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The COVID-19 pandemic has had a profound effect across society, but it has been especially devastating for people with substance use disorder.

A new study, published in the journal PLOS ONE, sheds light on the experience of patients with substance use disorder who were hospitalized during the initial surge of COVID-19 cases in Oregon last spring. Researchers with Oregon Health & Science University conclude that health systems nationwide could benefit from a better understanding of people who struggle with the basics.

"We need the system to be designed and implemented for patients who may lack phone access, who may not have access to WiFi or may be living on the streets," said lead author Caroline King, M.P.H., a health systems researcher and current M.D./Ph.D. student in the OHSU School of Medicine's bioengineering program.

King led the study with two other OHSU medical students, Taylor Vega and Dana Button.

Researchers conducted a series of interviews with 27 patients hospitalized at OHSU last April and May with acute medical or surgical conditions who also have substance use disorder.

The research was done through an OHSU program known as Project IMPACT, or Improving Addiction Care Team.

In normal circumstances, Project IMPACT brings together physicians, peer-recovery mentors, social workers and community addiction providers to address addiction when patients are hospitalized. However, during the first few months of the pandemic, IMPACT had more limited interactions with patients given new pandemic-related hospital policies implemented to prevent the spread of the SARS-CoV-2 virus.

Researchers identified four key takeaways from telephone interviews with patients.

Basic survival: For many of the patients who were interviewed, housing instability intensified due to the pandemic. They also struggled accessing food, employment, social services and bathrooms. Virtual recovery meetings such as Alcoholic Anonymous didn't help for many patients, half of whom didn't own a phone.

Hospital is a safety net: Although many participants were concerned about exposing themselves to the novel coronavirus by going to a hospital, many reported they had nowhere else to turn. Telehealth visits for outpatient services are not possible for those without phones or electronic devices. Some participants reported that a lack of readily available in-person medical care caused a cascade of medical issues that worsened to the point that they required hospitalization.

Hospital is isolating: Participants reported that they felt isolated due to the constraints on visitation and wearing of personal protective equipment by health care providers, although simultaneously comforted by the precautions taken to prevent the spread of the virus.

Uncertain transition home: Almost every patient interviewed expressed concern about leaving the hospital. For almost every patient, housing was a top worry. Participants worried they wouldn't be able to take care of their medical needs given shuttered community services and broad disruptions in the medical and social safety net.

Senior author Honora Englander, M.D., an associate professor of medicine (hospital medicine) in the OHSU School of Medicine who directs Project IMPACT, said the study makes clear that properly caring for these patients does not end when they're wheeled out of the hospital's front doors.

In some ways, the most difficult part of their journey only begins there.

"What does it mean to be 'medically ready' for discharge if a patient is leaving to an unsafe situation with no phone or housing in a pandemic?" Englander said. "We have a role to play as advocates in direct patient care, and as health care providers we can also apply pressure on powerful and sometimes-inflexible systems to make their care better."

Care homes are at high risk of experiencing outbreaks of COVID-19, the disease caused by SARS-CoV-2. Older people and those affected by heart disease, respiratory disease and type 2 diabetes - all of which increase with age - are at greatest risk of severe disease and even death, making the care home population especially vulnerable.

Care homes are known to be high-risk settings for infectious diseases, owing to a combination of the underlying vulnerability of residents who are often frail and elderly, the shared living environment with multiple communal spaces, and the high number of contacts between residents, staff and visitors in an enclosed space.

In research published in eLife, a team led by scientists at the University of Cambridge and Wellcome Sanger Institute used a combination of genome sequencing and detailed epidemiological information to examine the impact of COVID-19 on care homes and to look at how the virus spreads in these settings.

SARS-CoV-2 is an RNA virus and as such its genetic code is prone to errors each time it replicates. It is currently estimated that the virus mutates at a rate of 2.5 nucleotides (the A, C, G and U of its genetic code) per month. Reading - or 'sequencing' - the genetic code of the virus can provide valuable information on its biology and transmission. It allows researchers to create 'family trees' - known as phylogenetic trees - that show how samples relate to each other.

Scientists and clinicians in Cambridge have pioneered the use of genome sequencing and epidemiological information to trace outbreaks and transmission networks in hospitals and community-based healthcare settings, helping inform infection control measures and break the chains of transmission. Since March 2020, they have been applying this method to SARS-CoV-2 as part of the COVID-19 Genomics UK (COG-UK) Consortium.

In this new study, researchers analysed samples collected from 6,600 patients between 26 February and 10 May 2020 and tested at the Public Health England (PHE) Laboratory in Cambridge. Out of all the cases, 1,167 (18%) were care home residents from 337 care homes, 193 of which were residential homes and 144 nursing homes, the majority in the East of England. The median age of care home residents was 86 years.

