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New research has found one in five people in the south London live with multimorbidity.

The study, published today in the Lancet Regional Health by researchers from King's College London and the NIHR Guy's and St Thomas' Biomedical Research Centre and supported by Impact on Urban Health, examined the prevalence of multimorbidity - two or more long-term diseases at once - and identified key relationships between diseases.

Researchers analysed electronic health records from participants aged 18 and over between April 2005 and May 2020 in one London borough. The borough has a deprived, multi-ethnic and youthful population.

Research showed multimorbidity is more common among women and Black ethnic minority groups. An estimated 21% of the population had multimorbidity and the number of conditions increased progressively with age, with people aged 80 and above having a median of four conditions.

The study also identified clusters of conditions that commonly occur concurrently. The first cluster, affecting adults between 18-39, showed anxiety and depression to occur simultaneously. The second cluster associated with age and polypharmacy identified heart conditions and dementia. The third cluster identified cardiometabolic diseases and chronic pain among older ages and Black ethnic groups. The final cluster identified at-risk behaviours such as alcohol and substance dependency in young males who also smoke.

The research highlights the need for healthcare providers to tailor care for multiple long-term conditions. This need has been highlighted by the COVID-19 pandemic, as people with prior diseases such as hypertension, diabetes, or coronary heart disease are more likely to get severe symptoms or die from COVID. The same health inequalities that are pronounced in those with multimorbidity are also the ones that puts people at greater risk of hospitalisation or death from COVID-19, which includes Black ethnic groups and those living in deprived areas.

Lead author Alessandra Bisquera, from King's College London, said: "Multimorbidity is not restricted to older citizens. More young people around the world are being diagnosed with multiple conditions, and being less advantaged socioeconomically accelerates the process, so in deprived urban areas, multimorbidity occurs earlier in life. Many conditions are still treated in isolation, so there are patients out there who may be taking multiple drugs and seeing several specialists at any one time, further adding to their disadvantage. Medical training and service organisation in the UK needs to shift away from treating single diseases to potentially managing clusters of diseases. We hope that by identifying these common disease clusters, we are able to be more systematic in our approach to multimorbidity and delay its progression"

ATLANTA - FEBRUARY 24, 2021 - New study reports that early in the 2020 pandemic in the United States, one-third of cancer survivors worried about treatment and cancer care disruptions. Using a mixed methods approach, investigators utilized survivors' own words to more deeply describe their experiences and worries about the pandemic's impact on their overall health.

The article, appearing in the Journal of Psychosocial Oncology, finds the impact of the pandemic on cancer survivors and the broader health care system is widespread and exacerbated serious gaps in the health care system. For this study, investigators led by Corinne Leach, MPH, MS, PhD, from the American Cancer Society and colleagues, examined cancer survivor worries in relation to treatment, infection and finances early in the U.S. pandemic. Data for this study came from a survey dated March 25 to April 8, 2020 from the 2019-2020 American Cancer Society Cancer Action Network's (ACS CAN) Survivor Views Panel.

"This study demonstrates the importance of clear communication between healthcare providers and patients experiencing concerns and uncertainties that may affect mental health during the pandemic as the care provision landscape continues to change," said Dr. Leach.

Key findings from this study include:

Many survivors experienced disruptions in health care treatments.

77% worried they are high risk for serious health impact and were concerned about ICU admission or death if infected with COVID-19.

27% worried the pandemic will make it hard to afford cancer care. Respondents shared concerns of deciding what would be most important in terms of having medicine or food.

The fear of getting sick and uncertainty over just how worried survivors should be because of COVID was pervasive for cancer survivors, leading to reported self-induced measures to reduce their risk of infection, such as social distancing and mask wearing.

Many respondents described social isolation, including overall loneliness and feelings of being isolated due to social distancing, during the COVID-19 pandemic.

An unanticipated theme that emerged in the qualitative analyses was the concern expressed by survivors around the inability to bring a companion to in-person appointments. Although participants understood and respected the decision of healthcare systems to institute measures to protect staff and patients from COVID-19 infection, survivors seemed to be caught off-guard by the new rule, especially when receiving bad news, such as a cancer recurrence.

"The delays and cancellations noted by cancer survivors in the survey highlight the need for policy interventions and new delivery models that make it safe for cancer patients to receive care, and the need for public policies that address the financial worries associated with the pandemic," write the authors.

Those policies include increasing federal Medicaid funding to ensure people can get health coverage should they find themselves uninsured, continuing to offer and increase funding for Centers for Disease Control and Prevention cancer screening programs, and providing $15 billion to the National Institutes of Health to restart stalled clinical trials.

Before the corona pandemic, tens of millions international travellers annually headed to the tropics, getting exposed to local intestinal bacteria. A total of 20-70% of those returning from the tropics carry - for the most unknowingly - ESBL-producing bacteria resistant to multiple antibiotics. The likelihood of acquiring such superbacteria depends on destination and health behaviour abroad. The risk is greatest in South and Southeast Asia, and a substantial increase is associated with contracting travellers' diarrhoea and taking antibiotics while abroad.

An investigation led by professor of Infectious diseases Anu Kantele at Helsinki University together with MD Esther Kuenzli from Swiss Tropical and Public Health Institute involved a real-time scrutiny of superbacteria acquisition among a group of 20 Europeans over a three-week visit to Laos. The participants' daily stool samples were initially screened on site in Vientiane, Laos, and later, in Europe, the superbacteria strains isolated were analysed in detail by whole-genome sequencing.

The study was recently published in the Lancet Microbe. It belongs to a series of Kantele's studies exploring the spread of antimicrobial resistance by international travel.

"Our study revealed that travellers to the tropics are much more predisposed to acquiring superbacteria than previously thought. In conventional studies, stool samples are only collected before and after travel, not while abroad as we did now. Travellers to the tropics are known to be exposed to superbacteria, but the extent of the risk revealed by our real-time sampling was unexpected," Kantele says.

Travellers contracted superbacteria within the first week abroad

In Laos, daily stool samples from the participants were analysed locally in the Lao-Oxford-Mahosot Hospital-Wellcome Trust -Research laboratory. Had samples only been collected before and after travel, the proportion of superbacteria carriers had been approximately 70%. Daily real-time scrutiny already while abroad revealed, however, that all travellers had contracted a superbacter within a week after arrival.

