Body

Lower levels of lymphocyte blood cells -- a condition called lymphopenia -- could be an early warning for future illness, as low counts were associated with a 60% increase in death from any cause, found a Danish study in CMAJ (Canadian Medical Association Journal)

"Our study showed that participants with lymphopenia were at high risk of dying from any cause, regardless of any other risk factor for all-cause mortality including age," writes Dr. Stig Bojesen, with coauthors.

Lymphopenia is often detected during routine blood tests, and patients are not usually referred for further investigation because the value of lymphopenia as a predictor of future health was not known.

Researchers included 108,135 people of Danish descent aged 20-100 years who were enrolled in the Copenhagen General Population Study between 2003 and 2015. An incidental finding of a low lymphocyte count was associated with a 1.6-fold increase in the risk of death from any cause and a 1.5- to 2.8-fold increased risk of death from cancer, cardiovascular disease, respiratory disease, infections and other causes. During the study period, a total of 10,372 people died.

Older age was associated with decreasing lymphocyte counts.

The link between lymphopenia and death may be because of reduced immune capacity to survive potentially lethal diseases. Lymphopenia could also indicate frailty which could lead to illness and death.

The researchers hope their findings may help doctors identify at-risk people. "Using the absolute 2-year risks of all-cause mortality, physicians can identify high-risk individuals with lymphopenia (e.g., smokers older than 80 years) who might benefit from additional surveillance," they write, although the benefits of such surveillance are not known.

"Incidental lymphopenia and mortality: a prospective cohort study" is published January 13, 2020

All living things are made of carbon, and sugars, e.g. glucose, are a very common source of it. Consequently, most cells are good at eating sugars, using enzymes to digest them through a series of chemical reactions that transform the initial sugar into a variety of cell components, including amino acids, DNA building blocks, and fats. Because they help these sugar-metabolism reactions run efficiently, the enzymes called biocatalysts.

Given how critical all enzymes are to life itself, scientists have built several mathematical models that describe how the cells use enzymes to transform a sugar. Such models have been successfully used, for instance, to improve 2nd generation biofuel production or identify drug targets for malaria, but they don't take into account the metabolic "cost" of producing the enzymes that catalyze all these chemical reactions.

Accounting for this phenomenon, called "expression", is key to describing many other phenomena, including beer fermentation and the growth of cancer cells. But all this first depends on accurately modeling the mechanisms of expression.

Now, Professor Vassily Hatzimanikatis at EPFL and Pierre Salvy, a PhD student in his lab, have developed a mathematical model that can efficiently model the expression of enzymes in living cells, as well as its associated metabolic cost. The model is called ETFL for "Expression and Thermodynamics Flux" and draws its accuracy from taking into account both biochemistry and thermodynamics - a set of physico-chemical laws that describe how energy flows in systems. Combining this with mathematical tools from the field of optimization, the researchers were able to drastically improve the accuracy of the model's predictions.

"This integration of metabolism, expression, and thermodynamics is the first of its kind, and is 10 to 100 times faster than the previous state-of-the-art models, which do not feature thermodynamics," says Salvy.

To further increase its predictive power, the ETFL model was designed to take into account a wide variety of measurements made through the massive field of "omics", which measures characteristics of cells such as gene expression, protein profiles etc. "Our algorithm can be used to improve the production of biochemical products, or to accurately predict how cancer cells metabolize," says Salvy. "It can also open the door to applications in personalized medicine."

Lead researcher Lauren Bandy and her colleagues looked at the nutritional information of a range of soft drinks in the UK, including carbonated drinks, concentrates, 100% juice, juice drinks, energy drinks, sports drinks and bottled water, and combined this with sales data from 2015-2018. There has been considerable pressure on industry to reduce the sugar content of soft drinks and in April 2018, the British government introduced the Soft Drinks Industry Levy (SDIL) to help tackle childhood obesity.

Bandy said: 'This study is not designed to evaluate the specific effects of the SDIL, but nonetheless shows that sustained pressure on business, including using fiscal measures, has led to a striking reduction in the sugar content of soft drinks in the UK.'

The research, published in BMC Medicine, shows that individual soft drink companies in the UK are making a sizeable contribution to sugar reduction, with eight out of the top 10 companies reducing the sugar content of their products by 15% or more.

The two biggest companies, Coca-Cola and Britvic, had reduced the total quantity of sugars they sold in drinks by 17% and 26% respectively, although the sugar content of their flagship brands Coca-Cola and Pepsi remained unchanged. There were increases in volume sales of sugars in drinks sold by Innocent and Red Bull; the sugar content of their products was largely unchanged, but the companies had seen increases in overall volume sales.

The analysis shows that nearly three-quarters (73%) of the reduction seen in the amount of sugar sold in soft drinks was due to reformulation of existing products or the introduction of new, lower sugar drinks, and 27% was due to changes in purchasing behaviour.

