Culture

A group of researchers from Graduate School of Pharmaceutical Sciences at The University of Tokyo and Institute of Traditional Chinese Medicine and Natural Products at Jinan University, identified the biosynthetic gene cluster for the furanosteroid demethoxyviridin (1), and deciphered its biosynthetic pathway.

Furanosteroids, represented by wortmannin, viridin, and demethoxyviridin, are a special group of fungal-derived, highly-oxygenated steroids featured by an extra furan ring. They are nanomolar-potency inhibitors of phosphatidylinositol 3-kinase (PI3K), among which wortmannin has been developed as a commercial PI3K inhibitor widely used in various biological studies, exemplified by semisynthetic analogue of wortmannin, PX-866, tested in a Phase II clinical trial for treating cancers. The intriguing structures and excellent biological activities of furanosteroids have thus led to extensive efforts toward their total chemical synthesis over the past 20 years, and the stereoselective synthesis of wortmannin and (-)-viridin was finally achieved in 2017. However, as compared with the progress in chemical synthesis, the biosynthesis of these important molecules in fungi is poorly understood.

To identify the biosynthetic gene cluster of demethoxyviridin, the research group sequenced the whole genome of Nodulisporium sp. (a symbiotic fungus which produces demethoxyviridin), and identified a total of 103 cytochrome P450 monooxygenase genes in the genome. The CYP gene clusters in the genome could be potential targets, since demethoxyviridin possesses a highly oxygenated structure. Analyses of the relative localizations of these genes in the genome revealed twelve CYP clusters containing two or more CYP genes. To determine the candidate gene cluster of demethoxyviridin, one CYP gene from each gene cluster was randomly selected and its expression was analyzed by reverse transcription PCR, under demethoxyviridin productive and non-productive conditions. As a result of CRISPR-Cas9-based gene disruption of the candidate genes, the group identified the gene cluster for demethoxyviridin production in this symbiotic fungus. Successive analyses by using Aspergillus oryzae heterologous gene expression system, and an in vitro enzymatic assay further confirmed each of the biosynthetic step and yielded the fourteen biosynthetic intermediates. Structure-activity analyses of the intermediates revealed that the 3-keto group, the C1β-OH, and the aromatic ring C are important for PI3K inhibition. In addition, the in vitro studies revealed that the pregnane side-chain cleavage notably requires three enzymes, flavin-dependent Baeyer-Villiger monooxygenase, esterase, and dehydrogenase, in sharp contrast to the single CYP-mediated process in mammalian cells. Through extensive bioinformatic analyses, we revealed that these pregnane side-chain cleavage pathway is widely distributed in fungal genomes, and a conserved sterol metabolic pathway in the fungal kingdom.

This study set the stage to uncover the biosyntheses of other furanosteroids and expand the chemical diversity of pharmaceutically important furanosteroids by engineered biosynthesis. Because it also established the platform for genetic manipulation of symbiotic fungi, the knowledge obtained in this study will open the way to investigate the interaction between plants and symbiotic fungi.

The Computer Science and Engineering Research Team at the Toyohashi University of Technology has measured the pupil (referred to as the "black part" of the eye) when a person is inspired by an object. It is known that the pupil dilates and narrows to adjust the amount of light entering the eye, and that the extent of dilation/narrowing varies depending on the emotional state of the person. In the present study, we measured the reaction of the pupil when a person is shown a video made to elicit inspiration (a video in which an object gradually appears). Reactions at the moment of inspiration were compared to reactions when no inspiration occurred, and it was found that the extent of pupil dilation varies depending on whether or not a person is inspired by an object and also that the pupil is already largely dilated at a previous stage. The results of the present study were published in the British scientific journal Scientific Reports on May 2nd.

As indicated by inspiration being referred to as an "aha moment" or a "Eureka moment," people perceive inspiration as a momentary event. However, a previous study reported on changes in a person's brain activity prior to them being inspired during a quiz that asked for a common word based on multiple different words. The present study investigated this further by conducting an experiment under the hypothesis that memory retrieval, which involves inspiration in object understanding, occurs in association with pupil dilation. As a result, it was found that the pupils of the experiment participants had dilated before they reported inspiration, which predicted inspiration thereafter. It is therefore believed that this discovery may lead to externally monitoring and controlling new strategies for memory retrieval in the future.

Lead author of the study and PhD student Yuta Suzuki explains that, "Most of the time, we are not conscious of our brain's activity. Perception and recognition are merely one part of total brain function, and there are many mysteries still left to solve with regard to this unconscious part of our brain that accounts for the majority of its activity. We decided to focus on people's object recognition and were able to use biometry to monitor the processing that occurs before a person is aware they have recognized an object. Even more surprising is the fact that a participant's confidence surrounding object recognition during a recognition task did not come into play. In other words, the pupil reacted regardless of whether the participant subjectively believed they were close to getting the answer, and we only tracked whether or not they answered that they recognized the object. We believe this suggests that successful memory retrieval of an object in subconscious processing is in fact reflected in pupil dilation."

Research team leader and Associate Professor Tetsuto Minami says that, "Up until now, we mainly researched 'inspiration' by measuring brain waves, but we can now expect new developments with combinations of different measuring techniques thanks to this new discovery using non-contact pupil measurement technology."