The findings varied day by day. While some participants carried superbacteria for several days, others had a couple of days' breaks after which superbacteria were found again. Part of the travellers acquired several strains.

"It became evident that acquisition of superbacteria is a dynamic process: bacteria come and go, some strains persisting for a lengthy period of time," Kantele says.

Whole-genome sequencing revealed the great variety among strains of superbacteria

After returning home, to explore the isolated superbacteria strains in more detail, the researchers established a collaboration with Jukka Corander, professor of Statistics at the Universities of Helsinki and Oslo, and Alan McNally, professor of Microbial genetics at the University of Birmingham, England. Whole-genome sequencing and analyses proved colonization to be a dynamic process involving constant switches between the various strains. Indeed, all the travellers had been exposed to a much wider range of superbacteria than generally thought. Applying the traditional approach, about 20 new strains would have been detected after travel, but daily sampling abroad and whole-genome sequencing enabled the researchers to unravel that the participants acquired 83 different strains altogether.

Only in four cases did two travellers share the same strains, indicating that the bacteria were not in general transmitted from one to another.

None of the participants developed a clinical infection caused by the superbacteria. Had they not been delivered their screening results on a daily basis, the study participants would have remained totally unaware of them carrying superbugs.

"It was wonderful to see how our intestinal bacteria stand up to the incomers: the great majority of all alien strains disappeared already before the end of the journey," Kantele rejoices.

Professor Jukka Corander points out that the study provides a completely new perspective to the bacterial colonization diversity in geographic regions where superbugs are endemic.

"We have earlier obtained robust modelling results concerning the stability of E. coli colonization in populations with low levels of antibiotic resistance, however, the new study conducted in Laos implies that we need to start building the model anew, so that we gain thorough understanding about the role of superbugs also in those circumstances where they colonize the majority of the people," Corander says.

Antibiotic resistance increases at an alarming rate in the tropics

The worldwide growth of antibiotic resistance is particularly alarming in tropical regions with inadequate hygiene and uncontrolled use of antibiotics. Multidrug-resistant bacteria are carried both by animals and local inhabitants. Returning from such environments, many visitors carry superbacteria to their home countries.

Increasing resistance is also being witnessed by research: the proportion of travellers carrying these bacteria is growing. Usually acquisition of ESBL or other superbacteria does not cause any symptoms. After travellers return home, the strains usually disappear over time. Carriers can, however, pass these bacteria on to others. Among a small proportion, the superbacteria cause a symptomatic infection, most typically a urinary tract infection. Treatment of infections caused by superbacteria is more challenging than of those caused by sensitive bacteria. In some cases, the infection may even turn out life-threatening.

Antibiotic use during travel further adds to the risk of carriage: favouring the resistant bacteria, antibiotic treatment makes space for newcomers.

Kantele stresses the grave threat increasing resistance poses to healthcare worldwide.

"Antibiotics are not only needed to treat infections, but they also enable high-risk operations such as major surgery and organ transplants, where they are given to prevent infections," she says.

A new study, published today in Nature Digital Medicine, found that 'natural language processing' (NLP) of information routinely recorded by doctors - as part of patients' electronic health records - reveal vital trends that could help clinical teams forecast and plan for surges in patients.

The researchers from King's College London, King's College Hospital NHS Foundation Trust (KCH), and Guy's and St Thomas' Hospital NHS Foundation Trust (GSTT), used NLP algorithms to translate the electronic notes made by doctors into a standardised, structured set of medical terms that could be analysed by a computer.

Tracking trends in patients

In the same way social media posts can be tracked and aggregated by 'hashtags', the researchers detected words or phrases that were 'trending' in electronic health records at KCH and GSTT, during key stages of the COVID-19 pandemic last year. For instance, they tracked the number of patient records containing keywords for symptomatic COVID-19, such as 'dry cough', 'fever' or 'pneumonia'. Throughout the pandemic, hospital doctors have entered patient symptoms and test results into electronic health records, which are used to track the spread of COVID-19 at a national level.

However, these records often contain incomplete and unstructured data, that is difficult to access and analyse.

By analysing the text as a 'bag of words', the researchers were able to produce real-time maps of trending 'signals' (i.e., symptoms that were most frequently recorded by doctors), and these signals closely mirrored patterns of positive laboratory tests reported by each hospital. Clear spikes were visible in March 2020, for instance, during the first wave of COVID-19 cases, and in subsequent waves.

Providing advance warning for hospitals

The study indicates that these signals provide a real-time situational report of reflecting current activity levels in a hospital and up to four days advance warning for hospitals helping them to prepare for surges in COVID-19 admissions.

The study authors also reported a strong association between the trending signals and regional tracking of COVID-19 admissions in London hospitals. In addition, they found that as new COVID-19 symptoms emerged nationally, these symptoms were also recorded more frequently by doctors at KCH and GSTT.

Dr James Teo, Clinical Director of AI at King's College Hospital and Guy's and St Thomas' Hospital, said: "By teaching computers how to read and understand doctors' notes, we hope to reveal important patterns and trends that could help in the fight against COVID-19 and other diseases.

Tracking word trends in electronic health records offers an additional method for studying disease and healthcare activity, in a way that is very easy and cost-effective to run. While this method was shown to be effective in two individual hospital Trusts, the approach could be scaled up to a regional or even national level with the right privacy safeguards".

CogStack

The CogStack platform used in this study allows researchers to interrogate complex sets of data extremely rapidly, providing a real-time feed of what is happening in a particular hospital, allowing clinical teams to prepare for incoming patients.

Professor Richard Dobson, Head of the Department of Biostatistics & Health Informatics, NIHR Maudsley BRC, said: "The CogStack platform allows us to extract information from deep within hospital records at King's College Hospital NHS Foundation Trust in near real time. This means we can anticipate likely increases in pressure on the system before receiving information such as test results, giving clinical teams time to react and prepare in advance."

Knowing the environmental and human-related variables that characterize the favorable areas for the incidence of the West Nile virus, a flavivirus that is transmitted from birds to humans by mosquitoes, is essential to identify those places in Europe at high risk of experiencing outbreaks, even before these are registered, thus enabling preventive measures to be taken.