Lead researcher Lauren Bandy said: 'It is encouraging to see such a large reduction in sugars sold in soft drinks. This is largely a result of change in the composition of drinks but there have also been shifts in consumer purchasing behaviour, with more consumers choosing drinks with low, or no, sugar content. These changes are likely to be due to a combination of government action, mostly through the SDIL, changes in marketing practices on the part of the soft drinks industry, and greater awareness of the harms caused by sugary drinks amongst consumers. They show that it is possible for improvements in public health to be consistent with successful business practices.'

Co-author Susan Jebb, Professor of Diet and Population Health at the Nuffield Department of Primary Care Health Sciences, University of Oxford, said: 'National and international governments are calling for change in the food industry to improve public health. This new method allows researchers to monitor the progress being made and to make this information available to the public. This external scrutiny will hopefully encourage more positive and rapid action by the food industry to achieve healthier diets.'

TAMPA, Fla. - Patients with advanced melanoma who develop metastases in the leptomeninges, the fluid filled membranes surrounding the brain and spinal cord, have an extremely dismal prognosis. Most patients only survive for 8 to 10 weeks after diagnosis. One reason for this poor prognosis is that very little information is known about the molecular development of leptomeningeal melanoma metastases (LMM), making it difficult to develop effective therapies. Researchers in Moffitt Cancer Center's Donald A. Adam Melanoma and Skin Cancer Center of Excellence and the Department of Neuro-Oncology sought to change this by performing an extensive analysis of the molecular characteristics of the cerebrospinal fluid of patients with LMM. Their findings were published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

Cancer development and progression are highly regulated by intricate interactions between cancer cells and the surrounding environment. Melanoma cells that invade and metastasize into the leptomeninges interact with the surrounding cerebrospinal fluid. Moffitt researchers wanted to improve their understanding of the development of LMM by analyzing the protein and RNA composition of cerebrospinal fluid from patients with LMM. They compared the molecular profiles of 8 control patients without LMM to 8 patients with LMM, including one LMM patient who had an extraordinary response to treatment and was still alive more than 35 months after diagnosis.

They discovered that the cerebrospinal fluid from LMM patients was enriched for proteins involved in innate immunity, proteases and the IGF-signaling pathway. The most commonly altered protein was TGF-β1. Interestingly, the one patient who had an extraordinary response to treatment displayed high levels of these proteins at baseline, but expression levels decreased as the patient responded to treatment. However, the protein expression patterns in the remaining LMM patients who had poor responses to treatment were high at baseline and remained high throughout treatment and disease progression.

The researcher team, led by Keiran Smalley, Ph.D., director of the Donald A. Adam Melanoma and Skin Cancer Center of Excellence and Peter Forsyth, M.D., Chair of the Department of Neuro-Oncology, hypothesized that the cerebrospinal fluid of LMM patients could impact melanoma cells by modulating their molecular profile. They confirmed this hypothesis by incubating cerebrospinal fluid from the LMM patients with melanoma cells and discovered that the fluid was able to induce activation of proteins and signaling pathways involved in malignant progression, including the PI3K/AKT pathway, integrins, B cell signaling, mitotic cell cycle progression, TNFR, TGF-β and oxidative stress.

Their findings demonstrate that the cerebrospinal fluid from LMM patients who did not respond to treatment promoted survival of melanoma cells, while the cerebrospinal fluid from the extraordinary responder did not promote survival. These observations suggest that molecules exist within the cerebrospinal fluid that can stimulate melanoma cell survival and prevent cell death. The researchers reported that one of these survival molecules is TGF-β. The patient who responded well to treatment had very low to undetectable levels of cerebrospinal fluid TGF-β, while those patients who did not respond to treatment had much higher levels of TGF-β.

The researchers hope that their data will provide important knowledge about LMM and offer insights into potential therapeutic targets. "It is likely that the environment of LMM is a key regulator of both disease progression and therapeutic response. Improved knowledge about the microenvironment of LMM may allow novel therapeutic strategies to be developed that can delay disease progression," explained Smalley.

DALLAS - Jan. 10, 2020 - Patients who received Mohs surgery to treat the most serious form of skin cancer, melanoma, reported a 95 percent long-term satisfaction rate with their results, according to a new study by UT Southwestern Medical Center dermatologists.

Divya Srivastava, M.D.
Divya Srivastava, M.D.
The study, published in Dermatologic Surgery, is the first to poll patient satisfaction for Mohs surgery. The findings complement previous scientific studies that found Mohs surgery is as effective as wide local excision for early melanomas, says Divya Srivastava, M.D., a UT Southwestern board-certified dermatologist and fellowship trained Mohs surgeon who led the study and has been specializing in Mohs surgery for the past decade. She says her caseload of Mohs surgeries for melanoma has doubled in that time.

"Patient satisfaction is becoming such an important part of medicine these days, so we wanted to look to see what we can do to get patients more satisfied with the care that they are getting for their skin cancer treatment. That's a big area of interest for a lot of the subspecialties," she says.

More people are diagnosed with skin cancer each year in the U.S. than all other cancers combined, but how they attack their cancer is wildly different. "We are working to determine what treatments garner the highest satisfaction to better inform guidelines and decision-making," Srivastava says.