Associate Professor Tetsuto Minami further states that, "Being inspired by objects is deeply related to memory retrieval success. If we can, for instance, uncover a brain processing mechanism in which pupil dilation and problem solving based on inspiration are related in a different way, this could be used as an index when comparing healthy patients to patients with a cerebral function disorder (for example, patients on the autism spectrum and patients with schizophrenia). Externally controlling pupil dilation is also expected to help with both diagnosis and treatment if it can be used to promote cerebral processing."

URBANA, Ill. - Research has shown that consistently not getting enough sleep, or getting poor quality sleep, can put you at risk for a number of health conditions. But how does sleep, or the lack of it, affect how you parent?

A new study from Kelly Tu, a human development and family studies researcher at the University of Illinois, and colleagues, looks at the link between maternal sleep and permissive parenting during late adolescence. Findings show that mothers who don't get enough sleep or who take longer falling asleep have a greater tendency to engage in permissive parenting--parenting marked by lax or inconsistent discipline.

Results also show that sleep quality may be especially important for African-American mothers and mothers from socioeconomically disadvantaged households.

"Short and disrupted sleep patterns are common among parents, especially parents of young children, and can affect their mental and physical health and daily functioning," explains Tu, assistant professor in the Department of Human Development and Family Studies at U of I. "Extending this work beyond young children, we were curious as to how sleep affects the parenting of adolescents."

During adolescence--11 to 18 years of age--parental involvement is still an important contributing factor in how well kids are adjusting socially, emotionally, and behaviorally. Tu explains that research has shown a link between permissive parenting and adolescents' vulnerability to problematic or risky behaviors.

Those risky behaviors during adolescence could include affiliating with deviant or delinquent peers, engaging in delinquent behavior (vandalism or skipping school), or substance use and abuse, Tu explains. "Given that permissive parenting may heighten the risk of adolescents' risky behaviors, we wanted to take a step back to ask what's driving these permissive parenting behaviors, and to see if sleep could be a contributing factor.

"We found that when mothers were not receiving enough sleep, or receiving poor quality sleep, it had an effect on their levels of permissiveness with their adolescents. It may be that they're more irritable, experiencing impaired attention, or so over-tired that they are less consistent in their parenting. But on the plus side, we also find that mothers who are receiving adequate sleep are less likely to be permissive with their adolescents."

To examine maternal sleep duration and quality, 234 mothers were asked to wear actigraphs--a wristwatch-like device, think of a Fitbit--at bedtime for seven consecutive nights. The actigraph detects movement throughout the night and determines whether there is a disruption in sleep. Information about race/ethnicity and socioeconomic status of the mothers was also collected.

Adolescents, averaging 15 years of age, then completed questionnaires (subscales of the Parent Behavior Inventory) about how they perceived their mothers' parenting. They rated behavior on a scale of "likely or not likely to." Example statements included, "Lets me off easy when I do something wrong," "Can't say no to anything I want," or "Doesn't check up to see whether I have done what she told me."

Findings showed that mothers who had longer durations of sleep or who were able to fall asleep easily, had adolescents who reported lower levels of permissive parenting.

Race/ethnicity and socioeconomic status also emerged as significant factors in linking sleep quality with permissive parenting. African-American mothers and mothers from lower socioeconomic households who experienced higher quality sleep (higher sleep efficiency, fewer night wakings) had lower levels of permissive parenting. Yet, for these same mothers, poorer sleep quality resulted in higher levels of permissive parenting.

"Studies have documented sleep disparities among ethnic minority and socioeconomically disadvantaged individuals, and our findings are consistent with that. For socioeconomic status, we may need to consider the day-to-day stressors or challenges that these mothers are facing," Tu explains. "Mothers from lower socioeconomic households may be encountering additional stressors or financial hardships that could be affecting their sleep and/or parenting.
"But what's exciting is that we also find positive effects of high quality sleep on parenting behaviors for ethnic minority and socioeconomically disadvantaged mothers," Tu says.

The findings from the study, Tu says, point out the need for self-care and the importance of sleep.

"Sleep is an easier point to intervene in terms of changes individuals can make--things like not drinking caffeine or exercising too close to bedtime, establishing a bedtime routine, and thinking about the sleep environment," she says. "Parents may be thinking about these things when it comes to their children, but it's just as important for parents to get enough sleep as it may impact their family interactions and children's well-being."

ARLINGTON, Va.--May 21, 2018-- An overwhelming majority of Americans (95%) think infectious and emerging diseases facing other countries will pose a 'major' or 'minor' threat to the U.S. in the next few years, but more than half (61%) say they are confident the federal government can prevent a major infectious disease outbreak in the U.S., according to a new national public opinion survey commissioned by Research!America and the American Society for Microbiology.

About a third (34%) agree that the global community will experience an epidemic in the next 10 years that includes cases in the U.S. But few agree that the global community is prepared to respond to another epidemic like Ebola (28%) and that the U.S. is prepared to respond to such an epidemic (34%). A large majority of respondents (89%) say the federal government should fund international programs on the surveillance and detection of infectious disease outbreaks, and 70% say the federal government should do more to educate the public about global disease outbreaks and the risk to the U.S.