Researchers of the Biogeography, Diversity and Conservation Group of the University of Malaga have developed risk models for West Nile Fever, the disease caused in humans by this virus, which, based on historical incidence data, may predict areas of future outbreaks a year in advance, as well as detect their intensity.

Artificial intelligence to develop risk models

Particularly, using modelling based on fuzzy logic and artificial intelligence, they have analyzed the incidence of the disease in Europe in 2017 to explain and restate the "abnormally high" data of 2018, the year with the highest number of cases registered so far, a total of 1605. The results have been recently published in the scientific journal PLoS Negl Trop Dis.

"Based on the analyzed data, we could successfully predict the places where the disease appeared, the intensity of outbreaks and the time they occurred", explains Raimundo Real, scientist of the Animal Biology Department of the UMA.

This expert asserts that anticipating the possible incidence of the disease may lead to taking preventive measures specifically in risk areas. These measures include early spraying, advising the population on measures to avoid bites or controlling the water points where mosquitoes breed. Likewise, healthcare centers could be warned about the possible disease incidence in the area, contributing to early diagnosis and improving prognosis.

Spatial and environmental variables

For the development of the risk maps, the researchers used a spatial model related to bird migration routes, which act as reservoir of the virus. On the other hand, they determined that the environmental risk factors are high temperatures, presence of river courses, low altitude areas, which usually have a warmer climate and conditions of higher humidity, and the presence of certain livestock facilities, such as stables and poultry farms, which, as they assure, are the most favorable factors for the spread of the virus.

"We have observed that high temperatures speed up the life cycles of mosquitoes, shortening their gonotrophic cycle -period between the time mosquitoes feed on blood and the time they feed again-, therefore, in warmer areas mosquito bite rate is also higher, facilitating the transmission of the virus", emphasizes the professor of the UMA.

Early warning: basin scale

Likewise, rivers are related to the presence and proliferation of mosquitoes, so rivers also contribute to a higher infection rate.

"In 2017, the outbreaks began in the lower areas of large river basins and spread to higher areas, which highlights the importance of river basins in the propagation of outbreaks", says Raimundo Real, who adds that, consequently, the early warning should be based on a basin scale.

This way, the Head of the Animal Biology Department of the UMA states that some Spanish provinces of western Andalusia, southern Extremadura and southwestern Castilla-La Mancha, especially the lowest areas of the Guadalquivir and Guadiana valleys, are European sites that are environmentally favorable for the transmission of the disease, which directly affects the human nervous system.

Leesburg, VA, February 24, 2021--An open-access article in ARRS' American Journal of Roentgenology (AJR) describes the clinical and imaging features of axillary adenopathy detected during screening or diagnostic breast imaging after recent coronavirus disease (COVID-19) vaccination to inform the development of follow-up recommendations.

Shabnam Mortazavi of the University of California at Los Angeles reviewed electronic medical records to identify women with post-COVID-19 vaccination adenopathy found from December 2020 to February 2021. For mammography, Mortazavi considered a node abnormal when its size, shape, or density was deemed disproportionate to other axillary nodes (ipsilateral or contralateral). On ultrasound, she deemed a node abnormal based on subjective assessment for cortical abnormalities, including focal or diffuse thickening greater than 3 mm, as well as nodal prominence compared to the contralateral axilla (when available). For MRI, Mortazavi considered a node abnormal when asymmetric in size and/or number to the contralateral axilla.

Twenty-three women exhibited axillary adenopathy ipsilateral to the vaccinated arm on screening or diagnostic breast imaging, and according to Mortazavi, "13% were symptomatic (axillary lump with possible tenderness)." Meanwhile, the adenopathy was detected incidentally on screening breast imaging in 43% (mammography, 5; ultrasound, 2; both mammography and ultrasound, 1; high-risk screening MRI, 2) and on diagnostic imaging for other reasons in 43% (BI-RADS 3 follow-up for breast finding, 3; screening callback for other reason, 2; non-axillary breast pain or lump, 5). Noting that the median interval between the first vaccine dose and imaging showing the abnormal node was 9.5 days, Mortazavi's results counted a total of 57% of women with one abnormal node. BI-RADS 2 was assigned in one woman, BI-RADS 3 in 21 (ultrasound in 4-24 weeks), and BI-RADS 4 in one.

"The largest sample to our knowledge of COVID-19 vaccine associated axillary adenopathy on imaging," Mortazavi also wrote, "this study highlights axillary adenopathy ipsilateral to the vaccinated arm with Pfizer-BioNTech or Moderna COVID-19 vaccine as a potential reactive process with which radiologists must be familiar." Ultimately, vaccination date and laterality are critical to optimize assessment and management of imaging-detected axillary adenopathy in women with otherwise normal breast imaging.

DALLAS, Feb. 23, 2021 — Women face many female-specific risks for heart disease and stroke, including pregnancy, physical and emotional stress, sleep patterns and many physiological factors, according to multiple studies highlighted in this year’s Go Red for Women® special issue of the Journal of the American Heart Association, published online today.

“Although cardiovascular disease is the leading cause of death in men and women, women are less likely to be diagnosed and receive preventive care and aggressive treatment compared to men,” said Journal of the American Heart Association Editor-in-Chief Barry London, M.D., Ph.D., Ph.D., the Potter Lambert Chair in Internal Medicine, director of the division of cardiovascular medicine, director of the Abboud Cardiovascular Research Center, professor of cardiovascular medicine and professor of molecular physiology and biophysics at the University of Iowa’s Carver College of Medicine in Iowa City, Iowa. “Identifying and addressing the unique ways cardiovascular disease affects women is critical to improving outcomes and saving lives, and we’re pleased to highlight this very important and impactful research.”

