Culture

Researchers from the Department of Chemistry, Materials and Chemical Engineering "Giulio Natta" of the Politecnico di Milano and the Pediatric Research Center, Department of Biomedical and Clinical Sciences "L. Sacco ", University of Milan have recently published an article in the scientific journal Theranostics, which will help the international scientific community to understand the mechanisms of SARS-CoV-2 infection and to develop vaccines and therapeutic agents against COVID-19.

Starting from a careful analysis of the frontier technological tools by which infections are studied and new drugs and vaccines are tested, the researchers have come to affirm that the most suitable ones, and therefore those that could accelerate the discovery and preclinical development of antiviral drugs and vaccines for COVID-19, are undoubtedly the most innovative modeling tools such as 3D supports for cell cultures, microfluidic chambers for the culture of organoids and intravital microscopy in animals.

Specifically, the authors indicate some excellent research tools for this purpose, developed in the last ten years by the research group of Professor Manuela T. Raimondi of the Politecnico di Milano as part of the three ERC projects coordinated by her (NICHOID, NICHOIDS and MOAB): artificial niches for stem cell culture, microfluidic bioreactors for tissue culture, and miniaturised imaging windows for intravital microscopy.

Some of these devices are already used for research on neurodegenerative diseases in collaboration with the group of Dr. Stephana Carelli at the Pediatric Research Center of the University of Milan. In addition, the team of Prof. Raimondi at the Politecnico di Milano has developed a lymph node model engineered inside a miniaturised bioreactor called MOAB, which allows to study immunization mechanisms such as those produced by vaccines. These research tools are much more realistic than conventional ones and could even replace much of the pre-clinical research currently conducted on animals.

The Gerontological Society of America's highly cited, peer-reviewed journals are now publishing scientific articles on COVID-19. The following were published between May 26 and June 3; all are free to access:

APOE E4 Genotype Predicts Severe COVID-19 in the UK Biobank Community Cohort: Letter to the editor in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by Chia-Ling Kuo, PhD, Luke C. Pilling, PhD, Janice L. Atkins, PhD, Jane A. H. Masoli, MBChB, João Delgado, PhD, George A. Kuchel, MD, and David Melzer, MBBCh, PhD

COVID-19 Worries and Behavioral Changes in Older and Younger Men and Women: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Sarah J. Barber, PhD, and Hyunji Kim, MA

Age differences in COVID-19 risk perceptions and mental health: Evidence from a national US survey conducted in March 2020: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Wändi Bruine de Bruin, PhD

Understanding and Addressing Older Adults' Needs During COVID-19: Editorial in Innovation in Aging by Laura P. Sands, PhD, FGSA, Steven M. Albert, PhD, FGSA, and J. Jill Suitor, PhD, FGSA

New Infographics

Understanding Ageism and COVID-19 [https://www.geron.org/images/gsa/reframing/AgeismInfographic_final.pdf], which highlights several false narratives about older adults in the pandemic and reframes them in the context of science.

Aging and Immunity: Why Older Adults Are Highly Susceptible to Diseases Like COVID-19 [https://www.geron.org/images/navp/AgingImmunity_FINAL.pdf], which addresses why older adults are highly susceptible to diseases like COVID-19 and how manufacturers are compressing the timeline to bring a COVID-19 vaccine to market.

Researchers from North Carolina State University and the University at Buffalo have developed a technology called "Artificial Chemist," which incorporates artificial intelligence (AI) and an automated system for performing chemical reactions to accelerate R&D and manufacturing of commercially desirable materials.

In proof-of-concept experiments, the researchers demonstrated that Artificial Chemist can identify and produce the best possible quantum dots for any color in 15 minutes or less. Quantum dots are colloidal semiconductor nanocrystals, which are used in applications such as LED displays.

However, the researchers are quick to note that Artificial Chemist can identify the best material to meet any suite of measurable properties - not just quantum dots.

"Artificial Chemist is a truly autonomous system that can intelligently navigate through the chemical universe," says Milad Abolhasani, corresponding author of a paper on the work and an assistant professor of chemical and biomolecular engineering at NC State. "Currently, Artificial Chemist is designed for solution-processed materials - meaning it works for materials that can be made using liquid chemical precursors. Solution-processed materials include high-value materials such as quantum dots, metal/metal oxide nanoparticles, metal organic frameworks (MOFs), and so on.

"The Artificial Chemist is similar to a self-driving car, but a self-driving car at least has a finite number of routes to choose from in order to reach its pre-selected destination. With Artificial Chemist, you give it a set of desired parameters, which are the properties you want the final material to have. Artificial Chemist has to figure out everything else, such as what the chemical precursors will be and what the synthetic route will be, while minimizing the consumption of those chemical precursors.

"The end result is a fully autonomous materials development technology that not only helps you find the ideal solution-processed material more quickly than any techniques currently in use, but it does so using tiny amounts of chemical precursors. That significantly reduces waste and makes the materials development process much less expensive."

