We calculated MDs for selected quality of life instruments. Finally, we summarised data on adverse events from placebo-controlled trials and calculated risk differences (RDs) and numbers needed to harm (NNHs).
MAIN RESULTS: Twenty papers describing 17 unique trials met the inclusion criteria. Analysis of data from nine trials (1737 participants) showed that topiramate reduced headache frequency by about 1.2 attacks per 28 days as compared to placebo (MD -1.20; 95% confidence interval (CI) -1.59 to -0.80). Data from nine trials (1190 participants) show that topiramate approximately doubled the proportion of responders relative to placebo (RR 2.02; 95% CI 1.57 to 2.60; NNT 4; 95% CI 3 to 6). Separate analysis of different topiramate doses produced similar MDs versus placebo at 50 mg (-0.95; 95% CI -1.95 to 0.04; three studies; 520 participants), 100 mg (-1.15; 95% CI -1.58 to -0.71; six studies; 1620 participants), and 200 mg (-0.94; 95% CI -1.53 to -0.36; five studies; 804 participants). All three doses significantly increased the proportion of responders relative to placebo; ORs were as follows: for 50 mg, 2.35 (95% CI 1.60 to 3.44; three studies; 519 participants); for 100 mg, 3.49 (95% CI 2.23 to 5.45; five studies; 852 participants); and for 200 mg, 2.49 (95% CI 1.61 to 3.87; six studies; 1025 participants). All three doses also significantly improved three or more domains of quality of life as compared to placebo. Meta-analysis of the three studies that included more than one dose of topiramate suggests that 200 mg is no more effective than 100 mg. With regard to mean headache frequency and/or responder rate, seven trials using active comparators found (a) no significant difference between topiramate and amitriptyline (one study, 330 participants); (b) no significant difference between topiramate and flunarizine (one study, 83 participants); (c) no significant difference between topiramate and propranolol (two studies, 342 participants); (d) no significant difference between topiramate and relaxation (one study, 61 participants); but (e) a slight significant advantage of topiramate over valproate (two studies, 120 participants). Relaxation improved migraine-specific quality of life significantly more than topiramate. In trials of topiramate against placebo, seven adverse events (AEs) were reported by at least three studies. These were usually mild and of a non-serious nature. Except for taste disturbance and weight loss, there were no significant differences in the frequency of AEs in general, or of the seven specific AEs, between placebo and topiramate 50 mg. AEs in general and all of the specific AEs except nausea were significantly more common on topiramate 100 mg than on placebo, with NNHs varying from 3 to 25, and the RDs versus placebo were even higher for topiramate 200 mg, with NNHs varying from 2 to 17.
AUTHORS’ CONCLUSIONS: Meta-analysis demonstrates that topiramate in a 100 mg/day dosage is effective in reducing headache frequency and reasonably well-tolerated in adult patients with episodic migraine. This provides good evidence to support its use in routine clinical management. More studies designed specifically to compare the efficacy or safety of topiramate versus other interventions with proven efficacy in the prophylaxis of migraine are needed.

Source: Cochrane

 

A Randomized, Double-Blind, Controlled Trial Comparing Rifaximin Plus Lactulose With Lactulose Alone in Treatment of Overt Hepatic Encephalopathy. .


Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Drugs used in the treatment of HE are primarily directed at the reduction of the blood ammonia levels. Rifaximin and lactulose have shown to be effective in HE. We evaluated the efficacy and safety of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE.

