Body

First observed among British Expeditionary Forces in 1915, trench fever sickened an estimated 500,000 soldiers during World War I. Since then, the disease has become synonymous with the battlefield. But now, new research from an international team of scientists has uncovered evidence challenging this long-held belief.

The research, published this week in "PLOS ONE", outlines the discovery of DNA evidence of the disease in civilian remains predating WWI by thousands of years. In total, the team analyzed bone fragments and teeth of 145 individuals alive between the 1st and 19th centuries. Approximately 20% of those remains contained traces of Bartonella quintana, the bacteria responsible for trench fever.

Davide Tanasi, an associate professor with USF's History Department and member of the Institute for the Advanced Study of Culture and the Environment, excavated remains for this project from a Roman cemetery in Syracuse, Sicily. Tanasi, who is also the director of USF's Institute for Digital Exploration, first began work at the site to better understand the dietary habits and health of the Christian population living there during the 3rd and 4th centuries. Through a collaboration with French epidemiologists, researchers used real-time polymerase chain reaction testing to detect B. quintana DNA within the remains.

"Once contracted, there are diseases, like trench fever, that can leave traces within your DNA and can integrate your DNA with further information," Tanasi said. "This means that once a person dies, even as far back as 2,000 years ago, it is still possible to find traces of the bacterium that infected them."

Tanasi says the discovery sheds light on the complex history of trench fever and begins answering historical questions about the lives of Christian citizens in this region during the 3rd and 4th centuries.

"Archaeology isn't just the study of the past, but it's something that can make the present better through the study of the past," he said. "The more we understand about the behavior of these bacteria in the past, the more we can design plans to address them, contain them and eliminate them in the present."

While most associate this disease with WWI and WWII, occurrences of trench fever are still reported today, most prominently within homeless populations. The bacteria are spread to humans through contact with body lice (Pediculus humanus corporis), making poor personal hygiene a primary factor in its spread and infection rate. Researchers hope that by tracing the progression of B. quintana through history, they're able to identify ways to better manage the spread of the disease today.

For Tanasi, his work with the remains excavated in Sicily continues. Through stable-isotope analysis, his research group examines the diet and lives of those who once lived in the region. He hopes this work will further answer questions about the lifestyle and health of the Christian community of Roman Syracuse.

OAK BROOK, Ill. - A powerful type of artificial intelligence known as deep learning can help physicians detect potentially life-threatening cerebral aneurysms on CT angiography, according to a study published in the journal Radiology.

Cerebral aneurysms are weakened areas of blood vessels in the brain. Left untreated, they can leak or rupture, with sometimes fatal results. Detection and characterization of these aneurysms are critical, as the risk of rupture depends on the size, shape and location of the aneurysm.

CT angiography is usually the first choice for evaluating cerebral aneurysms. The exam is highly accurate, but cerebral aneurysms can be overlooked on the initial assessment due to their small size and the complexity of the blood vessels in the brain.

"In our daily work we are always faced with cases in which some important lesions have been missed by the human eye," said study senior author Xi Long, Ph.D., from the Department of Radiology at Tongji Medical College's Union Hospital in Wuhan, China. "Cerebral aneurysms are among those small lesions that may be overlooked on the routine assessment of radiological images."

Deep learning offers tremendous potential as a supplementary tool for a more accurate interpretation of cerebral aneurysms. A deep learning system is trained on existing images and learns to recognize abnormalities that can be difficult for a human observer to see. In radiology, deep learning has been recently been used as in a variety of roles assisting radiologists, such as in the detection of tuberculosis on chest X-rays.

In the new study, Dr. Long and colleagues developed a fully automated, highly sensitive algorithm for the detection of cerebral aneurysms on CT angiography images. They used CT angiograms from more than 500 patients to train the deep learning system, and then they tested it on another 534 CT angiograms that included 649 aneurysms.

The algorithm detected 633 of the 649 cerebral aneurysms for a sensitivity of 97.5%. It also found eight new aneurysms that were overlooked on the initial assessment.

Statistical analysis revealed that deep learning assistance enhanced radiologists' performance. The improvement was most pronounced in the less experienced radiologists.

"The developed deep-learning system has shown excellent performance in detecting aneurysms," Dr. Long said. "We found some aneurysms that were overlooked by the human readers on the initial reports, but they were successfully depicted by the deep-learning system."

The results suggest that the deep learning algorithm has promise as a supportive tool for detecting cerebral aneurysms with a potential to be used clinically for a second opinion during interpretation of head CT angiography images. It has a number of advantages in this setting, Dr. Long said, primarily due to the fact that the computer is not influenced by factors like the level of experience, working time and mood that affect human performance.

The system has some limitations, Dr. Long noted. It can miss very small aneurysms or aneurysms located close to similar density structures like bones. It also suffers from false positive results, meaning that it mistakenly identifies structures similar to aneurysms as aneurysms, which necessitates careful revision of the system suggestions by human readers.

"Simply put, the deep-learning system is intended to assist human readers, not to replace them," Dr. Long said.

The system needs further validation on more heterogeneous data, such as images from people in different parts of the world, which is essential for assessing its generalizability and applicability to daily clinical work.

"At this time, the role of this deep-learning system, which has been trained to recognize aneurysms, is to give suggestions to the human reader to improve their performance and reduce mistakes," Dr. Long said. "The combined work of the human reader and computer system improves the diagnostic accuracy for the patient's sake."