The Artificial Chemist has both a "body" for performing experiments and sensing the experimental results, and a "brain" for recording that data and using it to determine what the next experiment will be.

For their proof-of-concept testing, Artificial Chemist's body incorporated the automated Nanocrystal Factory and NanoRobo flow synthesis platforms developed in Abolhasani's lab. The Artificial Chemist platform has demonstrated that it can run 500 quantum dot synthesis experiments per day, though Abolhasani estimates it could run as many as 1,000.

The Artificial Chemist's brain is an AI program that characterizes the materials being synthesized by the body and uses that data to make autonomous decisions about what the next set of experimental conditions will be. It bases its decisions on what it determines will most efficiently move it toward the best material composition with the desired properties and performance metrics.

"We tried to mimic the process that humans use when making decisions, but more efficiently," Abolhasani says.

For example, Artificial Chemist allows "knowledge transfer," meaning that it stores data generated from every request it receives, expediting the process of identifying the next candidate material it is tasked with. In other words, Artificial Chemist gets smarter and faster over time at identifying the right material.

For their proof of concept, the researchers tested nine different policies for how the AI uses data to decide what the next experiment will be. They then ran a series of requests, each time asking Artificial Chemist to identify a quantum dot material that was the best fit for three different output parameters.

"We found a policy that, even without prior knowledge, could identify the best quantum dot possible within 25 experiments, or about one-and-a-half hours," Abolhasani says. "But once Artificial Chemist had prior knowledge - meaning that it had already handled one or more target material requests - it could identify the optimal material for new properties in 10 to 15 minutes.

"We found that Artificial Chemist could also rapidly identify the boundaries of materials properties for a given set of starting chemical precursors, so that chemists and materials scientists do not need to waste their time on exploring different synthesis conditions.

"I believe autonomous materials R&D enabled by Artificial Chemist can re-shape the future of materials development and manufacturing," Abolhasani says. "I'm now looking for partners to help us transfer the technique from the lab to the industrial sector."

LEBANON, NH - A research team at Dartmouth's and Dartmouth-Hitchcock's Norris Cotton Cancer Center has found that the same vaccination programs that target human papillomavirus (hrHPV) strains in the United States may not be as effective in protecting other populations of women from the disease. Years of work in Honduras, led by Gregory J. Tsongalis, PhD, has shown a very different prevalence of hrHPV there compared to the U.S. The majority of cervical cancers are caused by persistent infection with hrHPV with different vaccines available to protect against HPV infection. These findings, "HPV, Vaccines, and Cervical Cancer in a Low- and Middle-Income Country" are newly published in Current Problems in Cancer.

"After testing 2,645 women from multiple locations in Honduras for types of hrHPV and finding the prevalence of virus types to be quite different from those in the U.S., we asked what vaccine would be the most efficacious for the local situation, and which hrHPV types are most commonly found in cervical cancer tissues from Honduran women," says Tsongalis. "The divalent vaccine against two HPV types and quadrivalent vaccine against four HPV types would only protect approximately half of women infected with this virus in Honduras. The most expensive vaccine would protect the majority of women, however many vaccination programs in low- and middle-income countries use the less costly vaccine, and these vaccines are not providing adequate protection."

Appropriately vaccinating against HPV would help reduce the incidence of cervical cancer, however Tsongalis cautions that it's important to understand what it is that's being vaccinated against.

Infants born prematurely may require parenteral or intravenous nutrition to provide the necessary nourishment, as their digestive system is immature and cannot digest nutrients. However, prolonged parenteral nutrition is associated with complications, including cholestasis, or lack of bile flow from the liver into the small intestine, which leads to accumulation of bile acids and injury in the liver. Emerging clinical studies have shown that cholestasis can be prevented in preterm infants with parenteral administration of oil emulsions ? mixtures made of multiple oil components ? but the mechanism mediating this effect remains unclear.

Working with preterm piglets, an international group led by researchers at the USDA-ARS Children's Nutrition Research Center (CNRC) at Baylor College of Medicine and Texas Children's Hospital found evidence that the protective effect of parenteral oil infusions is accompanied by changes in the levels of gut bile acids (gut bile acid pools) and in the gut microbiome, making this study the first to connect parenteral oil infusions, the microbiome, metabolism and health. The study appears in the Journal of Lipid Research.

Studying parenteral oil emulsions

"The piglet model enables us to study parenteral nutrition-associated liver diseases, such as cholestasis, in a way that is clinically relevant," said senior author Dr. Douglas Burrin, research physiologist at the CNRC and professor of pediatrics at Baylor. "We treat preterm piglets similarly to how we treat preterm infants in the hospital and look at liver function and gene expression in the piglets to better understand the physiology."