"The findings indicate that many Americans are unaware of the cutting-edge research and public health strategies to protect citizens against deadly epidemics like Ebola," said Mary Woolley, president and CEO, Research!America. "With the recent Ebola outbreak in the Democratic Republic of Congo, it is essential for all stakeholders, from government to industry, to educate the public about efforts to prevent and contain threats to the health, safety and economic security of Americans and individuals worldwide."

A strong majority of respondents (81%) agree that Americans should be concerned about global health. As for the global health problem that concerns them the most, nearly half (47%) said vaccination for childhood diseases like polio. In thinking about the common vaccines available today such as polio, tetanus, measles and flu, 70% of Americans say vaccines are very important to the health of our society, a 10% decrease compared to a similar survey commissioned in 2008.

The findings reveal a shift over the last decade in Americans' attitudes about vaccines developed in the U.S. Seventy-seven percent are confident in the current system in the U.S. for evaluating the safety of vaccines and recommendations for when they should be given, an 8% decrease from 2008.

Roughly two-thirds (67%) are confident that the current system ensures an adequate supply of necessary vaccines to prevent shortages, down 11% from 2008. Fifty-nine percent of Americans strongly believe that they have benefited from the development of vaccines over the last 50 years, a 16% decrease from 2008.

When asked how important they believe it is for parents to have their children vaccinated, 71% of respondents said 'very important,' compared to 82% in 2008. And more than half of those surveyed (53%) say they did not get the flu vaccine during the last flu season. Among those who said no, 48% said they do not trust the flu vaccine, 40% said they do not feel they need it to prevent the flu and 26% said the flu vaccine is not effective and therefore not worth getting. But many agree (61%) that when parents decide not to vaccinate it puts their children and their communities at risk, a 10% increase from 2008. Forty-five percent do not think the public receives enough information from their doctors about vaccinations.

"The American Society for Microbiology has always been a strong proponent for vaccines as essential for public health and security around the world," said ASM President Peggy Cotter. "Partnering with Research!America to assess public attitudes and knowledge about vaccines is a crucial step toward promoting policies and funding that will keep us ahead of future challenges, whether they are emerging diseases or long-established ones."

A universal flu vaccine would safeguard against multiple strains of the flu over time, including those that can cause pandemics, and eliminate the need for an annual flu shot. Yet many do not know about the development of a universal vaccine. Less than a quarter of respondents (21%) say they recall hearing anything about a universal flu vaccine but nearly half (49%) strongly favor increased federal spending on research to improve and find new vaccines, a 15% increase compared to 2008. The FY18 omnibus bill included $100 million for the National Institutes of Health to develop a universal flu vaccine. The National Institute of Allergy and Infectious Diseases has released a strategic plan for a universal flu vaccine that would provide durable protection for all age groups.

Among other findings:

More than half of respondents (54%) say they have heard about vaccines in the media, followed by the internet (45%), doctor/healthcare provider (41%), advertisements (38%), social media (36%), friends/family (29%), government (10%), and patient organization (6%).

Sixty-two percent say they have spoken with a physician, pharmacist or another healthcare professional about getting the flu vaccine.

A vast majority (81%) agree if someone else's child is not vaccinated, other children are at risk for disease.

Seventy-nine percent agree that the U.S. is a global leader in research to improve health, a 9% increase compared to 2008, and an overwhelming majority (93%) think it is important that the U.S. is a global leader.

When asked who should be responsible for funding global health research, nearly three-quarters of respondents (73%) said the World Health Organization, followed by the U.S. government (65%), businesses (52%), United Nations (50%), foundations (45%), private citizens (36%) and state government (26%).

The nationwide survey of 1,004 U.S. adults was conducted by Zogby Analytics for Research!America and the American Society for Microbiology in May 2018. The margin of error is +/- 3.1 percentage points. To view the survey, visit http://www.researchamerica.org/outbreaksurvey.

Doctors may be able to modify or slow down the progress of the neurological condition Parkinson's disease in the future by spotting signs of it in patients with inflammatory bowel disease (IBD), suggest a study published in the journal Gut.

Danish researchers found patients with IBD appeared to have a 22% greater risk of developing Parkinson's disease in a study that monitored participants for almost 40 years.

IBD, Crohn's disease and ulcerative colitis are chronic conditions with onset in young adulthood.

It has already been suggested in previous studies that inflammation plays a role in the development of Parkinson's disease and multiple system atrophy.

Enteric inflammation - the main symptom of inflammatory bowel disease - can occur in patients with Parkinson's disease and may reflect the earliest manifestations of the neurological condition's development.

Experts have suspected for some time that there may be a 'gut-brain axis' where the intestinal environment influences the functioning of the central nervous system and intestinal imbalance may precede and cause Parkinson's disease.

Therefore, a team of Danish researchers led by Dr Tomasz Brudek of the Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospital, Copenhagen, set out to examine whether IBD was associated with risk of Parkinson's disease and multiple system atrophy.

They carried out a nationwide population-based cohort study involving all individuals diagnosed with IBD in Denmark between 1977 and 2014 - 76,477 people - and more than 7.5 million non-IBD individuals from the general population, who were comparable in terms of gender, age and vital status.

All participants were followed from IBD diagnosis/index date to the occurrence of Parkinson's disease and multiple system atrophy, using data from the Danish National Patient Register.