METHODS:In this prospective double-blind randomized controlled trial, 120 patients with overt HE were randomized into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63) and group B (lactulose (n=57) plus placebo). The primary end point was complete reversal of HE and the secondary end points were mortality and hospital stay.
RESULTS:A total of 120 patients (mean age 39.4+/-9.6 years; male/female ratio 89:31) were included in the study. 37 (30.8%) patients were in Child-Turcotte-Pugh (CTP) class B and 83 (69.2%) were in CTP class C. Mean CTP score was 9.7+/-2.8 and the MELD (model for end-stage liver disease) score was 24.6+/-4.2. At the time of admission, 22 patients (18.3%) had grade 2, 40 (33.3%) had grade 3, and 58 (48.3%) had grade 4 HE. Of the patients, 48 (76%) in group A compared with 29 (50.8%) in group B had complete reversal of HE (P<0.004). There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8% vs. 49.1%, P<0.05). There were significantly more deaths in group B because of sepsis (group A vs. group B: 7:17, P=0.01), whereas there were no differences because of gastrointestinal bleed (group A vs. group B: 4:4, P=nonsignificant (NS)) and hepatorenal syndrome (group A vs. group B: 4:7, P=NS). Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8+/-3.4 vs. 8.2+/-4.6 days, P=0.001).
CONCLUSION:Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.

Source: American  Journal  Gastroenterology

 

Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis.


 

Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but their effects on mortality and cardiovascular outcomes are unknown. We aimed to update our meta-analysis on the effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease.
METHODS: We did a systematic review of articles published in any language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase, International Pharmaceutical Abstracts, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. We included all randomised and non-randomised trials that compared outcomes between patients with chronic kidney disease taking calcium-based phosphate binders with those taking non-calcium-based binders. Eligible studies, determined by consensus with predefined criteria, were reviewed, and data were extracted onto a standard form. We combined data from randomised trials to assess the primary outcome of all-cause mortality using the DerSimonian and Laird random effects model.
FINDINGS: Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0.78, 95% CI 0.61-0.98).
INTERPRETATION: Non-calcium-based phosphate binders are associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in patients with chronic kidney disease. Further studies are needed to identify causes of mortality and to assess whether mortality differs by type of non-calcium-based phosphate binder.

 

Comments from Clinical Raters

Nephrology

Novel and potentially practice-changing. We currently use calcium-based phosphate binders to control lab abnormalities, usually switching to sevalamer when hypercalcaemia becomes an issue. This review shows that the mortality in RCTs is higher in people treated with calcium binders rather than sevalamer. Whether sevalamer is protective or calcium binders harmful is not addressed by this work, and there are no data to answer this important question. The cost of sevalamer compared with calcium is another important issue. We also do not know whether the harms associated with calcium could be mitigated by a different strategy with the calcium concentration in the dialysate. Finally, this meta-analysis has substantial heterogeneity, only 70 events separating the groups, and borderline statistical significance. Is this good enough evidence on which to change practice?

Nephrology

Although previous meta-analyses suggested similar results favouring non-calcium-containing phosphate binders on patient survival, this update appears to confirm it. It, therefore, has a stronger message about the need for changing clinical practice about first-choice phosphate binders. I do not necessarily agree with the phrasing in the conclusion about harm of calcium-containing phosphate binders per se, since many patients do not always like or tolerate the first-choice binder and could end up requiring a calcium-containing binder that nevertheless is probably better than not taking any binding at all. A good quality meta-analysis.

Source: Lancet

 

Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer.


Ovarian cancer is the eighth most common cancer in women and it is usually diagnosed at an advanced stage. The majority of ovarian tumours are epithelial in origin. Women with relapsed epithelial ovarian cancer (EOC) often have a reduced performance status with a limited life expectancy, therefore maintaining quality of life with effective symptom control is the main purpose of treatment. Drug treatment of relapsed disease is directed by the platinum-free interval: relapsed platinum-sensitive disease is usually re-treated with platinum-based therapy and platinum-resistant disease challenged with non-platinum drugs. However, the side-effects of chemotherapy agents may be severe and optimal treatment regimens are unclear. Pegylated liposomal doxorubicin (PLD), which contains a cytotoxic drug called doxorubicin hydrochloride is one of several treatment modalities that may be considered for single-agent treatment of relapsed EOC, or used in combination with other drugs. 