Some of the principal treatments for osteoporosis, denosumab, zoledronate and calcium, could have a protective effect against COVID-19 in patients who take them, specifically a 30 to 40% reduction in the rate of infection, according to the results of a joint study by Hospital del Mar, the Hospital del Mar Medical Research Institute (IMIM), Pompeu Fabra University and the Pere Virgili Health Park. The study, the first of its kind in the world, has just been published the journal Aging.

The last author of the study, Dr. Jordi Monfort, head of Rheumatology at Hospital del Mar and coordinator of the Cell Research on Inflammation and Cartilage research group at Hospital del Mar-IMIM, explains that "there are indications to allow hypothesizing that certain drugs used to treat rheumatic diseases could interfere positively in the natural history of COVID-19, either by decreasing its incidence or by decreasing its progression to more serious cases". The study analysed data from more than 2,000 patients with osteoporosis, osteoarthritis and fibromyalgia and their relationship with COVID-19 infection who are being followed up at Hospital del Mar and in the Mar Health Park healthcare sphere of influence.

The starting point was the perception by the specialists at Hospital del Mar of the low incidence of the pandemic in some of their patients. To analyse this, they worked jointly with the UPF Neuropharmacology Laboratory research group, the Hospital del Mar-IMIM Integrative Pharmacology and Systems Neuroscience research group, and physicians at the Vila Olímpica primary healthcare centre (CAP). They studied the different treatments and the evolution of rheumatology patients with non-inflammatory diseases and their relation to infection by SARS-CoV-2, their evolution, need for hospitalization and mortality.

Different activation mechanisms

In the case of some of the main treatments for osteoporosis, denosumab, zoledronate and calcium, data suggest a likely major reduction in the incidence of COVID-19 in patients who take them; specifically, between 30 and 40%, according to Dr. Josep Blanch-Rubio, head of Rheumatology, first author of the study and a researcher with the Cell Research on Inflammation and Cartilage research group at Hospital del Mar-IMIM. "The study suggests that some of these treatments may protect patients against infection by COVID-19, although further studies still need to be conducted on more patients to prove it", he states.

In the case of denosumab, it targets the RANK/RANKL system involved in the balance of the skeletal system, but also the response by the immune system through the activation and differentiation of some of its cells. Its inhibition modifies the inflammatory response and acts on cytokines, which play a key role in infection by COVID-19. Zoledronate can also modulate the immune response and can stimulate its activity against SARS-CoV-2.

The results also indicate that another common treatment for these patients, the antidepressant duloxetine, may also have a positive effect in reducing the incidence of COVID-19. Conversely, a commonly used painkiller, pregabalin, seems to have a tendency to increase the incidence of the disease. In view of these findings, Dr. Rafael Maldonado, study reference author and coordinator of the UPF Neuropharmacology Laboratory research group, suggests that "these antiosteoporotic drugs are safe and should continue to be administered to patients who take them. The promising results obtained with duloxetine are significant", while at the same time, "we conduct further studies to verify its possible beneficial effects on COVID-19" .

In the same vein, Dr. Alba Gurt, a physician at the Vila Olímpica CAP of the Pere Virgili Health Park and co-author of the work, points out that "the data from the study would indicate that the antiosteoporotic treatments and duloxetine administered to our primary care patients are safe against infection by COVID-19 and could even reduce its incidence. However, studies with a higher number of patients are required to verify this" .

The COVID-19 outbreak has significantly impacted the delivery of behavioral health services, which had to modify rapidly from in-person to remote, according to a Rutgers study published in the Community Mental Health Journal.

The researchers surveyed 238 behavioral health care providers throughout New York -- one of the early epicenters of the pandemic in the United States -- on the challenges they faced regarding staff providing services remotely, maintaining safety practices in person and the ability for clients to use technology to receive services, which are often more effectively provided in-person.

"Understanding this impact is particularly important as these services support vulnerable populations that may be at higher risk for coronavirus infection as well as other negative consequences," says lead author Kenneth Gill, chair of the Department of Psychiatric Rehabilitation and Counseling Professions at Rutgers School of Health Professions. He discusses their findings:

What are the challenges to patient care?

The most significant change was the move away from in-person, face-to-face contacts and the increased reliance on telehealth. The lack of in-person meetings made intakes, comprehensive assessments and engagement with clients more difficult. Some clients did not want to engage with staff by phone or video. Additionally, some clients refused remote services and others failed to answer the phone for scheduled appointments. Lack of in-person services also presented challenges around medication monitoring and administering injectable medications.

The reliance on telehealth has highlighted the digital divide that exists for people with lower socioeconomic resources, those with disabilities and those who live in rural areas. A big issue was client access to technology and reliable internet services. Many also had limited cell phone plans, which made even phone appointments difficult.

A recent Pew Research report showed that people with disabilities, including psychiatric disabilities, are three times more likely to report never going online and about 20 percent are less likely to own electronic devices such as tablets, smart phones and computers or have home broadband services. The pandemic has highlighted the need for increasing access to technology for people who are unable to take full advantage of remote and telehealth services.

However, if the digital divide can be bridged, telehealth services may be able to provide opportunities to promote wellness and recovery more broadly. Potentially, telehealth is an effective way to reach people who have limited accessibility due to geographic location, health concerns, transportation and time constraints.

How did the transition to telehealth affect the delivery of services?

