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New research shows transmission of the virus behind COVID-19 varies seasonally, but warmer conditions are not enough to prevent transmission.

The study, led by Imperial College London researchers and published today in Proceedings of the National Academy of Sciences, is the first to incorporate environmental data into epidemiological models of the transmission of SARS-CoV-2, the virus behind COVID-19.

The team show that temperature and population density are the most important factors determining how easily the virus spreads, but only in the absence of mobility-restricting measures, such as lockdowns.

First author of the study Dr Tom Smith, from the Department of Life Sciences at Imperial, said: "Our results show that temperature changes have a much smaller effect on transmission than policy interventions, so while people remain unvaccinated, governments mustn't drop policies like lockdowns and social distancing just because a seasonal change means the weather is warming up.

"However, our work also suggests that lower autumn and winter temperatures may lead to the virus spreading more easily in the absence of policy interventions or behavioural changes."

Seasonal variation has been a source of uncertainty in forecasts of SARS-CoV-2 transmission. Other viruses, like flu viruses and other coronaviruses, are known to be affected by environmental factors. For example, high temperatures and low humidity reduce the transmission of respiratory droplets, preventing the spread of flu. High temperatures are also known to inactivate other coronaviruses in the air and on surfaces.

However, quantifying the effects of environmental factors including temperature, humidity, and UV radiation (sunshine) on SARS-CoV-2 transmission has been difficult during the pandemic, since human factors like population density and behaviour have been the main drivers of transmission.

The differences in interventions and case-counting between countries and regions also makes comparing environmental factors on a global scale difficult, especially as some countries, like Brazil, India and Iran, have high transmission despite having warmer climates.

As a result, few epidemiological models have included environmental data, and those that do assume the response of SARS-CoV-2 is identical to other coronaviruses, as there is a lack of SARS-CoV-2-specific data.

To fill this gap, the team, from the Departments of Life Sciences and Mathematics at Imperial, as well as Imperial's MRC Centre for Global Infectious Disease Analysis, and Utah State University, compared transmission across the USA. The country has a large range of climates with comparable policies and case numbers, allowing the impact of environmental factors to be teased out.

They found strong evidence that lower temperature and higher population density are both associated with higher SARS-CoV-2 transmission.

Lead researcher Dr Will Pearse, from the Department of Life Sciences at Imperial, said: "While temperature and population density do influence SARS-CoV-2 transmission, our findings re-confirm that the most important drivers are public policy and individual behaviour. For example, during lockdowns, there was no meaningful signature of temperature influencing transmission.

"This means, for example, that warmer regions should not expect to ease mobility restrictions before colder regions. This is especially true as warmer regions tend to have higher population densities - for example, the population in Florida is more densely packed than in Minnesota."

The researchers are now extending their study to new variants, and say their environmental results should be incorporated into future forecasts to enhance predictions of disease spread.

Study co-author Dr Ilaria Dorigatti, from the MRC Centre for Global Infectious Disease Analysis at Imperial, said: "We found evidence that, in the early phases of the pandemic, places with colder temperatures were associated with higher SARS-CoV-2 transmission intensities. However, the effect of climatic seasonality on SARS-CoV-2 transmission is weaker than the effect of population density and in turn, of policy interventions.

"This implies that, as we move towards summer in the Northern Hemisphere, public health policy decisions remain of critical importance for epidemic control and adherence to recommendations will continue to play a key role against SARS-CoV-2 transmission."

June 9, 2021 - The first analysis of medical evidence on domestic mass shooters in the U.S. finds that a large majority of perpetrators have psychiatric disorders for which they have received no medication or other treatment, reports a study in the Journal of Clinical Psychopharmacology. The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Without losing sight of the larger perspective that most who are violent are not mentally ill, and most of the mentally ill are not violent, our message is that mental health providers, lawyers, and the public should be made aware that some unmedicated patients do pose an increased risk of violence," according to the report by Ira D. Glick, MD, of Stanford University School of Medicine and colleagues.

In-depth analysis of psychiatric evidence on domestic mass shooters

The researchers identified 115 persons identified as committing a mass shooting in the United States from 1982 to 2019, based on the most comprehensive listing available (the Mother Jones database). The database excluded shootings related to "conventionally motivated" crimes such as armed robbery or gang violence.

"In the vast majority of the incidents identified in the database, the perpetrator died either during or shortly after the crime," the researchers note. They focused on the 35 cases where the assailant survived and underwent criminal proceedings - providing the best information on their symptoms of mental illness and psychiatric state.

For each mass shooting event, the researchers spent hours analyzing records or interviewing the forensic psychiatrists or psychologists who examined the assailant after the crime. Other sources of information included court proceedings, public records, videotaped interviews, and social media posts or writings by the perpetrator. Dr. Glick's coauthors were Nina E. Cerfolio, MD, of the Icahn School of Medical at Mount Sinai Hospital, New York; Danielle Kamis, MD, of Stanford; and Michael Laurence, JD, a prominent capital defense attorney.

"Based on this data, 32 of the 35 perpetrators had signs and symptoms of brain illness, which fit scientific diagnostic criteria for a clinical psychiatric disorder," Dr. Glick comments. Eighteen of the shooters had schizophrenia while 10 had other diagnoses including bipolar disorder, delusional disorder, personality disorders, and substance-related disorders. In three cases, there was not enough information to make a diagnosis; in four cases, no psychiatric diagnosis was found.

Of the 28 surviving assailants with a psychiatric diagnosis, "None were medicated or received other treatment prior to the crime," the researchers write. They also analyzed 20 mass shooters who died at the crime scene, using available data from the media or significant others. Eight assailants had schizophrenia, seven had other diagnoses, five had unknown diagnoses. Similarly, none were receiving appropriate medications.

Despite the tragically high frequency of mass shooting events, there has been almost no medical research on the nature and incidence of brain illness among the perpetrators of these crimes. The study originated in Dr. Glick's clinical impression that many, if not most, mass shooters are people with unidentified psychiatric illness - complicated by a lack of support from family or significant others in getting the help they needed.

The authors acknowledge some important limitations of their study: it included only limited evidence on a small group of domestic shooters who survived, with no comparison group. "Nonetheless," the researchers write, "our data suggest that persons who commit mass murders may suffer from compromising and untreated psychiatric illness."