Of note in this issue is a report from the American Heart Association’s Go Red for Women Strategically Focused Research Network. Launched in Spring 2016, this initiative funded five research centers to extensively study cardiovascular (CVD) risk in women:

Columbia University Irving Medical Center in New York City - Sleep & CVD Risk in Women Across the Lifespan

Johns Hopkins University School of Medicine in Baltimore - Role of Sex Hormones and Cyclic GMP-PKG in Cardiac and Metabolic Disorders in Patients with Heart Failure with preserved Ejection Fraction (HFpEF)

Magee-Women’s Research Institute and Foundation in Pittsburgh - Women’s Cardiovascular Health and Microvascular Mechanisms: Novel Insights from Pregnancy

New York University Langone Medical Center in New York City - The Women’s Heart Attack Research Program: Mechanisms of Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA), Platelet Activity and Stress

University of California at San Diego - Sedentary Behavior & CVD Risk in Latina Women

This report highlights the findings of the centers, showing how insufficient sleep, sedentariness and pregnancy-related complications may increase CVD risk in women. It also details the presentation and factors associated with myocardial infarction with non-obstructive coronary arteries and heart failure with preserved ejection fraction in women. Additional collaborative studies assessed the relations among CVD risks and various lifestyle behaviors including nightly fasting duration, mindfulness and behavioral and physical risk factors. Other research focused on metabolomic profiling of heart failure with preserved ejection fraction in women.

Among the many findings:

Researchers at Columbia University Irving Medical Center found that both poor sleep quality and risk of obstructive sleep apnea affected systolic and diastolic blood pressure. Women who reported adequate sleep duration (seven or more hours a night), good sleep quality, no insomnia or snoring, low risk for obstructive sleep apnea and a tendency for morning activities and morning alertness had better overall cardiovascular health. These associations were stronger among postmenopausal women and women from underrepresented racial and ethnic groups. Researchers also found that poor sleep may negatively impact cardiovascular health through consumption of a higher-energy and lower-quality diet. It may also influence psychosocial risk factors for CVD including depression, low social support and caregiving.
Researchers at the University of California at San Diego were focused on understanding risk factors, intervention methods for and metabolic consequences of higher levels of sedentary behavior and sitting time among Latinas. In their analysis of data from 401 women of Mexican heritage women who participated in the Hispanic Community Health Study/ Study of Latinos Casitas Ancillary Study, participants were found to sit, on average, 5.65 hours per day. Women more most likely to spend their sedentary time in front of screens such as televisions or computers (3.15 hours per day), as compared to leisure time sitting (e.g., knitting, talking with friends - 1.77 hours per day) or transportation (1.02 hours per day). Through additional studies of interventions and the molecular consequences of sitting, researchers found the amount of time spent sitting can be reduced significantly by employing a behavior modification program and higher cumulative sitting time is associated with certain cardiometabolic risk biomarkers that can increase cardiovascular risk.

Many of the studies in the Association’s Strategically Focused Research Network have been published in scientific journals and presented at scientific meeting, and significant research continues. The findings generated by the initiative and the new investigators trained in multi-disciplinary research, will further promote awareness among the public and in the medical field about the female-specific factors that influence CVD.

Below are highlights of additional manuscripts focused on cardiovascular disease in women in this special issue of the Journal of the American Heart Association. The complete manuscripts can be here.

Early pregnancy atherogenic profile in a first pregnancy and hypertension risk 2-7 years after delivery – Janet Cotav, et al.

In the nuMoM2b-Heart Health Study, researchers evaluated whether cardiometabolic risk factors identified early in a first pregnancy were related to adverse pregnancy outcomes (APO) and/or gestational diabetes (GDM), as well as subsequent maternal hypertension 2-7 years after giving birth.

The multicenter cohort of 4,471 women were tracked for adverse pregnancy outcomes including hypertensive disorders of pregnancy, preterm delivery, low birthweight for gestational age and gestational diabetes and for their risk of hypertension (130/80 mmHg or antihypertensive use) 2-7 years after giving birth.

Among all participants, 24.6% of the women (1,102) experienced an adverse pregnancy outcome or gestational diabetes during a first birth. Women with at least one of these complications were, on average, more likely to be older than 35, to smoke, and to be of non-Hispanic Black race/ethnicity.

Women with an APO or GDM were more likely to have an elevated cardiovascular risk profile in the first trimester: they were more likely to have obesity (34.2% vs. 19.5%); had a higher mean blood pressure (SBP 112.2 mm Hg vs. 108.4 mm Hg; DBP 69.2 mm Hg vs. 66.6 mm Hg); had higher mean concentrations of glucose (5.0 vs. 4.8 mmol/L); had a higher median level of insulin (77.6 pmol/L vs. 27 60.1 pmol/L); high triglycerides (1.4 mmol/L  vs. 1.3 mmol/L) and hsCRP, high sensitivity c-reactive protein, a marker for inflammation (5.6 nmol/L vs. 4.0 nmol/L); or had lower HDL-C or good cholesterol (1.8 mmol/L vs. 1.9 mmol/L).

A total of 32.8% of women with APOs or GDM had hypertension (blood pressure ≥130/80 mmHg or took blood pressure medication) within 2-7 years after delivery, compared to 18.1% of women with no APO or GDM. Compared to women with no complications, those who had an APO or GDM had higher rates of elevated blood pressure (7.6% vs. 6.3%) and stage 1 (19.9% vs. 13.3%) and stage 2 hypertension (12.9% vs. 4.8%). After accounting for confounders (age, race/ethnicity, insurance status and smoking), early pregnancy BMI, total cholesterol, HDL-C, LDL-C, glucose, insulin, hsCRP, triglycerides, blood pressure, diet quality and physical activity were all related to increased risk of hypertension 2-7 years after giving birth.

The researchers said because women typically have access to health care during pregnancy and postpartum, assessment of cardiometabolic health early in pregnancy may help to identify risk for APO and GDM and to identify opportunities to improve cardiovascular health later in life.

The Associations of Job Strain, Life Events and Social Strain with Coronary Heart Disease in the Women's Health Initiative Observational Study - Yvonne Michael, et al

Researchers analyzed long-term health data for 80,825 women in the Women’s Health Initiative Observational Study, who had a mean age of 63.4 years when they enrolled in the study, and they were followed for an average of 14.7 years. They aimed to determine the independent and synergistic effect of different stress domains, including work, stressful life events and social relationships, on women’s coronary heart disease (CHD) risk.

Job strain was determined by factoring job control (whether workers can exert influence over tasks) and job demand (the workload and intensity of the job). Stressful life events and social strain were assessed through self-reported questionnaires. Cox proportional hazard models were used to evaluate associations of each stressor with CHD separately and together.

