Body

CLEVELAND, Ohio (Sept. 9, 2020)--Early menarche has been associated with many cardiovascular disease (CVD) risk factors, but little is known about its association with overall heart health. One new study suggests that age at menarche plays an important role in maintaining and improving cardiovascular health, although there are a number of age differences. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Because CVD is the leading cause of death in women, a lot of research is devoted to identifying ways for women to improve their heart health and prevent major cardiovascular events. Cardiovascular health takes into account factors such as blood pressure, total cholesterol, and glucose levels, as well as behavioral factors including cigarette smoking, body mass index, physical activity, and diet. Ideal cardiovascular health is associated with a lower risk of CVD, as well as with other outcomes such as cancer, cognitive impairment, and depression. Studies have shown that ideal cardiovascular health is prevalent in 50% of the US population at 10 years of age and declines to less than 10% by 50 years of age.

Some forms of CVD have their origins during childhood, which is one reason why they have been previously associated with early menarche. To date, however, few if any studies have focused on the association between early menarche (generally defined as the occurrence of first menstruation before 12 years of age) and overall cardiovascular health. This new study involving more than 20,000 women not only found that increases in age at menarche are significantly associated with increases in heart health in women but also that there are major age differences in the association. In fact, significant associations between age at menarche and ideal cardiovascular health were observed only in young women, whereas little association was documented in older women. This suggests that age at menarche may be less of a predictor of heart health as women age.

Similarly, the researchers found that the protective effects of late menarche on cardiovascular health were apparent in women aged 25 to 44 years, whereas the detrimental effects of early menarche were only observed in those aged 25 to 34 years. Further studies are necessary to better understand the reason behind these declining associations.

Results are published in the article "Age at menarche and cardiovascular health: results from the NHANES 1999-2016."

"This study highlights a link between age at menarche and cardiovascular health, findings that were evident only in younger women and may be driven by associations with body mass index. Given that heart disease is the number one killer of women, identifying those women who experienced early menarche (aged younger than 12 years) may allow for earlier intervention to reduce cardiovascular risk," says Dr. Stephanie Faubion, NAMS medical director.

(DENVER, Colorado) – Food allergies are on the rise, with more than five million children, about two kids in every school classroom, now suffering from allergy to at least one food. Researchers at National Jewish Health are working to discover what is responsible for this increase and have determined that many allergic conditions likely start with dry, cracked skin, which leads to a chain reaction of allergic diseases known as the atopic march. It begins in infancy with eczema and leads to food allergies, asthma and hay fever later in childhood. Now, their latest study reveals that the time of year a baby is born may be a risk factor for the atopic march.

“We looked at every child treated in our clinic, and those born in the fall were much more likely to experience all of the conditions associated with the atopic march,” said Jessica Hui, MD, a pediatrician at National Jewish Health and lead author of the study. “Now we are learning more about why that is and we strongly believe it stems from the bacteria on the skin on how they affect the skin barrier.”

Children with eczema often have high levels of a harmful bacteria called staph aureus on their skin, which weakens the skin’s ability to keep out allergens and pathogens.

“When food particles are able to penetrate the skin rather than being digested, the body sees them as foreign and creates antibodies against them, which causes the child to become allergic,” Dr. Hui said.

Researchers are now conducting a clinical trial to look at a wide variety of factors that may contribute to this weakened skin barrier in babies. They’re enrolling pregnant women and following their babies into early childhood to consider everything from environmental factors to genetics to medications taken and products used in the home. They hope that this will not only help explain why babies born in the fall are at greater risk, but will also help develop solutions to stop the atopic march in its tracks.

“We think if we can intervene at a very young age, even right after the baby’s out of the womb, then potentially that’s a way for us to try to stop the development of this atopic march,” Dr. Hui said.

Other potential solutions to prevent the atopic march is sealing the skin barriers of babies with eczema using wet wraps and lotions and introducing allergenic food early in life for kids at risk.

Guangzhou, September 9, 2020: New journal BIO Integration (BIOI) publishes its second issue, volume 1, issue 2. BIOI is a peer-reviewed, open access, international journal, which is dedicated to spreading multidisciplinary views driving the advancement of modern medicine. Aimed at bridging the gap between the laboratory, clinic, and biotechnology industries, it will offer a cross-disciplinary platform devoted to communicating advances in the biomedical research field and offering insights into different areas of life science, in order to encourage cooperation and exchange among scientists, clinical researchers, and health care providers.