Named after the late Frederic Mohs, M.D., Mohs micrographic surgery is a highly precise excision technique in which the cancer is removed in stages, one tissue layer at a time. After each removal step, the layer is examined under a microscope to determine whether cancer remains in the patient's skin and, if present, where exactly it is located so that the surgeon can pinpoint where to remove the remaining skin cancer. This allows for the smallest scar and best cosmetic result.

"You're looking at 100 percent of the margin under the microscope," Srivastava says. "You're really tracking the cancer out so you're giving people a great cure rate, and it's all done under local anesthetic so it's very safe."

UT Southwestern researchers surveyed 42 of its patients who underwent this technique. The majority of patients were white men with a mean age of 69. The highest percentage of U.S. patients diagnosed with melanoma are white men over age 55. Three-quarters of the tumors were located on the face. The remaining were on the scalp, extremities, and neck.

This small survey suggests patients are finding that the long-term benefits of excision with 100% margin control using Mohs surgery greatly outweigh any potential perceived inconvenience. At UT Southwestern, dermatologic surgeons also provide immediate local tissue reconstruction, using advanced reconstruction techniques to diminish the appearance of scars.

Mohs surgery has a nearly 99% cure rate for early melanoma and results in minimal scarring. Patients follow up with their dermatologists every three months for two years post-surgery.

Dermatologists expect the need for Mohs surgery to increase as the baby boomer population ages. The surgery can also be used to remove basal cell carcinoma and squamous cell carcinoma, which are the two most common types of skin cancers.

"If melanoma is left untreated, it definitely has the potential to grow in the skin and even spread to lymph nodes and organs," Srivastava says. "It can metastasize."

People with fair skin, hair, and eyes are at the highest risk. Just a few severe sunburns in one's lifetime also up the chance of developing skin cancer.

"Once you have one melanoma, you are at risk for more. It's a marker that you have had lot of sun exposure in your life," Srivastava says.

Srivastava is recognized as a national leader in the field. She authored textbook chapters and articles about dermatology. She serves in the House of Delegates in the American Medical Association and is a member of the American Academy of Dermatology, the American Society for Dermatologic Surgery, and the American College of Mohs Surgery.

Her study was funded by a $5,300 grant from the Cutting Edge Research Grant Program of the American Society for Dermatologic Surgery.

Experts in the Japanese phenomena of hikikomori say the condition of extreme social isolation is more widespread than previously acknowledged, and it deserves a clear and consistent definition to improve treatment across the globe.

In an article published in the February issue of the journal World Psychiatry, experts cite a lack of broad clinical understanding of the condition.

Although hikikomori is typically associated with young adults in Japan, the researchers say many of the same criteria of extended social isolation apply to people around the world, including among older adults and stay-at-home parents. A simplified and clear definition will improve the recognition and subsequent treatment for people who suffer from the condition, the authors write.

The article highlights four key aspects of the newly proposed definition of hikikomori:

* Confined at home: The proposed definition clarifies the frequency of time spent outside the home, while still meeting the definition of "marked social isolation."

* Avoiding people: Some people choose to avoid social situations and interaction not because they're anxious but because it meets their comfort level. The newly suggested definition therefore removes the avoidance of social situations as a criteria.

* Better defining distress: Many people diagnosed with hikikomori report that they feel content in their social withdrawal. However, as the duration of social withdrawal gets longer, their distress and feelings of loneliness increases.

* Other disorders: Co-occurring mental health conditions such as depression should not exclude patients from also being assessed for and diagnosed with hikikomori. "In our view, the frequency of co-occurring conditions increases the importance of addressing social withdrawal as a health issue," they write.

Senior author Alan Teo, M.D., associate professor of psychiatry in Oregon Health & Science University School of Medicine and a researcher and psychiatrist in the VA Portland Health Care System, said the medical profession hasn't traditionally recognized social isolation as a health issue.

"There is a cultural issue within the house of medicine whereby we don't pay attention to it and don't think it is in our lane to deal with," he said. "These are shared problems, whether it's an 80-year-old Portlander who's a meals-on-wheels recipient living by herself or an 18-year-old with hikikomori in Japan."

Ironically, modern tools to improve communication may be having the opposite effect.

"With advances in digital and communications technologies that provide alternatives to in-person social interaction, hikikomori may become an increasingly relevant concern," the authors write.

Spending time online can be damaging when it substitutes for interacting with people face to face, Teo said. Those person-to-person social relationships are a critical aspect of mental health.

"Your social life is critical to your quality of life - yet in health care, we often forget to think about that," Teo said. "A person's day-to-day social life is really what brings them meaning and value."

In addition to Teo, the other authors included Takahiro A. Kato, M.D., Ph.D., and Shigenobu Kanba, M.D., Ph.D., of Kyushu University in Japan.

The recommendations published online today in World Psychiatry represent an outgrowth of earlier collaboration between the three authors, including a perspective published in the journal Psychiatry and Clinical Neurosciences in 2019.