A total of 3,841 women (4.8%) developed coronary heart disease during an average of 14.7 years of follow-up. After adjustment for age, other stressors, job tenure and socioeconomic factors, highly stressful life events were associated with a 12% increased risk of CHD, and high social strain was associated with a 9% increased risk of CHD. While job strain was not independently associated with CHD risk, researchers observed a statistically significant interaction between job strain and social strain. Women who had high social strain but low job control and low job demand had a 21% increased risk of CHD.

Researchers concluded that stressful life events and social strain were each associated with increased risk of CHD among women. For job strain, the increased CHD risk was confounded by socioeconomic factors. Exposure to job strain and social strain interacted synergistically, resulting in a higher risk of CHD than expected from exposure to either stressor alone.

This study is accompanied by an editorial, Pearls and Purple: The Dawn of a Modern Age - Melissa Tracy, et al.

Sexual Assault and Carotid Plaque among Midlife Women – Rebecca Thurston, et al.

Researchers in this study examined whether women who reported being the victim of sexual assault had higher carotid artery plaque build-up levels and if those levels continued to rise during midlife. Study participants included 160 non-smoking, CVD-free women ages 40-60 years, 28% of whom reported being the victim of sexual violence. The women were assessed twice between 2012 and 2020, and at both evaluations, they completed questionnaires, physical measures, blood tests and ultrasounds to measure plaque build-up in the carotid artery.

Compared to women who did not report a history of sexual assault, the women who were victims of sexual violence were four times more likely to have plaque build-up of more than 30% of the carotid artery at baseline and three times more likely to have that extent of plaque build-up at follow-up.

Researchers said their findings indicate sexual assault is associated with a higher level of carotid atherosclerosis, and the levels appear to increase over midlife. The associations were not explained by standard CVD risk factors, depression or symptoms of post-traumatic stress.

Other studies in this special issue include:

Sex differences in the association of body composition and cardiovascular mortality - Preethi Srikanthan, et al.
Maternal coronary heart disease, stroke and mortality within one, three, and five years of delivery among women with hypertensive disorders of pregnancy and pre-pregnancy hypertension – Angela Malek, et al.
Gender issues in Italian catheterization laboratories: The GENDER-CATH Study - Chiara Bernelli, et al.
Breast cancer promotes cardiac dysfunction through deregulation of cardiomyocyte calcium handling protein expression that is not reversed by exercise training - Carlos Negrao, et al.
Long-term postpartum cardiac function among women with preeclampsia - Sajid Shahul, et al.
Sex differences in heart failure with preserved ejection fraction - Shungo Hikoso, et al.
Healthy lifestyle and clonal hematopoiesis of indeterminate potential - Results from the Women's Health Initiative - Bernhard Haring, et al.
Gender differences in publication authorship during COVID-19: A bibliometric analysis of high impact cardiology journals - Nosheen Reza, et al.
Developing an internally validated Veterans Affairs women’s cardiovascular disease risk score using Veterans Affairs national electronic health records - Haekyung Jeon-Slaughter, et al.
The Women in cardiology Twitter network: An analysis of a global professional virtual community from 2016 to 2019 - Janet Han, et al.
A paucity of female interventional cardiologists: What are the issues and how can we increase recruitment and retention of women? - Cindy Grines, et al.
Sex differences in rupture risk and mortality in untreated patients with intact abdominal aortic aneurysms – Rebecka Hultgren, et al.

Slight differences in clinical features can help physicians distinguish between two rare but similar forms of autoimmune brain inflammation in children, a new study by UT Southwestern scientists suggests. The findings, published online in Pediatric Neurology, could provide patients and their families with a better prognosis and the potential to target treatments specific to each condition in the future.

About half of all cases of encephalitis - a rare type of brain inflammation that affects about 1 of every 200,000 people in the U.S. each year - can be traced to an infection. For a portion of other cases in which the cause isn't initially clear, researchers have discovered a link with the patients' own immune systems inappropriately targeting and damaging the brain.

The most common forms of immune-related pediatric encephalitis are acute disseminated encephalomyelitis (ADEM) and autoimmune encephalitis (AE). Although these are two distinct disorders, explains UTSW pediatric critical care fellow Molly E. McGetrick, M.D., their presentation - including disorientation and other signs of altered mental status, seizures, or motor and sensory abnormalities - is largely the same in children, hindering an accurate diagnosis. In addition, the rarity of AE and ADEM makes amassing data to help distinguish these conditions more difficult.

"Despite their similarities in presentation, patients with AE tend to have a more prolonged and protracted condition that requires more therapies than those with ADEM," McGetrick explains. "Being able to definitively distinguish between these conditions could help doctors guide patients and their families on what to expect."

To reveal the unique features of each condition, McGetrick and her colleagues searched medical records spanning a decade ending in December 2019 for pediatric patients diagnosed at Children's Medical Center Dallas with encephalitis or encephalomyelitis. They identified 75 patients diagnosed with immune-related encephalitis: 23 with ADEM and 52 with AE.

When the researchers compared patient histories, lab and imaging results, and outcomes, they found slight differences between the two conditions. For example, patients with ADEM had a shorter time from symptom onset to diagnosis compared with those with AE, and those with ADEM universally had abnormal magnetic resonance imaging findings compared with just 61 percent of those with AE. AE patients were more likely than those with ADEM to have markers of elevated inflammation present in their blood and cerebrospinal fluid results. AE patients also tended to have longer hospital stays (21 days versus 13 days for ADEM patients) and were more likely to leave the hospital with a neurological disability that required significant physical and occupational therapy.

McGetrick notes that currently ADEM and AE patients are given similar therapies, including corticosteroids to reduce the body's inflammatory reaction to autoantibodies, intravenous immunoglobulins to bind and neutralize pathologic autoantibodies, or plasmapheresis to remove autoantibodies from the body over a series of sessions. Many times, symptoms for both conditions will resolve with these treatments, but they can take longer for AE and recur in some individuals. The more researchers can learn about the distinguishing characteristics of these conditions, she says, the more they may be able to target specific treatments for each condition, improving the outlook for these patients.

"One of the biggest take-home messages from this study is that we still have a lot to learn about these conditions," McGetrick says. "The more we know, the brighter the future will ultimately be for these patients."