The original lipid emulsion developed for parenteral nutrition in infants was based on one component, soybean oil, and it has been the only parenteral lipid option used for preterm infants for about 45 years. Although this oil emulsion has helped support infants' growth, physicians have been concerned that it could be involved in the development of several conditions, including liver disease. This prompted the development of new lipid emulsions with multiple oil components to prevent or treat parenteral nutrition-associated liver diseases.

When the first fish-oil and multicomponent lipid emulsions became available, Burrin and his colleagues were the first group to examine their metabolic effects in parenterally fed, preterm piglets. They published their first findings in 2014. The Baylor researchers and others have shown that pure fish oil and multicomponent oil lipid formulations can reduce cholestasis associated with long-term parenteral nutrition, but how this happens still is not completely understood.

In the current study, the researchers expanded their original investigations by comparing two previously studied oil emulsions ? soybean oil only (Intralipid) and a combination of soy, olive, coconut and fish oils (SMOFlipid) ? and a new experimental formulation (EXP), that was similar to SMOFlipid, but with additional DHA, an omega-3 fatty acid, and arachidonic acid.

An additional experimental group (ENT) used for reference consisted of piglets fed infant formula through a feeding tube. The experiment lasted 22 days.

New insights into how parenteral oil emulsions work

The researchers evaluated the effects of the different oil emulsions in preterm piglets by measuring cholestasis, gut bile acids pools and the composition of microbial communities in the colon as well as the profiles of the microbes' metabolic products or metabolites.

The findings confirmed that multicomponent oil emulsions (SMOF and EXP), but not Intralipid, can prevent cholestasis and restore bile flow in preterm piglets as observed in the ENT group.

"One of the important findings showed that prevention of cholestasis was accompanied by maintaining normal gut bile acid pools. They were lowest in the piglets treated with Intralipid but increased in the SMOF and EXP groups and were comparable to ENT," Burrin said.

A particularly interesting new finding was that cholestasis was associated with changes in the gut microbiome and their metabolite profile.

"It's exciting to see such a direct connection between gut bacteria and the lipid composition of parenteral nutrition," said first author Dr. Lee Call, a former Translational Biology and Molecular Medicine graduate student in the Burrin lab during the development of this work. Call currently is a postdoctoral fellow at Department of Energy Joint Genome Institute at Lawrence Berkeley National Lab.

"At first it may not seem likely that intravenous lipids could have a large effect on bacterial growth in the intestine, but in fact we see that there is a strong correlation between the type of lipids given parenterally and the relative abundance of certain groups of gut bacteria. And it seems that bile is the connecting link," Call said. "These results help us understand more about the effects of parenteral nutrition, which is often a life-saving treatment for preterm babies."

"We have been certain that the lipid emulsions contribute an important effect on growth and metabolism, but the mechanism and the direct causal effect was lacking. This work provides those missing links that offer newer insights that will go a long way in the development of better, safer lipid emulsions for use in preterm infants. It is exciting to be a part of this discovery," said co-author Dr. Muralidhar Premkumar, assistant professor of pediatrics-newborn at Baylor and Texas Children's.

Study Highlights

The Nurr1 protein maintains the health of neurons that produce dopamine and die off during the progression of Parkinson's disease.

Hormone-like compounds called prostaglandin A1 and E1 bind to and activate Nurr1.

Prostaglandin A1 or E1 treatment lessened symptoms in a mouse model of Parkinson's disease.

Investigators have identified two molecules naturally produced by the body that stimulate the production of dopamine, the molecule that is in short supply in the brains of patients with Parkinson's disease. Stimulating dopamine production may help reverse the progression of the disease. The research was led by scientists at McLean Hospital in collaboration with scientists at Nanyang Technical University, Singapore, and published in the journal Nature Chemical Biology.

The team designed the study based on the knowledge that a protein called Nurr1 is key for maintaining the health of neurons that produce dopamine, which helps control a person's movements and emotions. It is thought that decreased Nurr1 effectiveness may lead to a decrease in dopamine levels, which then results in the development of Parkinson's disease.

"We thought that small molecules that can activate Nurr1 may be promising drug candidates to treat Parkinson's disease. After many years of research, in 2015, we found three FDA-approved drugs that bind to Nurr1 and activate it," explained senior author Kwang-Soo Kim, PhD, director of the Molecular Neurobiology Lab at McLean Hospital and a professor of psychiatry at Harvard Medical School. "This finding prompted us to hypothesize that there may be natural molecules--that is, endogenous ligands--that also bind to Nurr1 but don't have side effects."

When the scientists looked for such molecules in various tissues from mice, they found hormone-like compounds called prostaglandin A1 and E1 as promising candidates that bound to and activated the Nurr1 protein. The collaborative team also created a model depicting the structure of these molecules when they are bound to the Nurr1 protein by performing X-ray co-crystallography and nuclear magnetic resonance studies. This information will be critical as treatment strategies that target Nurr1 are optimized.