The transition to telehealth brought many financial challenges, including revenue loss due to a reduction in services, increases in staff overtime pay, increased expense of purchasing personal protective equipment, an inability to forecast the upcoming budget year and uncertainty regarding billing insurance for remote services. Operations were also impacted by staff shortages due to layoffs, sick leave or personal reasons, changing regulations and remote working.

Staff had to learn telehealth technology quickly and expressed frustration with having technology issues and lack of access to HIPAA-compliant platforms. They also noted that "something was lost" by not being able to share the same physical space with a client, which negatively impacted engagement and the therapeutic process.

The limited availability of technology and the lack of staff skill in using that technology to deliver services are areas begging for research and development.

What were behavioral health care staffs' main concerns regarding clients?

Staff were concerned about clients meeting basic needs, such as nutritious food and stable housing. These challenges can lead to an increase in psychiatric issues such as depression and anxiety and substance use, including overdose deaths. Understandably, some clients, fearful of contracting the virus, refused to use services that remained open. Staying at home raised additional concerns regarding increased social isolation and losing connection with family, friends and regular routines.

What were the safety concerns for staff?

Staff concerns about contracting the virus was a significant concern. Many respondents reported shortages of PPEs, cleaning and sanitizing products and a difficulty developing, implementing and reinforcing safety protocols to reduce the risk of virus transmission, especially in residential and inpatient treatment settings. There was also limited access to testing for staff and clients.

Residential providers and inpatient facilities found difficulties in offering safe quarantine to clients who tested positive while maintaining the health of other clients and staff. In these facilities -- as well as in other programs that had to maintain some in-person activities -- safety concerns were prominent. Efforts were made to reduce risk, but fears remained. Education and skills instruction to clients regarding proper hygiene, social distancing and face coverings remain essential.

The death of both clients and staff contributed to these fears and added grief and loss to the challenges experienced.

What other stressors did staff experience?

There was a significant emotional toll on behavioral health staff due to the increased work demands, required adaptations and anxiety and stress related to the pandemic. According to our survey, the lack of in-person interaction with colleagues and the support provided by co-workers can further exacerbate this distress. As the pandemic evolves, it is important to develop alternative strategies to support staff, such as increased clinical supervision, group peer supervision, staff wellness initiatives and technology training and support.

New Rochelle, NY, November 3, 2020--Military and law enforcement personnel with extensive occupational blast exposure had statistically significant differences in brain imaging measures compared to nonexposed control personnel. A new study identified significant differences in brain structure, function, and blood biomarkers among those with occupational blast exposure, according to the peer-reviewed Journal of Neurotrauma. Click here (http://doi.org/10.1089/neu.2020.7141) to read the article now.

"This is an important communication," says Dr. John Povlishock, Editor-in-Chief of Journal of Neurotrauma. "It is of obvious significance to our military as it has occupational health implications related to low level blast exposure in our service members over their careers. This report is the first to deeply phenotype breachers, who regularly use explosives to gain entry into buildings and are exposed to blasts over their careers. It provides unique insight into the functional and structural neuroimaging alterations occurring in this population. This paper provides impressive insight into this problem and provides important baseline information on which future studies can be based."

"Career breachers reported an average of 4,628 (100-34,800) breaching blast exposures over their careers, whereas controls reported an average of three (0-35) exposures," state James Stone, MD, PhD, University of Virginia, and coauthors.

Differences in imaging measures included increased cortical thickness, increased radial diffusion, and increased neural inflammation/neural injury.

A new study has demonstrated that using the 'wisdom of crowds' (also known as collective intelligence) of three or more medical prescribers, can improve decisions about antibiotic prescribing and help combat rising levels of antibiotic resistance.

Published in Scientific Reports, an international group of researchers led by Dr Eva Krockow at the University of Leicester tested a novel approach to antibiotic stewardship using the concept of the 'wisdom of crowds', which argues that a group's collective judgement often outperforms the average individual.

The team investigated whether pooling treatment durations recommended by different prescribers can improve decisions about antibiotic prescribing. Using international survey data from 787 expert antibiotic prescribers, the team ran computer simulations to test the performance of the wisdom of crowds by comparing three data aggregation rules across different clinical cases and group sizes, and identified patterns of prescribing bias in recommendations about antibiotic treatment durations to quantify current levels of overprescribing.

Their results suggest that pooling the treatment recommendations (using the median) could improve guideline compliance in groups of three or more prescribers.

Dr Eva Krockow, Lecturer and Lead of the Health and Wellbeing Research Strand at the Department of Neuroscience, Psychology and Behaviour, University of Leicester, said:

"Antimicrobial overuse is widespread and presents a major public health threat. It promotes the emergence of drug-resistant infections, which--without action--are predicted to incur annual costs of more than 10 million lives by 2050, more than all cancer deaths combined.

"Collecting and aggregating independent judgements of medical prescribers in line with the concept of the wisdom of crowds appears to be a promising decision technique to improve guideline compliance in the context of antibiotic decision making and reduce antibiotic overuse."

Current evidence suggests that around 30-40% of antibiotic prescriptions for hospital patients and up to 60% of antibiotic prescriptions in primary care are inappropriate, although it has to be acknowledged that inappropriate prescribing is often context-dependent and measuring it thus presents a challenge.

To improve antibiotic use and preserve drug effectiveness for future generations, a crucial step is therefore to support doctors in their decision making and encourage guideline adherence to curb inappropriate prescribing.

This simulation study provided evidence for the respective benefits of different group aggregation techniques to reduce inappropriate choices about antibiotic prescribing durations. Overall, using the median group judgement appeared to yield the largest benefits.