"The psychiatric disorders seen in perpetrators of mass shootings are serious brain illnesses - as much in need of proper diagnosis and treatment as heart disease or any other medical condition," Dr. Glick adds. "We need to reduce the stigma associated with these diseases to enable patients to receive appropriate and adequate psychiatric medication and other treatments. By actually talking to patients and their significant others, we have the opportunity to save lives."

OAKLAND, Calif. -- The significant declines in heart attack hospitalizations and emergency care for possible strokes seen in Northern California at the beginning of the COVID-19 pandemic were not seen in subsequent surges, new research from Kaiser Permanente shows.

The study, published June 2 in JAMA, suggests public health campaigns that encouraged people to seek care if they were experiencing signs or symptoms of a stroke or heart attack were effective.

"In May 2020, we reported that, in the early months of the pandemic, the weekly number of patients admitted to our hospitals for a heart attack fell to nearly half of what would be expected," said the study's lead author Matthew D. Solomon, MD, PhD, a cardiologist for The Permanente Medical Group and a physician researcher with the Kaiser Permanente Northern California Division of Research. "This follow-up study suggests that we were successful in our efforts to reassure patients that it was important to leave their homes and seek emergency care if needed, and that they could do so safely."

The research team analyzed weekly incidence rates for adults hospitalized with a heart attack or suspected stroke from Jan. 22, 2019, through Jan. 18, 2021, in Kaiser Permanente of Northern California. The team then compared incidence rates for the time periods during the 3 COVID-19 surges in the spring (March 10 through May 4, 2020), summer (June 23 through Aug. 17, 2020), and winter (Nov. 3, 2020, to Jan. 8, 2021) to the same weeks in the prior year.

The study showed weekly hospitalized heart attack and suspected stroke rates declined during the spring COVID-19 surge but then recovered to 2019 rates. During the subsequent and much larger surges in COVID-19 infections and admissions, hospitalization rates for heart attacks remained stable. A small but statistically significant decline in suspected strokes was seen during the summer COVID-19 surge, but the rates rebounded and did not decrease during the largest winter COVID-19 surge.

"In August 2020, we published research that described decreased stroke presentations and discharges, which made us very concerned about patients who would be at risk for long-term disabilities because they were not coming to the hospital for evaluation and treatment," said study co-author Mai N. Nguyen-Huynh, MD, a research scientist with the Division of Research and the regional director of primary stroke for The Permanente Medical Group. "In response, we redoubled our efforts to educate our patients that if they have stroke symptoms, they should call 911 and go to the nearest stroke center. This study suggests those efforts paid off."

Kaiser Permanente in Northern California and the Division of Research were ideally positioned to carry out this research. "Our study highlights the unique ability of our embedded regional research team to respond rapidly in collaboration with a multidisciplinary team of clinical and methodological experts to gain insights from our electronic health record data to inform care planning and delivery for a large, diverse population," said the study senior author, Alan S. Go, MD, associate director of cardiovascular and metabolic conditions research at the Division of Research and regional medical director of clinical trials for The Permanente Medical Group.

The study by Dr. Solomon and Dr. Go that showed hospitalizations fell to nearly half of what would be expected during the first months of the pandemic was published May 19, 2020, in the New England Journal of Medicine. The research by Dr. Nguyen-Huynh and her colleagues on the decrease in stroke patients reporting to the emergency room after the onset of the pandemic was published Aug. 11, 2020, in Stroke.

"Our goal is to stamp out cardiovascular disease," said Dr. Solomon. "But until then, we want to ensure patients do not delay in seeking needed care."

A new study published in the Journal of the American Geriatrics Society suggests that survival rates after heart transplant surgery are similar in adults ages 18 to 69 and adults ages 70 and older.

Researchers examined a large U.S. database of patients who were listed as candidates for surgery to replace their failing hearts with healthier donor hearts. The researchers found that:

Only 1 in 50 people who are considered for heart transplant surgery and 1 in 50 people who receive a heart transplant are ages 70 or older.
For older adults in the study, the likelihood of surviving one or five years after a heart transplant was about the same as for younger adults.
Having a stroke after heart transplant surgery was more common in older adults, but the risk in both age groups was low.
Older patients were more likely to receive hearts from higher-risk donors, who are older and more likely to have diabetes and high blood pressure.
Advanced age alone should not prevent people from being considered as candidates for heart transplants.

Why We May Need Heart Transplants as We Age

Heart failure develops when your heart can no longer pump enough blood to provide your body with the oxygen and nutrients it needs. It is usually caused by other chronic conditions that become more common as we age and is the leading cause of hospitalizations in people over 65. When heart failure can no longer be treated with medication or medical devices, a heart transplant may be necessary.

Because the supply of donor hearts is limited, healthcare professionals must make decisions about who they think has the most potential for a good recovery and long-term survival. [1] Until recently, many believed that people aged 70 or older were only good candidates for the operation if they: (a) were strong enough; (b) were able to take all the medications needed to prevent their bodies from rejecting their new heart; (c) had strong support from family and friends; (d) did not drink alcohol or smoke; and (e) did not have other serious chronic diseases or infections.

That opinion is changing as the population of older adults increases in the U.S. and a growing number of older patients receive heart transplants with positive results. Because of improvements in patient screening and care after surgery, heart transplant surgery has become an option for people with heart failure who are expected to live five years or less.

What the Researchers Learned

Researchers at the Hartford Hospital in Connecticut included 57,285 adult patients (aged 18 and older) listed as candidates for heart transplant surgery in the U.S. between January 2000 and August 2018 in their study. They found that only one in 50 of these patients was 70 years old or older. Of the 37,135 patients who had heart surgery over the 18-year period, about the same proportion was at least 70 years old, but the number of older patients receiving a heart transplant each year has increased from 30 in 2000 to 132 in 2017.

The researchers looked at the difference between the percentage of patients ages 18-69 and patients aged 70 or older who died (the mortality rate) within one year and five years after heart transplant surgery. There was no significant difference between groups for the mortality rate in the first year after surgery, even though the older patients were more likely to receive hearts from older donors with chronic diseases like diabetes and blood pressure. The difference between the mortality rate for the older and younger patients within five years of heart transplant surgery disappeared when researchers took into consideration factors like patients’ body mass index (BMI) and the time patients spent on the transplant waitlist.