During the 37-year study period, 335 patients with IBD (0.4%) and 39,784 non-IBD individuals (0.5%) were diagnosed with Parkinson's disease, whereas 13 patients with IBD (0.02%) and 866 non-IBD individuals (0.01%) were diagnosed with multiple system atrophy.

Analysis of the results showed that patients with IBD had a 22% higher risk of Parkinson's disease compared with non-IBD individuals.

This increased risk was present independent of age at IBD diagnosis, gender or length of follow-up.

The overall incidence of multiple system atrophy was low in the study, but analysis suggested a tendency towards higher risk (41% higher) of developing multiple system atrophy in patients with IBD compared with non-IBD individuals. The estimates were similar for women and men.

There was a 35% greater risk of parkinsonism among patients with ulcerative colitis but not a significantly higher risk among patients with Crohn's disease.

This was an observational study, so no firm conclusions can be drawn about cause and effect, but the authors said they believed their work was the first epidemiological study investigating the risk of parkinsonism in an unselected, nationwide cohort of patients with IBD with long-term follow-up - patients were followed for more than 8 million person-years.

The authors concluded: "The study suggests that clinicians should be aware of symptoms of parkinsonism in patients with IBD, and the study demonstrates the need for further investigation into the role of intestinal inflammation and brain gut-microbiome axis in the aetiology of parkinsonism.

"The identification of risk factors associated with prodromal phases of Parkinson's disease may allow for early intervention studies that could modify or slow down disease progress."

Tsukuba, Japan -Innate fear is an essential emotion for animals to avoid danger in a severe natural environment. Rodents kept in a laboratory also show instinctive fear behavior against the smell of predators such as foxes, cats or snakes despite having never seen them. This innate fear represents an evolutionarily conserved and genetically encoded survival mechanism. However, the molecular basis of innate behaviors is largely unknown.

Scientists centered at the International Institute for Integrative Sleep Medicine (WPI-IIIS) at the University of Tsukuba in Japan used chemical mutagenesis to introduce random mutations into mice. The animals are screened for abnormal fear responses against a potent derivative of fox odorant. The screen identified a mutant pedigree, named Fearless, showing markedly attenuated freezing response (typical fear behavior in mice) against the odorant. The Fearless pedigree carried a mutation in the Trpa1 gene, which function as a pungency/irritancy receptor.

Loss of Trpa1 in mice diminished predator odor-evoked innate fear behaviors, although they exhibit a normal sense of smell. The research team then found that Trpa1 acts as a chemosensor to detect predator odors. Trpa1 is highly expressed in the trigeminal somatosensory system, which plays a crucial role in nociception, sensing harmful and potentially painful chemicals. They showed that Trpa1-expressed trigeminal neurons contribute critically to fear odor-evoked innate freezing behavior.

"Surprisingly, the trigeminal system, but the not the traditional olfactory system, triggers instinctive fear responses," says the senior author Qinguha Liu. "Predator odor-mediated activation of the Trpa1 nociceptive pathway should instinctively warn the mice of imminent dangers and trigger emergency responses to promote survival. Our studies provide a compelling molecular logic to explain how predator odor-evoked innate fear/defensive behaviors are genetically hardwired."

Furthermore, understating basic mechanism of emotion is important for therapeutics of human anxiety disorders. According to the National Institute of Mental Health (NIMH), approximately 40 million of Americans are affected by a spectrum of fear/anxiety disorders.

"We hope that identification of core fear genes, together with the use of 'fearful' mice as animal models, should facilitate our understanding of genetic origins and development of novel and effective therapeutics for human anxiety disorders," says a co-author Masashi Yanagisawa.

A new study reveals declines in prostate cancer screening and diagnoses in the United States in recent years, as well as decreases in the use of definitive treatments in men who have been diagnosed. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society.

There is considerable debate surrounding the value of prostate cancer screening with prostate-specific antigen (PSA) testing, and the 2012 United States Preventive Services Task Force (USPSTF) recommendation against PSA testing lies at the center of this debate. This recommendation was made in part due to the potential harms--such as erectile dysfunction and urinary incontinence--associated with the treatment of clinically insignificant prostate cancer with radical prostatectomy or radiation.

To examine the use of diagnostics and treatments for prostate cancer in the years surrounding the USPSTF recommendation, James Kearns, MD, of the University of Washington School of Medicine in Seattle, and his colleagues analyzed MarketScan claims, which capture more than 30 million privately insured patients in the United States. The team looked specifically at information related to PSA testing, prostate biopsy, prostate cancer diagnosis, and definitive local treatment in men aged 40-64 years for the years 2008-2014. Men under age 65 years may benefit most from radiation or surgery for their prostate cancer because prostate cancer tends to cause problems for men many years after diagnosis.

In the analysis of approximately 6 million men with a full year of data, PSA testing, prostate biopsy, and prostate cancer detection declined significantly between 2009 and 2014, most notably after 2011. The prostate biopsy rate per 100 patients with a PSA test decreased over the study period from 1.95 to 1.52. Prostate cancer incidence per prostate biopsy increased over the study period from 0.36 to 0.39. Of new prostate cancer diagnoses, the proportion managed with definitive local treatment decreased from 69 percent to 54 percent. Both PSA testing and prostate cancer incidence decreased significantly after 2011.