While decision accuracy increased with group size, improvements were found for groups as small as three prescribers. Follow-up research is necessary to explore the potential of collective decision making across a larger variety of prescriber samples and decision contexts.

Hospital ward rounds and larger, multidisciplinary team meetings, where complex patient cases are discussed and existing guidelines provide limited guidance, were considered most likely to benefit from such an approach.

Boston, MA -- One of the pressing questions about COVID-19 remains: How long does immunity last? One key indicator of immunity is the presence of virus-specific antibodies. Previous studies have provided conflicting accounts about whether people who have recovered from infection can sustain potentially-protective antibodies or not. A new study led by investigators from Brigham and Women's Hospital examined blood samples and cells from patients who had recovered from mild to moderate COVID-19 and found that while antibodies against the virus declined in most individuals after disease resolution, a subset of patients sustained anti-virus antibody production several months following infection. These antibody "sustainers" had a shorter course of symptoms, suggesting that some individuals who recover from COVID-19 faster may be mounting a more effective and durable immune response to the virus. Results are published in Cell.

"We've found a subset of individuals that heal quickly while sustaining virus-specific antibody levels after COVID-19," said Duane Wesemann, MD, PhD, an immunologist and associate physician in the Brigham Division of Allergy and Clinical Immunology and an associate professor at Harvard Medical School. "The kind of immune response we're seeing in these individuals is a bit like investing in an insurance policy -- it's the immune system's way of adding a potential layer of protection against future encounters with the virus."

The Wesemann lab studies the entire set of antibodies a host's immune system produces and how they learn to recognize pathogens. In the spring of 2020, the team turned its attention to the COVID-19 pandemic and the immune response of people who become infected. They are eager to understand the nature of the antibody response to the virus. To this end, the team recruited and enrolled 92 people in the Boston area who had recovered from COVID-19 between March and June of 2020. Five of the individuals were hospitalized but all others recovered at home. The team collected and analyzed blood samples monthly, measuring a range of antibodies, including immunoglobulin-G (IgG), against the virus that causes COVID-19. They split the cohort into two groups -- those that sustain virus-specific IgG levels over several weeks, and those that lose them. The team analyzed these groups and potential connections they had to clinical and other immunological data.

The team found that IgG levels against the virus tended to decline substantially in most individuals over the course of three to four months. However, in about 20 percent of individuals, antibody production remained stable or enhanced over the same time period. The team found that these "sustainers" had symptoms for a significantly shorter period of time compared to "decayers" (average of 10 days versus 16 days). Sustainers also had differences in memory T cell populations and B cells, two types of immune cells that can play a key role in immune memory and protection.

An important limitation of the study, the team noted, was that most of the volunteers were adult white women. The researchers said that future research must aim to enroll a more diverse population to further elucidate whether variations in immune response exist across people of different ages and ethnic and racial backgrounds. The researchers also point out that further research may help determine whether similar dynamics of immune response are also seen in people with asymptomatic and severe disease.

"The data point to a type of immune response that's not only adept at handling viral disease by leading to a swift resolution of symptoms, but also better at producing cells that can commit to longer term production of anti-virus IgG antibodies," said Wesemann. "Figuring out how these individuals are able to support longer-term antibody production is relevant to COVID-19, and will also have important implications for our understanding of the immune system in general."

Previous studies have shown that African American men are 2.4 times as likely to die from prostate cancer compared to non-Hispanic white men. This, plus a concern that African Americans may develop cancers that are more aggressive, has led to fewer Black men being offered active surveillance as a treatment strategy.

Prostate cancer is typically slow growing. Low-risk disease may not need to be treated right away, if ever. Instead, a physician may recommend active surveillance -- closely monitoring the disease for progression with prostate-specific antigen (PSA) blood tests, digital rectal prostate exams and biopsies -- to avoid overtreatment and associated side effects caused by surgery, chemotherapy and other treatments.

"Our research provides evidence that active surveillance is safe for African American men," said Brent Rose, MD, assistant professor in the Department of Radiation Medicine and Applied Sciences at University of California San Diego School of Medicine. "This means more African American men can avoid definitive treatment and the associated side effects of urinary incontinence, erectile dysfunction and bowel problems."

In a study, published in the November 3, 2020 online issue of JAMA, Rose and colleagues tested the hypothesis that African American men undergoing active surveillance are at a significantly higher risk of disease progression, metastases (spread) and death from prostate cancer compared to non-Hispanic White men.

They found that 59.9 percent of African American men experienced disease progression compared to 48.3 percent of white men. In addition, 54.8 of African Americans required treatment compared to 41.4 percent of white men. Both are statistically significant increases, said study authors.

However, African American men and white men experience comparable rates of metastasis (1.5 percent vs 1.4 percent) and prostate cancer-specific death (1.1 percent vs 1.0 percent).

After skin cancer, prostate cancer is the most common cancer among males. One in nine men will receive a prostate cancer diagnosis in their lifetime. Prostate cancer is more likely to develop in older men and in African American men. While the average age for diagnosis is 66, the number of younger men diagnosed with this disease is increasing.

Active surveillance is the preferred treatment option for many men with low-risk prostate cancer in order to avoid or delay the side effects of definitive treatments. African American men should not be excluded from active surveillance protocols.

Instead, write the authors, changes and improvement in patient selection and close follow-up need to occur to maintain favorable outcomes for all patients.