Having a stroke after heart transplant surgery was more common for older patients, but the risk was still very low (3.5 percent). In older patients, most strokes occurred during year three of the follow-up period.

Study Limitations

This study’s researchers looked at information collected in the past and observed the differences between the older and younger groups. This means they were unable to identify specific causes for their findings. What’s more, the number of older patients was very small, making it hard to draw definite conclusions from. Finally, most of the older patients who received heart transplants were white, not frail, and did not have other chronic diseases besides heart failure. The researchers noted that this group of older heart transplant recipients does not represent most older adults who have heart failure.

What This Study Means for You

If you’re 70 or older and have heart failure, heart transplant surgery might be a life-extending option for you. Consider asking your heart failure doctor whether you could be a candidate for a heart transplant.

BOSTON - A new analysis by researchers at Massachusetts General Hospital (MGH) offers a novel perspective on the disproportionate impact that COVID-19 has had on people of color, low-income populations, and other structurally disadvantaged groups. Their findings, published in a research letter to the Journal of General Internal Medicine, emphasize the urgency of addressing inequities that have been exposed by the coronavirus pandemic.

"At Mass General, we are deeply interested in uncovering disparities and then fixing them," says cardiologist Jason H. Wasfy, MD, MPhil, lead author of the research letter, director of Outcomes Research at the MGH Heart Center and a medical director of the Massachusetts General Physicians Organization (MGPO). In pursuit of that mission, Wasfy and several MGH colleagues decided to analyze the socioeconomic and demographic characteristics of patients tested for COVID-19 at 14 sites within the Mass General Brigham system from the earliest days of the pandemic until mid-December 2020. Those sites include not only hospitals also but community health centers and urgent care clinics. Combining the results of both inpatient and outpatient testing for COVID-19 distinguished this analysis from most earlier inquiries, which primarily focused on inpatient testing. "That made our sample more representative," says Wasfy. "It's a more valid way of looking at the total effect of COVID-19 on all patients."

Another factor that distinguishes this analysis is its sheer size: It is based on test results from 394,536 patients. Electronic health records were used to compile data regarding each patient's gender, race and insurance status, as well as where they lived (indicated by ZIP code). Publicly available data for information such as median household income and employment status was then compiled for each ZIP code.

The MGH team's analysis found that 29,977 patients (7.6% of those tested) had positive results for COVID-19. Males (8.2%) were slightly more likely than females (7.2%) to test positive. Stark contrasts emerged when Wasfy and his colleagues broke down positive cases by race and socioeconomic factors. For example:

The study found that 5.6% of white patients tested positive, compared to 17.2% of Hispanic patients and 11.9% of Black patients.

Using ZIP codes, they found that patients from communities where the median annual household income was $70,000 or less were nearly three times more likely to test positive for COVID-19 than patients from communities where median households were greater than $100,000 per year (13.3% compared to 4.7%).

Medicaid patients had more positive tests (14.2%) than those with commercial insurance (6.8%).

People who lived in areas where unemployment was higher than 5% were nearly twice as likely to have COVID-19 than those from communities with unemployment of 3.5% or less (10.7% compared to 5.8%).

On the other hand, in ZIP codes populated by a significant portion of people with jobs in the service sector--who couldn't stay home and work remotely during the pandemic--were more than three times as likely to contract COVID-19 than others from communities with relatively fewer service-sector employees (13.4% compared to 4.2%).

"Although our study is innovative in using patient-level data to assess the association between positive COVID tests and socioeconomic and demographic characteristics of individual patients, the results confirm that structural constructs in our society persevere and contribute to health outcomes inequities," says Marcela del Carmen, MD, who is interim president of the MGPO and senior author of the paper.

Wasfy echoes that sentiment, noting that social phenomena--not biology--have a large influence on who becomes infected with the coronavirus. "Societal disadvantages that were baked in before the pandemic led the pandemic to take a tremendously different toll on specific groups of patients," he says, noting that these factors (often called social determinants of health) influence the risk for other conditions, such as heart disease and type 2 diabetes. "Our results show how profoundly systemic, structural aspects of society are revealed by assessing the spread of disease."

Wasfy is an assistant professor of Medicine at Harvard Medical School (HMS). Del Carmen is a professor of obstetrics, gynecology, and reproductive biology at HMS.

For decades, physicians and dieticians have urged people to limit their intake of high fat foods, citing links to poor health outcomes and some of the leading causes of death in the U.S., such as diabetes, heart disease and cancer.

According to the Centers for Disease Control and Prevention, dietary components high in saturated fats such as red meat are thought to be risk factors for colon cancer. Diet is thought to strongly influence the risk of colorectal cancer, and changes in food habits might reduce up to 70% of this cancer burden.

Other known epidemiological risk factors are family history, inflammatory bowel disease, smoking and type-2 diabetes.

But out of all the risk factors that elevate colon cancer risk, diet is the one environmental and lifestyle factor that may be the easiest to control ---simply by changing people's behavior and eating habits----if we knew the exact connections.

"There's epidemiological evidence for a strong link between obesity and increased tumor risk," said School of Life Sciences assistant professor Miyeko Mana. "And in the intestine, the stem cells are the likely cell of origin for cancer. So, what is that connection? Well, diet is something that feeds into that cycle of obesity and colorectal cancer."

Now, a new ASU study led by Mana and her team has shown in greater detail than ever before of how high fat diets can trigger a molecular cascade of events that leads to intestinal and colon cancer. The study was published in the journal Cell Reports.

Tales from the crypts

As foods are broken down and make their way through the gut, they interact with intestinal stem cells (ISC) that lie along the inside surfaces of the gut. These ISCs reside in a series of regularly folded valleys of the gut, called crypts.

ISCs are thought to be the gateway that coordinates intestinal tumor formation when they adapt to high-fat diets, and elevate cancer risk. Within the ISCs are high-fat sensor molecules that sense and react to high-fat diets levels in the cells.