While the median number of cases per care home was two, the ten care homes with the largest number of cases accounted for 164 cases. There was a slight trend for nursing homes to have more cases per home than residential homes, with a median of three cases.

Compared with non-care home residents admitted to hospital with COVID-19, hospitalised care home residents were less likely to be admitted to intensive care units (less than 7% versus 21%) and more likely to die (47% versus 20%).

The researchers also explored links between care homes and hospitals. 68% of care home residents were admitted to hospital during the study period. 57% were admitted with COVID-19, 6% of cases had suspected hospital-acquired infection, and 33% were discharged from hospital within 7 days of a positive test. These findings highlight the ample opportunities for SARS-CoV-2 transmission between hospital and care home settings.

When the researchers examined the viral sequences, they found that for several of the care homes with the highest number of cases, all of the cases clustered closely together on a phylogenetic tree with either identical genomes or just one base pair difference. This was consistent with a single outbreak spreading within the care home.

By contrast, for several other care homes, cases were distributed across the phylogenetic tree, with more widespread genetic differences, suggesting that each of these cases was independent and not related to a shared transmission source.

"Older people, particularly those in care homes who may be frail, are at particular risk from COVID-19, so it's essential we do all that we can to protect them," said Dr Estée Török, an Honorary Consultant at Addenbrooke's Hospital, Cambridge University Hospitals (CUH), and an Honorary Senior Visiting Fellow at the University of Cambridge.

"Preventing the introduction of new infections into care homes should be a key priority to limit outbreaks, alongside infection control efforts to limit transmission within care homes, including once an outbreak has been identified."

The team found two clusters that were linked to healthcare workers. One of these involved care home residents, a carer from that home and another from an unknown care home, paramedics and people living with them. The second involved several care home residents and acute medical staff at Cambridge University Hospitals NHS Foundation Trust who cared for at least one of the residents. It was not possible to say where these clusters originated from and how the virus spread.

"Using this technique of 'genomic surveillance' can help institutions such as care homes and hospitals better understand the transmission networks that allow the spread of COVID-19," added Dr William Hamilton from the University of Cambridge and CUH. "This can then inform infection control measures, helping ensure that these places are as safe as possible for residents, patients, staff and visitors."

The absolute number of diagnosed COVID-19 cases from care home residents declined more slowly in April than for non-care home residents, increasing the proportion of cases from care homes and contributing to the slow rate of decline in total case numbers during April and early May 2020.

"Our data suggest that care home transmission was more resistant to lockdown measures than non-care home settings. This may reflect the underlying vulnerability of the care home population, and the infection control challenges of nursing multiple residents who may also share communal living spaces," said Gerry Tonkin-Hill from the Wellcome Sanger Institute.

The team found no new viral lineages from outside the UK, which may reflect the success of travel restrictions in limiting new viral introductions into the general population during the first epidemic wave and lockdown period.

The COVID-19 pandemic has caused unprecedented economic disruption and unemployment worldwide, and it may be challenging for career counselors to determine how best to provide effective career counseling to unemployed people in the post-COVID-19 world. In an article published in the Journal of Employment Counseling, experts suggest applying a holistic model of career counseling that addresses the multifaceted needs of long-term unemployed people.

The model was developed to address similar problems occurring in Greece in the aftermath of the 2008 financial crisis.

The authors note that career counselors should work on multiple levels--with individuals, with employers, with policy makers, and within the wider social context--to provide effective career counseling.

"The full impact of the pandemic crisis on the world of work is yet to be seen. Nonetheless, it is certain that career counselling will have to address the sharp rise of unemployment, and a holistic approach is essential," said lead author Nikos Drosos, PhD, an Assistant Professor at the European University Cyprus. "As we saw in the recent financial crisis in Greece, working just with clients is not enough, and we have to make multilevel and multifaceted interventions."

CLEVELAND, Ohio (March 3, 2021)--The length of the female reproductive period (the time from the onset of menses to the final menstrual period) has important health implications. A new study compared the length of reproductive periods for women with type 1 diabetes with women without diabetes to confirm the effect diabetes has on the female reproductive system. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Insulin plays a key role in regulating female reproductive function, and previous studies have shown the effect of insulin deficiency on a woman's reproductive system. Until now, however, little was known about the effect of type 1 diabetes on the age of natural menopause.