"Physicians and patients should discuss active surveillance for African American men with low-risk prostate cancer," said Rose, a radiation oncologist at Moores Cancer Center at UC San Diego Health and senior author on the paper. "Overall outcomes are similar among African American men and white men. However, due to the increased risk of progression, African American men need to be carefully followed and promptly treated if their cancer progresses."

The retrospective study looked and outcomes for 2,280 African American men and 6,446 non-Hispanic white men with low-risk prostate cancer who underwent active surveillance under the VA health care. The database included access to the health care records of 9 million veterans between 2000 and 2020 who received care at 1,255 health care facilities in the United States.

Oncotarget recently published "Predictive biomarkers for sacituzumab govitecan efficacy in Trop-2-expressing triple-negative breast cancer" which reported that the authors investigated whether Trop-2-expression and homologous recombination repair of SN-38-mediated double-strand DNA breaks play a role in the sensitivity of triple-negative breast cancer to SG.

Further, two Trop-2-transfectants of MDA-MB-231, C13, and C39, were treated in mice with SG to determine whether increasing Trop-2 expression improves SG efficacy.

SG mediated >2-fold increase in Rad51 in MDA-MB-231 but had no effect in SK-MES-1 or HCC1806, resulting in lower levels of dsDNA breaks in MDA-MB-231. SG and saline produced similar effects in parental MDA-MB-231 tumor-bearing mice.

However, in mice bearing higher Trop-2-expressing C13 and C39 tumors after Trop-2 transfection, SG provided a significant survival benefit, even compared to irinotecan.

These results suggest that SG could provide better clinical benefit than irinotecan in patients with HRR-proficient tumors expressing high levels of Trop-2, as well as to patients with HRR-deficient tumors expressing low/moderate levels of Trop-2.

SG could provide better clinical benefit than irinotecan in patients with HRR-proficient tumors expressing high levels of Trop-2, as well as to patients with HRR-deficient tumors expressing low/moderate levels of Trop-2

Dr. Thomas M. Cardillo from Immunomedics, Inc said, "In recent years, there has been an increased focus on personalized cancer therapy."

SG demonstrated significant clinical benefit across a range of solid tumors, including metastatic TNBC, hormone-positive breast cancer, small-cell lung cancer, non-small-cell lung cancer, and metastatic urothelial carcinomas.

It remains unclear from these results whether the overriding mechanism for SG sensitivity in these various tumor models is Trop-2 expression or defective HRR pathways, or their combination.

Herein, the Oncotarget authors examined the HRR response in MDA-MB-231, being unresponsive to SG, including upregulation of Rad51 and levels of dsDNA breaks mediated by SG exposure, and compared it to that of SG-sensitive tumor lines to elucidate the role that this pathway plays in protecting cells from SG-mediated dsDNA breaks.

Additionally, MDA-MB-231 cells transfected to express higher levels of Trop-2 were assessed in vivo for SG antitumor effects in comparison to parental tumors with low Trop-2 expression.

However, this does not rule out SG being active in tumors with low Trop-2 expression and deficiencies in HRR.

The Cardillo Research Team concluded in their >Oncotarget Research Paper that, these data strongly support the hypothesis that as a biomarker, high surface Trop-2 expression on a patient's tumor may be predictive of a positive clinical outcome for SG therapy.

Further, there are secondary biomarkers that may need to be considered for those patients with low/moderate Trop-2 expression or those with high Trop-2 expression that failed previous irinotecan therapy for reasons other than acquired resistance.

Moreover, while high expression of Trop-2 was found to be a primary biomarker for SG efficacy, it should not be a limiting factor, because other secondary biomarkers coupled with Trop-2 expression may likewise be predictive of clinical benefit.

For these reasons, future clinical trials will need to comprehensively examine potential biomarkers, in addition to Trop-2 expression, to generate a profile that will better identify those patients likely to benefit from SG therapy.

A virus can stop bacteria from sharing genes for antibiotic resistance among themselves, Texas A&M AgriLife researchers have discovered. The results hint at new ways to treat infections and describe a new feature of a highly diverse, largely unexplored part of the biosphere.

The study, published recently in Proceedings of the National Academy of Sciences, was led by Lanying Zeng, Ph.D., associate professor in the Texas A&M College of Agriculture and Life Sciences Department of Biochemistry and Biophysics.

How some phages infect bacteria

Viruses that only infect bacteria are called bacteriophages, or phages for short. Phages are the most numerous biological entities on Earth. Soil is rife with phages, as is the human gut, and phages that infect and destroy bacteria have found promising uses in combating antibiotic-resistant bacterial infections.

Some phages only infect bacteria whose surface contains cylindrical structures called pili. Named after the Latin word pilus, for spear, pili allow bacteria to transfer genes for advantageous traits, such as drug resistance, and enhance bacteria's ability to move and to attack host cells. Because of pili's link to bacterial virulence, researchers have wondered whether new medications could be created to inactivate this feature. While the ways bacteria benefit from pili are clear, how phages use pili to infect bacteria has remained elusive.

Phage competition

Zeng's team used fluorescence microscopy to delve into how a phage, MS2, enters an E. coli cell. The researchers created MS2 phages that fluoresce and are fully infectious and stable. The phages attach to pili on E. coli cells, making the pili visible through a fluorescence microscope.

Through a series of experiments, Zeng, her graduate student Laith Harb, and the other coauthors obtained a detailed description of what happens when an MS2 phage infects an E. coli.