"In addition to finding decreased prostate cancer screening, we found that fewer men were being diagnosed with prostate cancer, and even fewer men were being treated with surgery or radiation for their prostate cancer. This means that that they are likely choosing active surveillance for low risk prostate cancer," said Dr. Kearns. "This is important because active surveillance has been shown to be safe in many men, and it avoids problems associated with prostate cancer treatment, such as urinary incontinence and erectile dysfunction. Part of the controversy surrounding prostate cancer screening was that men who didn't need surgery or radiation for their prostate cancer were still undergoing those treatments. If those men are instead undergoing active surveillance of their low risk prostate cancer, then the harms of screening will be lower."

In an accompanying editorial, Christopher Filson, MD, MS, of Emory University School of Medicine notes that additional research is needed to determine which men will gain the most value from screening and to identify and correct gaps in the delivery of prostate cancer care to minimize overtreatment while abrogating the incidence of metastatic prostate cancer in the future. "The key will be performing PSA screening--in addition to biopsies and prostate cancer treatment--more intelligently, not more frequently," he writes.

The Journal of Physical Chemistry Letters, where original works in the field of chemistry and physics are published, has printed an article by an international team of scientists describing a discovery of the mechanism for the formation of the simplest polycyclic aromatic hydrocarbon (PAH), naphthalene. The mechanism depicted by the scientists will help in creating physically based combustion models required for the development of fundamentally new ecologically friendly combustion chambers for gas turbine engines.

In Samara University, the research continues within the mega-grant allocated by the government of the Russian Federation. The works are conducted under the leadership of Professor of Florida International University Alexander Mebel. A scientific publication "VUV Photoionization Study of the Formation of the Simplest Polycyclic Aromatic Hydrocarbon: Naphthalene (C10H8)" of a group of scientists from Samara University, University of Hawaii at Manoa, Lawrence Berkeley National Laboratory and Florida International University is an important link in the development of these studies.

"On the Earth polycyclic aromatic hydrocarbons are harmful substances, formed due to incomplete combustion of fuel. They are carcinogenic, lead to the formation of soot, which pollutes the environment and contributes to global warming, - says Alexander Mebel. - At the same time in the interstellar space, PAHs are precursors of biochemical molecules and an important factor in the chemical evolution in the Universe. For these reasons, a detailed understanding of PAH formation and growth mechanisms is important, both for the development of environmentally friendly combustion technologies, and for answering the eternal question of the origin of life. "

In the article published in the Journal of Physical Chemistry Letters, a chemical reaction is described for the formation of a polycyclic aromatic hydrocarbon (naphthalene) from the phenyl and vinylacetylene at elevated temperatures corresponding to the conditions of flames or circumstellar envelopes.

The scientists from the Samara University - Doctor of Physical and Mathematical Sciences, Professor Marsel Zagidullin and Chief Researcher of the Research and Education Centre for Physics of Open Nonequilibrium Systems (REC PhNOS-73), Professor Valeriy Azyazov calculated this chemical reaction using theoretical modeling. Their colleagues - chemists from Florida International University, University of Hawaii at Manoa and Lawrence Berkeley National Laboratory, confirmed the results of the theoretical calculations in the laboratory experiment in a vacuum chamber with a microreactor.

"This work allowed us to understand the details of the synthesis of the simplest PAH prototyps and to develop a physically based and quantitatively accurate model of this process," - concluded Alexander Mebel.

For reference:

In Samara University within the mega-grant allocated by the government of the Russian Federation, an experimental setup is being created to study combustion reactions. Only three such installations currently exist in the world - in the USA (in Berkeley and in Hawaii) and in China (Hefei). The task of the laboratory staff of Samara University under the leadership of Alexander Mebel is to develop physically based combustion models by obtaining new data on chemical combustion processes and flames characteristics.

The project is aimed at solving the important problem - prevention of environmental pollution. International standards for harmful emissions are constantly tightened and new ecologically clean combustion technologies are necessary to ensure the competitiveness of Russian producers.

It is necessary to minimize the formation of soot, carcinogenic substances at the design stage of internal combustion engines, diesel, gas turbines, aircraft and rocket engines. And in order to minimize them, it is necessary to understand how they are formed. To this end, within the work on the mega-grant, appropriate fundamental mechanisms are investigated.

ANN ARBOR, Mich. -- No parent wants to come home from a picnic or restaurant with a little one whose stomachache turns into much worse.

But few parents are using some simple strategies to protect kids from food poisoning outside the home, such as at a potluck or restaurant, according to a new report from C.S. Mott Children's Hospital National Poll on Children's Health at the University of Michigan.

One in 10 parents say their child has gotten sick from eating spoiled or contaminated food, with restaurants named as the most common source (68 percent.) But just a fourth say they check health inspection ratings before dining out.

"In most cases children recover quickly from food poisoning, but in certain cases it can be debilitating," says Mott Poll co-director Gary L. Freed, M.D., M.P.H.

"It's impossible to completely protect children from food-borne illness. However, there are strategies to try to reduce the risk of getting sick from eating spoiled or contaminated food. We found that while parents paid closer attention to food safety in their own home, they were not always as cautious about outside sources."

Among parents of children who had gotten sick from spoiled or contaminated food, just a third say their child has gotten sick from food eaten at their own home.