This new study involving nearly 300 women compared the length of reproductive periods for women with type 1 diabetes with women without diabetes. It concluded that women with type 1 diabetes have shorter reproductive periods, with delayed menarche and earlier natural menopause as a result of insulin deficiency and hyperglycemia disrupting their reproductive system's normal function. Of note, however, is the fact that these findings only relate to women who were diagnosed with type 1 diabetes before reaching the age of menarche.

Because menopause is associated with a number of physiologic and metabolic changes, and early natural menopause is linked to increased cardiovascular disease and mortality, there is ongoing interest in identifying factors that provide some indication of when a woman will enter menopause. The researchers suggest that more research is needed to help determine modifiable factors that contribute to early menopause to improve the reproductive health of women with diabetes.

Results are published in the article "Women with type 1 diabetes (T1D) experience a shorter reproductive period compared with nondiabetic women: The Pittsburgh Epidemiology of Diabetes Complications (EDC) study and the Study of Women's Health Across the Nation (SWAN)."

"This study found that women with the onset of type 1 diabetes before menarche were at increased risk for a shorter reproductive lifespan. Thus, these women are not only at risk for premature ovarian aging because of early onset type 1 diabetes, they are also at increased risk for cardiovascular disease, osteoporosis, and early mortality because of early natural menopause. Understanding these risks and targeting appropriate risk-reducing strategies are key to optimizing the health and quality of life of these women," says Dr. Stephanie Faubion, NAMS medical director.

CLEVELAND, Ohio (March 3, 2021)--The loss of estrogen after menopause is associated with rapid bone loss. A new study compared the bone health outcomes in women with primary ovarian insufficiency (POI) and early menopause with women who experienced menopause at the standard age to confirm the association between POI and osteoporosis. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Osteoporosis is a skeletal condition characterized by low bone mass and deterioration of bone tissue that leads to fragility and an increased risk of fracture. The debilitating disease, which affects more women than men, is associated with significant morbidity and mortality when osteoporotic fractures occur, leading to an increased rate of institutionalization and risk for mortality.

Previous studies have suggested an association between osteoporosis and POI, which is the loss of ovarian function before age 40 years. This new study, however, is the first one done on a larger scale, with more than 12,000 participants. It confirms the findings of smaller studies that demonstrated an association between POI and early menopause (described as the loss of ovarian function between 40 and 45 years) on bone mineral density and osteoporosis. Specifically, women with POI were shown to have higher odds of osteoporosis and were more likely to be taking osteoporosis drugs.

The researchers also found that the use of hormone therapy reduced the odds for osteoporosis but that many women were not being adequately treated or even made aware of the benefits of hormones in reducing their risk. In addition, the study confirmed that women with POI were more likely to be obese, have decreased physical activity levels, and currently smoked.

It is estimated that 1% to 4% of women worldwide have POI, which means a significant number of women are at increased risk for osteoporosis.

Results are published in the article "The association between primary ovarian insufficiency and osteoporosis in the Canadian Longitudinal Study on Aging."

"This study highlights the elevated risk of osteoporosis for women experiencing menopause before the age of 40 years and underscores the importance of the use of hormone therapy at least until the natural age of menopause in order to reduce the significant morbidity and mortality associated with osteoporotic fractures," says Dr. Stephanie Faubion, NAMS medical director.

Proof of immunization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may soon be required in many parts of the globe. The authors discuss how immunization passports could work, what Canada needs to do, and potential barriers and limitations in a CMAJ (Canadian Medical Association Journal) commentary.

"We expect that immunization passports may be imminently introduced for international travel," writes Dr. Kumanan Wilson, Department of Medicine, University of Ottawa and Bruyère and Ottawa Hospital Research Institutes, with Colleen M. Flood, University of Ottawa Centre for Health, Law Policy & Ethics, Ottawa, Ontario. "Canada will need to ensure alignment with global standards for security, authentication, privacy and data exchange developed by the WHO Smart Vaccination Certificate initiative."

The World Health Organization (WHO), International Air Traffic Association and World Economic Forum have been exploring standards for these digital passports, indicating they may be used first for international travel but could also be required for large gatherings and within some workplaces.

A properly constructed approach to immunization passports could help to limit the spread of SARS-CoV-2 while allowing society to reopen and the global economy to be revitalized. The foundation must be an accurate, comprehensive vaccination record that allows individuals access to their records and those of their children and family members.

Elements key to implementing immunization passports include

Technological capacity

Adherence to international standards

Ability of provincial and territorial governments to issue secure digital immunization records that meet pan-Canadian standards

Input from legal and ethical experts and the development of standards to ensure that those who can't be vaccinated are not discriminated against or denied access to services

Safeguards to protect the privacy of personal information

"If governments do not develop the necessary capacity to implement immunization passports, it is likely that private corporations (e.g., airlines and large event venues) will develop their own requirements and systems, potentially leading to problems related to equity, privacy and coercion," the authors write.