Featured papers in this issue:

The first featured article in this issue is an original research article entitled "Automated Stage Discrimination of Parkinson's Disease" by authors Vered Aharonson, Nabeel Seedat, Simon Israeli-Korn, Sharon Hassin-Baer, Michiel Postema and Gilad Yahalom. A device has been available since 2017 that successfully detects Parkinson's Disease (PD) and operates for people who cannot walk without support. In this study, the suitability of this device for automated discrimination of PD stages was tested. Walking trajectory, velocity, acceleration and force were automatically recorded by the device throughout testing. Correlations were established between these results, additional spatiotemporal quantities, disease duration, L-dihydroxyphenylalanine-(L-DOPA) dose, motor fluctuation, dyskinesia and the mobile part of the Unified Parkinson Disease Rating Scale (UPDRS).

The second featured article in this issue is a case report entitled "Drug-induced Interstitial Lung Disease in Breast Cancer Patients: A Lesson We Should Learn From Multi-Disciplinary Integration" by Zijun Zhao, Zhanghai He, Hongyan Huang, Jiewen Chen, Shishi He, Ailifeire Yilihamu and Yan Nie. Taxanes represented by paclitaxel and targeted therapy including trastuzumab are two common agents for human epidermal growth factor receptor-2 (HER-2)-positive breast cancer patients. Effectiveness, however, usually comes at the cost of many side effects such as drug-induced interstitial lung diseases (DILDs). Through case studies, and reference to related studies in medical databases, the authors discuss how multi-disciplinary integration of clinical practice and pharmacological mechanisms can make anti-cancer agents less harmful and reduce the incidence of DILD in breast cancer patients during systemic therapy.

The third featured article in this issue is an opinion article entitled "Breast Cancer Multidisciplinary Management during COVID-19 Pandemic: Experiences and Strategies Used by a Singapore Breast Surgical Unit" by Chi Wei Mok, Yert Li Melissa Seet, and Su-Ming Tan. The authors describe the challenges faced and measures adopted by the division during the pandemic in multidisciplinary management of non-COVID breast cancer patients providing insights to serve as a guide for physicians in similar settings who are managing breast cancer patients amidst the pandemic.

WASHINGTON (Sept. 9, 2020) - Spironolactone is not associated with increased risk of female breast cancer recurrence, according to research from the George Washington University (GW) Department of Dermatology. The study, published in the Journal of the American Academy of Dermatology, found that the drug may be safe for use in treating breast cancer survivors with female pattern hair loss.

Androgens contribute significantly to the pathogenesis of female patterned hair loss. The current treatment of topically applied minoxidil (also known as Rogaine), thought to increase scalp blood flow and maintain hair growth, is approved by the U.S. Food and Drug Administration. However, antiandrogen drugs, like spironolactone, have also been used to treat female patterned hair loss, but used off-label. Research confirming the safety of this drug for breast cancer survivors is critical for patients considering this treatment option.

"Spironolactone is used for androgenic alopecia because of its ability to halt the progression of hair loss and its long-term safety profile," said Adam Friedman, MD, interim chair and professor in the Department of Dermatology at the GW School of Medicine and Health Sciences, director of the Supportive Oncodermatology Clinic at GW Cancer Center, and the senior author on the study. "However, little is known about its safety in breast cancer survivors, which is of concern considering the drug's estrogenic effects could pose a theoretical risk of breast cancer recurrence."

The multidisciplinary research team, led by first author Chapman Wei, a fourth-year MD student and research fellow in the GW Department of Dermatology, conducted a retrospective analysis of data from the Humana Insurance Database. They identified patients with a history of breast cancer and stratified groups based on spironolactone usage. They then analyzed patient characteristics and cancer recurrence rates between the cohorts.

The breast cancer recurrence rate for the group prescribed spironolactone was not statistically different from the cohort of patients who did not take spironolactone after adjusting for patient characteristics, both of which were well within the range of expected recurrence rates.

"According to our analysis, spironolactone is not independently responsible for increased risk of breast cancer recurrence," Friedman said. "The drug could be used as an additional treatment option for alopecia in female breast cancer patients who are disease-free."

The authors recommend additional prospective studies and clinical trials to further assess the efficacy and safety of spironolactone in patients who have cancer remission to confirm its safety.

