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Lack of data on contraception uptake prior to the pandemic means no clear picture of the impact Covid-19 had on contraception use

Study from Warwick Medical School highlights need to maintain access to contraception during disasters

Researchers recommend making more contraception prescription-free and discuss the benefits and pitfalls of telehealth

Limited data on the uptake of contraception prior to and during crises such as the Covid-19 pandemic could mean unforeseen issues for sexual and reproductive health services, research from the University of Warwick concludes.

It identifies additional barriers that women faced in accessing contraception during the Covid-19 lockdown, including disruption to sexual health services and fears about contracting the virus, as well as a pressing need to ensure that access to contraception is maintained to avoid the health and social impacts of unplanned pregnancies beyond the pandemic.

The research, published in the European Journal of Contraception and Reproductive Health Care, is a scoping review of existing research into the impact of disasters on contraception in higher income countries such as the United Kingdom to assist in disaster response planning. It aims to establish existing knowledge from previous disasters and epidemics, with a significant focus on the Covid-19 pandemic.

Previous research has shown that disasters are associated with increased rates of early pregnancy loss, stillbirth and premature birth, as well as with increased birth rates. However, until now there has not been a review of how the uptake of contraception is affected, and what impact this may have on women's reproductive health.

Policies on accessing contraception vary by country and include access to:

Oral contraceptive pills

Contraceptive injection

Intrauterine device (IUD) or Intrauterine system (IUS)

In the United Kingdom contraception is free through the NHS but requires a prescription. However, the Covid-19 pandemic created new barriers that may have prevented women from accessing contraception. They might avoid going to a healthcare provider due to the fear of contracting Covid-19, or concerns about travelling, especially if relying on public transport.

However, the research highlighted examples of good practice in overcoming these barriers, such as drive-through or kerbside provision of contraception. Some health providers were able to maintain access to contraception using telehealth (i.e. video or phone consultations), however these presented safeguarding and privacy issues. Evidence from outside the UK also showed that making emergency contraception prescription-free rather than cost-free has a greater impact on unplanned pregnancies.

As data were not collected on the uptake of contraception prior to the pandemic, it is unclear how successful these methods have been, nor how women's access to contraception has been affected. The researchers recommend collecting more data on the uptake of contraception, awareness of the benefits and pitfalls of telehealth methods, and a move to making more contraception prescription-free, as is currently being considered for the progestogen-only pills.

Co-author Dr Julia Gauly from Warwick Medical School said: "We don't have a clear picture of how the uptake of contraception changes during disasters or the Covid-19 pandemic, because we don't have enough data from before, during and after the crisis to compare. Collecting better data would put us in a better position in the future to predict things like birth rates.

"It's important that women can access contraception and have a choice, especially during disasters. Many people lost their jobs during the pandemic or they became sick with Covid, so the needs of women for contraception may have changed. Someone who was planning to start a family might change their mind during a crisis or pandemic, due to financial or health reasons. So it's important that women and their partners have a choice in their family planning."

People with a rare autoimmune disease, who likely experience more serious isolation during a global pandemic, saw their anxiety and depression improve after receiving online mental health intervention through an international study involving investigators from Michigan Medicine.

The paper, published in the Lancet Rheumatology, analyzed the mental health progress of over 150 people with scleroderma, a disease that causes tightening of the skin and connective tissues. Researchers randomized patients to either receive video support intervention or be put on a waitlist, finding mental health outcomes improved after the program finished.

"COVID-19 isolation has had a very serious impact, especially on these scleroderma patients who are immunocompromised and have a higher chance of dying if they catch it," said John Varga, M.D., a co-author of the study, chief of the Michigan Medicine Division of Rheumatology and associate director of the U-M Scleroderma Program. "This shows that virtual intervention can be very effective in mitigating these mental health issues in a cost-effective way across large cohorts of patients."

The Scleroderma Patient-centered Intervention Network designed a four-week program that offered group mental health intervention from trained peer support leaders three times each week. To ensure access, members of the waitlisted control group were still offered the SPIN therapy.

The intervention did not show improvements for the global cohort immediately following the program. However, anxiety and depression symptoms dropped significantly six weeks later, potentially revealing the time it took for new skills and social support to take effect.

While this intervention took place before the COVID-19 vaccine was widely available, the disease is a paradigm for public health issues that cause people increased anxiety, Varga said.

"If something else comes along where people with a chronic disease are vulnerable or anxious, you can intervene in a virtual way that has a measurable impact," he said. "This allows participants to be educated on staying connected, physical activity, and managing worry and stress. It sends a very positive message."

PHILADELPHIA - Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disease that strikes nearly 5,000 people in the U.S. every year. About 10% of ALS cases are inherited or familial, often caused by an error in the C9orf72 gene. Compared to sporadic or non-familial ALS, C90rf72 patients are considered to have a more aggressive disease course. Evidence points to the immune system in disease progression in C90rf72 patients, but we know little of what players are involved. New research from the Jefferson Weinberg ALS Center identified an increased inflammatory signal in C90rf72 patients compared to other ALS patients, pointing to immune characteristics that distinguish this subgroup of ALS patients and informing potential anti-inflammatory therapies. The study was published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration on April 30th, 2021.

In comprehensive analyses, the researchers collected cerebrospinal fluid (CSF), via a small puncture in the spine, as well as serum from 15 C9orf72 patients, 9 sporadic ALS patients and 14 control patients, and conducted a test to measure the levels of around 40 different immune molecules and chemicals. They found an increase in pro-inflammatory molecules in the serum and CSF of both sporadic and C9orf72 ALS patients compared to controls, but the increase was more pronounced in C9orf72 patients.