Parents reported putting a lot of effort into food safety in the home. Most parents said they wash their hands before preparing a meal (87 percent), wash fruits and vegetables before serving (80 percent), and check the expiration dates on refrigerated food (84 percent). If a refrigerated product was more than two days past its expiration date, 57 percent of parents said they would smell or taste it themselves to see if it was OK to eat, while 43 percent said they would automatically throw the food away. If parents heard that a food product in their home had been recalled, almost all would not feed it to their children with 58 percent reporting they would throw it away and 40 percent returning it for a refund or replacement.

Other sources of kids getting sick from spoiled or contaminated food included school (21 percent), a friend's house (14 percent), or at a potluck (11 percent).

Foodborne illness affects more than 75 million people a year, most often caused by toxins, parasites, viruses, and bacteria - such as salmonella and E. coli. Food poisoning can occur when germs, either certain bacteria or viruses, contaminate food or drinks. This can happen at many different places in the process as food moves from harvesting to packaging to preparation to serving. Once contaminated food enters the body, some germs release toxins that can cause diarrhea, vomiting and sometimes fever or muscle aches. Hand washing, keeping cutting boards clean and washed and storing and cooking food at proper temperatures are also important when preparing and serving meals

Freed says an increasingly common germ passed on by unwashed hands is the virus, Hepatitis A. Hepatitis A vaccine is recommended for all children at one year of age and can prevent almost all cases in those immunized.

Symptoms of food poisoning start anywhere from an hour to three days after eating contaminated food. Freed says the most important initial treatment for food poisoning is making sure a child drinks plenty of fluids to prevent dehydration. Although food poisoning is a usually mild illness, there are multiple hospitalizations and even some deaths in the U.S each year.

"Contaminated food can make both kids and adults very sick very quickly. For very young children, whose immune systems are not fully developed, this kind of illness can present a greater risk of serious complications," Freed says.

"Simple precautions, like checking restaurant inspections and following food safety rules when cooking and storing food, can help keep your family safe."

People with prediabetes have blood sugar levels higher than normal but below Type 2 diabetes levels. People with OSA experience times during sleep when air is obstructed from flowing normally into the lungs. CPAP is considered the "gold standard" treatment for OSA.

According to Sushmita Pamidi, MD, lead study author and a sleep physician-scientist at McGill University, previous studies have found that OSA is associated with increased sympathetic activity, which activates our "fight or flight" response. This response, in turn, raises our heart rate.

"Both prediabetes and higher resting heart rates have been linked to cardiovascular disease," she said. "We wanted to see if CPAP would lower resting heart rates both during the day and at night in this group of patients with abnormal glucose metabolism."

Of 39 participants in this study, twice as many were randomly assigned to CPAP as an oral placebo for 14 days. All-night adherence to CPAP was assured by monitoring all participants in a sleep lab throughout the two weeks. Resting heart rates were measured 24 hours a day for the two weeks using a portable monitoring device.

The study found that those using CPAP had significantly lower resting heart rates throughout the day and night than those in the placebo arm of the study. The differences between the two groups were more pronounced during the second week of the trial.

"The effect of CPAP on resting heart rate is comparable to using beta blockers," said Esra Tasali, MD, senior study author and director of the Sleep Research Center at the University of Chicago. Commonly prescribed for heart problems, beta blockers block stress hormones, such as adrenaline that raise heart rates.

"OSA is exceedingly common among individuals with abnormal glucose tolerance," Dr. Tasali added, noting recent estimates indicate that 80 percent of those with OSA in the general U.S. population are undiagnosed. "Our study is a first step in demonstrating that optimal treatment of sleep apnea reduces cardiovascular risk in those with prediabetes."

SAN FRANCISCO - Physicians at the University of Arizona College of Medicine - Tucson are developing a new tool that detects urine, or urethral, blockage. The technique may soon make it easier for patients to test themselves for the condition from the comfort of their own homes.

Urethral strictures are a slowing or blocking of the natural flow of urine due to an injury or infection. The uncomfortable condition, which affects both men and women, normally is diagnosed with uroflowmetry, a test administered at a physician's office.

"The problem is that patient follow-up after we treat this condition is very poor," explains Matthew Gretzer, MD, UA associate professor of surgery. "But we need patients to come back to our clinic for a uroflow test to determine if the obstruction is still present."

To make thing easier for patients, Dr. Gretzer and Sunchin Kim, MD, a resident at the UA College of Medicine - Tucson, are investigating a new technique that may one day allow patients to use their smartphones to record the data necessary to diagnose the blockage. The two presented their findings in San Francisco today at the annual meeting of the American Urological Association.

A normal uroflow test measures the amount of urine passed, its speed and the time it takes to pass the urine. Patients take this test using a toilet or urinal that's fitted with a special measuring device that records this data.

Dr. Gretzer hypothesized that a technique to bypass this tool could be high-speed photography. Photos, he thought, could capture subtle differences between a normal steady stream of liquid and a stream of liquid with an obstruction.

To test the theory, the team created a model of a urethral stricture using tubing hooked to a saline bag that could drain through. Then, saline fluid was passed through the tubing with and without blockages. Blockages were created using 3D printed strictures that were placed within the tubing. High-speed photography captured both the regular and blocked stream of liquid exiting the tube.

"We showed that you can see a difference in the images," Dr. Gretzer said. "Photos can be used to test for urethral strictures."