JACKSONVILLE, Fla. (September 9, 2020) - The September issue of Progress in Pediatric Cardiology will exclusively feature articles by pediatric cardiologists at Nemours Children's Health System on echocardiography and other cardiac imaging techniques used in the care of children with cardiovascular disease. The 15 original papers and four case studies highlight best practices for imaging to screen, diagnose, and manage congenital heart disease (CHD) and other forms of cardiovascular disease over the entire lifespan to improve patient outcomes.

CHD affects approximately 1 in 100 children. Many of these conditions are now highly treatable, with research showing that more than 90% of children born today with CHD live into adulthood.

"Cardiovascular disease is a leading cause of morbidity and mortality, and making the diagnosis is critical. Echocardiography is the primary non-invasive tool for assessing cardiac structure and function and can image any patient from fetuses during pregnancy to adults," said Gul H. Dadlani, MD, an author on several articles in the issue, and chief of pediatric cardiology at Nemours Children's Hospital in Orlando. "As children with rare cardiovascular disorders live longer, there is a need for greater awareness of imaging techniques for these complex patients to improve the quality of their care."

The issue includes review articles, technical papers on specific uses of echocardiography, case studies of patient illnesses, and discussion on the use of echocardiography in specific disorders, as well as the role of advanced non-invasive cardiac imaging, such as magnetic resonance imaging and computed tomography. Also included are articles highlighting important modifications made during COVID-19. Specific articles of interest, available free, include:

Segmental approach to performing a standard pediatric echocardiogram (Madueme, et al.) describes protocol for a segmental format to improve pediatric cardiac assessment with guidance for capturing imaging in a predictable, consistent ,and reproducible manner to yield accurate information, understanding the need for flexibility and modifications needed when treating pediatric patients.

Cardiovascular screening in Williams syndrome (Dadlani, et al.) details a systematic screening approach for clinicians caring for patients with Williams syndrome, a rare genetic disorder, to use for the detection of cardiovascular disease to help prevent sudden cardiac arrest.

Severe cardiac dysfunction in a patient with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19: Retrospective diagnosis of a puzzling presentation. A case report (Vari, et al.) reviews key details in the care, diagnosis, and treatment of one of the first U.S. cases of MIS-C. This and subsequent cases at Nemours led to the development of clinical guidelines for the evaluation and care of children with this novel presentation of COVID-19.

The evolution of fetal echocardiography before and during COVID-19 (Nigam, et al.) highlights changes made in fetal echocardiography for screening critical congenital heart disease during the COVID-19 pandemic, and guidance for using a fetal tele-echocardiography approach in the future.

"There are gaps in awareness about how to complete high quality echocardiograms that will allow us to diagnose congenital anomalies that can be life-threatening," said Shubhika Srivastava, MD, an author on several articles in the issue, and chief of pediatric cardiology at Nemours/A.I. duPont Hospital for Children in Delaware. "Standardization and continued quality improvement through the review of best practices, like those outlined in the issue, allow for a continuous learning environment leading to consistent approaches, fewer errors and better patient outcomes."

The special issue's articles, authored and co-edited by physicians from Nemours' Cardiac Centers, stem from Nemours' deep expertise in pediatric cardiology. The multi-state health system has world-class Cardiac Centers at its two free-standing children's hospitals with dedicated surgical suites, interventional and electrophysiology labs, cardiac intensive care units, non-invasive imaging exercise physiology labs. The two hospitals are united via a common electronic medical record and imaging systems. Each site has dedicated cardiac surgeons, anesthesiologists, intensivists, interventional cardiologists, electrophysiologists, pediatric cardiologists, cardiac genetics, psychologists, nurse practitioners and nurses committed to providing exceptional cardiac care.

In a new paper published in the Harvard Kennedy School Misinformation Review, researchers from the George Washington University, University of Maryland and Johns Hopkins University assessed content from the most active vaccine-related accounts on Twitter and found that even accounts with pro-vaccination views and higher public health credibility can be vectors of misinformation in the highly uncertain and rapidly changing environment caused by the COVID-19 pandemic.

The researchers sought to better understand how existing online communities contributed to an “infodemic” during the early stages of the pandemic. In February 2020, the World Health Organization warned that the growing infodemic – a deluge of both accurate and inaccurate health information – would be a major challenge in sharing effective health communication during the COVID-19 pandemic.