The team discovered that after a phage attaches to a pilus, the pilus retracts, bringing the phage to the bacterial cell surface. The pilus then breaks off behind the phage. Whereas healthy E. coli replenish broken pili, cells infected by MS2 do not. In this way, other phages are prevented from infecting the same cell. The first phage to reach the cell gains a competitive advantage.

"It's like, 'OK, this cell is mine.' Phages set up their own territory," said Zeng, who is a core faculty member of the Center for Phage Technology, a part of Texas A&M AgriLife Research.

Because the phenomenon gives such a boost to the infecting phage, this occurrence may be widespread among other phage strains that employ pili to infect bacteria, Zeng added.

New ideas for medicine

The results may be of use in medicine, Zeng said. First, using phages to decrease bacterial virulence may give the immune system time to fight off an infection. Second, the results point to a way of dealing with infections that may be gentler for patients than antibiotics or than using phage therapy to destroy bacteria.

"One advantage of our method versus traditional phage therapy is that you do not kill the cell, you just disarm it," Zeng said. "Killing the cell may cause a problem, because inside the cell you may have a toxin that could be released into the host."

Phages that target pili could also reinforce the action of antibiotics. Some bacterial infections only respond to high doses of antibiotics, which can cause side effects. Adding phages to the mix may allow doctors to decrease the needed antibiotic dosage.

Following a brain-injuring bump or blow to the head, brain cells and blood vessels typically swell. This can lead to a potentially life-threatening increase in pressure inside the skull, and managing swelling is critical for patients with traumatic brain injuries (TBIs). But researchers at University of Utah Health have discovered that swelling may also be important for protecting the brain.

According to animal studies led by Punam Sawant-Pokam, Ph.D., and K.C. Brennan, M.D., of the department of neurology, swollen neurons are less likely to exhibit troublesome patterns of overactivity associated with long-term complications of TBI than neurons that are treated after injury to reduce swelling. The findings reported in The Journal of Clinical Investigation suggest that patients with these injuries may benefit from a more targeted approach to managing cerebral swelling, also known as edema.

"This data prompts a pretty big reconsideration of how we view edema after brain injury," Brennan says. "When edema is about to cause death, it is the number one priority. We're not saying this is not true. But we're opening up more nuance to the phenomenon in a way that might allow us to eventually get to more specific treatments and better outcomes."

The research was carried out in collaboration with Cameron Metcalf, Ph.D., in the College of Pharmacy at U of U Health and Jamie Maguire, Ph.D., at Tufts University School of Medicine.

In 2017, more than one million hospitalizations and emergency department visits were associated with TBIs in the United States. Brennan explains that one of the consequences of these injuries is what he calls toxic brain excitability. Activity in the brain's neural networks can surge in the days following injury, damaging tissue and establishing patterns that leave patients vulnerable to seizures, headaches, and other complications for months or years after their acute symptoms resolve.

Brennan's team investigated what happens to neurons in the week following a TBI, as swelling in the brain builds and eventually subsides. Sawant-Pokam, a research assistant professor, led the experimental work, using sophisticated brain imaging and electrical recording tools that have never been used before to study TBI.

Her experiments showed that 48 hours after injury--the point at which patients usually experience the most swelling--individual neurons in the brains of mice were enlarged and misshapen, confirming that edema directly affects the brain's neural circuits. However, this swelling was accompanied by a surprising reduction in the nerve cells' activity. One week after injury, when swelling had subsided, neurons were more excitable than they had been prior to injury.

Alleviating the swelling immediately following an injury appeared to put the animals at greater risk for harmful brain activity. When the researchers gave injured mice drugs to reduce edema, neurons returned to their normal shape but became more active, signaling excessively. That overactivity was associated with an increase in seizures, as well as massive waves of neural firing known as spreading depolarizations. In patients, both seizures and spreading depolarizations are associated with poor long-term outcomes from brain injury.

Researchers still need to more fully explore the impacts of cerebral edema, which may differ at different time points after an injury. But Sawant-Pokam, Brennan, and colleagues are hopeful that this unexpected protective role presents an opportunity to improve the long-term prognosis for patients with TBIs.

"It's very exciting to know that neuronal edema is not only reducing cellular excitability, it's also protecting the brain from dangerous network events," Sawant-Pokam says. With a deeper understanding of exactly how neurons swell, it may be possible to devise new treatments that relieve intracranial pressure without interfering with this protective mechanism, she says.

Poor awareness of a condition known as Heart Failure with preserved Ejection Fraction (HFpEF) - the cause of a half of all cases of heart failure in England - could be hindering opportunities to improve care for patients, say researchers from the Universities of Cambridge, Manchester, and Keele.

HFpEF - pronounced 'heff peff' - is a condition whereby heart muscles are too stiff, preventing the organ's chambers from filling properly with blood. Symptoms include shortness of breath, swelling in the legs, ankles, feet or in the lower back or abdomen, and extreme tiredness. It affects half of the 920,000 people in the UK with heart failure but frequently goes undiagnosed.

The National Institute of Clinical Excellence (NICE) recommends that 'integrated' care should be provided for HFpEF, bringing together specialist clinicians with GPs and primary care, and including support for patients to help them manage their condition.

In a new study published today in the British Journal of General Practice, the researchers argue that the problems they have identified may help to explain why the condition is difficult to diagnose and why there is a persistent gap between the national guidance on managing the condition and the kind of service patients receive.

The problems were uncovered in a study carried out in the East of England, Greater Manchester and the West Midlands, in which 50 people with HFpEF, nine carers and 73 clinicians, were interviewed. The clinicians included GPs and nurses from 26 GP practices, as well as heart failure specialist nurses and cardiologists from nine hospitals.