Losing weight is an effective treatment for Obstructive Sleep Apnea (OSA), but why exactly this is the case has remained unclear. Now, researchers in the Perelman School of Medicine at the University of Pennsylvania have discovered that improvements in sleep apnea symptoms appear to be linked to the reduction of fat in one unexpected body part -- the tongue.

Using magnetic resonance imaging (MRI) to measure the effect of weight loss on the upper airway in obese patients, researchers found that reducing tongue fat is a primary factor in lessening the severity of OSA. The findings were published today in the American Journal of Respiratory and Critical Care Medicine.

"Most clinicians, and even experts in the sleep apnea world, have not typically focused on fat in the tongue for treating sleep apnea," said Richard Schwab, MD, chief of Sleep Medicine. "Now that we know tongue fat is a risk factor and that sleep apnea improves when tongue fat is reduced, we have established a unique therapeutic target that we've never had before."

Twenty-two million Americans suffer from sleep apnea, a serious health condition in which breathing repeatedly stops and starts, causing patients to wake up randomly throughout their sleep cycles. The condition, which is usually marked by loud snoring, can increase your risk for high blood pressure and stroke. While obesity is the primary risk factor for developing sleep apnea, there are other causes, such as having large tonsils or a recessed jaw. CPAP (continuous positive airway pressure) machines improves sleep apnea in about 75 percent of patients, studies suggest, but for the other 25 percent -- those who may have trouble tolerating the machine -- alternative treatment options, such as oral appliances or upper airway surgery, are more complicated.

A 2014 study led by Schwab compared obese patients with and without sleep apnea, and found that the participants with the condition had significantly larger tongues and a higher percentage of tongue fat when compared to those without sleep apnea. The researchers next step was to determine if reducing tongue fat would improve symptoms and to further examine cause and effect.

The new study included 67 participants with mild to severe obstructive sleep apnea who were obese --those with a body mass index greater than 30.0. Through diet or weight loss surgery, the patients lost nearly 10 percent of their body weight, on average, over six months. Overall, the participants' sleep apnea scores improved by 31 percent after the weight loss intervention, as measured by a sleep study.

Before and after the weight loss intervention, the study participants underwent MRI scans to both their pharynx as well as their abdomens. Then, using a statistical analysis, the research team quantified changes between overall weight loss and reductions to the volumes of the upper airway structures to determine which structures led to the improvement in sleep apnea. The team found that a reduction in tongue fat volume was the primary link between weight loss and sleep apnea improvement.

The study also found that weight loss resulted in reduced pterygoid (a jaw muscle that controls chewing) and pharyngeal lateral wall (muscles on the sides of the airway) volumes. Both these changes also improved sleep apnea, but not to the same extent as the reduction in tongue fat.

The authors believe that tongue fat is a potential new therapeutic target for improving sleep apnea. They suggest that future studies could be designed to explore whether certain low-fat diets are better than others in reducing tongue fat and whether cold therapies -- like those used to reduce stomach fat -- might be applied to reducing tongue fat. However, Schwab notes, these types of interventions have not yet been tested.

Schwab's team is also examining new interventions and other risk factors for sleep apnea, including whether some patients who are not obese but who have "fatty" tongues could be predisposed to sleep apnea, but are less likely to be diagnosed.

In a recent related study, Schwab found that ethnicity may also play a role in sleep apnea severity. His research team compared the upper airway anatomy of Chinese and Icelandic patients with sleep apnea, and found that, compared to Icelandic patients of similar age, gender, and symptoms, Chinese patients had smaller airways and soft tissues, but bigger soft palate volume with more bone restrictions. This means that Asian patients may generally be more at risk for severe sleep apnea symptoms. The bottom line, according to Schwab, is that all patients who suffer from snoring or sleepiness should be screened for sleep apnea, whether or not they appear to fall into the typical "high-risk" obese categories.

"Primary care doctors, and perhaps even dentists, should be asking about snoring and sleepiness in all patients, even those who have a normal body mass index, as, based on our data, they may also be at risk for sleep apnea," Schwab said.

Highlights

In adults followed for a median of 17.5 years, cardiovascular diseases--including heart failure, atrial fibrillation, coronary heart disease, and stroke--were each linked with a higher risk of developing kidney failure.

Heart failure was associated with the highest risk: adults hospitalized with heart failure had an 11.4-times higher risk of developing kidney failure than individuals without cardiovascular disease.

Washington, DC (January 9, 2020) -- New research indicates that cardiovascular diseases--including heart failure, atrial fibrillation, coronary heart disease, and stroke--are each linked with a higher risk of developing kidney failure. The findings, which appear in an upcoming issue of JASN, highlight the importance of protecting the kidney health of individuals diagnosed with cardiovascular disease.

The heart and the kidneys have a bi-directional relationship, whereby dysfunction in either may compromise the function of the other. Many studies have investigated the risks of kidney disease on heart health, but few have examined the reciprocal relationship.

To investigate, a team led by Kunihiro Matsushita, MD, PhD and Junichi Ishigami, MD, PhD (Johns Hopkins Bloomberg School of Public Health) examined information on 9,047 US adults who did not have signs of heart disease when they enrolled in a community-based study.