These findings point to important distinguishing characteristics of this subgroup of ALS patients, which could be detectable in a peripheral test of serum. Serum tests would be less invasive than testing CSF. The results also indicate that any future strategies for developing anti-inflammatory treatments would benefit from distinguishing the C9orf72 subtype from other types of ALS. The researchers are looking to build a bank of patient samples to continue studying key differences between patient subtypes.

"This is a step in better characterizing this sub-population of ALS patients," says senior author Hristelina Ilieva, MD, PhD, assistant professor and medical director of the Weinberg ALS Center, "and an impetus to continue the search for biomarkers for this disease."

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2021.0013, Sharen Lee, Gary Tse, Xin Wang, Adrian Baranchuk and Tong Liu from Laboratory of Cardiovascular Physiology, Hong Kong, China, Second Hospital of Tianjin Medical University, Tianjin, China and Queen's University, Kingston, Ontario, Canada consider ST-segment depression in leads I and aVL.

The 12-lead electrocardiogram (ECG) is a routinely performed test but is susceptible to misinterpretation even by experienced physicians. The authors report a case of a 72-year-old lady with no prior cardiac history presenting with atypical chest pain. Her initial electrocardiogram shows an initial ST depression followed by positive deflections leads I and aVL. Non-physiological ST segment and T-wave changes were also observed in the precordial leads V2 to V6. By contrast, these abnormalities were notably absent in lead II. A repeat of the ECG taken 30 minutes later revealed the resolution of most abnormalities seen in the initial ECG on a background of high-frequency noise in the limb leads. The patient was referred to the cardiology department for further management. An urgent echocardiogram revealed no regional wall motion abnormalities with preserved ejection fraction, and her coronary angiogram revealed no significant coronary stenosis.

This case illustrates the importance of understanding different factors that can cause ST segment abnormalities, notably artifactual changes that can mimic ST segment myocardial infarction.

PHILADELPHIA (June 16, 2021) - The current Medicare reimbursement policy for nurse practitioners (NPs) allows NPs to directly bill Medicare for services that they perform, but they are reimbursed at only 85% of the physician rate. A growing number of states are granting full practice authority to nurse practitioners. Even more states have loosened practice restrictions due to COVID-19. Both of these reasons illustrate why payment parity is essential.

In an article in The Online Journal of Issues in Nursing, Alycia Bischof, MSN, APRN, PNP-BC, Senior Lecturer at the University of Pennsylvania School of Nursing (Penn Nursing), argues that given the increased role of NPs (particularly during the pandemic) and their proven ability to provide care comparable to physicians, Congress should allow Medicare to increase the NP reimbursement rate to 100% of the physician pay rate.

"The COVID- 19 pandemic serendipitously led to the removal of many restrictions on NP practice, a positive change that needs to become permanent. This is the time for NPs to seize the opportunity to work with MedPAC to achieve full reimbursement for care provided," she says.

In the article, she summarizes the evolution of the practice of NPs and the rationale for reimbursement parity for nurse practitioners. She also outlines the potential benefits of providing NPs with 100% reimbursement, including incentivizing them to practice in primary care settings where there is a shortage.

Bischof encourages nurse advocacy groups and researchers to direct future studies to investigate how full practice authority and the removal of practice barriers due to the COVID-19 pandemic have affected the level of care that NPs provide. "Such studies can then be used to support further evolution of reimbursement policy, if NPs indeed produce an equal or better product than physicians," she says.

Why can some people weather the stress of social isolation better than others, and what implications does this have for their health? New research from the Communication Neuroscience Lab at the Annenberg School for Communication at the University of Pennsylvania found that people who felt a strong sense of purpose in life were less lonely during the COVID-19 pandemic. Did they achieve less loneliness by flouting public health guidance? No. Although lonelier people were less likely to want to follow public health guidance, people with a stronger sense of purpose also expressed more willingness to engage in social distancing, hand washing, and other COVID-19 protective behaviors.

Purpose in life, or a sense that your life is guided by personally meaningful values and goals — which could involve family ties, religion, activism, parenthood, career or artistic ambitions, or many other things — has been associated in prior research with a wide range of positive health outcomes, both physical and psychological.

"In the face of adversity, people with a stronger sense of purpose in life tend to be more resilient because they have a clear sense of goals that motivate actions that are aligned with personal values," says Yoona Kang, Ph.D., lead author and a Research Director of the Communication Neuroscience Lab. "People with strong purpose may also experience less conflict when making health decisions. We felt that the COVID-19 pandemic was an important context to test whether purpose in life relates to individuals' willingness to engage in behaviors to protect themselves and others."

Based on their prior research, Kang and her collaborators expected that people with higher sense of purpose would be more likely to engage in COVID-19 prevention behaviors than individuals with a lower sense of purpose. In order to test their theory, the researchers surveyed more than 500 adult participants to capture their levels of purpose in life, their current and pre-pandemic levels of loneliness, and the degrees to which they intended to engage in behaviors known to prevent the spread of COVID-19.

They found that higher levels of loneliness made people be less focused on protecting themselves from COVID-19, and more skeptical that behaviors to prevent COVID-19 would be effective. However, having a stronger sense of purpose was associated with lower levels of loneliness and a greater desire to take action to protect themselves from COVID-19. Those with a higher sense of purpose also expressed a stronger belief that COVID-19 prevention behaviors would work. Even when people who had a strong sense of purpose did report being lonely, they still felt strongly about taking precautions to prevent COVID-19.