In recent years, hummus has become a pop culture food phenomenon, drawing praises from dieticians for the health benefits and chefs for the flavor.

However, the core ingredient, the chickpea, has had its production threatened.

The chickpea has played a significant role in the vegetarian diet for thousands of years. It is high in protein and rich in important carbohydrates and minerals.

Grown in the Pacific Northwest and Northern Plains of the United States, the chickpea has an integral role in the agriculture systems of these regions. Recently this role has been threatened by a soil-born water mold, Pythium ultimum.

George Vandemark and his team have worked to improve chickpea varieties and develop new ways to control disease in legumes. Their research was recently shared in Crop Science, a publication of the Crop Science Society of America.

"For over 30 years, common pathogens in chickpeas and other legumes have been controlled by fungicides," says Vandemark. "We discovered this approach was not working effectively when one of my coworkers visited a field where seedlings had not emerged."

The planted seeds died shortly after they started to germinate. As the seed grew to the top of the soil, the disease attacked the plant and killed it.

To identify the cause, researchers isolated the chickpea seeds in the soil. They discovered that the pathogen P. ultimum developed resistance to fungicide. This resistance allowed the mold to infect the plant.

"Our approach looked at two different types of chickpeas - kabuli and desi," says Vandemark. "The kabuli chickpea is almost exclusively grown in the United States because of the large export market."

Kabuli chickpeas are larger, have a clear or light beige seed coat, and are typically canned and used to make hummus. Desi is smaller, has a colored seed coat, and is used for making stews.

The researchers examined different lines of the chickpea to identify natural sources of resistance to P. ultimum.

The most popular varieties of chickpea grown in the United States were susceptible to the disease. The team did discover other chickpea varieties that showed resistance to the soil-born mold.

"We identified many desi chickpeas that were resistant to the pathogen," said Vandemark. "Luckily, several kabuli also displayed intermediate levels of resistance."

These resistant chickpea varieties excited the researchers because they produce chickpeas that look similar to what consumers are used to.

"These traits are not ones we want to lose," said Vandemark. "Consumers expect the kabuli type chickpea to come from the United States. The lines we identified with resistance to the disease have the shape and seed color that are desirable."

With this discovery, the research team is using the resistant plants to breed new kabuli varieties. The resistance chickpeas are crossed with current commercial varieties. This will develop a type that is more resistant to the disease.

"Moving forward, this will lead to new chickpea varieties with improved resistance to P. ultimum," explains Vandemark. "This research will also lead to new methods for controlling diseases that rely less on fungicides and more on genetic resistance."

From this research, scientists can gain a better understanding of disease and disease resistance. This will push researchers to use plant breeding as a means to combat diseases, rather than synthetic chemicals.

"P. ultimum has a broad range of hosts," says Vandemark. "While we looked at chickpeas, it can affect small grains like wheat and other legumes like soybeans. The chickpea has a small genome size, making it easier to examine."

Future researchers can build upon this research to examine potential disease resistance to P. ultimum in other crops. Naturally controlling the disease using genetics and breeding can lead to a more sustainable production system.

Red ginseng, which has long been used as an ingredient in traditional Korean medicine, has recently drawn increased attention as a functional material for its health-promoting effects. The composition and activities of red ginseng vary depending on the processing method, and this has become an active area of research. Recently, a research team in Korea has entered the spotlight as they discovered that red ginseng has inhibitory effects against lung cancer metastasis.

The Korea Institute of Science and Technology (KIST) reported that a joint study conducted by Dr. Jungyeob Ham from the Natural Product Research Center at the KIST Gangneung Institute of Natural Products and Dr. Hyeonseok Ko of Seoul Asan Medical Center revealed that two components of red ginseng, Rk1 and Rg5, can significantly suppress lung cancer metastasis.

Dr. Ham of KIST developed a new microwave processing method for red ginseng that is based on the same principle as a microwave oven, which when compared to existing processing methods, such as repetitive steaming and drying, increases the concentration of the three main active components, Rg3, Rk1, and Rg5, more than 20 times. The research team previously demonstrated that red ginseng produced by this microwave processing method, which they have called KMxG, is effective against prostate, cervical, and skin cancers, and has protective effects against by drug-induced kidney damage. This technology was transferred to Ponin Bio Co., Ltd. in 2020 for a technology fee of KRW 800 million and is currently being developed for commercialization.