The investigators showed that physiological concentrations of prostaglandin A1 or E1 in the nanomolar ranges can protect dopamine neurons against neurotoxins. Next, the investigators found that when mouse models induced to develop symptoms similar to Parkinson's disease were treated with prostaglandin A1 or E1, the animals' motor skills and functions improved significantly without any signs of side effects, such as abnormal dyskinesia-like behavior. Analyses of the animals' brains revealed that the treatment protected the dopamine-producing brain cells from dying and made them produce higher levels of dopamine.

"Although we showed that these molecules can correct Parkinson's-like symptoms in animal models in a neuroprotective manner, further studies are essential to determine whether they can work in human clinical trials," said Kim.

ABERDEEN PROVING GROUND, Md. (June 4, 2020) -- As the U.S. Army revamps its small arms training and raises rifle qualification standards, researchers are studying alternative training and tools to help improve Soldier performance.

The U.S. Army Combat Capabilities Development Command's Army Research Laboratory, Army Medical Department Field Element, located at Fort Sam Houston, Texas, recently conducted a series of examinations of neurocognitive temporal training and Soldier performance.

"Recent armed conflicts require close quarter warfare tactics, re-emphasizing the need of military marksmanship in combat ground operations," said Dr. Valerie Rice, a licensed occupational therapist, and human factors engineer at the laboratory. "We conducted a series of examinations of neurocognitive temporal training and Soldier performance."

The first studies found positive associations between neurocognitive temporal assessment scores and service members' academic scores, Army physical fitness test scores, musculoskeletal injuries and consequent lost duty days and symptoms of attention deficits during advanced individual training, researchers said.

"Recently, a consequent study examined the training for improving basic rifle marksmanship," Rice said. "In all studies, the interactive metronome, or IM, was used to measure temporal abilities and to administer the neurocognitive temporal training. This is the first use of the IM device for examining and training military essential skills."

Rice said the device was originally developed for use with children experiencing learning and attention difficulties, however its successful use has expanded to other patient and non-patient populations.

"The IM provides visual and auditory stimuli and feedback -- paired with physical exercises involving coordinated same-side and opposite-side movements of the upper and lower extremities," she said. "These activities purportedly strengthen neural pathways and signal transmission in the human brain, subsequently improving timing and rhythm capabilities--its use has been shown to improve cognition, attention, focus, memory, executive functioning, perceptual motor skills and sports performance."

Daily life activities involve fundamental physiological functions of voluntary and involuntary timing and rhythmic sequencing. For example, walking, reading, washing dishes and sports depend on a persons' timing and rhythm abilities.

"Similarly, there are fundamental rhythmic principles to rifle marksmanship," Rice said. "These principles include eye-to-sight-to-target alignment, breath and muscle control, eye-hand coordination and decision making. Taken together, the research and conception of timing and rhythm underlying movement patterns, suggests the training with the device could be beneficial to improving marksmanship performance among Soldiers, especially those who may experience attention or coordination difficulties."

Researchers measured marksmanship pre- and post-training with the engagement skills trainer, or EST 2000, using stationary and moving targets at two distances using measures of accuracy and measures of precision.

EST 2000 is a visual weapons simulator computer system designed to enable service members to carry out cost-effective marksmanship training and other weapon exercises in numerous environments without ammunition restrictions.

"Results revealed reduced variability and improved precision for self-paced firing at closer range, stationary targets for the training group, but not for the control group," Rice said. "No other significant differences were found."

A new marksmanship measure called total path length, or TPL, was also introduced during this study.

"TPL is a unique measure quantifying shot-to-shot variability, loosely based on a measure of balance known as center of pressure path length," said Leah Enders, researcher and one of the authors on the research paper. "This measure gave researchers a closer look at how the neurocognitive temporal training impacted shot-to-shot realignment."

Researchers said the results of this study suggest neurocognitive timing and rhythm training can improve marksmanship precision and that TPL is a sensitive and useful marksmanship performance measure.

"The research concept and series were conceived by Dr. Rice, who used the IM device during her military career and achieved positive results with individual patients," said Gary Boykin, researcher and coauthor on the research paper. "She recognized its potential use with non-patient populations."

The Effects of Neurocognitive Temporal Training on Weapon Firing Performance study is published in the journal Perceptual and Motor Skills.

The liver filters blood, detoxifies chemicals and metabolizes drugs. Hepatitis, alcohol and primary liver diseases are common sources of damage in the liver and can result in scarring, known as fibrosis. Long-term fibrosis can lead to thicker liver tissue which in turn leads to other issues like increased blood pressure in the liver. Known as portal hypertension, high blood pressure in the liver is often unrecognized, and can be lethal.