As fluid exits an opening, a natural breakpoint occurs where the liquid stream forms droplets. But with obstructions in place, this breakpoint changes. The team found that by analyzing photos, they could measure the length to this point of droplet formation. This length then directly related to the presence of an obstruction in the tube.

The team's next step is to test high-speed photography's accuracy in patients with actual urethral strictures. Photos will be captured before and after a surgical repair known as urethroplasty.

Once clinical studies confirm the hypothesis, Dr. Gretzer plans to create an app that patients can download on their phones.

"All patients would need to do is take high-speed images of their urine flow using a strobe light," he says. "Strobe light apps are readily available right now for people to use on their phones."

Dr. Gretzer envisions people sending him these images to analyze and make the diagnosis. But the team also may develop an algorithm that can make the diagnosis within the app itself.

Fasting every other day to lose weight impairs the action of sugar-regulating hormone, insulin, which may increase diabetes risk, according to data presented in Barcelona at the European Society of Endocrinology annual meeting, ECE 2018. These findings suggest that fasting-based diets may be associated with long-term health risks and careful consideration should be made before starting such weight loss programmes.

Type-2 diabetes is a growing global epidemic that is often attributed to poor diet and a sedentary lifestyle, so is closely linked to obesity. Blood sugar is partially regulated by the hormone insulin, which is produced by the pancreas, if insulin levels are too low, or the body becomes resistant to its effects, type-2 diabetes results and high blood sugar levels can cause serious health issues, including heart, kidney and eye damage. In addition to medical strategies used to treat type-2 diabetes, patients are also advised to make lifestyle and dietary changes to lose weight. Recently, intermittent fasting diets have gained general popularity for weight loss, however, evidence on their success has been contradictory and there is a lack of knowledge and some debate on their potentially harmful long-term health effects. Previous research has also shown that short-term fasting can produce molecules called free radicals, which are highly reactive chemicals that can cause damage to the body at a cellular and may be associated with impaired organ function, cancer risk and accelerated aging.

In order to investigate whether an intermittent fasting diet could also generate damaging free radicals, Ana Bonassa and colleagues, from the University of Sao Paulo in Brazil, examined the effects of fasting every other day on the body weight, free radical levels and insulin function of normal, adult rats, over a 3-month period. Although the rats' body weight and food intake decreased as expected over the study period, the amount of fat tissue in their abdomen actually increased. Furthermore, the cells of the pancreas that release insulin showed damage, with the presence of increased levels of free radicals and markers of insulin resistance were also detected.

Ana Bonassa comments, "This is the first study to show that, despite weight loss, intermittent fasting diets may actually damage the pancreas and affect insulin function in normal healthy individuals, which could lead to diabetes and serious health issues."

The researchers now plan to investigate how this diet impairs pancreas and insulin function. There are many conflicting reports on the benefits and disadvantages, and many different types of intermittent fasting diets. Although these data were obtained in normal weight rats with positive effects on weight gain and food intake, the results suggest that in the long-term harm may be caused and that more investigation is needed to assess how people may be affected, particularly those with existing metabolic issues.

Ana cautions, "We should consider that overweight or obese people who opt for intermittent fasting diets may already have insulin resistance, so although this diet may lead to early, rapid weight loss, in the long-term there could be potentially serious damaging effects to their health, such as the development of type-2 diabetes."

Using a novel imaging method, a Massachusetts General Hospital (MGH) research team is investigating the mechanisms behind a potential targeted treatment for a subtype of the deadly brains tumors called gliomas. In their report published in Nature Communications, the researchers describe using magnetic resonance spectroscopy (MRS) imaging - which reflects metabolic rather than structural aspects of tissues - to determine whether treatment with an investigational IDH1 inhibitor reduced levels of a tumor-associated metabolite in patients with IDH1-mutated gliomas participating in a clinical trial.

"Gliomas are aggressive, primary brain tumors that lack effective treatments, and patients invariably succumb to the disease," says lead author Ovidiu Andronesi, MD, PhD, of the MGH-based Martinos Center for Biomedical Imaging, lead author of the paper. "There is a desperate need for progress in glioma treatment, and IDH mutations, which occur commonly in these tumors, offer a pathway for targeted therapy. With the new metabolic imaging method that we developed to probe treatment effects, we showed that a novel IDH1 inhibitor can quickly reduce levels of the oncometabolite 2HG in patients with this mutation. This type of methodology has the potential to accelerate clinical trials and translation of targeted therapies, such as mutant IDH inhibitors, and makes the concept of precision oncology feasible in glioma patients."

While patients with gliomas characterized by mutations in the isocitrate dehydrogenase (IDH) enzyme tend to live three to five times longer, with better response to chemo- and radiation therapy, than do patients whose tumors do not carry IDH mutations, the mutations themselves may initiate and drive the growth of the tumor. IDH mutant tumors produce elevated levels of 2-hydroxyglurate (2HG), which is believed to contribute to tumor initiation by interfering with gene expression control. While it is unclear whether reducing 2HG level would reverse the process in patients, it could be used as a biomarker for diagnosis and monitoring of IDH mutant tumors.