"We were following up on mechanisms that might be required for stem cells to adapt to the high fat diet ---and that's where we came across the PPARs," said Mana. These peroxisome proliferator-activated receptors (or PPARs) trigger a cellular program that elevates cancer risk, but the exact mechanisms were unclear because there are multiple types of PPARs, and complexities in teasing out their roles.

"There is a family of 3 PPARs, named delta, alpha and gamma. At first, I thought just PPAR delta was involved, but in order to see if that gene is really responsible for the phenotype, you have to remove it."

Mana's team was able to explore and unmask the role of individual PPAR delta and alpha using a mouse model that controlled their activity in the cell. In her team's study, mice were given a long-term high fat or normal diet, and the activity of each PPAR was carefully monitored to study the effects on cancer risk.

In their knockout study, they first removed the PPAR delta gene.

"But when we removed it from the intestine, we still observed the phenotype. So, we wondered if maybe another PPAR was compensating and that's where we thought about PPAR alpha. Both of those (PPAR delta and PPAR alpha) appear to be required for this high fat diet phenotype within the stem cells."

This was frustrating to Mana because she knew right away that developing a potential therapeutic to offset the PPARs just became a much taller task.

"When you think about this therapeutically, if you are incorporating a lot of fat into your diet and you want to reduce your risk of colon cancer, targeting two different factors is more challenging then if you are targeting just one."

Looking farther downriver

To further tease out the genetic complexity, Mana next turned her attention downstream of the PPARs.

From their studies, and using new tools of the trade, they were able to slowly tease out the details---down to the level of doing molecular sequencing from individual cells from different areas of the small intestine and colon, mass spectrometry to measure the amounts of different metabolites, and radiolabeled isotopes of fuel sources to measure the carbon flow.

Their first big clue came from the metabolic analysis. The high fat diet found in the ISC crypt cells they isolated increased the metabolism of fats, while at the same time, decreasing the breakdown of sugars.

"So, we looked more downstream at what these two factors (PPARs) may target, and that was this mitochondrial protein, Cpt1a," said Mana. "This is required for the import of long chain fatty acids (LCFAs) into mitochondria for use. The LCFAs are part of the high fat diet."

And when they performed the mouse knockout study of Cpt1a, they found they could stop tumor formation in its tracks. The loss of Cpt1a prevented both the expansion and proliferation of the ISCs in the crypts.

"If you remove Cpt1a, you are spared this high fat diet phenotype in the intestinal stem cells," said Mana. "So, you lower your risk of tumorigenesis at this point."

A new model emerges

From their data, Mana' team could trace the development of cancer, from diet all the way to tumor formation.

First, fats are broken down to free fatty acids. The free fatty acids then stimulate sensors such as the PPARs and turn on genes that can break down the fatty acids.

Next, the surplus free fatty acids are transported to the mitochondria, which can burn them up by oxidation to make more energy to feed the stem cells, which multiply, grow and regenerate gut tissue. But when the ISCs numbers are expanded, there is a greater likelihood that mutations can occur---just from random mutations and sheer numbers of cells---that lead to colon cancer.

"The idea is that this larger pool of cells remain in the intestine and accumulate mutations, and that means they can be a source of mutated cells leading to transformation and tumor initiation," said Mana. "We do think that is a likely possibility when there are conditions that expand your stem cell pool."

Mana's group also found that feeding a high fat diet dramatically accelerated mortality in this model compared with the control condition, by accelerating tumorigenesis.

"The levels of these fats that you can get through your diet are going to impact your stem cells, probably in a fairly direct way," said Mana. "I think one of the surprising things we are finding in our studies is that fatty acids can have such a direct effect. But you can remove these PPARs, you can remove CPT1a, and the intestine is fine."

New hopes

With the new evidence from the study, the hope is to one day apply their work to human colon cancers.

"These studies have all been in these mouse models to date," said Mana. "One idea we started with was to understand the metabolic dependencies of the tumors that can arise in a natural or pharmacological context and then target these metabolic programs to the detriment of the tumor but not the normal tissue. We are making progress with the high fat diet model. Ultimately though, the goal is to eliminate or prevent colorectal cancer in humans."

Millions of people with diabetes are at risk of developing foot ulcers, which often lead to amputations and other health complications. Now, Scientists from the Centre for Biomechanics and Rehabilitation Technologies (CRBT) have developed a new method to reliably detect this risk without the need for complex electronic in-shoe sensors.

Dr Panagiotis Chatzistergos, Associate Professor in Orthopaedic Biomechanics, explained: "In the UK alone, 169 people have a toe, foot or limb amputated as a result of diabetes every week, yet importantly up to 80% of these amputations could have been prevented with correct management.

"Routine overloading of the sole of the foot during daily activities can trigger the onset of foot ulcers, so being able to identify which areas in the sole of the foot are most affected is extremely important."

A common method involves assessing plantar pressure to prescribe special footwear or insoles, however many clinicians cannot use this because it is expensive and difficult to use. Dr Chatzistergos and colleagues have developed a novel concept to address this problem, using 3D-printed, tuneable structures that will help clinicians better understand the cause of ulcer development and lead to improved patient outcomes.

Dr Chatzistergos, who led the study, said: "Our work has demonstrated a method to reliably detect overloading using a low-cost non-electronic technique. We have used a 3D-printed thin-wall structure that changes its properties when repeatedly loaded above or below a tuneable threshold. We believe that this is a step change from current practice."

Patients would be required to wear the sensor-insoles in their everyday footwear for a representative time period, for example a day or a week, before returning them for analysis. During the analysis of the sensor-insole, plantar areas that were routinely subjected to higher pressures should be identifiable, against those where pressure was below that threshold.

The concepts behind the work, published in Royal Society Open Science, have been fully developed at Staffordshire University and the intellectual property has been protected.

Professor Nachi Chockalingam, Director for CRBT who co-authored the study, said: "Plantar pressure assessment is common amongst clinical practice and it contributes to insoles and footwear prescription. However, the current technologies are expensive and difficult to use in an everyday clinic.

"Each year more than 26 million people worldwide develop diabetic foot ulcers and the lifetime incidence of foot ulcers in developing countries is more than 20% among people with diabetes. Establishing low-cost methods to help prevent foot ulcers will reduce the global socioeconomic burden of diabetes and ultimately save lives. The concept reported within this paper, with further development, has the potential to transform clinical management of foot ulcer risk across the world."