Researchers at the Medical University of South Carolina (MUSC) who study liver disease have dissected one mechanism that regulates the activity of endothelial nitric oxide synthase (eNOS), an enzyme that produces nitric oxide (NO). Their results, published recently in the Proceedings of the National Academy of Sciences, showed that beta-arrestin2 (beta-Arr2) acts as a scaffolding protein to activate eNOS, leading to increased NO synthesis. Upon liver damage, levels of beta-Arr2 are decreased in epithelial cells causing a disruption in NO synthesis and an increase in portal hypertension. This research shows that beta-Arr2 is a potential therapeutic target.

"The molecular mechanisms that regulate eNOS function are complex and likely vary in normalcy and disease," said Don C. Rockey, M.D., professor and chair of the Department of Medicine at MUSC, who studies liver fibrosis and portal hypertension.

The Rockey Lab focuses on understanding the underlying mechanisms of portal hypertension. Liver sinusoidal endothelial cells (SECs) play a critical role in liver homeostasis. SECs control blood pressure and flow through the production of NO, which is produced by eNOS. As a signaling molecule, beta-Arr2 has been suggested to influence eNOS, but how these proteins interact to influence NO production was unclear.

The current work delineated the role of beta-Arr2 in regulating eNOS activity. In normal, healthy SECs, beta-Arr2 activated eNOS. In contrast, injured SECs showed a significant reduction in beta-Arr2 levels and decreased eNOS activity. Interestingly, overexpression of beta-Arr2 enhanced NO production in both normal and injured SECs. Furthermore, mice that lacked beta-Arr2 had a significant reduction in sinusoid area, highlighting the physiological effects of reduced eNOS activity. Together, these data show that beta-Arr2 is a critical regulator eNOS activity.

Previous work from the Rockey lab has shown that GPCR kinase-interacting protein-1 (GIT-1) is a potent activator of eNOS. Examination of GIT-1 localization revealed that GIT-1, beta-Arr2 and eNOS all localize together in SECs. Importantly, the loss of beta-Arr2 prevented the activation of GIT-1 and the subsequent activation of eNOS. Therefore, beta-Arr2 acts as a scaffolding protein to help activate GIT-1 and in turn activate eNOS.

In summary, healthy SECs produce NO by stimulating beta-Arr2, which then forms a signalosome, an active protein complex that helps transduce cell signals, to activate GIT-1. Active GIT-1 in turn activates eNOS to produce nitric oxide. In contrast, during liver injury, levels of beta-Arr2 are reduced and this pathway is perturbed.

"The big message is that eNOS signaling is complex and is controlled by multiple mechanisms and is dysregulated after injury to endothelial cells," said Rockey.

As a central component of the eNOS signaling axis, beta-Arr2 has the potential to be a novel therapeutic target for the restoration of SEC function. However, before a potential therapeutic makes it to the clinic, there are still several questions remaining about the biology of beta-Arr2. As a signaling scaffold that activates eNOS, it is important to determine what other proteins interact with beta-Arr2. Additionally, the Rockey lab is pursing the mechanism(s) that influence beta-Arr2's localization and/or activity.

New images of an enzyme in action as it interacts with the chromosome could provide important insight into how cells--including cancer cells--regulate their genes.

The enzyme, LSD1, can "turn off" gene expression by removing chemical flags (methyl groups) from the nucleosome--tightly packed units of DNA and protein in chromosomes. This LSD1 histone demethylase is over-expressed in multiple cancer types, resulting in disruption to normal cell development, and the new structure could inform therapeutic interventions that target the enzyme.

A paper by Penn State researchers describing the crystal structure of the LSD1-nucleosome complex publishes in the June 4 issue of the journal Molecular Cell and also explains the previously unclear but important role of a separate accessory protein, CoREST.

"While previous studies have imaged LSD1 and CoREST with only a small portion of the nucleosome--a histone tail--we managed to image these proteins with the entire nucleosome core particle to better understand their role in gene regulation," said Song Tan, professor of biochemistry and molecular biology, director of the Center for Eukaryotic Gene Regulation at Penn State, and leader of the research team. "We knew that LSD1 required the accessory protein CoREST in order to work on the nucleosome, but we didn't know what CoREST was doing. When we saw the structure, we were initially surprised but then realized everything made sense."

The research team found that LSD1 unexpectedly binds outside of the core of the nucleosome, where most activities on the nucleosome take place. LSD1 instead binds to DNA that extends away from the core, and CoREST acts as an intermediary, binding to both the nucleosome core and to LSD1.

"This was astonishing because all other enzymes that have been imaged bind directly to the nucleosome core where they do their job," said Tan.

The structure also explains how the CoREST accessory protein enables LSD1 to work on nucleosomes. The researchers believe that the LSD1-CoREST system could serve as a model for how other accessory proteins target chromatin enzymes to nucleosomes.

"LSD1 is like a pilot who needs a navigator to know where to go," said Tan. "The CoREST accessory protein acts as the navigator to target LSD1 to nucleosomes."