The team used a theoretical framework known as Normalisation Process Theory to make sense of the large amount of data generated by the interviews. The theory considers how healthcare interventions are integrated into routine practice, or 'normalised'.

For any intervention to be routinely adopted, there needs to be a clear understanding - and differentiation between - aspects of the illness, tests and treatments, for example. The team found that this understanding is often missing for the clinicians dealing with patients experiencing HFpEF. In addition, some patients described how they were not aware they had the condition despite severe symptoms and, in some cases, multiple hospital admissions, and were unclear on how the condition can be best managed.

The data confirmed that diagnosis and treatment of HFpEF is not part of everyday practice in general practice, and that the condition was not widely visible, understood, or diagnosed within primary care. The researchers identified three clear tensions that contributed to this.

First, diagnosis of HFpEF is difficult and often delayed. A common method for identifying heart disorders is through the use of an echocardiogram, but in patients with HFpEF, the 'ejection fraction' - the percentage of blood leaving the heart each time it contracts - often appears normal or almost normal, confusing diagnosis. Many clinicians indicated a need for specialist opinion but referral systems were varied and inconsistent.

Patients' descriptions of their diagnoses frequently conveyed a convoluted and protracted series of hospital admissions or visits to specialist clinics. Diagnosis was often slowed down by the presence of other co-existing health conditions, non-specific symptoms and breathlessness.

Second, there are varying perceptions of this complex condition and the data show little shared understanding between clinicians, patients and carers. Several clinicians indicated there is professional scepticism with the label of HFpEF, and most expressed a need for more knowledge and understanding of the condition.

Many patients had partial or incomplete knowledge of the condition, which often related to existing heart problems. Few patients provided a clear understanding of their heart failure.

Finally, once patients are diagnosed, the services they can access are variable. Roles and responsibilities are not well understood and there are big gaps in care. A sense of clinical inertia was revealed within some patient and clinician accounts, apparently due to a lack of evidence-based practice and a feeling that there was little that could be done.

"Our research paints a picture of a cloud of clinical uncertainty surrounding the diagnosis and treatment of HFpEF, which often leads to a failure to manage the condition," said lead author Dr Emma Sowden from the University of Manchester. "Patients' descriptions of their diagnoses suggest they are far more convoluted than the clinical guidelines spell out, leading to a protracted series of hospital admissions or specialist visits."

Professor Christi Deaton, Chief Investigator from the Department of Public Health and Primary Care at the University of Cambridge and a Fellow at Wolfson College, added: "We heard some clinicians asking: what's the point of diagnosis if there is no specific treatment? But identification of HFpEF is critical if we are going to develop new treatments and ways for patients to better manage their condition, and there are actions that we can take now."

The study is part of a larger programme of work on HFpEF, which aims to improve the management of people with HFpEF in primary care. The programme is funded by the NIHR School for Primary Care Research.

Living with HFpEF: Mike and Anna

Mike and Anna, who live in Mossley, Greater Manchester, are, in their own words, 'glass-half-full' people. But Mike has heart failure with HFpEF.

Until he retired on health grounds two years ago, aged 66, Mike was a police community support officer, a job that he loved. Anna, his wife of 17 years, is a retired health visitor and nurse midwife - "It's a good thing I have medical knowledge," she said. "I've needed it."

HFpEF comes on slowly, Mike explained. He has had heart problems for 24 years and despite a pacemaker and later a stent, and now a regime of 13 different medications a day, his symptoms don't seem any better. He is tired all the time, breathless and his activity is severely limited.

"From a personal point of view it is so frustrating to go from being someone who swam three times a week and walked eight miles a day to being all washed up," said Mike.

"My GP says it's multifactorial. But no matter what you say to a consultant, [they say] it's because I eat too much. You do get a condescending attitude about food. I get conflicting advice from various professionals about what I should and shouldn't be doing. They say exercise and lose weight, but I set all the alarms off on the monitors when the cardiac physiotherapist was assessing me and she told me to stop right there.

"I do end up asking: why am I taking all these medications and I still feel so bad? I'm treading water just waiting for the next consultation."

Anna is determined to help Mike get access to treatment that might improve his quality of life.

"I'm like a dog with a bone," said Anna. "I said, why is he still breathless if he has the stent and all the medications? I think I was the one who found out about the possibility of HFpEF, and I researched the medical terminology, like diastolic dysfunction and what ejection fraction means.

"HFpEF seems to be classed as a second class citizen of heart failure. The medics don't tell you that you have it and they don't tell you it's serious. It's frustrating for the doctors too, because the test results are not clear and they don't know how to treat it. But we have had to fight for every little bit [of help]."

Pancreatic cancer cells avert starvation by signaling to nerves, which grow into dense tumors and secrete nutrients. This is the finding of a study with experiments in cancer cells, mice, and human tissue samples published online November 2 in Cell.

The study addresses pancreatic ductal adenocarcinoma (PDAC), the deadliest cancer of the pancreas with a five-year survival rate below 10 percent. Such tumors encourage the growth of dense tissue that presses on blood vessels, reducing the supply of blood-borne nutrients like serine. This amino acid is used as a building block for proteins, and is required for cancer cells to multiply.