People who have a high sensation-seeking personality trait may be more likely to develop an addiction to cocaine, according to a Rutgers study.

"Although many people try illicit drugs like cocaine or heroin, only a small proportion develop an addiction," said lead author Morgan James, a member of the Rutgers Brain Health Institute and an assistant professor in the department of psychiatry at Rutgers Robert Wood Johnson Medical School. "The interaction found between sensation-seeking traits and the drug-taking experience show that predisposition to addiction has a genetic basis, and that this interacts with environmental factors such as patterns of drug use. The sensation-seeking trait was predictive of rats' likelihood to exhibit stronger motivation for drugs when we gave them the opportunity to take cocaine."

The findings, published in the journal Neuropharmacology, shed light on what predisposes people to addiction and may help with substance use screening and treatment.

The lab study found that high sensation-seeking rats -- those with a strong desire for new experiences and a willingness to take risks to be stimulated -- were more prone to developing behavior that reflects human addiction. The findings suggest that high sensation-seeking people have a greater risk of losing control over their drug intake, which makes them more vulnerable to drug addiction.

A major goal of addiction research is to identify behavioral biomarkers that predict addiction vulnerability. Future studies can build on these findings to determine what is different in the brains of those who are high sensation-seeking to see what predisposes them to addiction.

STUDY SAYS FAILURE TO RID AMYLOID BETA PROTEIN FROM BRAIN MAY LEAD TO ALZHEIMER'S DISEASE

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

Alzheimer's disease is one of medicine's most elusive thieves, a disease that slowly and irreversibly robs a person's ability to think, reason, remember and maintain normal body functioning. The underlying cause of Alzheimer's disease is unknown, but researchers believe that one of the prime suspects is a microscopic fragment of protein known as amyloid beta (Aß). Scientific evidence suggests that tangled, sticky masses of Aß called plaques disrupt communication between brain cells and eventually, lead to their death.

A recently published study, conducted by Johns Hopkins Medicine researchers David Nauen, M.D., Ph.D., assistant professor of pathology, and Juan Troncoso, M.D., professor of pathology, may be one of the first to provide evidence that in humans, Aß proteins exit the brain via the glial-lymphatic (glymphatic) system -- the vascular network that helps clear waste materials during sleep from the central nervous system.

"This observation supports the hypothesis that the glymphatic system contributes to the clearance of amyloid beta from the brain, and that failure to do so may lead to plaque formation," Troncoso says.

The findings were first reported online May 31, 2021, in Alzheimer's & Dementia, The Journal of the Alzheimer's Association.

Nauen says animal studies in recent years have demonstrated the role of the glymphatic system as the brain's "trash remover," clearing Aß and other metabolites. However, he says, this glymphatic cleansing was difficult to verify in humans.

"In the absence of an imaging method that would enable us to see the glymphatic system in action, we decided instead to look for Aß-labelled cells in lymph nodes that had been surgically removed, as part of standard cancer treatments, from 27 patients [17 women and 10 men]," says Troncoso. "Evaluating lymph nodes taken from two different regions -- the neck [cervical area] and the inguinal [groin] area -- enabled us to define whether Aß was present, and if so, whether it was likely drained from the brain [which would be predominantly cervical] or from the lower extremities [which would be predominantly inguinal]."

What Nauen and Troncoso found was that the levels of Aß-containing cells were more than 40 times higher in the excised cervical lymph nodes compared with the inguinal nodes, strongly suggesting that the glymphatic system helps remove the destructive protein from the brain.

The researchers say their finding needs to be validated in an autopsy study where there is access to cognitive histories of the decedents, before-death measurements of Aß levels in the cerebrospinal fluid and plasma, data from neurological and pathological evaluations, and detailed examinations of the cervical and inguinal lymph nodes to document the presence of Aß fragments.

Nauen and Troncoso are available for interviews.

JOHNS HOPKINS MEDICINE TEAM DISCOVERS NOVEL MEDIATOR OF ONCE MYSTERIOUS CHRONIC ITCH

Media Contact: Sheree-Monet Wisdom, swisdom1@jhmi.edu

Although it was first reported in 1880, there has been little research conducted on prurigo nodularis (PN), an inflammatory chronic skin disorder characterized by firm, intensely itchy nodules that appear across the arms, legs and torso. PN disrupts the sleep and quality of life of those afflicted, and while its cause is largely unknown, it's often linked to additional health complications such as cardiovascular disease, chronic kidney disease and type 2 diabetes. It also disproportionately affects African Americans.

Unfortunately, PN does not have any U.S. Food and Drug Administration approved therapies. However, as a result of new research from Johns Hopkins Medicine, more is now known about the underlying causes of this condition and its associated diseases -- insight that could pave the way for new treatments.

In their study, first posted online March 22, 2021, in the Journal of Investigative Dermatology, the researchers looked at the relationship between skin cell messenger RNA -- genetic material that directs cells to make proteins -- and molecules circulating in the blood that mediate systemic inflammation, to identify potential causes of PN.

Such research is vital, says Shawn Kwatra, M.D., assistant professor of dermatology at the John Hopkins University School of Medicine, because PN is "tremendously understudied" compared with other inflammatory skin conditions, such as psoriasis, which has multiple approved therapies.

"There is an urgent need to better understand the development of this condition, which greatly impacts the lives of patients, causing unbearable itch, sleep disturbance and psychosocial distress," he explains.

To provide new data that might enable targeted therapies, Kwatra and his colleagues focused on the connection between systemic inflammation in the blood and the skin. Specifically, they discovered that circulating blood CD4+ T lymphocytes -- known as helper T cells because they enable the immune system to adapt to different conditions -- and CD8+ T lymphocytes -- commonly referred to as killer T cells because they seek and destroy infected or damaged cells -- secrete increased levels of interleukin-22 (IL-22), a protein (known as a cytokine) that causes skin inflammation, thickening and scarring. IL-22 also has been shown to be associated with type 2 diabetes in patients.