"Many physicians probably recognize that patients with cardiovascular disease are at risk of kidney disease progression, but to my knowledge, this is the first study quantifying the contribution of different cardiovascular diseases to the development of kidney failure," said Dr. Matsushita.

During a median follow-up of 17.5 years, 2,598 participants were hospitalized with cardiovascular disease--1,269 with heart failure, 1,337 with atrial fibrillation, 696 with coronary heart disease, and 559 with stroke--and 210 patients developed kidney failure.

The incidence of major cardiovascular disease was associated with a higher risk of kidney failure, with the highest risk for heart failure. Participants hospitalized with heart failure had an 11.4-times higher risk of developing kidney failure than participants without cardiovascular disease.

"Individuals with a history of cardiovascular disease should be recognized as a high risk population for kidney failure. In this context, physicians should be aware of cardiovascular disease as an important risk condition, and thereby minimize treatments that are toxic to the kidneys in such individuals," said Dr. Ishigami. "Additionally, our findings may have implications for monitoring kidney function, although current cardiovascular disease guidelines do not necessarily specify the frequency of evaluating kidney function following the incidence of cardiovascular disease."

Patients with the inflammatory bowel disease ulcerative colitis have a higher risk of dying from colorectal cancer, despite modern therapy, even though the risk has declined in recent years. This is according to a new study published in the scientific journal The Lancet by a team of Swedish and Danish researchers.

Previous research has shown that patients with ulcerative colitis have an increased risk of colorectal cancer. Screening recommendations are therefore in place for this patient group. But to what extent have new therapeutic methods helped to reduce this risk? This much-debated question has now found new answers. A large study involving 96,000 patients diagnosed with ulcerative colitis between the years 1969 and 2017 has now shown that these patients run a higher risk of developing and dying of colorectal cancer.

"The risk of colorectal cancer has dropped substantially over the past 30 years, but in spite of this patients who have had access to modern treatments for ulcerative colitis and screening for colorectal cancer still have a significantly elevated risk," says Ola Olen, senior researcher at the Department of Medicine in Solna at Karolinska Institutet in Sweden.

Seen over the entire study period (1969 - 2017) the chances of a patient with ulcerative colitis being diagnosed with colorectal cancer were 66 percent higher than the control group, with the corresponding mortality rate 59 percent higher. For the latest five-year period only, however, these figures were, respectively, 38 percent and 25 percent.

This study differs from previous ones in that it factored in both the tumour stage when the cancer risk was assessed and the mortality rates, which the researchers included to ensure that the risks were not being over-estimated. The reason for examining mortality from colorectal cancer and not only incidence for this cancer is that regular endoscopic screening might detect relatively early forms of colorectal cancer that would otherwise go undetected.

"An important result of the study is that the risks are indeed elevated but there are major differences from one patient group to another," says Olen.

At particularly high risk of developing colorectal cancer are the patients with extensive colitis, primary sclerosing cholangitis (a liver complication sometimes seen in ulcerative colitis), heredity for colorectal cancer susceptibility or childhood onset ulcerative colitis.

According to co-author and Professor Jonas F Ludvigsson, the study indicates a need to develop the care provided for these patients even further.

"Our study shows that screening and treatment of these patients can likely be further improved, since patients with ulcerative colitis are still more likely to die of colon cancer," he says.

BOSTON - Persistent genital arousal disorder (PGAD)--which is almost exclusively experienced by females and characterized by spontaneous and unwanted sexual arousal unrelated to desire--can compromise individuals' mental health and well-being and severely damage relationships with partners. Results from a new study by investigators at Massachusetts General Hospital (MGH) indicate that PGAD can be caused by altered firing of nerves that carry sensations from the genitalia or by damage to the lowest parts of the spinal cord. The study also found that neurological treatments benefit many patients.

"It's important that people know of this medical condition and that it is primarily a neurological problem, not a psychiatric one," said senior author Bruce Price, MD, an MGH Department of Neurology investigator who is also chief of Neurology at McLean Hospital. "Many affected women are silent and undercover--it's in no way a fun condition, and it is difficult for patients to address their symptoms with their doctors, who have typically never heard of PGAD." The problem can be especially troubling for adolescents, causing confusion, shame, and fear.

The study, published in PAIN Reports, included 10 females whose PGAD symptoms began between ages 11 to 70 years. Although the study involved only a small number of patients, it's still one of the first to carefully examine PGAD in a thorough and scientific manner.

Spinal nerve-root cysts were detected in four patients and generalized sensory nerve damage (neuropathy) in two. One patient with symptoms since childhood was born with a small defect in her lowest spinal cord, one had a lumbosacral herniated disc in the lower back, and another developed short-lived PGAD when she abruptly stopped a prescribed antidepressant medication.

All psychiatric and gynecological treatments were ineffective, and injecting local anesthetics had no lasting benefit. In contrast, neurological treatments--such as cyst removal and treating nerve damage--were effective in 80% of patients.