OBJECTIVES: To assess the efficacy and safety of PLD in women with relapsed epithelial ovarian cancer (EOC). SEARCH
METHODS: We searched the Cochrane Gynaecological Cancer Group (CGCG) trials register, CENTRAL, MEDLINE and EMBASE from 1990 to February 2013. We also searched online registers of clinical trials, abstracts of scientific meetings and reference lists of included studies.
SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated PLD in women diagnosed with relapsed epithelial ovarian cancer.
DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data to a pre-designed data collection form and assessed the risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions guidelines. Where possible, we pooled collected data in meta-analyses using RevMan 5.2 software.
MAIN RESULTS: We included 14 RCTs that evaluated PLD alone or in combination with other drugs. Four RCTs contributed no data to the meta-analyses. Two studies compared PLD plus carboplatin (carbo) to paclitaxel (PAC)/carbo in women with platinum-sensitive relapsed EOC. Overall survival (OS) was similar for these treatments, however progression-free survival (PFS) was longer with PLD/carbo (1164 participants; hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.74 to 0.97; I(2) = 7%; P value 0.01). PLD/carbo was associated with significantly more anaemia and thrombocytopenia than PAC/carbo, whereas PAC/carbo was associated with significantly more alopecia, neuropathies, hypersensitivity reactions and arthralgias/myalgias. PLD/carbo was well-tolerated and women receiving this treatment were significantly less likely to discontinue treatment than those receiving PAC/carbo (two studies, 1150 participants; risk ratio (RR) 0.38, 95% CI 0.26 to 0.57; I(2) = 0%; P < 0.00001).Five studies compared other agents to PLD alone. None of these agents were associated with significantly better survival or severe adverse-event profiles than PLD. Topotecan and gemcitabine were associated with significantly more haematological severe adverse events than PLD, and patupilone was associated with significantly more severe neuropathies and diarrhoea. Severe hand-foot syndrome (HFS) occurred consistently more frequently with PLD than the other drugs.Three studies compared PLD combination treatment to PLD alone. Two combinations resulted in a significantly longer PFS compared with PLD alone: trabectedin (TBD)/PLD (one study, 672 women; HR 0.79, 95% CI 0.65 to 0.96; P value 0.02) and vintafolide (EC145)/PLD (one study, 149 women; HR 0.63, 95% CI 0.41 to 0.97; P value 0.04). TBD/PLD appeared to benefit the partially platinum-sensitive subgroup only. Further studies are likely to have an important impact on our confidence in these estimates. TBD/PLD was associated with significantly more haematological and gastrointestinal severe adverse events than PLD alone, whereas EC145/PLD appeared to be well-tolerated.For platinum-resistant relapsed EOC, the median PFS and OS for single-agent PLD across seven included studies was 15 weeks and 54 weeks, respectively. Severe HFS occurred significantly more frequently in women receiving a 50 mg/m(2) dose of PLD than those receiving less than 50 mg/m(2) (17% versus 2%, respectively; P value 0.01).
AUTHORS’ CONCLUSIONS: In platinum-sensitive relapsed epithelial ovarian cancer, PLD/carbo is more effective than PAC/carbo and is better tolerated; PLD/carbo should therefore be considered as first-line treatment in women with platinum-sensitive relapsed EOC. PLD alone is a useful agent for platinum-resistant relapsed EOC, however it remains unclear how it compares with other single agents for this subgroup and in what order these agents should be used. There is insufficient evidence to support the use of PLD in combination with other agents in platinum-resistant relapsed EOC.

Source: Cochrane Database

Mystery of Earth’s radiation belts solved.


Van Allen belts accelerate their own particles rather than just trapping them.

The two concentric rings of high-speed particles that encircle the Earth are finally giving up the secrets of their origin — 55 years after their discovery. Two NASA probes have found evidence that the Van Allen belts, as the rings are known, are responsible for accelerating the particles, rather than collecting energetic particles that originated elsewhere. Space scientists think that their latest findings1 could also account for the even more energetic belts circling Saturn and Jupiter, as well as high-energy radiation associated with worlds beyond the Solar System and even some Sun-like stars.