Of the 2,000 Twitter accounts assessed, the researchers found:

Even well-meaning vaccine proponents shared unreliable information about COVID-19 and vaccines, though at a lower rate than vaccine opponents and other low-credibility sources. According to the researchers, the novel nature of the pandemic meant that emerging data often corrected initial content, making it possible for well-meaning, credible sources to post information that later proved false.
Vaccine opponents shared the greatest proportion (35%) of unreliable information, including a mix of conspiracy theories, rumors and scams.
Among both vaccine proponents and vaccine opponents, the largest single topic of conversation was “disease and vaccine narratives,” where users made comparisons between COVID-19 and other diseases, most notably influenza. The researchers noted these messages likely added to public confusion around COVID-19 and the seriousness of the virus and disease.
Much of the misinformation came from actual people as opposed to bots.
By focusing on only the most conspicuous forms of misinformation perpetuated by anti-vaccination and other low-credibility sources — such as blatant conspiracy theories, bot-driven narratives and known communities linked by conspiracist ideologies — scholars may fail to address the more subtle types of falsehoods that could be shared more broadly.

*Note: For a full graphic illustration figure of the results that you may use in your stories, see:
https://diabetologia-journal.org/wp-content/uploads/2020/08/Yuan-GA.pdf

A new 'global atlas' study published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) is the first to identify insomnia as a risk factor associated with increased risk of developing type 2 diabetes (T2D). The study identifies 34 risk factors that are thought to increase (19) or decrease risk (15), as well as a further 21 'suggestive' risk factors where evidence was not quite as strong.

The study by Associate Professor Susanna Larsson and by Shuai Yuan of the Karolinska Institutet, Stockholm, Sweden, used a technique called 'Mendelian Randomisation' (MR), which uses genetic variation as a natural experiment to investigate the causal relations between potentially modifiable risk factors and health outcomes in observational data. MR is less likely to be affected by confounding or reverse causation than observational studies.

To identify possible risk factors for T2D, the authors conducted a review of meta-analyses and review articles in the PubMed database and found 1,360 relevant articles. They found a total of 97 risk factors that could be investigated using the MR method. For the study population, they used summary-level data from the DIAbetes Genetics Replication And Meta-analysis consortium (74,124 type 2 diabetes cases and 824,006 controls of European ancestry). The team then checked that these potential causal associations could be replicated in a separate independent population, using the FinnGen consortium (11,006 type 2 diabetes cases and 82,655 controls of European ancestry).

They found evidence of causal associations between 34 exposures (19 risk factors and 15 protective factors) and T2D. Insomnia was identified as a novel risk factor, with people with insomnia being 17% more likely to develop T2D than those without.

The other 18 risk factors for T2D were depression, systolic blood pressure, starting smoking, lifetime smoking, coffee (caffeine) consumption, blood plasma levels of the amino acids isoleucine, valine and leucine, liver enzyme alanine aminotransferase (a sign of liver function), childhood and adulthood body mass index (BMI), body fat percentage, visceral (internal) fat mass, resting heart rate, and blood plasma levels of four fatty acids.

The 15 exposures associated with a decreased risk of type 2 diabetes were plasma alanine (an amino acid), high density lipoprotein (good cholesterol) and total cholesterol, age at beginning puberty in women (menarche), testosterone levels, sex hormone binding globulin levels (adjusted for BMI), birthweight, adulthood height, lean body mass (for women), four plasma fatty acids, circulating vitamin D and years of education.

After adjusting for adulthood BMI, 8 risk factors remained statistically significantly associated with T2D risk, suggesting they are independent of body weight (see figure 2 full paper). Insomnia remained as one of these factors, however the increased risk for those with insomnia compared to those without fell from 17% to 7% after adjustment for BMI, indicating that part of the effect of insomnia on T2D risk is mediated by BMI. Systolic blood pressure, lifetime smoking and levels of liver enzyme remained as risk factors (positively associated with T2D). Increasing total cholesterol, good cholesterol, testosterone levels and sex hormone levels remained as protective factors (inversely associated with T2D) after adjustment.

Among the further 21 'suggestive' causal factors for type 2 diabetes (where the evidence was weaker than for the other factors above) were alcohol consumption, breakfast skipping, daytime napping, short sleep, urinary sodium (salt) levels, and certain amino acids and inflammatory factors.

The authors conclude: "Our study confirmed several previously established risk factors and identified novel potential risk factors for type 2 diabetes using the latest summary-level data. Findings should inform public health policies for the primary prevention of type 2 diabetes. Prevention strategies should be constructed from multiple perspectives, such as lowering obesity and smoking rates and levels, and improving mental health, sleep quality, educational level and birthweight."