"When faced with extreme loneliness and social isolation, like during the COVID-19 pandemic, wanting to connect with other people, despite the health risks, is a natural response," Kang says. "And yet, amidst this drastic shift in social life, we found that people with a higher sense of purpose were more likely to engage in prevention behaviors. This is striking because it shows that purpose in life can empower people to make life-saving health decisions that protect their own health and those around them."

Additionally, the researchers found that older people expressed less loneliness during the COVID-19 pandemic than younger people. Kang sees this as a sign of the resilience of older adults, and she hopes to further study how to enhance purpose in life and resilience in aging populations.

"Having a stronger sense of purpose was associated with really important, positive outcomes across the lifespan," says Emily Falk, senior author, Director of the Communication Neuroscience Lab, and Professor of Communication, Psychology, and Marketing. "Our upcoming work will test interventions to increase their sense of purpose, in hopes of bringing these benefits to more people."

Boston - New study results indicate that different comorbid conditions affecting individuals diagnosed with COVID-19 may impact how long they continue to receive positive SARS-CoV-2 polymerase chain reaction (PCR) test results. Individuals diagnosed with COVID-19 who are aged 60+, have three or more chronic medical conditions, particularly diabetes, obesity, rheumatologic disease, or an organ transplant, have positive PCR tests for longer periods of time compared to younger individuals without these comorbidities. However, the data showed no significant difference in the duration of positive PCR tests results by the degree of immunocompromise or for individuals receiving chemotherapy or steroids to treat COVID-19.

Published online in Open Forum Infectious Diseases and led by researchers at Boston Medical Center, this study is the largest sample size to date of SARS-CoV-2 PCR retesting in both immunocompromised and non-immunocompromised patients, allowing for the comparison between these two groups.

"There are limited data on how long immunocompromised individuals continue to test positive for COVID-19 after initial infection," said Rachel Epstein, MD, MScE, an infectious diseases physician at Boston Medical Center and the study's corresponding author. "This study challenges whether the current recommendations to consider retesting severely immunocompromised individuals and use negative SARS-CoV-2 PCR test results to end isolation is necessary."

According to the Centers for Disease Control and Prevention (CDC), severely immunocompromised individuals are likely to have prolonged positive SARS-CoV-2 PCR test results. The conditions that cause immunocompromised status represented in the CDC definition include: people on chemotherapy or high dose steroids; those with untreated HIV; those with a primary immunodeficiency; or those who recently received an organ transplant.

The researchers examined data from 3,758 individuals who were retested using the SARS-CoV-2 PCR test following an initial positive result. The individuals were separated into groups by age as well as immunocompromised severity:

Severe - active chemotherapy, HIV with a CD4 count less than 200, organ transplant in the last year, or chronic high-dose steroids (7.4 percent of study group)

Moderate - solid organ transplant recipient greater than 1 year prior, HIV with a CD4 count greater than 200, and others taking chronic biologic medications (4.2 percent of study group)

Not immunocompromised (88.4 percent of study group)

The median length of time for severely immunocompromised patients to receive a negative SARS-CoV-2 PCR test result was 22 days; for moderately and non-immunocompromised individuals, the time was 20 and 16 days, respectively. For individuals who had a solid organ transplant, are older than 60, have diabetes, obesity or rheumatologic disease, as well as those with more than three comorbid conditions, it took longer for a negative SARS-CoV-2 PCR test result.

"Retesting individuals to end isolation precautions can delay care, and may not be necessary even for most severely immunocompromised people, particularly as most transmission studies demonstrate that it is highly unlikely for someone to transmit infection more than 20 days into their illness," said Epstein, an assistant professor of medicine and pediatrics at Boston University School of Medicine. The authors note that retesting recommendations should perhaps consider a combination of conditions or include only certain groups of extremely immunocompromised individuals. There have been a few cases in the literature showing positive COVID1-9 test results months out from initial infection in patients who have undergone a solid organ or bone marrow transplant or received chimeric antigen receptor (CAR) T-cell therapy.

Additional studies that directly measure transmission or transmissibility from individuals with a positive PCR test result more than 20 days into illness with COVID-19 would be helpful to better inform current CDC guidelines.

Makeup wearers may be absorbing and ingesting potentially toxic per- and polyfluoroalkyl substances (PFAS), according to a new study published today in Environmental Science & Technology Letters. The researchers found high fluorine levels--indicating the probable presence of PFAS--in most waterproof mascara, liquid lipsticks, and foundations tested. Some of the products with the highest fluorine levels underwent further analysis and were all confirmed to contain at least four PFAS of concern. The majority of products with high fluorine, including those confirmed to have PFAS, had no PFAS listed on the label.

"Lipstick wearers may inadvertently eat several pounds of lipstick in their lifetimes," said Graham Peaslee, senior author of the study and professor of physics at the University of Notre Dame. "But unlike food, chemicals in lipstick and other makeup and personal care products are almost entirely unregulated in the U.S. and Canada. As a result, millions of people are unknowingly wearing PFAS and other harmful chemicals on their faces and bodies daily."

Some PFAS have been associated with a wide range of serious health harms, from cancer to obesity to more severe COVID-19 outcomes, and they contaminate the drinking water of millions. Only a small fraction of the many thousands of PFAS have been tested for toxicity, but all PFAS are either extremely persistent in the environment or break down into extremely persistent PFAS.

In addition to PFAS being ingested from lip products, PFAS in cosmetics may be absorbed through the skin and tear ducts. On top of these direct exposure routes, PFAS can make their way into our drinking water, air, and food during the manufacture of makeup and after it's washed down the drain.

The research team screened 231 cosmetic products purchased in the U.S. and Canada for fluorine. More than three-quarters of waterproof mascara, nearly two-thirds of foundations and liquid lipsticks, and more than half of eye and lip products had high fluorine concentrations.