NASA_twin storm probes 711904main_rbsp-in-orbit-orig_full

For several years after 1958 — when space scientist James Van Allen and his colleagues identified the radiation belts that now bear his name, using instruments aboard the first US space mission — researchers theorized that the rings’ electrons came from distant reaches of Earth’s magnetosphere, the bubble of space dominated by the planet’s magnetic field. They proposed that as the particles drifted closer to Earth and encountered stronger magnetic fields, they would accelerate and settle into a ring-like configuration.

But this type of acceleration process would take days to weeks and best describes radiation belts that vary only gradually over time. In the 1990s, satellites began to reveal that the energy and density of the Van Allen belts changed more quickly. As a result, a competing theory for the origin of the belts’ electrons began to take hold: that charged particles do not come from afar, but are produced locally, when electric fields within the belts rip electrons off from wandering atoms and accelerate those electrons to nearly the speed of light. This process could alter the density and energy of the belts on scales of seconds to hours, a theory that matched better with the observations from the 1990s.

However, the satellite observations were still too sparse and the craft were not designed to measure rapidly changing properties of the belts at different locations — as would be needed to fully distinguish between the two proposed acceleration mechanisms, says space scientist Harlan Spence of the University of New Hampshire in Durham, a co-author of the study.

That data gap drastically narrowed with the August 2012 launch of NASA’s Van Allen Probes, two identical satellites that simultaneously study the belts from different locations and viewing angles. In early October, a week after a solar storm had depleted the outermost belt of most of its electrons, the two probes recorded a nearly 1,000-fold jump in electron density in less than 12 hours. The twin set of observations clinches the case for electric fields within the belt accelerating the electrons, Spence says.

Heart of the matter

“We have in this one event been able to really distinguish between the different ways that particles can be accelerated,” says Spence. “The radiation belts were the first discovery of the space age,” he adds, “and it’s just really exciting with the Van Allen probes to have seen right to the heart of the process.”

The measurements “clearly show that substantial particle acceleration can occur locally in the heart of the radiation belts”, comments space physicist David McComas of the Southwest Research Institute in San Antonio, Texas, who was not involved in the study.

Spence suggests that the frequency of some of the electromagnetic waves in the belt matches the frequency at which electrons travel around the local magnetic field, a synchrony that makes it easy to rev up the charged particles.

Local acceleration of energetic particles is a general physical process, notes McComas, “so if it occurs in the heart of the Earth’s Van Allen belts, it also probably does so in the more intenseradiation belts around Jupiter and Saturn and even in planets around magnetized stars beyond the Solar System.” Stars that radiate a high concentration of X-rays and have magnetic fields shaped like that of Earth’s — which is essentially a large bar magnet — may be candidates for sporting a similar acceleration process, Spence adds.

Source: Nature

Gastric bypass makes gut burn sugar faster.


Diabetic rats control blood glucose better after weight-loss surgery.

A procedure increasingly used to treat obesity by reducing the size of the stomach also reprogrammes the intestines, making them burn sugar faster, a study in diabetic and obese rats has shown.

If the results, published today in Science1, hold true in humans, they could explain how gastric bypass surgery improves sugar control in people with diabetes. They could also lead to less invasive ways to produce the same effects.

“This opens up the idea that we could take the most effective therapy we have for obesity and diabetes and come up with ways to do it without a scalpel,” says Randy Seeley, an obesity researcher at the University of Cincinnati in Ohio, who was not involved in the work.

As rates of obesity and diabetes skyrocket in many countries, physicians and patients are turning to operations that reconfigure the digestive tract so that only a small part of the stomach is used. Such procedures are intended to allow people to feel full after smaller meals, reducing the drive to consume extra calories. But clinical trials in recent years have shown that they can also reduce blood sugar levels in diabetics, even before weight is lost23.

“We have to think about this surgery differently,” says Seeley. “It’s not just changing the plumbing, it’s altering how the gut handles glucose.”