WASHINGTON, September 8, 2020 -- Hepatocellular carcinoma is a particularly stubborn form of cancer with few treatments and a high mortality rate. It is usually treated by blocking the flow of blood to the tumor to induce cancer cell death. The common treatment, transarterial chemoembolization, is invasive and too imprecise to be a local drug delivery method.

Aiming to increase the precision, researchers at Tulane University created a combination treatment that involves vaporizing tiny droplets of perfluorocarbon, a common organic material composed of carbon and fluorine that is used in pharmaceuticals, anesthetics, and industrial fluids. The method of gas embolization, published in APL Bioengineering, by AIP Publishing, is relatively new, and it is the authors' specialty.

"By changing the treatment parameters in this paper, we were able to achieve tumor regression, and by combining our method with chemotherapy, we were able to reduce regrowth following treatment," author Joseph Bull said. "Gas embolization has never been used in patients. Demonstrating that it can induce tumor regression is really new. We're very excited about the work in this paper."

Their study tested gas embolization alone and in combination with two common cancer drugs, doxorubicin (DOX) and tirapazamine. Gas embolization stops blood flow to the tumor, and it was highly effective used in combination with DOX.

In the gas embolization method, perfluorocarbon liquid is administered intravenously, and it interacts with DOX that has been administered in the body. DOX binds to the surface of the droplets of liquid, which are small enough to travel through capillaries and do not cause blood vessel blockage until they are vaporized, so treatment can be applied at the specific site of the tumor.

To turn these tiny liquid droplets into microbubbles and cut off the blood flow to the tumor, ultrasound is applied from outside the body. The fluid mechanical interface of the droplet focuses the ultrasound in a cavitationlike event, in which gas bubbles inside the liquid droplet grow due to a drop in pressure, until the droplet turns completely into microbubbles.

The drug DOX binds to the shell of the droplet, and the medicine becomes available to diffuse into the tumor, while the microbubbles cut off blood supply to the tumor.

The combination of gas embolization and DOX was so effective that, on average, tumors shrank to 2.9% of their initial size, while using DOX alone slowed tumor growth but still allowed them to grow to 300% of their initial size.

The cover for issue 36 of Oncotarget features Figure 7, "Knockdown of APOBEC3B is associated with a lower tumor growth in an adrenocortical carcinoma xenograft mouse model," by Gara, et al. which reported that the role of APOBEC3B in adrenocortical carcinoma and the mechanisms through which its expression is regulated in cancer are not fully understood.

Here, the authors report that APOBEC3B is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. They show high APOBEC3B expression is associated with a higher copy number gain/loss at chromosome 4 and 8 and TP53 mutation rate in ACC.

GATA3 was identified as a positive regulator of APOBEC3B expression and directly binds the APOBEC3B promoter region.

Both GATA3 and APOBEC3B expression levels were associated with patient survival.

This Oncotarget study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability.

This Oncotarget study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability.

Dr. Electron Kebebew from Stanford University said, "Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy."

The distinct pattern of DNA base alterations has been characterized in the cancer genome using high throughput deep sequencing technologies, that reflect the underlying mutational process.

Whole-genome and exome mutation analysis of The Cancer Genome Atlas data on multiple cancers has revealed that this pattern is consistent with the deaminase activity of the AID/APOBEC family of enzymes, therefore, implying its significance as an endogenous mutator and a crucial contributor to somatic mutations and genomic instability.

APOBEC3B is overexpressed in ovarian cancer cell lines and high-grade primary ovarian cancers.

In addition, APOBEC3B expression is positively correlated with the total mutation load, as well as, elevated levels of transversion mutations.

Given there are no well-established exogenous factors associated with ACC, the Oncotarget authors postulated whether APOBEC3B could be an endogenous mechanism of genomic instability/mutations in ACC and investigated its function in vitro and in vivo.

The Kebebew Research Team concluded in their Oncotarget Research Paper, "APOBEC3B overexpressed in ACC, and is associated with DNA damage, S phase arrest, higher copy number alterations and TP53 mutations in ACC. For the first time, we demonstrated that GATA3 directly regulates the expression of APOBEC3B and that both are prognostic markers in ACC."

PHILADELPHIA (September 8, 2020) - HIV prevention remains a public health priority in the United States. Pre-exposure prophylaxis (PrEP) is a drug regimen recommended for individuals who have engaged in behaviors that place them at elevated risk for HIV. When used consistently, daily oral PrEP has been shown to reduce HIV transmission by 99 percent. However, despite increases in PrEP awareness and uptake over the past several years, data show that four of five people who could benefit from PrEP did not access the medication in 2018.