The MGH and Dana-Farber Cancer Institute are one of the sites for a Phase 1 clinical trial of the IDH1 inhibitor IDH305 for IDH1-mutated glioma treatment. Of eight patients who had enrolled in the trial at time of the current study, MR imaging data collected before and a week after treatment began was available for five. Three-dimensional MRS imaging of the data found that 2HG levels dropped around 70 percent after treatment initiation. Levels of additional metabolites connected with the mutant IDH1 pathway - including glutamine and glutamate - were altered in response to IDH305 treatment, indicating a potential metabolic reprogramming of the tumor.

"MR spectroscopy is quick, noninvasive and can be performed on any clinical MR scanner, making results available before any biopsy or surgical procedure have begun," says Andronesi, and assistant professor of Radiology at Harvard Medical School. "It also can be used to track the response to treatment, since repeat biopsies are not feasible for patients with brain tumors, by directly probing the activity of the mutant IDH1 enzyme. Of course, our small study needs to be replicated in a larger group with longer follow-up times, as well as determining the long-term benefit of IDH1 inhibitor treatment."

WASHINGTON, D.C. - Rheumatologists and rheumatology health professionals convened on Capitol Hill this week to urge legislative action on pressing policy issues affecting rheumatology care during the American College of Rheumatology's Advocacy Leadership Conference, held May 16-17, 2018 in Washington, D.C.

Noting the rising costs and increasing access barriers in rheumatologic care, specialists encouraged lawmakers to support legislation that would create reasonable exceptions to the use of step therapy, grow the rheumatology workforce, increase transparency in drug pricing, and hold pharmacy benefit managers accountable for pricing practices that increase out-of-pocket costs for patients.

"We are at a critical juncture in rheumatology care," said David Daikh, MD, PhD, President of the ACR. "According to the latest federal estimates, as many as 54 million Americans have a doctor-diagnosed rheumatic disease, and a recent academic study suggests that number could be as high as 91 million when taking into account symptoms reported by undiagnosed individuals. The rheumatology workforce is not growing fast enough to keep up with demand and too many of our patients struggle to access and afford the breakthrough therapies they need to manage their pain and avoid long-term disability. America's rheumatologists are urging our lawmakers to act now and support bipartisan, common-sense legislation that would increase access to high-quality rheumatology care for their constituents."

The American College of Rheumatology urged Congressional leaders to support the following legislation to address access and cost barriers in rheumatologic care:

Restoring the Patient's Voice Act (H.R. 2077), bipartisan legislation which would create a clear and transparent process for patients with employer-sponsored insurance to seek exceptions to step therapy;

Know the Lowest Price Act of 2018 (S. 2553) and the Patient Right to Know Drug Prices Act (S. 2554), bipartisan legislation which would allow pharmacists to inform patients when the cash price of their medicines is lower than the price they would pay with insurance coverage;

Prescription Transparency Act of 2018 (H.R. 5343) bipartisan legislation that would allow pharmacists to inform patients about alternative options to lower out-of-pocket drug costs;

Ensuring Children's Access to Subspecialty Care Act (H.R. 3767; S. 989), bipartisan legislation that would allow pediatric subspecialists to participate in the National Health Service Corps loan repayment program;

Conrad State 30 and Physician Access Act (H.R. 2141, S.898), bipartisan legislation which would allow international doctors trained in the U.S. to remain in the country if they practice in underserved areas; and

Standardizing Electronic Prior Authorization for Safe Prescribing Act of 2018 (H.R. 4841), bipartisan legislation which would require the Centers for Medicare and Medicaid Services to develop electronic prior authorization standards for Medicare Part D and Medicare Advantage plans.

Rheumatology leaders also advised members of the House and Senate Appropriations Subcommittees on Defense to establish a line item in the Congressionally Designated Medical Research Program (CDMRP) for arthritis at the Department of Defense using $20 million in existing funds. Such a program would meet the growing needs of active duty military personnel and veterans, a disproportionate number of whom live with osteoarthritis and other rheumatic diseases.

May 18, 2018 - A new case report in the Journal of the Endocrine Society documents how a patient's use of a common biotin supplement, also known as vitamin B7, caused her to have clinically misleading test results, which prompted numerous consultations and unnecessary radiographic and laboratory testing.

The patient in the case report took a 5000 mcg dose of biotin daily. Biotin supplements in that dosage are commonly sold over-the-counter, without a prescription, in many grocery and drug stores for about $8-$20 a bottle. They are marketed as being good for healthy hair, skin and nails, but there is no scientific evidence to support this claim.

In this patient's case, "The negative clinical impact included weeks of psychological distress concerning the possibilities of hypercortisolemia or a testosterone-producing tumor. Most significantly, these abnormal test results nearly resulted in an unnecessary invasive procedure for a complex patient with a hypercoagulable state," the case report says. Hypercortisolemia is a condition involving a prolonged excess of cortisol -- a steroid hormone -- in blood.

Maya Styner, MD, associate professor of endocrinology and metabolism in the department of medicine, is the case report's corresponding author.

"The literature is lacking with regard to biotin interference with serum cortisol and testosterone immunoassays, as in our case-report," Styner said. "Patients are ingesting supplements in a higher frequency, and higher doses, and therefore this case is timely and relevant from both a clinical and basic-science perspective."

She added, "Our manuscript is a product of a collaboration between endocrinology, reproductive endocrinology/gynecology and clinical chemistry at UNC and at the Mayo Clinic. This collaboration enabled us to ascertain the underlying diagnosis and perform relevant research-based biotin quantification in our patient's sample."