All 29 products selected for targeted analysis contained detectable levels of at least four specific PFAS. This included PFAS that break down into other PFAS that are known to be highly toxic and environmentally harmful. Fluorotelomer methacrylates were also detected, indicating the breakdown of side-chain fluoropolymers which are marketed as a more "environmentally friendly" alternatives to individual PFAS.

Many of the products with PFAS were advertised as "wear-resistant" or "long-lasting." Importantly, almost none of the products studied with targeted analysis had any PFAS listed on their ingredient labels. This makes it impossible for consumers to avoid PFAS-containing cosmetics by reading labels.

"PFAS are not necessary for makeup. Given their large potential for harm, I believe they should not be used in any personal care products," said Arlene Blum, a co-author and executive director of the Green Science Policy Institute. "It's past time to get the entire class of PFAS out of cosmetics and keep these harmful chemicals out of our bodies."

A tickle in the nose can help trigger a sneeze, expelling irritants and disease-causing pathogens. But the cellular pathways that control the sneeze reflex go far beyond the sinuses and have been poorly understood. Now, a team led by researchers at Washington University School of Medicine in St. Louis has identified, in mice, specific cells and proteins that control the sneeze reflex.

"Better understanding what causes us to sneeze -- specifically how neurons behave in response to allergens and viruses -- may point to treatments capable of slowing the spread of infectious respiratory diseases via sneezes," said Qin Liu, PhD, an associate professor of anesthesiology and the study's senior investigator.

The findings are published June 15 in the journal Cell.

"We study the neural mechanism behind sneezing because so many people, including members of my own family, sneeze because of problems such as seasonal allergies and viral infections," said Liu, a researcher in the university's Center for the Study of Itch and Sensory Disorders. "Our goal is to understand how neurons behave in response to allergies and viral infections, including how they contribute to itchy eyes, sneezing and other symptoms. Our recent studies have uncovered links between nerve cells and other systems that could help in the development of treatments for sneezing and for fighting infectious respiratory diseases."

Sneezing is the most forceful and common way to spread infectious droplets from respiratory infections. Scientists first identified a sneeze-evoking region in the central nervous system more than 20 years ago, but little has been understood regarding how the sneeze reflex works at the cellular and molecular level.

In the new study, Liu and her team established a mouse model in an attempt to identify which nerve cells send signals that make mice sneeze. The researchers exposed the mice to aerosolized droplets containing either histamine or capsaicin, a pungent compound made from chili peppers. Both elicited sneezes from the mice, as they do in people.

By examining nerve cells that already were known to react to capsaicin, Liu's team was able to identify a class of small neurons linked to sneezing that was caused by that substance. The researchers then looked for molecules -- called neuropeptides -- that could transmit sneeze signals to those nerve cells, and found that a molecule called neuromedin B (NMB) was required for sneezing.

Conversely, when they eliminated the NMD-sensitive neurons in the part of the nervous system that evoked sneezes in the mice, they blocked the sneeze reflex. Those neurons all make a protein called the neuromedin B receptor. In mice without that receptor, sneezing again was greatly reduced.

"Interestingly, none of these sneeze-evoking neurons were housed in any of the known regions of the brainstem linked to breathing and respiration," Liu said. "Although we found that sneeze-evoking cells are in a different region of the brain than the region that controls breathing, we also found that the cells in those two regions were directly connected via their axons, the wiring of nerve cells."

The researchers also found they could stimulate the sneeze reflex by exposing part of the mouse brain to the NMB peptide. Further, the animals began to sneeze even though they had not been exposed to any capsaicin, histamine or other allergens.

Because many viruses and other pathogens -- including the majority of human rhinoviruses and coronaviruses such as Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2, the coronavirus that causes COVID-19 -- are spread in part by aerosolized droplets, Liu said it may be possible to limit the spread of those pathogens by targeting NMB or its receptor to limit sneezing in those known to be infected.

"A sneeze can create 20,000 virus-containing droplets that can stay in the air for up to 10 minutes," Liu explained. "By contrast, a cough produces closer to 3,000 droplets, or about the same number produced by talking for a few minutes. To prevent future viral outbreaks and help treat pathological sneezing caused by allergens, it will be important to understand the pathways that cause sneezing in order to block them. By identifying neurons that mediate the sneeze reflex, as well as neuropeptides that activate these neurons, we have discovered targets that could lead to treatments for pathological sneezing or strategies for limiting the spread of infections."

Chemotherapy kills tumour cells by causing damage to them. One of the most effective ways of causing damage is to prevent the two DNA strands from separating so that the cellular machinery cannot read the instructions written in the genes. But sometimes, the cell manages to repair the damage and survive, evading the effect of chemotherapy. CNIO researchers have found out how the cell does that and plan to use this knowledge to enhance cancer treatments.

The key lies in a peculiar protein called PrimPol, as explained in a publication in The EMBO Journal by the CNIO's DNA Replication Group, led by Juan Méndez.

The DNA molecule harbours the genes that direct the life of the cell and, by extension, the life of the whole organism. It consists of two intertwined strands, the famous double helix. For the instructions written in the genes to be read by the cellular machinery, the two strands of DNA must be pulled apart and put back together again, like a zipper that opens and closes. If this does not happen, the cell cannot function and, of course, cannot replicate.

That is why lesions that prevent DNA strands from separating are among the most serious that a cell can suffer. They are called interstrand cross-links (ICLs). ICL lesions can appear naturally, as a result of cell metabolism, or as a consequence of certain toxins, such as chemotherapeutic drugs. Cisplatin, used in the treatment of among others ovarian and lung cancers, kills tumour cells by inducing ICL lesions.