"Physicians need to be aware of PGAD and inquire about it when patients experience other pelvic pain or urological symptoms that often accompany PGAD," said first author Anne Louise Oaklander, MD, PhD, an investigator in the Department of Neurology at MGH. "It's treatable, but the treatment depends on the cause. By identifying some common causes--and localizing them to specific regions of the sacral nervous system--our study provides direction on how to help patients and to guide future research."

Teenagers in the US simply don't get enough shut eye. The consequences of this epidemic of sleep deprivation are extensive and include increasing rates of anxiety and depression among adolescents, as well as suicidal thoughts and actions. Sleep-deprived teens are more likely to be involved in car crashes, and run a higher risk of injury during sports-related activities.

Experts have pointed to various reasons for the chronic teenage sleep deficit: growing homework loads, too many extra-curricular activities, caffeine consumption, school start times that run counter to middle and high schoolers' natural circadian rhythms, and the use of electronic devices and backlit screens, which may disrupt sleep patterns, before bedtime.

But researchers at the University of Rochester have found that a simple and timeworn solution yields solid results: a clear bedtime that parents consistently adhere to.

"Greater enforcement of parent-set bedtimes for teenagers aged 14-to-17 are associated with longer sleep duration," says Jack Peltz, lead author of a recent study, which was published in the academic journal Sleep. Peltz, now an assistant professor of psychology at Daemen College, earned his PhD in psychology at Rochester in 2013 and conducted the study as part of a research appointment at the University of Rochester Medical Center's Department of Psychiatry.

Study participants included teenagers and their parents. The team asked their teenage participants to keep twice-daily sleep diary entries over seven days, collecting reports of sleep duration, daytime energy levels, and depressive symptoms. Parents, meanwhile, provided information about their enforcement of sleep-related rules and bedtimes.

Among the key findings:

Parent-enforced bedtimes--along with later school start times--are the greatest predictors of sleep duration, daytime energy level, and depressive symptoms.

More than 50 percent of parent respondents reported no specific or enforced bedtime rules, consistent with rates measured in previous research across families in the US.

Evening screen time and caffeine consumption did not, contrary to the researchers' hypotheses, significantly affect teenagers' sleep duration over the course of the study.

In 2014, the American Academy of Pediatrics responded to the sleep deprivation epidemic by urging school districts to start classes no earlier than 8:30 am, especially for middle and high schoolers. But to date, only about 14 percent of US high schools have heeded the recommendation, which makes the rule-setting role of parents all the more important.

The researchers acknowledge that setting a bedtime for teenagers might be difficult; but their results suggest that even with pre-bedtime conflict, parents' enforcement of bedtimes yielded better mental health outcomes for their offspring. That said--"ideally parents should be able to work collaboratively with their teenagers to develop bedtimes that still support the child's autonomy," says Peltz.

The bottom line, according to coauthor Ronald Rogge, an associate professor of psychology at Rochester, is that "even though adolescents start gaining self-sufficiency and independence, they still need sleep and might not prioritize that if left to their own devices."

Absent an iron-clad rule, there are nevertheless healthy ranges, says Heidi Connolly, a professor of pediatrics and chief of the Division of Pediatric Sleep Medicine at Rochester, who is also a coauthor of the study. Most teenagers need 8.5 to 9.5 hours of sleep each night, she says, mirroring recommendations made by the American Academy of Sleep Medicine and endorsed by the American Academy of Pediatrics.

As for an appropriate bedtime, that of course depends on the wake-up time. "It's inherently more difficult for teenagers to fall asleep earlier than later because of their circadian rhythm," says Connolly. "That's why it's so important for high school start times to be later, as the American Academy of Pediatrics has recommended across the board."

The ideal is to feel well rested during the daytime, and spontaneously awaken at around your scheduled wake-up time even when allowed to sleep in.

The team notes that future studies may be necessary to determine if their findings hold true across a range of populations; they caution that their sample was predominantly white, well-educated, and economically advantaged.

Lack of insurance coverage is a major cause of delayed breast cancer screening and treatment among minority women, which could lead to a decrease in a patient's chance of survival. Nearly half of the disparity in later-stage diagnosis between non-Hispanic white women and black, Hispanic and Asian/Pacific Islander women was mediated by being uninsured or underinsured, according to a new study conducted at the University of Illinois at Chicago and Boston Medical Center/Boston University School of Medicine.

Non-Hispanic white women were insured at a higher rate at the time of diagnosis compared with non-Hispanic black women, American Indian/Alaska Native, Asian/Pacific Islander and Hispanic women, according to the study published in JAMA Oncology. The research was led by Gregory Calip, assistant professor of pharmacy systems, outcomes and policy at the UIC College of Pharmacy, and Dr. Naomi Ko, assistant professor at the Boston University School of Medicine.

"Diagnosing cancer at a later stage and lack of health insurance have negative consequences for patients and their families," said Calip, who is also a member of the University of Illinois Cancer Center. "Studies have examined the association of premature cancer-related mortality with lost productivity, and one estimated that in 2020 it will be just over $147 billion. The figure exceeded $308 billion when lost productivity of caregivers was considered."

"Inadequate health insurance coverage also mediates the growing survivorship gap experienced by racial and ethnic minorities with cancer."