The research team also investigated a version of the LSD1 enzyme with a mutation believed to render it inactive. Such inactive mutants have been used to test the effects of eliminating LSD1's activity in cells. However, the team found that the mutant is actually active in the presence of the nucleosome.

"The LSD1 K661A mutant was presumed to be inactive based on assays using just a histone tail portion of the nucleosome," said Tan. "However, when we use the entire nucleosome core particle, which is more representative of what actually exists in the cell, we see that the mutant is very active. This means the conclusions of studies which used LSD1 K661A as an inactive mutant will need to be reassessed since the enzyme's activity was not actually eliminated."

DALLAS – June 4, 2020 – Surgeons at UT Southwestern Medical Center have pioneered a new technique that prevents nipple discoloration and preserves shape in men who undergo breast reduction surgery following significant weight loss.

The procedure, described in a paper published in Aesthetic Surgery Journal Open Forum, involves cutting below the lower part of the breast and lifting it like a flap up toward the collarbone to remove unwanted breast tissue surgically and reducing the extra skin of the chest.

Male breast reduction surgery is often performed on men who have lost over 100 pounds through lifestyle changes, bariatric surgery, or both. The standard surgery involves temporarily removing the nipple.

Jeffrey Kenkel, M.D., chair of the plastic surgery department at UT Southwestern, said men with darker skin can lose the natural color in their nipples because blood vessels are lost when the nipple is removed and then grafted back to the breast. Darker skinned men have a nearly 50 percent chance of having nipple discoloration.

With the new technique, blood vessels can be maintained by surgically cutting and lifting the breast without leaving any unnecessary bulk or fullness. The breast flap is brought back down in the final stage of the surgery, providing the flat-chested look that the patients want without eventual discoloration of the nipple.

“This is a nice alternative to the standard nipple grafting techniques we have used for years.  It allows us to preserve the shape of the nipple and in many cases the color in patients of color,” says Kenkel. 

For men with darker nipples, traditional surgery can sometimes not only lightens the color of the nipples but may leave them with an undesirable spotty appearance. Color can often go from dark to pink. Kenkel says many men start with having a flat chest as their main concern; nipple discoloration is often not a concern until it happens.

Kenkel says he first did the flap procedure in 2011 on a patient who was open to a new approach and expanded to 13 other men over a period of eight years. The men had previously lost about 160 pounds each, going from an average body mass index of 52 percent to slightly less than 30 percent. The patients had sagging skin and some remaining fat in their breasts that they wanted removed.

The surgical procedure took about 90 minutes for each patient with strong results in retaining natural nipple color. Post-surgery progress was followed for up to 18 months. Four of the 14 patients experienced minor complications such as delayed wound healing and seroma, in which clear fluid develops under the skin.

Kenkel says the men who underwent the procedure made the tradeoff of accepting scarring across the chest in return for flatter chests with better contour and shape and little chance of discoloration of their nipples.

“These are operations that allow people – we like to say – to look as good as they feel,” Kenkel says. “There are tradeoffs, you have to trade a scar for shape, but in most patients, this is very acceptable.”

Patients had to maintain a steady weight for three months to be eligible for the surgery. Healthy diets and active lifestyles are required to keep weight gain from recurring.

Nearly twelve years ago, Michigan voters approved the use of medical cannabis by residents with certain health conditions. A year and a half ago, they voted to approve its use by all adults, for any reason.

What happened between those two dates is the focus of a comprehensive new report just issued by the University of Michigan Injury Prevention Center.

The report documents everything from who's using cannabis in the state for medical and recreational purposes, to downstream effects including motor vehicle crashes, emergency department visits and criminal justice cases. It aims to provide a baseline for future studies on the impact of state-level recreational cannabis legalization that occurred in late 2018, and to inform future policies and public health messaging.

The report, available at http://michmed.org/cannabisreport, includes a wide range of findings compiled from original research and official sources.

Some key observations:

One in nine Michiganders report using cannabis at least once in the last month, a percentage that increased 60% over a 14-year period

About three percent of all state residents hold a medical cannabis card, nearly all of them for chronic pain

Medical cannabis led to net revenue for the state of $5 million to $7 million a year

One in 30 pregnant Michigan women reported using cannabis; the percentages were higher among those with the lowest incomes and education levels, potentially reflecting disparities

The percentage of fatal motor vehicle crashes in Michigan that involve cannabis is increasing, even as the total rate of fatal crashes decreases. Among drivers tested for cannabis after such crashes, the percent that were positive more than tripled between 2004 and 2017, when 23.4% of tested drivers in fatal crashes had cannabis in their bloodstream at the time of the crash.