A 'staple' that holds the double helix together

As Méndez explains, "The ICL is a chemical bond between the two strands, a kind of staple that prevents them from separating. If the cell tries to divide, the chromosomes end up breaking."

The cell, however, knows how to repair these lesions, which in fact only become lethal when their frequency is very high. In the paper now published in The EMBO Journal, the CNIO group reveals that the cell achieves this in part thanks to PrimPol.

PrimPol belongs to a family of proteins called "primases" that appeared very early in the evolution of life and is still present today in a great many species, which indicates its importance for the functioning of organisms. In 2013, Juan Méndez and Luis Blanco, from the Centro de Biología Molecular Severo Ochoa (CSIC), discovered why PrimPol is so important: it allows the cellular machinery to use the instructions written in the DNA even when it contains an error. In other words, PrimPol makes the cell more resilient by helping it to survive when its DNA is damaged.

PrimPol helps to keep reading the DNA

Usually, DNA-copying proteins are blocked when they detect defects in the double helix, and if the blockage persists for too long, the cell will die. But PrimPol enables the reading of the DNA to continue after the error, like keeping on reading a text after skipping a misspelt or misunderstood word. "PrimPol," explains Méndez "offers 'an immediate solution' to bypass the blockage, giving the cell a chance to repair the error in the DNA at a later time."

The new study focuses on PrimPol's function when the error is an ICL lesion. The researchers found that PrimPol is required for the DNA copying phase that precedes the repair of the staple in the DNA strands. Thanks to the intervention of this enzyme, the cell not only survives ICL lesions but also mobilises the machinery responsible for repairing them.

Repressing PrimPol to potentiate chemotherapy

It is a basic finding, but "with very interesting clinical implications," says Méndez, because "by facilitating the repair of ICLs, PrimPol is interfering with the effectiveness of chemotherapy."

That suggests that if PrimPol were absent, the tumour cell would be more sensitive to chemotherapy. The authors, therefore, believe that the new results "open the possibility of targeting PrimPol to enhance the therapeutic effects of molecules that produce ICL lesions," they write in The EMBO Journal.

In another recent study in which Méndez participated together with researchers from Washington University (St Louis, USA), it was found that ovarian tumour cells produce more PrimPol to tolerate DNA damage caused by cisplatin-based chemotherapy.

"If we can repress PrimPol function in these cells, we could improve the efficiency of chemotherapy," Méndez points out. To this end, his team is working together with CNIO's Experimental Therapeutics Programme to identify specific PrimPol inhibitors.

Fanconi anaemia

The new study is also of interest for Fanconi anaemia, a rare and severe disease. The CNIO researchers show that PrimPol facilitates the repair of ICL lesions by a family of proteins called FANC. And genetic defects that reduce the activity of these proteins cause Fanconi anaemia.

"Patients with Fanconi anaemia have very few therapeutic options, but very promising results are beginning to be obtained with gene therapy," says Méndez. "Any advances that lead to a better understanding of the ICL repair pathways may prove useful in the near future."

Hippopotamus aren't the first thing that come to mind when considering epidemiology and disease ecology. And yet these amphibious megafauna offered UC Santa Barbara ecologist Keenan Stears(link is external) a window into the progression of an anthrax outbreak that struck Ruaha National Park, Tanzania, in the dry season of 2017.

Through surveys and GPS monitoring, Stears and his colleagues, Wendy Turner, Doug McCauley and Melissa Schmitt, revealed that reduced dry-season flows in the Great Ruaha River indirectly spread the disease by affecting hippo movement. The results, which appear in the journal Ecosphere(link is external), present a unique perspective on disease ecology and illustrate how anthropogenic changes can impact wildlife and human health.

The ecology of wildlife disease was far out of mind during the dry season in 2016, when Stears and his team outfitted 10 male hippos with GPS collars. The researchers sought to track the animals' movements to better understand their behavior and ecology, especially in light of reduced flows along many of Africa's major rivers. The resulting study was the first to track hippo movement and land use, and finally uncovered some of the basic facts about hippos' spatial ecology.

Then the anthrax came.

"This wasn't something I actually set out to study," said Stears, a postdoctoral researcher in the Department of Ecology, Evolution and Marine Biology. "You can't plan for an outbreak to occur; it just happens."

Stears was in the field from 2016 to 2017 conducting hippo counts and maintaining equipment. The GPS tracking collars had been on the animals for about a year, roughly as long as they're supposed to last before dropping off. Noticing one of the collars hadn't moved for a couple of days, he figured it had fallen off. It appeared to be in a nearby pool, so Stears hiked out to retrieve it. "I turned around a bend in the river, and there was a hippo pool with about six or so hippo carcasses," he recalled. Stears had stumbled upon an anthrax outbreak.

Anthrax is an infection caused by the bacterium Bacillus anthracis, which can manifest in a variety of ways depending on how it's contracted. The bacterium is notable for its ability to produce spores that can lie dormant in the soil for years. Notably, in outbreaks like the one in this study, animals can only spread the disease once they die.

Although he isn't a disease ecologist, Stears quickly realized his GPS data could illuminate aspects of the outbreak. There didn't seem to be any existing studies that combined a spatio-temporal account of an active anthrax outbreak with wildlife movement, he explained. "So this was really a unique opportunity to answer some questions that hadn't really been answered before."