Insurance is a modifiable risk factor, and "having adequate health insurance for all could reduce the persistent racial outcome disparities in breast cancer," Ko said.

"Patients diagnosed with breast cancer at a later stage typically require more intensive treatment and are at a higher risk for treatment-related morbidity and poorer overall quality of life, especially compared to those who receive chemotherapy," she said. "Diagnosing breast cancer early is not only beneficial for individual patients and families but also on society as a whole to decrease medical costs and promote equity among all populations."

More than 177,000 women age 40 to 64 who were diagnosed with invasive stage I to III breast cancer between 2010 and 2016 were included in the study, which used data from the National Cancer Institute's Surveillance, Epidemiology, and End Results, or SEER, program. Funded by the National Cancer Institute, SEER includes population-based cancer incidence data for about 28% of the U.S. population, including demographic and clinic information.

This is the first study to use statistical mediation methods and a large cancer registry database to quantify the extent that adequate health insurance is a factor in the stage of breast cancer diagnosis among a diverse population of women in the United States.

Assisting Calip and Ko were Dr. Susan Hong, director of survivorship at the University of Illinois Cancer Center; and Dr. Robert Winn, director of the Virginia Commonwealth University Massey Cancer Center.

Scientists at Rutgers University-Newark have discovered that when a key protein needed to generate new brain cells during prenatal and early childhood development is missing, part of the brain goes haywire - causing an imbalance in its circuitry that can lead to long-term cognitive and movement behaviors characteristic of autism spectrum disorder.

"During brain development, there is a coordinated series of events that have to occur at the right time and the right place in order to establish the appropriate number of cells with the right connections," said Juan Pablo Zanin, Rutgers-Newark research associate and lead author on a paper published in the Journal of Neuroscience. " Each of these steps is carefully regulated and if any of these steps are not regulated correctly, this can impact behavior."

Zanin has been working with Wilma Friedman, professor of cellular neurobiology in the Department of Biological Sciences, studying the p75NTR protein - needed to regulate cell division - to determine its exact function in brain development, gain a better understanding of how this genetic mutation could cause brain cells to die off and discover whether there is a genetic link to autism or neurological diseases like Alzheimer's.

Although p75NTR is not a gene specifically linked to autism, it is a part of a family of proteins needed for brain cells to develop, function and survive. The exact timing of the expression of this protein is critical.

"This protein has been examined in regard to neurodegeneration as occurs in Alzheimer's disease and cell death after brain injury," said Friedman, coauthor of the study. "But it has not been looked at regarding the importance it has in generating new neurons."

Working in the laboratory with genetically engineered mice, the Rutgers-Newark scientists found that mice without the p75NTR protein had more brain cells than should normally exist - causing problems in the cerebellum, the working unit of the brain that regulates movement and balance as well as cognitive function, and is one of the key brain regions affected by autism.

In the Rutgers-Newark study, researchers trained mice - with and without the p75NTR protein - to associate a quick puff of air with a blinking light. Mice with the protein learned to blink and shut their eyes when they saw the light while mice without the protein did not.

Other scientific studies have found this same learning deficit in mice with mutations in genes that are associated with autism.

According to the Centers for Disease Control and Prevention, about one in every 59 children in the U.S. is diagnosed with autism, up from one in every 150 in 2000.
Although symptoms vary, the disorder causes difficulties in social interactions with others and often results in repetitive behaviors, speech issues, memory problems and difficulties in understanding non-verbal cues.

While scientists have no clear answer as to the consequences of a brain with too many neurons, autism, primarily a genetic disease, has been associated with an unusually large brain size and some scientists think that early brain overgrowth could be a marker for the disorder.

"It is important to understand how the brain's circuitry is built and how it regulates behavior normally," said Friedman. "This research shows us that when it is not generated properly it is going to have an impact on many behaviors."

January 9, 2020 - New research into the biology of depression, along with new and evolving technologies, provides the basis for developing the next generation of treatments for major depressive disorder (MDD), according to the special January/February issue of Harvard Review of Psychiatry. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"By embracing a multifactorial understanding of MDD, by attending carefully to the sex difference in its prevalence and manifestation, and by harnessing new technology, we should be increasingly able to prevent and treat depression," writes Guest Editor Diego A. Pizzagalli, PhD, of McLean Hospital, Belmont, Mass.

Research in Five Key Areas May Point to New Treatments for Depression

Contributed by international experts, the five articles in the special issue provide updates on neuroscience and technology that may inform the development of much-needed treatments for depression. Topics include:

Gender Differences in Depression. After age 12, MDD is twice as common in girls compared to boys. Studies have yielded insights into the affective, biological, and cognitive factors contributing to this gender difference - for example, negative emotionality, pubertal hormones, and negative cognitive style. While each factor has a relatively small effect on risk, past and present stressors amplify their impact. Continued research may lead to evidence-based treatments that better take into account the particular needs and circumstances of girls and women.