Unlike normal cells, which die when separated from their original tissue, cancer cells can spread to other tissues where they invade and grow, in a process called metastasis. TGF-β1, a cytokine protein that functions as a signaling substance in the body, induces lung cancer metastasis and promotes the development of stem cell-like properties in cancer cells. The KIST research team treated lung cancer cells with Rk1 and Rg5, the main components of KMxG red ginseng and showed that both components effectively inhibited various processes related to cancer metastasis induced by TGF-β1.

"Although components of red ginseng previously have been shown to kill cancer cells, this study proved that these components of red ginseng have other anti-cancer effects and can inhibit lung cancer metastasis. This provides scientific evidence that may lead to the future development of anti-cancer drugs derived from natural products," remarked Dr. Ham. He added, "Because we can control the active ingredient contents of red ginseng by using microwave processing methods like the one that produced KMxG, it may be possible to develop customized functional materials for various diseases."

A detailed analysis of mental health treatment trends during the COVID-19 pandemic found a 7% increase in visits during the initial shelter-in-place period in 2020, compared with the same 3-month period in 2019.

The study, published in The Journal of Clinical Psychiatry March 3, examined patient visits for psychiatric diagnoses among members of Kaiser Permanente in Northern California.

The greatest increases in visits were for substance use (up 51%), adjustment disorder (up 15%), anxiety (up 12%), bipolar disorder (up 9%), and psychotic disorder (up 6%). Adjustment disorder is diagnosed when someone responds to a stressful life event with symptoms such as sadness and hopelessness.

"The increases we found in patients seeking care for substance use and anxiety are consistent with other data showing the pandemic and shelter-in-place orders were difficult for many people," said lead author Kathryn Erickson-Ridout, MD, a psychiatrist with Kaiser Permanente in Northern California and a member of the Physician Researcher Program with the Kaiser Permanente Northern California Division of Research. "These findings reflect what I experienced with my patients who sought out care."

The analysis focused on a period when Kaiser Permanente pivoted to virtual visits by video and telephone to ensure that patients continued to have access to care when shelter-in-place orders were implemented. "COVID-19 has created huge psychosocial disruption," Dr. Erickson-Ridout said. "It's impacting people's ability to work, socialize, and have relationships, and that is having mental health consequences. We were able to respond to that with a robust telehealth system, to reach those patients and give them good care."

The study was a retrospective observational analysis comparing 165,696 psychiatric outpatient contacts between March 9 and May 31, 2019, with 181,015 during the same period in 2020, an increase of 7%. The researchers also confirmed the shift away from in-person visits, tallying a 264% increase in telephone and video visits from the year before. Kaiser Permanente clinicians also offer mental health support by secure email message, but this study did not count those.

The study found 42% more addiction clinic visits than the same period in 2019. This could be related to patients having more difficulty coping with the pandemic, but it could also reflect existing patients having good connections with their addiction medicine providers, said study senior author Esti Iturralde, PhD, a research scientist with the Division of Research. "They may have been able to seek care more easily from the health system because of the strong connections and supports Kaiser Permanente provides, including case management," she said.

The results also suggest some people did not immediately adjust to the new virtual visit format. Visits with new patients declined by 42%, as did visits by children and adolescents (down 23%), and older adults (down more than 5%).

The authors said these results may reflect which patients were most comfortable reaching out for telehealth care, at least during the first few months of the pandemic. Reliance on caregivers to facilitate visits, or healthcare avoidance during this time, may be behind these changes. Future research may reflect how patients adjusted to virtual visits past May 2020.

To increase use of virtual visits by these groups, and people with new mental health symptoms, the authors suggested outreach through collaborative care, such as getting referrals from primary care providers and other clinicians patients see for physical health concerns.

For women who had participated in both of their previous two screening examinations, the incidence of breast cancers proving fatal within 10 years of diagnosis was 50 per cent lower than in women who did not attend either of the last two screening examinations. Compared with women who attended only one of the two previous screens, women who attended both had a significant 22-33 per cent reduction in breast cancer mortality.

Lead author, Professor Stephen Duffy of Queen Mary University of London, said: "While there is ample evidence that breast cancer mortality is reduced in those who attend screening, these results demonstrate that repeated attendance confers greater protection than attendance at a single screen. We need to ensure that the screening experience is as stress-free as possible, so that people will come back."

The Principal Investigator of the study, Professor Laszlo Tabar of Falun Central Hospital, Sweden, said: "This comprehensive study is the result of a long-term cooperative effort of the physicians and other professional staff in nine Swedish counties, all of whom were trained in the Falun School. The analysis of the massive dataset was masterfully handled by the statisticians of the Swedish Organized Service Screening Evaluation Group. This work adds additional evidence confirming the value of early detection of breast cancer through regular attendance at mammography screening, helping women and their physicians make informed decisions."