"We can't predict when an anthrax outbreak will occur, so it's impossible to plan such a study," added co-author Wendy Turner of the U.S. Geological Survey and the University of Wisconsin-Madison. "This project is in part a fantastic bit of luck (for understanding disease transmission, not for the hippos), and in part very clever and quick thinking by Keenan and Melissa at UCSB, to capitalize on such a unique opportunity.

"I have been studying anthrax for years in Namibia, with many more GPS-collared hosts monitored than the 10 in this study," she continued, "and I still haven't had any of our individuals succumb to the disease."

The team first had to determine how many hippos in this population had interacted with potentially infected pools. That meant identifying which of the many disconnected pools along this stretch of the Great Ruaha River were infected. Stears' colleagues at Ruaha National Park conducted sampling for the pathology to confirm the anthrax outbreak.

Stears and his team conducted daily counts of both live and dead hippos in these pools. The surveys enabled them to track the disease's spread, its rate and direction. The scientists were also curious where the hippos were coming from, where they were going and whether the outbreak was influencing their behavior.

The researchers linked this information with the hippo movement data they had from the GPS collars. Four of the 10 hippos they had tracked could have caught the disease, Stears said, and of those, three died.

The team found that infection had no noticeable effect on a hippo's movement. Infected individuals roamed just as much as healthy hippos. "This has important implications for how far a single individual could potentially vector the disease before its death and create new infectious reservoirs," Stears said. Under certain conditions, wildlife can succumb to infection within a few days. Even if this is the case, a hippo can walk about seven kilometers over the course of a night in search of water. Thus, hippos can quickly move the disease over large distances.

What's more, the animals didn't appear to actively avoid carcasses. Why? Well, dry times are not good times to be a hippo. Normally, species avoid the bodies of their own kind. But with suitable ponds so scarce, the amphibious animals were forced to remain in pools alongside the dead.

"The drying of rivers is one of the major reasons why these outbreaks have gotten so bad over the years," Stears explained. "As the river dries, hippos are forced to congregate in the remaining river pools. Now this paper's showing that their movements spread the disease as well."

Anthrax outbreaks are a natural occurrence, but drying rivers are making them worse. As pools dry up, hippos either pack into those that remain or move to find new ones. Increased crowding and social interactions can drive up physiological stress, which scientists have linked to a greater susceptibility to infection.

Additionally, altered hippo movements as they search for new pools raise the risk of exposure to anthrax reservoirs as well as the duration that they interact with these reservoirs. Aggressive interactions around the remaining pools mean that hippos frequently visit several in a given night. All these factors have exacerbated anthrax outbreaks in hippo populations.

Stears noted that hippos also appear particularly susceptible to these outbreaks, aggregating as they do in small, dirty pools during the dry season. Other animals avoid drinking from hippo pools during these times because of all the dung that has accumulated due to the lack of river flow. Instead, they seek out shallower puddles that are cleaner, which potentially protects them from contracting lethal doses of the disease.

"Understanding disease outbreaks in hippos is especially important," said co-author Doug McCauley(link is external), an associate professor of ecology, evolution, and marine biology (EEMB) at UC Santa Barbara. "People don't often realize that hippos are a vulnerable species that has declined in many areas. There are far less hippos, for example, than African elephants. Their outlook is further complicated by potential impacts that climate change may have on rivers and how this change might amplify disease outbreak risk."

Stears plans to start looking at historical records of river flow across Africa and linking changes in hydrology to past anthrax outbreak timing and severity. There hasn't been much research on anthrax and river flow, he said; most of the work has been terrestrial. The historical records could be a treasure chest of information.

Shedding light on the factors that influence disease dynamics helps scientists predict how disturbances might affect future outbreaks. With this information, they can begin to assess how future circumstances could affect the extent and severity of an anthrax outbreak, as well as the probability that it jumps to other species of wildlife, livestock and even humans.

"Hippos can be considered the canary in the coal mine," added co-author Melissa Schmitt(link is external), an EEMB postdoctoral researcher. "Their sensitivity to adverse conditions makes them a good indicator of how global change may influence disease dynamics and overall wildlife health.

In all, the paper represents a confluence of events that offered an unparalleled opportunity to explore novel disease dynamics. "You can only get this kind of information from having an animal that is collared and actually infected," Stears said. "So this unique situation allowed us to answer questions that you just can't normally answer without having everything lined up."

Two new studies have cast unprecedented light on disease processes in tuberculosis, identifying key genetic changes that cause damage in the lungs and a drug treatment that could speed up recovery.

Tuberculosis (TB) is a lung infection that has killed more humans than any other and until last year was the top infectious killer around the world. Globally, an estimated 10 million people develop the disease each year.

The findings are reported in two papers in the Journal of Clinical Investigation.

In the first study, a team from the University of Southampton used a new 3D culture system they have developed to observe the changes that occur in cells infected with TB. Unlike the laboratory-standard 2D culture system, where cells are placed in a flat plastic dish, the 3D system uses an engineering technique to suspend them in droplets - like frogspawn. The team found that the TB-infected cells in droplets responded very closely to cells in the lungs of patients with the disease.

This observation has widespread implications for further studies into infectious diseases, including COVID-19.

A second team from the University of Southampton then carried out complex sequencing techniques on the cells to identify the events through which TB causes excessive inflammation and damage to the lung.

Human genome sequencing methods generate information on tens of thousands of changes in genes from each sample, making it difficult to work out which changes are important and which are from chance. The Southampton Systems Immunology Group combined different mathematical approaches, such as clustering algorithms, to whittle this down to seven genes which seem to underpin the lung destruction that occurs in TB.

Dr Michaela Reichmann of the University of Southampton who conducted the study said "The integration of modern sequencing techniques with clinical samples is permitting unprecedented insight into disease mechanisms, while our 3D cell culture system then lets us replicate conditions in patients and identify new treatment approaches."