In an article for the September issue of Health Affairs, researchers from the University of Pennsylvania School of Nursing (Penn Nursing) explored associations between state-level policies and PrEP uptake. They found that states with HIV criminalization laws (i.e., statutes that criminalize status non-disclosure) had a lower PrEP-to-need ratio, and states with comprehensive nondiscrimination laws for sexual and gender minorities had a higher PrEP-to-need ratio.

"Our study corroborates the growing consensus that HIV criminalization laws offer little to no public health benefit and inhibit HIV prevention efforts," says Stephen Bonett, PhD, RN, the first author of the article, and postdoctoral fellow at Penn Nursing's Program for Sexuality, Technology and Action Research (PSTAR).

"Given the evolving state of HIV prevention and the growing body of evidence showing that HIV criminalization may hinder public health efforts, state governments should move toward repealing HIV criminalization laws," the authors write. "In addition, legislative efforts should be directed toward improving access to HIV treatment and prevention and reducing stigma and discrimination against people living with HIV."

A new Boston University School of Public Health (BUSPH) study maps changes in homicide rates across Brazil from 2000 through 2014. Published in the journal Injury Epidemiology, the research shows the success of anti-violence efforts in major urban areas such as São Paulo, Rio de Janeiro, and Espirito Santo, but the explosion of homicides in fast-developing northeastern areas is a warning for other countries.

"As homicide rates decreased in municipalities with larger population sizes, it increased in municipalities with smaller population sizes," says study lead author Dr. Elaine Nsoesie, assistant professor of global health at BUSPH.

"This is a warning to other countries," says study senior author Adauto Martins Soares Filho, a technologist in health information systems in the Department of Health Surveillance at Brazil's Ministry of Health.

Brazil has a severe epidemic of lethal violence driven by drugs and arms trafficking and by land conflicts. Over the last two decades, the country has seen homicide rates go down in large cities even as the national rate continues to climb: Brazil had 63,880 homicides in 2017 (the most recent year with available data), its highest ever recorded.

To understand how Brazil's geography of violence has changed, the researchers used data from the Brazil Ministry of Health Mortality Information System and sociodemographic data from the Brazil Institute of Geography and Statistics, and created space-time models to identify patterns in homicide rates and assess the roles of different structural factors.

The researchers found that the strongest predictors for an area having a higher homicide rate included higher crude domestic product, being near an international border, and having a larger proportion of the population between the ages of 15 and 29. They also found that, as efforts to reduce violence in large cities succeeded, that violence appeared to simply move to neighboring, less urban areas.

"We propose the need for policies that account for possible spatial spillover as interventions are focused on particular locations," Nsoesie says. "We also propose adopting policies that address the increase in poverty rates in specific populations that tends to occur in tandem with economic development."

But Nsoesie and Soares Filho acknowledge that the challenges are enormous, especially now that the COVID-19 pandemic threatens to reverse decades of progress in many areas--and as the government enacts policies that threaten to increase fatal violence, such as the country's 2019 law loosening gun ownership restrictions.

"A successful trajectory in reducing homicides depends on the political will and capacity to lead the construction of a peaceful, just, and inclusive society," Soares Filho says.

A new UCLA study shows partially overlapping patterns of brain function in people with anorexia nervosa and those with body dysmorphic disorder, a related psychiatric condition characterized by misperception that particular physical characteristics are defective.

The study, published in the peer-reviewed journal Brain Imaging and Behavior, found that abnormalities in brain function are related to severity of symptoms in both disorders, and may be useful in developing new treatment methods.

The results reinforce the understanding that eating disorders and body dysmorphic disorder are more than simply choosing to eat or not eat or not liking how you look. "These are brain abnormalities, and how we treat those brain abnormalities could be with psychotherapy, or psychiatric medications, but brain changes need to happen in order to address these disorders," says Dr. Wesley Kerr, neurology resident and biostatistics researcher at UCLA.

For the study, the researchers recruited 64 female participants: 20 with anorexia nervosa, 23 with body dysmorphic disorder, and 21 healthy controls. Patients with anorexia nervosa have a distorted body image and an intense fear of gaining weight, leading them to eat very little. Body dysmorphic disorder (BDD) is characterized by obsessions with a particular body part or a perceived flaw rather than with weight.

Participants were shown images of male and female bodies while researchers observed their brain activity via MRI. Three types of images were used: normal photos, "low spatial frequency" (LSF) images, which had details blurred out, and "high spatial frequency" (HSF) images, in which the edges and details were accentuated.