The researchers found IL-22 secretion by a subset of CD4+ T cells known as Th22 cells resulted in a "downstream" increase of chemical signaling throughout the skin that mediated inflammation leading to PN. The research team used a technique known as gene set variation analysis to show that these Th22 cells are part of a very dysregulated immune pathway (a disruption in the normal balance of the immune system often leading to overactivation) and correlated most strongly with the itch intensity reported by patients with PN.

"This study provides direct evidence that PN is a systemic inflammatory disorder, with circulating blood inflammation serving as a link between skin disease and other comorbidities, such as insulin resistance and high blood pressure," says Kwatra. "Identifying the links between chronic itch conditions and other underlying health issues shows us that it is important for patients with PN to get treated early so the systemic inflammation does not contribute to the development of more serious health issues."

Kwatra is available for interviews.

STUDY SUGGESTS MOLECULAR CHANGES IN TISSUE MICROENVIRONMENT MAY PROMOTE COLORECTAL CANCER

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

According to the National Cancer Institute, colorectal cancer is the fourth most common cancer diagnosed in the United States, predicted to strike nearly 150,000 people in 2021. The agency also estimates the disease will kill approximately 53,000 Americans this year, making it the nation's second leading cause of cancer mortality. Even more disturbing, say the experts, is the worldwide trend of increased incidence for early-onset colorectal cancer in people younger than 50.

Because catching colorectal cancer early is the key to saving lives, a Johns Hopkins Medicine team has been focusing its research on better understanding the molecular-level characteristics of the cell lining -- known as the epithelium -- of the colon (large intestine) in order to define how cancer may begin there.

"Our goal is to study this epithelial 'soil' in which cells, transformed into cancer-causing 'weeds,' can arise and proliferate," says Tatianna Larman, M.D., assistant professor of pathology at the Johns Hopkins University School of Medicine. "Finding what conditions in the epithelial stem cell niche [microenvironment] promote neoplasia [abnormal cell growth] and the acquisition of cancer driver mutations [changes in genetic sequences that cause cells to become cancerous] may help us identify ways to 'clean the garden' before cancer can emerge."

In a study published in the May 2021 issue of the journal Neoplasia, Larman and her colleagues used normal colon intestinal organoids -- cell lines grown from intestinal stem cells that function like miniature colons -- to see if changing the microenvironment alone would lead to epithelial changes that are precursors to cancer.

"We know from research studies that intestinal stem cells require certain 'niche factors' to maintain normal growth and function -- a balance known as homeostasis-- and that precursors to cancer can grow without these factors," says Larman. "When we removed one of those niche factors, a protein known as epidermal growth factor [EGF], most organoids died as expected. However, over many months, the rare survivors surprisingly adapted to growth without EGF and exhibited many features of neoplasia, such as abnormal morphology and chromosome numbers."

Studies have shown that inflammatory bowel disease and the resulting colitis -- a form of chronic injury and inflammation in the colon -- confers an increased risk for colorectal cancer. So, the researchers looked specifically at organoids derived from mice with colitis and found they could adapt to an EGF-free microenvironment more rapidly.

Since the research team showed that such EGF-independent cells exhibit many molecular characteristics of early-stage tumors, Larman says this provides evidence that chronic inflammation and molecular-level repair of the epithelium may "reprogram" the cells to lower the threshold for malignancy.

The team hopes its findings will expand the thinking about cancer initiation to encompass how "microenvironmental remodeling" may promote and synergize with early mutations that drive cells toward cancer.

"As a pathologist, I examine countless polyps [growths that are often precursors to colorectal cancer] under the microscope from patient screenings after colonoscopies," says Larman. "Those samples made me wonder what microenvironmental molecular changes allowed the polyps to arise and grow. Our study provides one possible pathway, paving the way for future investigations into how we can return the niche and epithelium to normal, cancer-free homeostasis."

Larman is available for interviews.

RESEARCHERS ID ANTI-INFLAMMATORY PROTEINS AS THERAPY TARGETS FOR NASAL AND SINUS PROBLEM

Media Contact: Ayanna Tucker, atucke25@jhmi.edu

Johns Hopkins Medicine researchers have identified a protein -- DMBT1S8 -- as a target for potential therapies to treat inflammation in the nasal and sinus cavities.

The researchers' findings were published March 20, 2021, in the journal Glycobiology.

Nasal and sinus inflammation -- known medically as chronic rhinosinusitis -- is one of the most common chronic illnesses in the United States, according to the U.S. Centers for Disease Control and Prevention. But for people with the most severe form of the condition, chronic rhinosinusitis with nasal polyps, it isn't your average stuffy nose.

Patients with this disorder are more susceptible to developing nasal obstruction, asthma or asthma like symptoms, sleep apnea, or loss of taste and smell. Corticosteroids are sometimes prescribed to treat severe forms, but are known to have dangerous side effects if used too long.

Fifteen years ago, Jean Kim, M.D., Ph.D., associate professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine, and colleagues found that a protein called DMBT1 (deleted in malignant brain tumors-1) was elevated in nasal polyp tissues. However, the significance of this finding was unclear.

A more recent study by a team led by Ronald Schnaar, Ph.D., the John Jacob Abel Professor of Pharmacology at the Johns Hopkins University School of Medicine, found that a key process controlling this type of inflammation requires a specific molecular structure known as siglec-8 (S8) in order to occur. Siglec-8, the researchers learned, binds with DMBT1 to form the isoform, or nearly identical twin, of DMBT1 called DMBT1S8.

Building on this research and searching for rhinosinusitis therapies with fewer side effects, Kim and her team conducted their latest study, an analysis of nasal secretions and biopsies from patients with chronic rhinosinusitis with nasal polyps. They wanted to understand more about the mechanism of the condition, specifically which type of sinusitis patient expresses the DMBT1S8 protein and from where in the nose it is produced.

"It was important for us to not only identify that DMBT1S8 is made in the airway, but also to understand its role in the development of nasal polyps," Kim says.

The researchers discovered that the level of DMBT1S8 proteins was more elevated in patients with chronic rhinosinusitis with polyps than in those with the nasal inflammation but no polyps.

The researchers also found that the DMBT1S8 protein is more likely to be located in the portion of a polyp where it is made, a region known as the submucosal glands. They speculate that from there, the protein is secreted into the airway and functions to control the inflammatory response involved in nasal polyp formation.