In the second study, a clinical trial led by Dr Catherine Ong of the National University of Singapore studied the use of a common antibiotic, doxycycline, to reverse these changes. The phase 2 double blind trial in 30 patients showed that doxycycline, in combination with TB drug treatment, reduces the size of lung cavities and accelerates markers of lung recovery towards health. These bioinformatics analyses were performed by the Systems Immunology Group in Southampton.

The treatment was found to be safe, with similar side effects to those experience by patients on placebo pills. The study shows promise in delivering a new standard-of-care which can potentially prevent long term complications.

Dr Ong said "Pulmonary TB patients tend to suffer from lung damage after TB, which is associated with mortality, and poorer quality of life. Doxycycline is a cheap and widely available antibiotic that can decrease lung damage, and potentially improve quality of life for these patients."

The team now are seeking funds for a fully-powered larger scale phase 3 trial to verify these findings.

The international team are also aiming to translate these new insights into approaches that may shorten treatment from the current minimum of six months and improve treatment of drug resistant disease, which is progressively increasing.

The clinical trial was based on a collaboratory network involving the National University of Singapore, the University of Southampton and St George's London, while the basic science study also involved the African Health Research Institute, Durban, and Yale and Colombia Universities in the United States.

Photoemission is a property of metals and other materials that emit electrons when struck by light. Electron emission after light absorption was already explained by Albert Einstein. But since this effect is a highly complex process, scientists have still not been able to fully elucidate its details. Prof. Dr. Bernd von Issendorff and his team at the University of Freiburg's Institute of Physics have now succeeded in detecting a previously unknown quantum effect in the angular distributions of photoelectrons from cryogenic mass-selected metal clusters. The angular distributions resemble those of classical particles, a behavior that is surprisingly explainable by the strong electron-electron interaction in these many-electron systems. The researchers published this finding in the current issue of Physical Review Letters.

Electrons with well-defined angular momenta

Metal clusters may be seen as quantum systems consisting of a countable amount of quantum particles - in this case electrons - in a simple spherical box potential. Electrons in simple metal clusters possess relatively well-defined angular momenta, although a cluster is never perfectly round. This is due to the virtually optimal shielding of the atomic nuclei by the electron system. Hence, a single electron experiences only an average interaction that is remarkably close to the interaction with a spherical box potential. As a consequence, the electrons practically assume angular momentum eigenstates, i.e., rotate with a well-defined angular momentum. Moreover, the photoemission of the electron occurs only at the cluster surface, because only there can the required radial momentum be transferred to the electron.

Electron emission occurs only at the surface

Researchers expected that the electron's momentum would be preserved parallel to the surface during photoemission, as there are no forces acting in this direction. "Since an electron with a defined angular momentum at the surface has a defined momentum parallel to it, it could be assumed," explains von Issendorff, "that the angular distribution of the electrons corresponds to that of balls simply released by children from a rotating merry-go-round. They do not fly radially outward but tangentially to the circular path." The Freiburg researchers observed just this effect on metal clusters, thus verifying that the electrons indeed can be seen as particles rotating in a box potential and that the electron emission actually does occur only at the surface. The surprise, however, says von Issendorff, is that this observation is completely contradictory to quantum mechanical simulations, which always predict a much more complex behavior dominated by inferences and resonances in the ionization process.

Mathematical description of the angular functions

However, the Freiburg researchers were able to resolve this contradiction: On the basis of their earlier work and in discussions with researchers at the Max Planck Institute for the Physics of Complex Systems in Dresden, they derived a complete mathematical description of the angular functions that corresponds very well to the experiment. The core assumption of this new description is that the cluster is completely non-transparent for electrons: Electrons are strongly decelerated inside the cluster. This leads to a suppression of the interference and resonance effects and thus to an almost classical behavior. It was already known that decoherence suppresses interferences. What is new, however, is that the strong dissipation does not lead to a complete washout of the angular distributions of the electrons but, on the contrary, produces very structured and almost classical distributions.

Behavior like a classical particle

"We're used to quantum effects predominating at small scales, whereas a classical description is often a good approximation for effects at larger scales," explains von Issendorff. "Here, classical behavior arises even at a small scale through dissipation. The complicated interplay between a multitude of electrons results in one of these electrons behaving like a classical particle."

BIRMINGHAM, Ala. - Clinical evaluation of three COVID-19 vaccine candidates in 2020-21 during a worldwide pandemic that killed or sickened millions was unprecedented in terms of urgency and scope. Responsibility for the safety, integrity and scientific validity of the trials in the United States fell to 12 experts of the federally appointed COVID-19 Vaccine Data and Safety Monitoring Board, or COVID-19 DSMB, who in turn report to an oversight group.

This COVID-19 DSMB team -- which included co-contributing author Richard Whitley, M.D., distinguished professor of pediatrics in the University of Alabama at Birmingham School of Medicine -- has now taken the unusual step of publishing details of their review process in The Journal of Infectious Diseases.

Their goal, they say, is to assure the public of the board's independence and lack of interference from external actors, while they operated under exceptional conditions. Challenges the board faced included:

The remarkable scale and pace of the trials.

The frequency of safety events among a combined enrollment of more than 100,000 people, many of whom were older adults or persons with comorbidities that put them at independent risk of serious health events.

The need to monitor a portfolio of related trials rather than a single trial, and the need to harmonize these studies.

The politicized setting in which the trials have taken place, including a United States presidential election.