New research shows that people diagnosed with a genetic condition, called alpha-1 antitrypsin deficiency (AATD), are far more likely to stop smoking and therefore prevent the development of lung disease.

The study, led by researchers from RCSI University of Medicine and Health Science, is published in COPD: Journal of Chronic Obstructive Pulmonary Disease.

It is estimated that 265,000 people on the island of Ireland are affected by either severe or moderate AATD, but the vast majority of people with AATD have not been diagnosed.

Previously, it was assumed that only people with severe AATD were at risk of lung disease. Recent Irish research has shown that people with the far more common moderate form of AATD are also at risk of lung disease if they are smokers.

With the smoking rate in the general population in Ireland at 17%, this means there are approximately 45,000 current smokers with either severe or moderate AATD who are at increased risk of lung damage due to cigarettes. According to the latest figures from the national targeted detection programme for AATD based at RCSI Beaumont Hospital, 90% of these smokers with AATD remain undiagnosed.

The researchers surveyed patients enrolled in the National AATD Registry with a questionnaire relating to demographics, parental smoking history, personal smoking history, AATD awareness and personal medical history.

Of the 293 respondents, 58 reported being smokers at the time of their AATD diagnosis. Their subsequent reported quit rate was 70.7%.

"Our study has shown that those who receive a diagnosis of alpha-1 antitrypsin deficiency are far more likely to stop smoking. We hope this study will lead to increased testing for AATD, with more people being diagnosed and choosing to stop or completely avoid smoking in order to prevent lung disease from developing," said Dr Tomás Carroll, senior lecturer at RCSI and the study's corresponding author.

"People with AATD who use electronic cigarettes are also potentially at risk, but more research is needed."

The research also found that people who reported having a parent who smoked were far more likely to become smokers themselves. Those with a parent who smoked were 84% more likely to smoke than those who did not.

For a diagnosis of AATD, a simple blood test is available in most large hospitals in Ireland that can identify those who need further testing. The more precise definitive test is provided for free by Alpha-1 Foundation Ireland as part of a HSE funded national targeted detection programme.

PITTSBURGH, March 3, 2021 - Women who experience an accelerated accumulation of abdominal fat during menopause are at greater risk of heart disease, even if their weight stays steady, according to a University of Pittsburgh Graduate School of Public Health-led analysis published today in the journal Menopause.

The study--based on a quarter century of data collected on hundreds of women--suggests that measuring waist circumference during preventive health care appointments for midlife women could be an early indicator of heart disease risk beyond the widely used body mass index (BMI)--which is a calculation of weight vs. height.

"We need to shift gears on how we think about heart disease risk in women, particularly as they approach and go through menopause," said senior author Samar El Khoudary, Ph.D., M.P.H., associate professor of epidemiology at Pitt Public Health. "Our research is increasingly showing that it isn't so important how much fat a woman is carrying, which doctors typically measure using weight and BMI, as it is where she is carrying that fat."

El Khoudary and her colleagues looked at data on 362 women from Pittsburgh and Chicago who participated in the Study of Women's Health Across the Nation (SWAN) Heart study. The women, who were an average age of 51, had their visceral adipose tissue--fat surrounding the abdominal organs--measured by CT scan and the thickness of the internal carotid artery lining in their neck measured by ultrasound, at a few points during the study. Carotid artery thickness is an early indicator of heart disease.

The team found that for every 20% increase in abdominal fat, the thickness of the carotid artery lining grew by 2% independent of overall weight, BMI and other traditional risk factors for heart disease.

They also found that abdominal fat started a steep acceleration, on average, within two years before the participants' last period and continued a more gradual growth after the menopausal transition.

Saad Samargandy, Ph.D., M.P.H., who was a doctoral student at Pitt Public Health at the time of the research, explained that fat that hugs the abdominal organs is related to greater secretion of toxic molecules that can be harmful to cardiovascular health.

"Almost 70% of post-menopausal women have central obesity--or excessive weight in their mid-section," said Samargandy, also the first author of the journal article. "Our analysis showed an accelerated increase of visceral abdominal fat during the menopausal transition of 8% per year, independent of chronological aging."

Measuring abdominal fat by CT scan is expensive, inconvenient and could unnecessarily expose women to radiation--so El Khoudary suggests that regularly measuring and tracking waist circumference would be a good proxy to monitor for accelerating increases in abdominal fat. Measuring weight and BMI alone could miss abdominal fat growth because two women of the same age may have the same BMI but different distribution of fat in their body, she added.