Kim says that learning how to manipulate DMBT1S8 structure and function may enable the development of novel therapies that can boost the anti-inflammatory response against chronic rhinosinusitis with nasal polyps.

Kim is available for interviews.

Prostate cancer is the second most common cancer among men, according to the American Cancer Society. It's also one of the trickiest cancers to diagnose and treat.

But new research from the University of Georgia has identified a protein that appears to prevent the cancer from spreading to and colonizing the bone, providing a new target for future therapeutics.

"Unfortunately, prostate cancer that has spread to the bone is very aggressive, often lethal and very difficult to treat," said Brian Cummings, corresponding author of the study and head of the College of Pharmacy's pharmaceutical and biomedical sciences department. "Even in cases of successful treatment, the patient's quality of life is severely lessened due to bone loss."

Prostate cancer that hasn't spread beyond nearby organs has nearly a 100% survival rate, meaning almost all of these patients will live at least another five or more years after their initial diagnosis and treatment. But for men whose cancer has spread to other organs or the bone, that five-year survival rate plummets to 30%, according to the American Cancer Society. In the U.S., about one in every eight men will be diagnosed with prostate cancer and more than 34,000 men die each year from the disease.

The new study, published by Scientific Reports, focused on cancer-associated fibroblasts, which are the most abundant type of cell in tumors and are responsible for cancer growth and spread. The researchers found that knocking out a specific protein, called glypican-1, could prevent tumor cells from spreading into nearby bone.

The study supports a previous report from Cummings' laboratory suggesting that this protein may prevent tumor growth. The researchers found that the protein doesn't alter the cancer cells themselves. Instead it affects a group of neighboring cells called fibroblasts.

Fibroblasts are cells that help make up connective tissues in people and animals. But fibroblasts can also be present in cancerous tumors, where they facilitate cancer growth and spread.

To determine the glypican-1 protein's role in helping cancer spread, the researchers combined human prostate cancer cells and human bone-derived cells to examine how the cancer cells transformed the fibroblast. Then they genetically modified the cancer cells and the fibroblast to knock out the protein.

Without the protein, the prostate cancer cells had problems transforming the fibroblast.

The study was the first to demonstrate such a role for glypican-1 and suggests that this protein may have the same effect on tumor growth in people.

"Part of the significance of this study is that it demonstrates how cancer cells are able to change their environment in ways to facilitate their own growth," Cummings said. "Prostate cancer cells alter their environment so that they can colonize bone. This study identifies a role for a protein that appears to inhibit the harmful changes that prostate cancer makes to the bone."

"This protein appears to stop the ability of cancer cells to change their environment, which decreases the cancer's aggressiveness. The fact that this protein is found in the bone, where many aggressive prostate cancer cells reside, further increases the potential impact of this work."

For the first time, Australian scientists have confirmed a link between the role of regular fish oil to break down the ability of 'superbugs' to become resistant to antibiotics.

The discovery, led by Flinders University and just published in international journal mBio, found that the antimicrobial powers of fish oil fatty acids could prove a simple and safe dietary supplement for people to take with antibiotics to make their fight against infection more effective.

"Importantly, our studies indicate that a major antibiotic resistance mechanism in cells can be negatively impacted by the uptake of omega-3 dietary lipids," says microbiologist Dr Bart Eijkelkamp, who leads the Bacterial Host Adaptation Research Lab at Flinders University.

"In the experiments, and complementary supercomputer modelling, we found that these fatty acids in fish oil renders the bacteria more susceptible to various common antibiotics."

"This chink in the armour of harmful bacteria is an important step forward in combatting the rise of superbugs that are developing multidrug resistance to antibiotics," says co-author Associate Professor Megan O'Mara, from the Australian National University.

The research is vital in the field of infectious diseases caused by bacteria such as Acinetobacter baumannii, a leading hospital-acquired pathogen with unprecedented levels of antibiotic resistance around the world.

"With the rise of superbugs, we have now been able to show that greedy bacterium cannot distinguish between 'good and bad' host fatty acids and will consume all of these during an infection," says another co-author Dr Felise Adams, from Flinders University.

"Our research showed that fish oil fatty acids become part of the bacteria membrane and thus make the invading bacteria membrane more permeable and susceptible to the antibiotics being used to attack it."

"We know Acinetobacter baumannii is one of the world's most notorious multidrug resistant pathogens, yet how it responds to host-mediated stress is poorly understood."

"These studies provide new insights into the potential benefits of omega-3 supplements for bacterial infection, in particular during antibiotic treatment," says Professor Anton Peleg, director of the Department of Infectious Diseases at The Alfred Hospital, Melbourne.

As many older adults get back to normal life across the United States thanks to high rates of vaccination and lower COVID-19 activity, a new poll suggests many should watch their alcohol intake.

In all, 23% of adults over 50 who drink alcohol reported that they routinely had three or more drinks in one sitting, according to new findings from the National Poll on Healthy Aging. And 10% of adults who drink use other drugs while drinking, including marijuana or prescription medications that can interact with alcohol in risky ways.

The poll asked adults age 50 to 80 to reflect on their drinking habits shortly before the pandemic and during its first ten months. Routinely having three or more alcoholic drinks on any day they drink, and occasional binge drinking, are both considered signs of problematic drinking in any adult.

While overall only 14% of older adults who drink alcohol said their drinking increased during the first ten months of the pandemic, that percentage was much higher among the minority of older adults who said they drink as part of their routine, to boost their mood or to relax, or to cope with boredom, stress or pain. A third to half of such adults reported drinking more in the past year. Those who reported feeling isolated or lonely were also more likely to say they'd increased alcohol intake.

Among older adults who drink, 10% said there was a time when they thought they were drinking too much during the pandemic, though few of them had sought help.

Meanwhile, half of older adults say they mainly drink for social reasons. Members of this group were more likely to say they decreased their drinking in 2020. This suggests that as social interactions increase during the new phase of the pandemic, their alcohol consumption may rise.

The poll is based at the University of Michigan's Institute for Healthcare Policy and Innovation and receives support from AARP and Michigan Medicine, U-M's academic medical center. It draws from the answers of a national sample of more than 2,000 adults aged 50 to 80 to a poll in late January, when COVID-19 case rates were high across the nation and vaccination of older adults had just begun. One-third of the respondents said they did not drink alcohol in the past year.