Functional MRI is a brain imaging technique that detects the blood flow within the brain, allowing researchers to see which parts of the brain are active while a person is doing various tasks. It can also be used to understand what brain regions' activities are in sync with each other; that is, "connected."

Each of the women performed a "matching" task while inside the MRI scanner. On the top of the screen, the person would see an image of a body, and would have to choose the matching body from two images shown on the bottom of the screen.

While viewing the images that differed from those of healthy individuals, people with anorexia nervosa and those with BDD showed patterns of activity and connectivity in visual and parietal brain networks. These abnormalities in activity were different in BDD and anorexia nervosa, whereas the connectivity abnormalities were largely similar. The more severe the symptoms, the more pronounced the pattern of brain activity and connectivity when the images were viewed, particularly for the LSF images. Further, connectivity and activity abnormalities were associated with how the participants judged the appearance and body weight of the individuals in the photos.

What the researchers saw indicated that while the brains of patients with anorexia nervosa and those with BDD abnormally process images with high, low, or normal levels of detail, the abnormalities for low level of detail, that is "low spatial frequency" images, have the most direct relationships to symptom severity and body perception. The results may help researchers understand the underlying neurobiology that leads to the characteristic body image distortions in both cases.

"This gives us a clearer picture of neurological basis for what is one disorder, what is the other, and what characteristics they share," said Dr. Jamie Feusner, senior author and professor of psychiatry and biobehavioral sciences at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.

A next step for the research will be to see whether, with existing psychotherapy and medication treatments, the brain activity in patients begins to normalize, or else changes in a different way to compensate for underlying abnormalities.

New research from Texas A&M University and the University of Pennsylvania on opioid prescribing practices across the country after outpatient knee surgeries found that prescription strength and number of tablets is prescribed highest in Oklahoma and lowest in Vermont.

The study led by Benjamin Ukert, PhD, assistant professor in the Health Policy and Management department at the Texas A&M University School of Public Health, along with colleagues from the University of Pennsylvania, analyzed the rates and dosages of opioid prescriptions after arthroscopic knee surgery from January 2015 to June 2019. The researchers used data on health insurance claims from a large national private health insurer that operates in all 50 states and insures 7.5 million people each year.

Higher prescription rates were found in Arizona, Washington State, Ohio, Utah and others, with lower rates in Texas, South and North Dakota and largely along the east and west coasts. Of interest were the number of tablets per prescription and the strength of the medication measured in morphine milligram equivalent (MME).

The researchers analyzed data on nearly 100,000 opioid knee surgery patients. They found that patients who received a prescription were more likely to be younger, male and white, to have higher income and education levels and to have undergone a more invasive procedure involving bone. Prescription data showed a wide variation in the number of tablets and MME from state to state. Vermont had the lowest median tablet quantity and MME (24.1 and 157) and Oklahoma had the highest (44.9 and 371). The Centers for Disease Control and Prevention has determined 50 MME per day as being the threshold for increased risk of opioid overdose death.

Pain should not vary from state to state, thus the wide variation in prescribing shows that there is room to adjust prescribing practices. Ukert and colleagues estimate that over 5 million MME could have been prevented from being distributed if the MME level would not have exceeded the median total MME dosage in each year.

Using practices in states with lower quantities and MME levels as a guide, it may be possible to develop prescribing guidelines that allow effective pain management while reducing the risk of opioid misuse. With better guidance, physicians can help patients manage post-surgical pain while significantly reducing the risks of opioid misuse and unintentional death.

Metastases are formed by cancer cells that break away from the primary tumor. A research group at the University of Basel has now identified lack of oxygen as the trigger for this process. The results reveal an important relationship between the oxygen supply to tumors and the formation of metastases. This research may open up new treatment strategies for cancer.

The chances of recovery significantly worsen when a tumor metastasizes. Previous research has shown that metastases are formed by clusters of cancer cells that separate from the primary tumor and migrate to new tissue through the bloodstream. However, thus far little has been known about why these clusters of circulating tumor cells (CTCs) leave the tumor in the first place.

Lack of oxygen leads to more metastases

Professor Nicola Aceto's research group at the University of Basel's Department of Biomedicine has now shown that a lack of oxygen is responsible for the separation of CTC clusters from the tumor. This is an important starting point for the development of new cancer treatments.