"Historically, there's been a disproportionate emphasis on BMI and cardiovascular disease," said El Khoudary. "Through this long-running study, we've found a clear link between growth in abdominal fat and risk of cardiovascular disease that can be tracked with a measuring tape but could be missed by calculating BMI. If you can identify women at risk, you can help them modify their lifestyle and diet early to hopefully lower that risk."

Late last year, El Khoudary led a team in publishing a new scientific statement for the American Heart Association that calls for increased awareness of the cardiovascular and metabolic changes unique to the menopausal transition and the importance of counseling women on early interventions to reduce cardiovascular disease risk factors.

El Khoudary noted that more research is needed to determine if certain diet, exercise or lifestyle interventions are more effective than others, as well as whether there is a clear cut-off point for when growth in waist circumference becomes concerning for heart disease risk.

SALT LAKE CITY - Utah researchers report significant new insights into the development of blood cancers. In work published today in Blood Cancer Discovery, a journal of the American Association for Cancer Research, scientists describe an analysis of published data from more than 7,000 patients diagnosed with leukemia and other blood disorders. Their findings provide new clues about mutations that may initiate cancer development and those that may help cancer to progress.

The researchers sought to identify mutation hotspots, or frequent changes in specific locations of the cancer patients' genetic information. The researchers then used these hotspots to look for whether the same mutations were present in the DNA data of more than 4,500 people who were not known to have a cancer diagnosis. They found that approximately 2 percent of these presumably healthy participants had, at low levels, mutations identical to those frequently observed in the cancer patients.

"Understanding how a disease develops is greatly benefited by studying persons who are currently healthy but are on a trajectory for disease onset," said Clint Mason, PhD, assistant professor of pediatrics at the U of U, who specializes in cancer genomics and bioinformatics and led the study.

Mutations occur throughout the 3 billion bases of DNA that are present in human cells. Many will have no impact on health, yet certain mutations may cause or support development of diseases, including cancer. Therefore, scientists are working to discern which mutations have a significant impact on health. In this study, the researchers sought to understand which mutations are most frequently present in adults and children both with and without blood cancers. They hope this information may illuminate an understanding of these cancers, and further, may potentially be used to identify people who are progressing towards cancer.

The team of researchers consisted nearly entirely of University of Utah (U of U) faculty and students. Mason was joined by co-first authors Julie Feusier, PhD, a trainee in the department of human genetics and now a postdoctoral fellow at Huntsman Cancer Institute, and Sasi Arunachalam, PhD, a postdoctoral fellow at Huntsman Cancer Institute and now a research associate at St. Jude Children's Research Hospital, in performing analyses along with other co-authors.

For the first part of the study, the researchers completed a large data mining analysis to examine published data from 48 cancer studies that reported mutations present in persons who were being diagnosed with leukemia or other hematologic malignancies. Across the 7,430 pediatric and adult cancer patients of those studies, 434 DNA locations were identified as frequently mutated. Then, in a subsequent analysis of many terabytes of publicly available genetic data, the researchers identified these same cancer-relevant mutations at low levels among 83 of the 4,538 persons who were presumably free from cancer.

"When identical mutations are found to be present in a small percentage of blood cells of a healthy person, it may indicate that something abnormal has begun to occur," explained Mason.

This abnormal process (known as clonal hematopoiesis) has previously been found to be increasingly common as people age. As a result, researchers generally focus on the study of adults when investigating this phenomenon. Yet in this study, in addition to adults, the researchers analyzed data from 400 children who were likely to be free from cancer. They found preliminary evidence that early cancer mutations could be detected in this age group.

In an accompanying commentary, to be published by Blood Cancer Discovery in its "In the Spotlight" section, Barbara Spitzer, MD, and Ross Levine, MD, of the Memorial Sloan Kettering Cancer Center, wrote, "This work demonstrates the first evidence that [clonal hematopoiesis] is observed in children outside of those with advanced malignancies." They further commented, "This expansion of the range of hematologic malignancy hotspot mutations goes beyond an improved understanding of the molecular repertoire of hematologic malignancies... More complete knowledge of relevant mutations may increase our detection of patients at highest risk for malignant transformation."

Finding a low-level mutation identical to one that is frequently present at cancer diagnoses could be alarming to a currently healthy person screened for such events. But fortunately, because cancer frequently requires multiple mutations to be present in a sizeable fraction of cells, most persons with a single low-level mutation are not likely to develop cancer for many years or decades--if they develop cancer at all. Large longitudinal studies are needed to identify the timeframe over which specific mutations or combinations of mutations accelerate progression to cancer.