This study, published recently in the international journal Insects, was conducted by researchers from the University of Granada, the Doñana Biological Station, and the Biomedical Research Networking Centre for Epidemiology and Public Health (CIBERESP)

Researchers from the University of Granada (UGR), the Doñana Biological Station (EBD-CSIC), and the Biomedical Research Networking Centre for Epidemiology and Public Health (CIBERESP) have carried out the most comprehensive study to date of the eating patterns of the tiger mosquito (Aedes albopictus) and other invasive species of the same genus in Europe. The results of the study were recently published in the international journal Insects.

This research, which reviews all previously published studies on this topic, shows that these species of mosquitoes feed off different groups of vertebrates, especially mammals, and humans are also common hosts. Not surprisingly, human blood represents 93% of the blood meals of Aedes aegypti, the mosquito responsible for yellow fever.

Mosquitoes are one of the main groups of vector insects--that is, insects involved in the transmission of major pathogens that adversely affect people, livestock, and wildlife. As with other groups of animals, different species of invasive mosquitoes have become established in areas outside their original range. This is the case with different species of mosquitoes of the Aedes genus, which are of particular importance from the public health perspective, due to their capacity to transmit pathogens that cause serious diseases.

"Thus, the appearance of these species can modify the local epidemiology of many pathogens in invaded areas, including pathogens that circulate naturally in the environment, or imported pathogens," explains one of the authors of the work, Josué Martínez de la Puente, a researcher at the UGR's Department of Parasitology.

So far, four invasive species of the Aedes genus have established populations in Europe, which include such relevant vector species as the tiger mosquito, Aedes albopictus.

Blood meals

To complete their life cycle and the development of their eggs, female mosquitoes require blood meals taken from different vertebrate hosts. In addition to causing discomfort, the bites they cause can transmit different pathogens. "Therefore, this blood-feeding behaviour represents a fundamental factor, the relevance of which needs to be studied to understand the epidemiology of different diseases. In this review article, we study the feeding patterns of those four invasive mosquitoes of the Aedes genus in Europe," explains Martínez de la Puente.

The results show that these species of mosquitoes feed off different groups of vertebrates, especially mammals. Humans are common hosts for these mosquitoes, representing 93% of the blood meals of the Aedes aegypti species. In addition, mosquitoes are capable of feeding on the blood of other groups of vertebrates, including birds and even ectothermic animals (those whose body temperature changes in line with the temperature of the environment).

Given their capacity to transmit different pathogens and their feeding rates among humans, invasive mosquito species of the Aedes genus may have a significant impact on the transmission of these pathogens in urban and periurban areas, the authors conclude.

WHAT:
A randomized, placebo-controlled Phase 1 clinical trial of two monoclonal antibodies (mAbs) directed against the coronavirus that causes Middle East respiratory syndrome (MERS) found that they were well tolerated and generally safe when administered simultaneously to healthy adults. The experimental mAbs, REGN3048 and REGN3051, target the MERS coronavirus (MERS CoV) spike protein used by the virus to attach to and infect target cells. The mAbs were discovered and developed by scientists at the biopharmaceutical company Regeneron, located in Tarrytown, New York. The trial was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The trial was the first to test the experimental antibodies
Hyperlink Code in people. Conducted at WCCT Global, a clinical trial site in California, the study enrolled 48 healthy adults, 36 of whom received the mAbs. All volunteers were followed for 121 days after receiving mAbs (or placebo) by intravenous infusion. No serious adverse events occurred.

In preclinical studies, investigators at Regeneron and the University of Maryland, College Park, also administered REGN3048 and REGN3051 sequentially and in combination to genetically modified mice that, unlike wild-type mice, can be infected with MERS CoV. When administered one day prior to coronavirus exposure, both REGN3048 and REGN3051 reduced the levels of virus later detected in the lungs, with co-administration providing more potent protective effects than either mAb alone. Similarly, co-administering the mAbs one day after MERS CoV exposure provided a therapeutic benefit in mice by lowering viral levels and lessening tissue damage in the lungs as compared to mice that received placebo.

Together, the findings from the clinical trial and the preclinical mouse studies "demonstrate the potential efficacy and utility of monoclonal antibody therapy for the prevention or treatment of MERS-CoV and lays the groundwork for the development of spike-targeted mAb therapies for other infectious disease threats, including SARS-CoV-2," which causes COVID-19, the authors conclude.

Inflammatory lung diseases such as asthma, COPD and, most recently, COVID-19, have proven difficult to treat. Current therapies reduce symptoms and do little to stop such diseases from continuing to damage the lungs. Much research into treating chronic inflammatory diseases has focused on blocking chemicals called cytokines, which trigger cascades of molecular events that fuel damaging inflammation.

Now, scientists at Washington University School of Medicine in St. Louis have found that such cytokines can drive inflammation in more ways than previously understood, perhaps revealing new routes to potential treatments for chronic inflammatory conditions.

A new study demonstrates that in addition to raining down directly into tissues and triggering damaging events, cytokines can come packaged in tiny compartments called exosomes, making the packaged cytokines extremely difficult to detect and nearly impossible to study without specialized instruments. Not being able to study these exosomes means scientists could be missing important strategies to treat or prevent inflammatory disease.

The study, in JCI Insight, also demonstrates that understanding how these inflammatory cytokines are packaged can reveal new ways to block them, preventing lung disease from developing, at least in mice.

"In trying to understand and better treat inflammatory disease in patients, scientists have focused heavily on blocking cytokines, which we know are key players in setting off inflammatory processes and keeping them smoldering," said senior author Jennifer Alexander-Brett, MD, PhD, an assistant professor of medicine in the Division of Pulmonary and Critical Care Medicine. "How a particular family of cytokines gets out of cells to trigger inflammation has been a mystery that has stymied the field for a long time. At the same time, people started to recognize that these structures called exosomes are doing something, though it was unclear what. They're small, difficult to isolate and easily overlooked. But with new technology, we're starting to understand that key cytokines can be packaged in exosomes in ways that completely change the way we would target them to develop anti-inflammatory therapies."