"Even before the pandemic, heavier and more risky drinking habits were increasing in older adults at a faster rate than among younger adults," said Anne Fernandez, Ph.D., a psychologist in the U-M Department of Psychiatry who specializes in studying alcohol use and who worked with the poll team on the report.

"While not every older adult who drank more during the past year may have gone from non-risky to risky drinking, but the overall level of drinking, and the potential for interaction with other substances, is very concerning," she said. "As we all toast the end of the worst part of the pandemic in our country, it's important to address or prevent problematic drinking of all kinds."

Aging-related alcohol concerns

The body's ability to process alcohol changes with age, said poll director Preeti Malani, M.D., a Michigan Medicine infectious disease physician also trained in geriatrics.

Older adults may find that the same amount of alcohol that they consumed with a meal or at a social occasion in the past will affect them differently now. That could include balance issues that could lead to falls and other injuries. Long-term drinking habits can accelerate the immune system decline that typically comes with age, and are associated with more memory loss.

"We get especially concerned when older adults are drinking multiple drinks at a sitting, so the 20% of older men who said they drink three to four alcoholic drinks on a typical day of drinking is concerning," she says. "And 27% of those who drink said that at least once in the past year, they had had six or more drinks - which is a 'binge' level of alcohol consumption that is risky at any age, but more so as we age."

Combining alcohol with substances that act on the central nervous system can pose special risks. Many older adults may not realize that they should not drink alcohol, or strictly limit their intake, if they are taking opioid pain medications, sleeping aids, sedatives, tranquilizers and medications for depression or other mental health concerns. As cannabis use for medical and recreational reasons rises in older adults, Fernandez says special attention is needed to this kind of interaction.

People with heart issues, diabetes, liver disease or other chronic illness should also reduce alcohol use because of the impact on their bodies.

Help for cutting back on drinking

Research has proven that there are effective ways for older adults - and adults of any age - to cut back on their drinking, or stop drinking altogether.

Counseling from professional therapists, peer support and recovery groups, and medication are all available treatments for alcohol use disorder or alcohol addiction, and for those who don't meet the criteria for that condition but want to cut back. Older adults can get referrals to such services, and potentially access coverage from their insurance, by talking to their regular health care provider.

In all, 27% of the older adults polled said they had been concerned about their own alcohol use at some time in their life - but only one in five of these who had been concerned had ever sought professional help for their drinking.

"Heavier drinking among older adults has been on the rise for several decades. Because unhealthy alcohol behaviors become more problematic as we age, it's important to seek treatment if you are worried about your alcohol consumption," said Alison Bryant, Ph.D., senior vice president of research for AARP.

Therapy based on the Nintendo® Wii Balance Board can help improve balance in children with cerebral palsy, according to an analysis published in Developmental Medicine & Child Neurology.

For the analysis, researchers from the University of Jaén, in Andalusia, Spain examined data from all relevant randomized controlled trial published to date. In 11 trials with 270 children with cerebral palsy, there was very low-quality evidence of a large effect of Nintendo® Wii therapy on functional balance (compared with no intervention) and moderate-quality evidence for a benefit to using Nintendo® Wii therapy plus conventional physical therapy (compared with conventional physical therapy alone) in sessions of approximately 30 minutes and interventions lasting longer than 3 weeks.

For dynamic balance (involving balance while in motion or when switching positions), investigators found very low-quality evidence for a medium effect for using Nintendo® Wii therapy plus conventional physical therapy vs. conventional physical therapy alone.

"Our results suggest that Nintendo® Wii therapy may be a useful tool that can be included in neurorehabilitation physiotherapy protocols to improve balance in children with cerebral palsy," said corresponding author Esteban Obrero-Gaitán, PT, PhD. "Virtual reality-based rehabilitation using Nintendo® Wii is considered a multi-sensory and active therapy that encourages the child's participation, increasing motivation and adherence to therapy due to its playful nature. In addition, it is a low-cost tool that can be used at home for therapeutic purposes, a fact that is of great relevance during the COVID-19 pandemic."

A study published in Arthritis Care & Research has uncovered an elevated risk of Parkinson's disease in individuals with osteoarthritis.

The retrospective study using Taiwan's Longitudinal Health Insurance Database 2005 included 33,360 patients who were 50-64 years old and had osteoarthritis in 2002-2005. A comparison group consisted of 33,360 age- and sex- matched individuals without osteoarthritis. The osteoarthritis group had a 41% higher risk of developing Parkinson's disease, after adjustments. Patients with knee or hip osteoarthritis appeared to have a higher risk of Parkinson's disease than patients with non-knee and non-hip osteoarthritis or with uncategorized osteoarthritis.

Although the mechanisms behind a potential link between osteoarthritis and Parkinson's disease are unknown, both conditions involve inflammation.

"Coexisting osteoarthritis and Parkinson's disease can additively increase the risk of falling. Moreover, osteoarthritis-related mobility impairments may mask early motor symptoms of Parkinson's disease," said senior author Shin-Liang Pan, MD, PhD, of National Taiwan University. "Health professionals need to be alert to the potential link between these two diseases."

Advanced age is often considered a contraindication for heart transplantation, but a new study published in the Journal of the American Geriatrics Society (JAGS) found that post-heart transplant survival among recipients aged ?70 years is not inferior to that of younger recipients.

The study included 37,135 patients who underwent heart transplantation, 806 (2.2%) of whom were ?70 years old. Among patients ?70 years old, the 1- and 5-year mortality rates after transplantation were 10.4% and 19.2%, respectively. After adjusting for kidney health, body mass index, and other factors, there was no significant difference in 5-year mortality between patients

"Rising prevalence of congestive heart failure with age and our aging population demand a relook into the management of advanced heart failure in elderly individuals," said lead author Abhishek Jaiswal, MD, of Hartford Hospital. "Our data suggest that advanced age by itself should not be considered an ineligibility criteria for heart transplantation; however, careful selection of such patients is warranted."

For public education summaries of topical JAGS articles like this, visit the American Geriatrics Society's Health in Aging blog.