Despite these challenges, they say that the COVID-19 Vaccine DSMB also "can serve as a model for future situations in which there is an urgent need for coordinated development of multiple therapeutic or preventive interventions to address rapidly evolving public health threats."

The story began in May 2020, as the federal government launched Operation Warp Speed to accelerate COVID-19 vaccine development. The operation included funding for multiple large randomized trials to assess the safety and efficacy of candidate vaccines and agreements to purchase hundreds of millions of doses to assure timely manufacture of ample quantities of vaccine.

To ensure rigorous, independent and unbiased scientific and ethical oversight of the vaccine field trials, the National Institute of Allergy and Infectious Diseases, or NIAID, empaneled the COVID-19 Vaccine DSMB. The board has 11 members from the United States, Brazil, South Africa and the United Kingdom, including experts in infectious disease, vaccinology, immunology, biostatistics, pharmacoepidemiology, public health and bioethics, as well as a biostatistician, who is a full-time NIAID employee and serves as executive secretary.

The DSMB's Journal of Infectious Diseases article details their study review process as they reviewed three formal interim efficacy analyses of trials for vaccine makers Moderna, Janssen and AstraZeneca. The board currently is monitoring the Moderna, Janssen, AstraZeneca and Novavax trials. The trial of the Pfizer/BioNTech vaccine, which was not federally funded, has a separate DSMB.

The DSMB reports that it has met by videoconference more than 25 times, generally for two to three hours at a time. As needed, the board holds ad hoc meetings to address emerging safety concerns. If accrual or event milestones were met between scheduled meetings, the board met to review interim analyses.

The board focused on trial conduct, safety and vaccine efficacy. This included a close look at accrual of trial participants, including the numbers and proportions of people in relevant subgroups like age, sex, race, ethnicity and people with risk factors that predispose them to severe COVID-19.

"The DSMB's role in overseeing a portfolio of multiple trials," the board writes, "has facilitated its ability to perform safety monitoring across all trials. For example, when concerns first surfaced about thromboembolic events associated with AstraZeneca's vaccine in Europe, the DSMB was able to review relevant categories of adverse events across its portfolio of trials to look for broader patterns associated with SARS-CoV-2 vaccines as a class."

Participant safety was a central responsibility for the board, which devoted much attention at each meeting to review interim safety metrics. Given the large number of participants in the trials, the board also received regular reports of individual adverse safety events between meetings and determined what further information or actions in response might be needed.

Among the political challenges the board faced was what Science magazine called its "extraordinary rebuke" last March, when the board said the company had used potentially misleading and outdated data in its initial analysis.

The highly politicized atmosphere also included an August 2020 tweet by then-President Donald Trump that the United States Food and Drug Administration "deep state" was delaying COVID-19 vaccines, and his September suggestion that a vaccine for COVID-19 could be ready by Election Day. Another political challenge came when then-FDA Director Stephen Hahn said he was prepared to authorize a vaccine before Phase 3 trials were complete.

Yet politics did not affect the board's work. In its report, the COVID-19 Vaccine DSMB concluded that "Operation Warp Speed is an unprecedented effort to develop safe and effective vaccines that will help end the COVID-19 pandemic.

"Conducting clinical trials under these circumstances requires the utmost attention to participant safety and to data integrity, so that the public and the medical community will ultimately have trust in the vaccines and the process used to develop them. Although (the board) operates behind the scenes, by virtue of its access to unblinded interim data, its charge to recommend changes to ongoing studies based on these data, and its ability to examine emerging data across multiple parallel trials, the COVID-19 Vaccine DSMB is uniquely positioned to ensure that these goals are met."

Reston, VA (Embargoed until 6:15 p.m. EDT, Tuesday, June 15, 2021)--A new positron emission tomography (PET) radiotracer can detect abdominal aortic aneurysms (AAAs) and potentially predict when they will rupture, according to research presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting. Targeting a novel biomarker associated with AAA, the radiotracer is effective both in diagnosis and in providing information to assist in the development of AAA treatments, of which there currently are none.

AAA is a life-threatening degenerative vascular disease. It occurs when blood vessels weaken and a bulge forms in the abdominal aorta (the vessel that supplies blood flow to the abdominal organs and the legs). AAAs typically remain asymptomatic until they rupture, leading to high mortality and a substantial burden on the health care system.

"Right now, clinical diagnosis of AAA relies on anatomic measurements of AAA diameter, which is a poor marker for the prediction of rupture," noted Gyu Seong Heo, PhD, a post-doctoral researcher at Washington University School of Medicine in St. Louis, Missouri. "Thus, there is an unmet clinical need for a novel molecular biomarker to determine the underlying processes that lead to aneurysm expansion and rupture and to serve as a therapeutic target for better management of AAA patients."

To explore this clinical need, researchers identified chemokine receptor type 2 (CCR2) as a potential, novel biomarker for AAA evaluation. They developed the novel PET tracer, 64Cu-DOTA-ECL1i, and it has been used to perform first-in-AAA patient imaging. 64Cu-DOTA-ECL1i PET was confirmed to be safe and effective for imaging CCR2 in AAA patients.

64Cu-DOTA-ECL1i was also utilized to assess CCR2-targeted treatment in preclinical animal AAA rupture models. In the models, 64Cu-DOTA-ECL1i imaging was highly suggestive of subsequent AAA rupture. Additionally, in a designated cohort of animals that received a CCR2 inhibitor as a form of therapy, researchers were able to demonstrate the effective prevention of AAA rupture.

"Given the availability of CCR2 inhibitors for human uses, our work holds great potential to assess AAA vulnerability, screen AAA patients for CCR2-targeted treatment, and determine treatment response for optimal outcome," said Heo.