1.5% of Michiganders experience symptoms of cannabis use disorder

Emergency department visits and hospitalizations related to cannabis poisoning increased recently, with older teens and young adults accounting for a disproportionate share of cases

Cannabis-related misdemeanors and felonies accounted for nearly 4% of convictions in the state's criminal justice system, about half of which occurred at the same time as other felony convictions.

To compile the report, a team headed by Injury Prevention Center faculty Kipling Bohnert, Ph.D. and Erin Bonar, Ph.D., worked with two state agencies -- the Michigan Department of Health and Human Services and the Michigan Department of Licensing and Regulatory Affairs -- and the federal Michigan High Intensity Drug Trafficking Area coalition. The report was funded by the IPC's core funding from the Centers for Disease Control and Prevention.

The researchers also note key areas where more data needs to be generated and shared, including broader biological testing for cannabis among drivers in motor vehicle crashes, additional study of vaping of substances derived from cannabis, workplace issues, societal costs and access to cannabis use disorder treatment.

Members of the project team are also members of the U-M Department of Psychiatry's Addiction Center, the U-M Institute for Healthcare Policy and Innovation and the VA Center for Clinical Management Research.

The authors will hold a Twitter chat about the report on June 24 from 2 p.m. to 3 p.m. ET, using the hashtag #MiMJReport and the Injury Prevention Center's Twitter handle, @UMInjuryCenter.

Questions about the report, and questions for the Twitter chat, may be sent to uminjurycenter@umich.edu

Prescriptions for an FDA-approved treatment for opioid addiction have increased over the past decade in all age groups except the youngest (age 15-24), a new analysis of prescription data by researchers at Columbia University Irving Medical Center has found.

Expanded access to the treatment among adults is being driven primarily by an increase in prescriptions from primary care providers, rather than psychiatrists or other specialists, the researchers found, while decreased access among young adults and teens mostly stems from a decrease in prescriptions from psychiatrists and addiction medicine specialists.

To prescribe buprenorphine, physicians must complete a training course and obtain a waiver from the U.S. Drug Enforcement Administration. Amendments to federal legislation in 2006 and 2016 extended eligibility for the waivers and waiver limits.

"More than any other provider group, primary care providers offer greater potential for expanding access to buprenorphine treatment because there is such a large number of them who either do not have waivers or are not near their waiver limits," says the study's leader Mark Olfson, MD, MPH, the Elizabeth K. Dollard Professor of Psychiatry, Medicine, and Law at Columbia University Vagelos College of Physicians and Surgeons.

Between 2000 and 2018, buprenorphine treatment initiated by prescriptions from primary care providers more than doubled, from 12.9 per 10,000 people to 27.4 per 10,000 people. Among psychiatrists and addiction medicine specialists, buprenorphine prescriptions increased from 8.7 to 12 per 10,000 people.

But when data from different age groups were examined, prescriptions for adolescents and young adults (age 15 to 24) actually dropped, from 20.4 per 10,000 people to 14 per 10,000 people.

"This is a worrisome trend, given the high rate of opioid-related overdose deaths among young people," says Olfson. "We hope that awareness of this trend will encourage expansion of substance use treatment programs that accept adolescents and cater to young adults."

The study also found that while there was a slight increase in the percentage of patients continuing the medication for at least 180 days -- an important benchmark in addiction treatment -- less than one-third of patients achieved this target.

"In response to the COVID-19 pandemic, clinicians may be finding new ways to continue their patients' treatment with buprenorphine, as providers relax requirements such as direct observation of treatment induction or urine drug screening," says Olfson. "Such changes will hopefully increase access to treatment without adding risks. It will be important to monitor community buprenorphine treatment patterns through this critical period."

p>Most children with rare genetic diseases spend years undergoing medical tests and waiting for a diagnosis -- a long, exhausting process that takes its toll on children and their families. Almost half of these children never get a definitive diagnosis.

Now an international team led by scientists and clinicians from the University of Colorado, University of Calgary, and University of California, San Francisco (UCSF) has developed a prototype tool based on three-dimensional (3D) facial imaging that could shorten that diagnostic odyssey by making it easier for clinicians to diagnose genetic syndromes.

"Families tell us having a diagnosis for their child's rare disease is life-changing," said Benedikt Hallgrímsson, PhD, professor and head of the Department of Cell Biology & Anatomy, and scientific director (basic science) at the Alberta Children's Hospital Research Institute in the Cumming School of Medicine at the University of Calgary. "A diagnosis is essential to children getting the right treatments and connecting with other children and families with the same syndrome."

Most developmental genetic syndromes affect multiple organ systems, and clinical geneticists have long relied on distinctive facial features as an important guide to diagnosis.

In a new study published online in Genetics in Medicine on June 1, 2020, the research team created a unique library of 3D facial images of participants of diverse ages and ethnicities, including 3327 children and adults with 396 different genetic syndromes, 727 of their unaffected relatives and 3003 other unaffected individuals from the United States, Canada, and the United Kingdom. The secure database is hosted by FaceBase, an international consortium funded by the National Institute of Dental and Craniofacial Research, part of the U.S. National Institutes of Health (NIH).