A mouse model for breast cancer formed the basis of the experiments: the researchers analyzed the oxygen supply inside these tumors, which are equivalent to human cancer tissue, the detachment of CTCs and their molecular and cell biological properties.

It turned out that different areas of a tumor are supplied with different levels of oxygen: cancer cells with a lack of oxygen were found wherever the tumor had comparatively fewer blood vessels - in the core of the tumor as well as in clearly defined peripheral areas. Next, the research team investigated the CTC clusters that had separated from these tumors and found that they similarly suffered from a lack of oxygen. This led to the conclusion that cells leave the tumor if they do not receive enough oxygen. "It's as though too many people are crowded together in a small space. A few will go outside to find some fresh air," says Aceto.

Further experiments showed that these CTC clusters with a lack of oxygen are particularly dangerous: in comparison to clusters with normal oxygen content, they formed metastases faster and shortened the mice's survival time. "If a tumor does not have enough oxygen, these CTC clusters, which have a particularly high potential to develop metastases, will break away," says Aceto.

Stimulating blood vessel formation as a treatment approach

This insight led the researchers to take a closer look at the effect of what is called proangiogenic treatment: they stimulated the formation of blood vessels, thus boosting the supply of oxygen to the tumor cells. As expected, the number of separating CTC clusters dropped, the mice formed fewer metastases, and they lived longer - but at the same time, the primary tumor increased in size significantly.

"This is a provocative result," says Aceto. "If we give the tumor enough oxygen, the cancer cells have no reason to leave the tumor and metastasize. On the other hand, this accelerates the growth of the primary tumor."

The next challenge is to transfer these findings to a clinical environment, where the characteristics of tumors vary from patient to patient: "But we speculate that substances that improve oxygen supply to the tumor can inhibit the formation of metastases in breast cancer, alone or in combination with other agents."

New research led by the University of South Australia shows that a blanket approach to prescribing medication during pregnancy may put low birth weight babies at risk for the rest of their lives.

UniSA and New Zealand fetal physiologists say that smaller fetuses metabolise medication taken by the mother in a less efficient way than normal weight babies, which may lead to long term health consequences.

In a review published in Placenta, UniSA Professor Janna Morrison says growth restricted babies may be exposed to higher concentrations of some prescribed or over-the-counter drugs that a woman takes during pregnancy due to a 'one size fits all' approach when it comes to dosing.

"If the fetus is smaller and a mother takes 20 milligrams of a drug, it may effectively be a higher dose than in a normal sized baby," Prof Morrison says. "The actual drug doesn't make the fetus smaller, but if it is already smaller, the fetus may be less able to metabolise the drug and get rid of it."

"The idea that a complicated pregnancy is different from a normal pregnancy is new in terms of drugs that may be metabolised by the fetus," Prof Morrison adds.

The researchers looked at how enzymes that break drugs down are less effective in growth restricted fetuses.

Globally, one in seven babies are born under 2500 grams due to the placenta failing to deliver adequate nutrients and oxygen to the fetus. This can be linked to pre-eclampsia, poor placental development or smoking.

Intrauterine growth restricted (IUGR) babies are at increased risk of diabetes, heart diseases, lower immunity and metabolic diseases throughout their life and may themselves require drug treatments in adulthood. It is not known if they will metabolise these drugs differently.

"We know that most women take prescription or over-the-counter drugs during pregnancy, either to treat a condition they suffer from themselves, or to treat a condition in the unborn child," according to UniSA Assoc Prof Michael Wiese.

"For example, gestational diabetes affects up to 15 per cent of women, requiring insulin. In Australia, 13 per cent of women take antidepressants during pregnancy, 11 per cent have asthma, 18 per cent have cardiovascular disease and 4.6 per cent have diabetes.

"The use of drugs to treat vomiting is also common, with at least one in five pregnant women taking medications such as Ondansetron," Assoc Prof Wiese says.

The researchers say that neither the drug companies nor doctors are at fault as there are no existing guidelines for administering dosages based on complicated pregnancies.

"Based on our findings, however, we believe that more work needs to be done to better understand the interaction between pregnancy and fetal growth on how drugs are metabolised. It would then be possible to determine the right dosages for both mother and unborn child," Prof Morrison says.

The dosages could be lower or higher depending on how the fetus metabolises the drug.

"It doesn't automatically correlate that a lower dose would be better if the fetus metabolises it faster. It may mean that with some complicated pregnancies, a higher dosage is needed with some drugs. It's about making sure that the right dose is given to help the mother, without harming the baby."