Based on prior work from Alexander-Brett, Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine, and other investigators at Washington University, it has long been known that a specific cytokine called IL-33 is a central player in the development of chronic lung diseases, such as COPD and asthma. Indeed, this cytokine also is implicated in arthritis, inflammatory bowel disease, hepatitis, heart failure, inflammation of the central nervous system and cancer. But how it triggers inflammation was unknown. The new research shows that IL-33 is released into the airway, packaged with an exosome. Complicating matters further, IL-33 doesn't travel inside the exosome; it piggybacks on the outside.

With a new understanding of the packaging, the researchers tried a different method to block the inflammatory signaling of IL-33. They studied mice that develop lung disease due to inhaling a type of fungus; the disease, mimics, for example, the development of asthma due to an inhaled allergen. The researchers showed that they could block airway disease from developing in mice exposed to the fungus by treating them with a compound that blocks exosome secretion, rather than IL-33 directly.

"This study opens up many new questions about how cytokine signaling might be different when the cytokine is bound to an exosome," Alexander-Brett said. "It's possible exosome packaging is a key feature of cytokines that are not secreted in the classical way. This new understanding of cytokine signaling could lead to completely different ways of targeting it to treat diseases such as COPD. At the moment, we have no treatments that reverse or even slow COPD. We can only treat symptoms."

Alexander-Brett said that until recently, this type of exosome activity would have been extremely difficult to detect. Her lab has a relatively new instrument called a single-particle interferometric reflectance imaging system (SP-IRIS) that lets her team study exosomes using very small amounts of biological samples.

For asthma and COPD, Alexander-Brett said her lab is seeking more precise ways to block specific exosomes, since a strategy that blocks all of them across the board, as in this mouse study, likely would stop some beneficial processes as well.

"We need more research to find an inhibitor that might block IL-33 from even being incorporated into the exosome, which would theoretically stop the initial trigger of chronic lung disease," Alexander-Brett said. "Ideally, we would like to find something that we could deliver as an inhaled drug that would target the effects to the airway, where it's needed."

Neuroblastoma is a cancer that develops in nerve tissue, most commonly in the glands around the kidneys. The gene MYCN is overexpressed in 20-25% of neuroblastoma, and MYCN-amplified neuroblastoma contributes to a considerable percentage of pediatric cancer-related deaths.

Anthony Faber, Ph.D., and a team of researchers at VCU Massey Cancer Center were awarded a grant from the American Cancer Society to study how MYCN and an abundance of iron can drive cancer cell death in neuroblastoma and potentially be targeted with novel treatments. This award is the first part of a potential two-stage grant worth a combined total of $600,000.

"Iron is a double-edged sword in a cancer cell. It can help the cancer grow and survive, but it also creates these toxic molecules within the cell called reactive oxygen species," said Faber, Natalie N. and John R. Congdon Chair in Cancer Research and co-leader of the Developmental Therapeutics research program at Massey and associate professor in the Philips Institute for Oral Health Research at the VCU School of Dentistry.

Reactive oxygen species (ROS) are highly unstable chemical molecules that react with other molecules within a cell and cause damage to genes and cell death (ferroptosis). Ferroptosis is a recently discovered type of cell death that is largely influenced by the accumulation of iron. Faber said there is a relatively small scientific understanding of ferroptosis, and even less is known about which cancers may be prone to ferroptosis-inducing drugs.

Through recent research published in Cancer Research, Faber and his collaborators have determined that the MYCN gene creates a vulnerability to drugs that induce ferroptosis because MYCN uses a lot of iron to help power the cancer cell and grow uncontrollably.

By ramping up the systems that remove toxins on a cellular level, MYCN generates so much iron that it also initiates a weakness to drugs that block the ability of the cell to eliminate ROS, as discovered by Konstantinos Floros, Ph.D., postdoctoral fellow at Massey and the Philips Institute for Oral Health Research whose extensive background in cell death effectively advanced this research project.

The researchers found that blocking these detoxifying systems with available drugs makes MYCN-amplified cells sick and die.

"As MYCN continues to be one of the most important targets in cancer therapeutics, this study highlights a new and clinically important strategy for treating MYCN-associated cancers," Faber said.

Using preclinical tumor models, Faber's team will use the grant funding to test the ability of sulfasalazine and auronofin - drugs FDA-approved for rheumatoid arthritis - to induce ferroptosis and tumor responses in neuroblastoma cells with high levels of MYCN.

"Fortunately, the Cancer Mouse Models Core run by Jennifer Koblinski, Ph.D., and Bin Hu, Ph.D., at Massey is spectacular and will allow us to robustly test these FDA-approved drugs in both patient-derived models and orthotopic models, where the tumors grow atop the adrenal glands similar to the way they grow in patients," Faber said.

Faber said that if they show positive results testing these drugs in cancer models, then they can confidently test these therapies in clinical trials.

"This Mission Boost Grant from the American Cancer Society allows us to conduct one of the earliest studies to link a cancer-driving gene to ferroptosis," Faber said. "This is a significantly important field of study that may have far-reaching implications in cancers beyond neuroblastoma, including some small cell lung cancers and triple negative breast cancer, which rely on a similar protein (c-MYC) to drive their growth."

If Affordable Care Act protections for pre-existing condition coverage are no longer available, the coronavirus pandemic would leave many Americans - a disproportionate number of whom are people of color - without health insurance, a new Oregon Health & Science University study indicates.

Published in the Journal of the American Board of Family Medicine, the study's findings reveal a third of the more than 7,500 COVID-19 patients who received care at U.S. community health centers between March and October 2020 did not have a pre-existing condition prior to contracting the novel coronavirus.

People of color made up at a significant portion of the COVID-19 patients studied: 51 percent were non-Hispanic Asian, 36 percent Hispanic, and 28 percent non-Hispanic Black. In comparison, the U.S. Census reports America's 2019 population was about 5.9 percent Asian alone, 18.5 percent Hispanic, and 13.4 percent Black alone.

Because Black, Asian and Hispanic residents experienced higher unemployment than Americans as a whole in 2020, the study notes this "puts them at increased risk for losing employer-sponsored health insurance."

"If COVID-19 is considered a pre-existing condition and health insurance coverage of pre-existing conditions is curtailed, the situation would be made worse, and health disparities could increase," said the study's lead author, Nathalie Huguet, Ph.D., who is also an assistant professor of family medicine in the OHSU School of Medicine.