The Utah researchers next hope to determine the stability of mutations identified at younger ages. This will give a preliminary glimpse into their potential to serve as biomarkers for those having greatest risk of cancer. Future intervention studies will require such an identification.

"Our goal has been to help fill in gaps in the understanding of cancer development so that future prevention work can take place more quickly and effectively," said Mason. "We are grateful to have been able to contribute a few puzzle pieces to that monumental effort."

Systemic fungal infections are much rarer than other illnesses, but they are potentially deadly, with limited options for treatment. In fact, fungi are becoming increasingly resistant to the few drugs that are available, and infections are growing more common. A cover story in Chemical & Engineering News, the weekly newsmagazine of the American Chemical Society, details how scientists are working to improve our antifungal arsenal.

At present, there are only four types of antifungal drugs approved by the U.S. Food and Drug Administration (FDA), and some infections are resistant to those drugs, making surgery the only option for treatment, writes Senior Correspondent Bethany Halford. Fungi can be found almost everywhere, but only a few hundred species are able to infect humans, and most people's immune systems can fight them off. However, people with compromised immune systems (for instance, cancer patients being treated with certain chemotherapies) are at a higher risk for developing fungal infections. The FDA has not approved a drug from a new antifungal class in 20 years, and the ones available all have downsides, including drug resistance and kidney toxicity. This dearth of treatments has doctors concerned that the problem will only get worse as time goes on.

Creating a new antifungal drug is challenging because of the biological similarities between humans and fungi. Many molecules that are harmful to fungi are also harmful to people. Experts say that exploiting the differences between humans and fungi is key to developing new treatments; for example, fungal cells have walls, but human cells do not. In addition to developing new treatments, pharmaceutical researchers are working to improve established antifungal drugs to make them more potent and have fewer side effects. Although scientists and doctors are hopeful that new antifungals will be approved, establishing clinical trials has proven challenging because most of the people who get fungal infections are already very sick. However, the COVID-19 pandemic could change how pharmaceutical companies think about therapies for infectious diseases, prioritizing them in the future.

BOSTON - As the speed and scale of vaccinations against the SARS-CoV-2 virus ramps up globally, researchers at Massachusetts General Hospital (MGH) are calling for greater awareness and communication around a delayed injection-site reaction that can occur in some patients who have received the Moderna mRNA-1273 vaccine.

In a letter to the editor published online in The New England Journal of Medicine (NEJM), the authors note Phase 3 clinical data from the Moderna vaccine trial did show delayed skin hypersensitivity in a small number of the more than 30,000 trial participants. However, the authors say the large, red, sometimes raised, itchy or painful skin reactions were never fully characterized or explained, and they warn clinicians may not be prepared to recognize them and guide patients on treatment options and completion of the second dose of the vaccine.

"Whether you've experienced a rash at the injection site right away or this delayed skin reaction, neither condition should prevent you from getting the second dose of the vaccine," says Kimberly Blumenthal, MD, MSc, lead author of the letter and co-director of the Clinical Epidemiology Program in the division of Rheumatology, Allergy and Immunology at MGH. "Our immediate goal is to make physicians and other care providers aware of this possible delayed reaction, so they are not alarmed, but instead well-informed and equipped to advise their patients accordingly."

In the letter, Blumenthal and her co-authors also note their own clinical observations of the delayed, large, local reactions to the Moderna vaccine, and report on a series of 12 patients with the reactions. In that group, symptom onset ranged from four days after the first dose up to 11 days post-vaccination, with a median onset of symptoms on day eight. Photographs show the varied size and severity of the reactions. Most patients were treated with ice and antihistamines, although some required corticosteroids and one was erroneously treated with antibiotics.

"Delayed cutaneous hypersensitivity could be confused - by clinicians and patients alike - with a skin infection," says letter co-author Erica Shenoy, MD, PhD, associate chief of the MGH Infection Control Unit. "These types of reactions, however, are not infectious and thus should not be treated with antibiotics."

On average, symptoms cleared up after nearly a week for the group of 12 reported in the letter. Half of the patients went on to experience a reaction after the second dose - at or around 48 hours post-vaccination. No patient experienced a dose two reaction that was more severe than their dose one reaction.

The authors also say samples taken from skin biopsies confirmed their suspicion of a delayed allergic immune response that is commonly seen in drug reactions.

"For most people who are experiencing this, we believe it's tied to the body's immune system going to work," says Esther Freeman, MD, PhD, director of Global Health Dermatology at MGH and co-author of the NEJM letter. "Overall, this data is reassuring and should not discourage people from getting the vaccine."