Neuroscience and Behavioral Interventions. "Neuroscience-based augmentation strategies" are being pursued to address two key aspects of depression: anhedonia (loss of interest in pleasurable activities) and cognitive deficits/biases. An approach called Positive Affect Treatment targets issues related to motivation, reward attainment, and reward learning. In an initial clinical trial, this approach showed benefits including decreases in depression symptoms, suicidal thoughts, and stress.

Role of the Microbiome. Evidence suggests that the gut microbiome - the community of bacteria and other microbes living in the intestinal tract - may contribute to the development and persistence of MDD. The microbiome is altered in patients with depression, and commonly used antidepressant drugs affect the microbiome. For example, studies have suggested that a diet high in anti-inflammatory foods (such as the Mediterranean diet) may shorten episodes of depression.

Opioid-Based Therapies. Compelling evidence suggests that abnormal opioid signaling may play a role in the development of MDD. This may help to explain why many patients don't respond to current antidepressant medications. Opioid mechanisms might also account for rapid antidepressant responses to the anesthetic drug ketamine. Strategies targeting one or more of the four opioid receptor subtypes might open new approaches to treating MDD and other stress-related disorders.

Technology in Depression Treatment. Wearable devices, global positioning systems (GPS), and other technologies may provide valuable tools for understanding the wide variation in symptom and disease expression (phenotype) of MDD. For example, GPS devices or fitness trackers may provide useful information on symptoms of social isolation, physical inactivity, and sleep disruption. These and other approaches such as natural language processing and ecological momentary assessment could provide real-time assessment of depression's impact on the lives of individual patients.

While current evidence-based treatments, including antidepressant medications and psychotherapy, are helpful for many people, an "unacceptably high" proportion of patients with depression derive no benefit from these treatments. "There's an acute need for new understandings of depression and its impact on patients' lives," Dr. Pizzagalli comments. "We hope the insights provided by the special issue papers will help to spur the development of new and better treatment approaches that our patients urgently need."

January 9, 2020 - Imagine living with unwanted sexual arousals, occurring unexpectedly and repeatedly, unrelated to any sexual desire or pleasure. That's the situation for women with a rare and disabling condition called persistent genital arousal disorder (PGAD), according to a case series in PAIN Reports®, the official open-access journal of the International Association for the Study of Pain (IASP). The journal is published in the Lippincott portfolio by Wolters Kluwer.

The study provides new insights into the experience of women with PGAD, and strongly suggests that it should be evaluated and treated as a neurological condition. "This report associates PGAD with disorders and lesions of the lower spinal cord, roots, and nerves that control sexual arousal and orgasm," according to the paper by Saurabh Sharma, MD, of McLean Hospital and Harvard Medical School and colleagues.

Neurological Evaluation Provides Clues to Causes and Effective Treatments

The researchers describe ten women evaluated by university medical center neurologists for PGAD: a rare condition characterized by "out-of-context sexual arousal and/or orgasm." Most of the women had daily episodes of sexual arousal, lasting from minutes to hours. Some had longer, near-continuous episodes lasting for days or even years.

Arousals could be triggered by a wide range of factors, or by nothing at all. Nearly all patients tried masturbation to end the episodes; though not pleasurable, this provided temporary respite for some. "Chronic PGAD always terminated sexual relations," Dr. Sharma and coauthors wrote. "Every patient reported that PGAD caused new or worse anxiety or depression."

Psychiatric treatments for PGAD were "universally ineffective." In the oldest patient, this included many psychiatric hospitalizations and electroconvulsive therapy sessions. Medications, injections, and nerve blocks were also ineffective, and sometimes made symptoms worse.

In contrast, neurological evaluation helped identify associated factors and possible causes of PGAD. All but one of the women had "co-localizing somatosensory symptoms," such as pelvic, buttock, or leg pain. Neurological tests provided additional information in several patients, with findings including spinal nerve root lesions, nerve conduction abnormalities, and sensory nerve disorders.

In several cases, neurological evaluation led to effective neurological treatments. One patient was cured by surgery to remove nerve cysts in the sacral region (lower spine and pelvis). One patient got lasting relief from tapering use of an antidepressant drug linked to the onset of symptoms. In another patient, IV immune globulin led to improvement in PGAD and other neurological symptoms.

Although the true prevalence of PGAD is unknown, it appears to occur mainly in women - only a handful of cases have been reported in men. "Women's complaints of inappropriate arousal are typically attributed (by predominantly male evaluators) to psychopathology or misinterpreted as beneficial," according to the authors. They note that there are thousands of posts on Internet forums, usually by women, seeking information about PGAD or similar symptoms.

Given the locations, cause, and accompanying neurological signs and symptoms, Dr. Sharma and coauthors write, "[W]e propose that at least some PGAD cases arise from lesions affecting the sacral [pelvic] sensory networks that transmit sexual arousal." They suggest that PGAD should be regarded as "a disorder of special sensation akin to neuropathic pain and itch."

The article includes suggestions for neurological evaluation and treatment for patients affected by this rare "special sense neuropathy." Dr. Sharma and colleagues conclude: "Our findings will have clinical implications if confirmed, because most PGAD patients now linger medically undiagnosed and untreated."