The study comes as the U.S Supreme Court considers another legal challenge to the Affordable Care Act, which is commonly referred to as Obamacare and was signed into law by then-President Barack Obama in 2010. The court heard arguments in the California v. Texas case in November 2020 and is expected to rule sometime in 2021.

On Jan. 28, President Joe Biden signed an executive order that directed federal agencies to re-examine "policies that undermine protections for people with pre-existing conditions, including complications related to COVID-19."

"Our findings highlight that minority patients would be most impacted if the ACA mandate differentiating coverage based on pre-existing conditions was altered or revoked. ... Although the future of the ACA is uncertain, it is clear that ensuring protection for patients with pre-existing conditions is essential to achieving health equity," the study reads.

UCLA RESEARCH BRIEF
Enrique Rivero

FINDINGS
Older people correctly ascertained basic information such as dosage and duration of use for more than 70% of the medications they were prescribed, regardless of whether their physician explained it during an office visit. But when physicians failed to verbally provide information about potential side effects, people incorrectly assumed that about 55% of their prescribed medications had none. Even when physicians did discuss possible side effects, their patients incorrectly assumed there were no side effects for 22% of the medications.

BACKGROUND

There is a shortage of data about how well people understand basic information about the medications they are prescribed. This information is important for ensuring that people take their medications safely and properly and adhere to medication regimens.

METHOD

The researchers examined data from 2009 and 2010 for 81 people age 50 and older who were subjects in a previous study aimed at improving how physicians communicate about newly prescribed medications.

The researchers note that more than half of the people in the study had high levels of health literacy and at least some college education. Also, people were allowed to refer to information that had been provided to them about the medications when they were responding to the survey. These factors may limit the applicability of the findings to the general population.

IMPACT

The findings suggest that although physicians might not need to spend much time conveying information on dosage, the number of pills in a prescription or how frequently medications must be taken, they should spend more time explaining side effects to ensure their older patients are fully informed.

Gaps in knowledge about side effects may put people, particularly older people, at risk for medication nonadherence. Patients may be less likely to take or continue taking medications if they discover the existence of potential adverse effects without having the opportunity to discuss those side effects with their physicians in a timely manner.

The reintroduction of 32 bobcats to an island off the coast of Georgia more than three decades ago created an ideal experiment to examine the accuracy of a genetic-modeling technique that predicts extinction of isolated wildlife populations.

That's the conclusion of Penn State researchers who continue to monitor the bobcat population on Cumberland Island National Seashore, and who conducted a study comparing and contrasting the Cumberland Island bobcats to a population of bobcats on Kiawah Island off the coast of South Carolina.

The research was led by Cassandra Miller-Butterworth, associate professor of biology at Penn State Beaver, and Duane Diefenbach, Penn State adjunct professor of wildlife ecology who, as a doctoral candidate at the University of Georgia in 1989, reintroduced bobcats captured on the Georgia mainland to Cumberland Island. Before freeing the bobcats on the island, he drew blood samples from the animals and froze them. DNA in those samples now serves as a baseline to compare how the population is faring.

The bobcat reintroduction was part of Diefenbach's doctoral research, in which he documented the survival and reproduction of the reintroduced bobcats and collected blood samples from the first litters of kittens born on the island. Since then, he has returned to the island many times over the years with students and volunteers to collect bobcat scat from which to extract DNA to monitor the population's genetic health.

There now are 24 bobcats on Cumberland Island, which is separated from the mainland by open water that prevents bobcats from the mainland from immigrating. DNA from the scat allows the scientists to identify individual bobcats, which enables them to estimate abundance and survival rates and measure levels of inbreeding.

"Because we had DNA from the founding population, we were able to document the loss in genetic diversity over time in the population," said Diefenbach, leader of the Pennsylvania Cooperative Fish and Wildlife Research Unit, which is housed in Penn State's College of Agricultural Sciences. "Over the past 30 years, the population has lost about 15% of its genetic diversity. There appears to be some inbreeding, but generally it is low."

Over the last decade, Diefenbach has collaborated with Miller-Butterworth, a wildlife population geneticist, to analyze the bobcats' DNA. Her laboratory handled all the molecular analyses from the blood samples.

Diefenbach and Miller-Butterworth also assessed the bobcat population on Kiawah Island. After trappers in 2015 and 2016 donated tissue samples from bobcats on the South Carolina mainland, the researchers determined that bobcats do occasionally travel on and off that island, likely over a bridge for vehicles.

"On Kiawah, we studied the genetics and found that about every five years, a bobcat from the mainland contributes genes to the island population," Miller-Butterworth said. "Consequently, genetic diversity on Kiawah Island is lower than on mainland South Carolina, but still higher than on Cumberland Island."

The research findings, recently published in Global Ecology and Conservation, indicate that the probability of Cumberland Island bobcats becoming extinct will continue to increase over time. By 2040, the researchers predicted, the risk of extinction will increase to about 20% without any human intervention to restore the loss in genetic diversity, perhaps by introducing a bobcat from the mainland every four or five years.

However, the findings provide good news for people trying to protect endangered species, Miller-Butterworth pointed out.

"We found that population viability models that predict the fate of the population did a good job in predicting the loss in genetic diversity and the long-term population size," she said. "I was surprised at how closely the modeling data and the empirical data matched -- you don't see that often. When we were running the population viability analyses, the predictions that we got for genetic variation, or heterozygosity, matched almost exactly what we were finding with our empirical DNA data."

The Cumberland Island bobcat study is valuable because it yielded information that may be useful in future research used to rescue endangered felid populations, such as Iberian lynx or Eurasian lynx, for which extinction risk may be high, Miller-Butterworth explained. Bobcats are not threatened as a species, but the isolated population on Cumberland Island simulates an endangered species scenario in which a population becomes isolated due to habitat loss and fragmentation and loses genetic variation over time -- an increasingly common scenario for many endangered species.

"The benefit is we can use this as a case study, or a test case, to figure out what works to re-establish the population's viability, and then that knowledge potentially can be used to extrapolate what would work for an endangered species where the situation is dire," she said. "If we make a mistake in our calculations on Cumberland Island, it would be sad, but it wouldn't result in losing a species."