The researchers then used this secure database to train a machine learning algorithm to identify most of the genetic syndromes included in the dataset with moderate-to-high accuracy. Based on facial shape, 96 percent of study subjects could be correctly classified as either unaffected or having a syndrome, and for most, the algorithm was able to provide a prioritized list of likely diagnoses with high accuracy.

The COVID-19 pandemic has accelerated a rapid shift to telemedicine by genetics clinics, including those at UCSF, University of Colorado, and University of Calgary, but the study team says the field still lacks tools to replace many aspects of the in-person physical exam. The automated diagnostic approach developed in this study could extend the ability of clinical geneticists to diagnose patients without requiring travel to a specialized clinic. It could also help general practitioners without genetic training to home in on potential diagnoses, enabling them to connect patients with appropriate specialty care and community support.

"Clinical genetics is labor-intensive," said Ophir Klein, MD, PhD, the Larry L. Hillblom Distinguished Professor in Craniofacial Anomalies and the Charles J. Epstein Professor of Human Genetics at UCSF, where he is chief of the Division of Medical Genetics. "Some clinics have a two-year waiting list to get in. Using 3D imaging could dramatically enhance clinicians' ability to diagnose children more quickly and inexpensively."

The researchers emphasize that the current study represents an important proof-of-concept for facilitating genetic diagnoses, but further work is required to deploy a clinically available, privacy-protected tool. Currently, the approach relies on expensive 3D cameras, but this is expected to change with advances in smart-phone camera technology.

"We have designed a prototype with significant potential to become a clinical tool around the world," said Richard Spritz, MD, professor of Pediatrics and director of the Human Medical Genetics and Genomics Program at the University of Colorado School of Medicine. "Our hope is that one day soon, our patients can securely take a photo of their face with a smart phone and send it to their doctor for analysis in a confidential database."

Added Hallgrímsson, "In low-income countries where genetic testing and medical geneticists aren't available, this could become a transformational new tool."

A group of scientists led by Philipp Khaitovich, a professor at Skoltech, conducted a large-scale study of gene expression in 33 different brain regions of humans, chimpanzees, macaques and bonobos using the single-cell-resolution transcriptomics technologies and made a map of the different brain regions with their specific cell structures. Such maps are highly valuable for the human evolution research.

The human brain is amazingly complex, and its evolution has long been a subject of unfailing interest for scientists. What are the most significant evolutionary changes that distinguish the modern brain from that of our distant ancestors and make humans so different from other species?

An international group of scientists from Russia, China, Germany and Switzerland led by Philipp Khaitovich, a professor at the Skoltech Center for Neurobiology and Brain Restoration (CNBR), with the participation of Ekaterina Khrameeva, the first author of the paper and an assistant professor at the Skoltech Center for Life Sciences (CLS), studied 422 brain samples taken from 33 different brain regions in humans, chimpanzees, macaques, and bonobos. The scientists looked at gene expression focusing on how specific genes operate in those regions and analyzed a total of 88,047 individual cells using the single-cell-resolution method. The study helped identify the brain regions that are the most distinctive in humans and, therefore, undergo faster evolution. These include the cerebral cortex, hypothalamus, and cerebellar gray and white matter. Also, oligodendrocytes and astrocytes displayed more differences in the human evolutionary lineage than neurons as compared to similar cells in other primates.

"We are not the first to look into gene expression in the brain. This is an important area of research that someday will shed more light on how human consciousness appeared. However, the tricky point here is that there can be two possible reasons for evolutionary changes in expression: a change in the cellular structure in some area of the brain or a change in the expression of genes in the cells. Previously, scientists could not draw the line between these two possibilities, and now, with the advanced single-cell-resolution method, we finally did it! Our new findings will help better understand the ins and outs of the evolution of gene expression on a more subtle level that was unavailable till now," says Ekaterina Khrameeva.

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

1. Serodiagnostics for Severe Acute Respiratory Syndrome-Related Coronavirus-2

Accurate serologic tests to detect host antibodies to SARS-CoV-2 will be critical for the public health response to the COVID-19 pandemic. As such, urgent research is needed to link specific serologic variables with immunity against SARS-CoV-2. Researchers lead by a team at McGill University reviewed available research to identify key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies. They discuss currently available assays, highlight key areas of ongoing research, and propose potential strategies for test implementation. They found that despite a rapid increase in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal or no external validation or have poorly described validation panels, which hinders assay selection and interpretation of results. In addition, interpretation of serologic assays is limited at present because of critical knowledge gaps. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-2854.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. The lead author, Matthew P. Cheng, MDCM, can be reached through Fabienne Landry at Fabienne.Landry@MUHC.MCGILL.CA.