Nicholas Stylopoulos, an obesity researcher at the Boston Children’s Hospital in Massachusetts, and his colleagues decided to learn more about this mechanism by studying one of the most popular weight-loss procedures, the Roux-en-Y bypass. The surgery reduces the stomach to about the size of a hen’s egg, and rearranges the intestines into the shape of a Y. The arm of the Y that is connected to the reduced stomach pouch is called the Roux limb.

Stylopoulos and his team performed the surgery on obese and non-obese diabetic rats, and then watched for changes in the Roux limb. They found that blood levels of compounds and proteins indicative of sugar use were higher in these rats than in controls that underwent a sham operation. The researchers then injected the Roux-en-Y-treated rats labelled glucose and imaged the animals’ digestive tracts. They found that the Roux limb was taking up and using the sugar, perhaps to compensate for receiving fewer digested nutrients from the shrunken stomach.

The team now hopes to study this process in biopsies from humans who have undergone the procedure, says Stylopoulos. In particular, he and his colleagues want to focus on the role of a protein called GLUT1, which transports glucose into cells. Rats that had been given a Roux-en-Y bypass had higher levels of GLUT1 in the Roux limb than controls, and chemically inhibiting the protein halted the uptake of labelled glucose by the Roux limb.

That, says Stylopoulos, suggests that GLUT1 may be a useful target in the hunt for drugs that could reproduce the effects of a gastric bypass.

The hunt may heat up as surgeons weigh the risks of performing bypasses on obese children, and on adults with diabetes who are only slightly overweight, notes Stylopoulos. “It’s all still very controversial,” he says. “The hope is that one day we can bypass the bypass.”

Source Nature

 

Women are more vulnerable to infections.


Public-health officials discount role of sex in people’s response to flu and other infections.

Sabra Klein came to the annual meeting of the Society for the Study of Reproduction this week armed with a message that might seem obvious to scientists who obsess over sex: men and women are different. But it is a fact often overlooked by health researchers, says Klein, an immunologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland.

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Her research on influenza viruses in mice, presented at the meeting in Montreal, Canada, helps explain why women are more susceptible to death and disease from infectious pathogens — and the reason is intimately linked with reproduction. “She’s one of the people that really gets the bigger picture as far as why do we see these patterns,” says Marlene Zuk, an evolutionary biologist at the University of Minnesota, Twin Cities, in St. Paul.

Women generally suffer more severe flu symptoms than men, for example, despite the fact that they tend to have fewer viruses during an infection. To Klein, this suggests that women quickly mount a substantial immune-system attack to clear infections — and suffer the consequences of the inflammatory responses that flood their systems. “This is where females run into trouble,” Klein says.

She and her collaborators have found this disparity in mice infected with flu viruses1. But when the researchers castrated the males and removed the ovaries from the females, the difference disappeared as the males became more sensitive to infection.

But testes are not simply protective. Klein found that giving the neutered females the female sex hormones oestrogen and progesterone actually protected them from disease.

For females, infections appear to throw these cycling sex hormones out of whack. They elongate the oestrus cycle in non-neutered female mice — stretching the part of the cycle associated with the lowest amounts of oestrogen from 4-5 days to 8-9 days.

Researchers have long known that immunological cells have receptors for sex hormones, and that autoimmune disease strikes women more frequently than men. Nevertheless, Klein says that her work should have implications for current public-health practices.

Women, who are often less likely than men to get vaccinated against flu, should be encouraged to do so, she says. And researchers may want to examine whether hormone-replacement therapies and contraceptive drugs have unintended — possibly positive — effects on some types of infectious disease.

But most importantly, Klein says, medical studies should take sex differences into account. Many epidemiological studies do not break down results by sex, a practice that she has found can obscure crucial trends2. And clinical trials have traditionally worked around the female oestrus cycle, because it can interfere with results.

To Zuk, Klein has provided a voice of reason here. “Why is it viewed as interference when you have interaction with the endocrine system or some other aspect of the reproductive system?” she asks.

“The age-old answer we get is that funding is tight and if we’re going to compare sexes, we’ll have to double the groups,” says Klein. But on the basis of her work, she says, “I don’t know that that’s actually true”.

Source Nature