Led by researchers from NYU Grossman School of Medicine, the Department of Radiation Oncology at NYU Langone Health, and Perlmutter Cancer Center, the new study found that starving pancreatic cancer cells secrete a protein called nerve growth factor, which sends signals to extensions of nerve cells, instructing them to grow deeply into tumors. The researchers found further that such extensions, called axons, secrete serine, which rescues pancreatic cancer cells from starvation and restores their growth.

"Our study offers more proof that pancreatic cancers are remarkable metabolic scavengers, which contributes to their deadliness," says corresponding author Alec Kimmelman, MD, PhD, the Anita Steckler and Joseph Steckler Chair of the Department of Radiation Oncology at NYU Langone. "The ability of nerves to funnel nutrients from the bloodstream to the more austere pancreatic tumor microenvironment is a fascinating adaptation, and could lead to therapeutic approaches that interfere with this unique flexibility."

The study found that pancreatic cancer cells starved of serine take advantage of the process by which messenger RNA (mRNA) strands, copies of DNA instructions, are translated into proteins. Backbones of mRNA molecular strands, called bases, are decoded into amino acids using three-base units called codons. Cellular machines called ribosomes read each codon as they link amino acids together in the right order, but ribosomes stall if there is a lack of available amino acids.

Surprisingly, the research team found that serine-starved pancreatic cancer cells more significantly slow the rate at which two of the six serine codons (TCC and TCT), but not all six as assumed, are translated into amino acid chains. Under serine-starved situations, this variability lets cancer cells minimize the production of certain proteins (to preserve energy stores during starvation), but continue to build stress-adaptive proteins like nerve growth factor (NGF), which happens to be encoded by few TCC and TCT codons.

NGF and other factors are known to encourage nerves to grow into pancreatic tumors, and to increase tumor growth as well. The current study is the first to show that axons, extensions of neuronal cells that transmit their signals, provide metabolic support to cancer cells by secreting serine in nutrient-deprived areas, say the authors.

The new publication is one of many by Perlmutter researchers in recent years that describes the ways in which pancreatic cancer cells find energy. A 2016 study revealed that such cells send signals to nearby stellate cells, causing them to break down their own cell parts into building blocks that can be used by tumors. Then a December 2019 study found that pancreatic cancer cells also hijack a process called macropinocytosis, which normal cells use to pull nutrients in through their outer membranes. Interestingly, the new work found that stellate cells and macropinocytosis cannot supply enough serine for these cancer cells to grow, and that axonal delivery is required.

In a glimpse of potential future applications for the study, mice with PDAC tumors fed serine-free diets saw 50 percent slower tumor growth. To go beyond what diet alone could achieve, the researchers also blocked the recruitment of axons into PDAC tumors using a drug already approved by U.S. Food and Drug Administration called LOXO-101. The drug blocks the activation of a receptor protein on the surface of neurons that interacts with nerve growth factor (also called TRK-A), thereby inhibiting the ability of neurons to send their axons into tumors.

The drug alone did not slow PDAC tumor growth in mice, say the authors, but slowed it by an additional 50 percent when combined with a serine-free diet, compared with the diet alone. This suggests that nerves were necessary to support PDAC cell growth in serine-deprived tumor regions, researchers say.

"As TRK inhibitors are approved in the treatment of some cancers, they might have value in combination with a low serine diet following surgery in the perhaps 40 percent of patients with PDAC tumors that can't make serine," said lead study author Robert Banh, a post-doctoral scholar in Kimmelman's lab. "Whether this approach could decrease tumor recurrence by limiting the nutrient supply would need to be confirmed in clinical trials."

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19. The following articles make up the latest issue of Public Policy & Aging Report, titled "Policy Considerations for a Post-COVID Presidency":

Has It Really Become Us Versus Them? Considering the Use of Age in Public Policy, by Brian Kaskie, PhD

Recovering From Coronavirus Disease 2019 (COVID-19): Resisting Ageism and Recommitting to a Productive Aging Perspective, by Nancy Morrow-Howell, MSW, PhD, and Ernest Gonzales, MSW, PhD

The Fourth Wave of Technology and Aging: Policy Innovation to Ensure Equity and Inclusion, by Joseph .F Coughlin, PhD

Age-Related Vulnerability to Coronavirus Disease 2019 (COVID-19): Biological, Contextual, and Policy-Related Factors, by Eileen M. Crimmins, PhD

How Elections Under COVID-19 May Change the Political Engagement of Older Voters, by Paul Gronke, PhD, Paul Manson, MPA, Jay Lee, BA, and Canyon Foot, BA

Early Evidence on the Impact of Coronavirus Disease 2019 (COVID-19) and the Recession on Older Workers, by Truc Thi Mai Bui, MA, Patrick Button, PhD, and Elyce G. Picciotti, BSFS, MBA

Retirement Security in a Post-Pandemic World, by G. Lawrence Atkins, PhD

Post-Coronavirus Disease 2019 Aging Agenda for 2021 and Beyond, by Gretchen E. Alkema, PhD

What Does a Post-Pandemic Presidency Mean for Medicare?, by Aimee Cicchiello, BA, and Gretchen Jacobson, SM, PhD

Always Essential: Valuing Direct Care Workers in Long-Term Care, by Kezia Scales, PhD, and Michael J. Lepore, PhD

Addressing the Needs of Rural Caregivers of Individuals With Alzheimer's Disease and Related Dementias During and Beyond Coronavirus Disease 2019 (COVID-19), by Heather J. Williamson, DrPH, Michael J. McCarthy, PhD, Yolanda E. Garcia, PhD, Rachel Bacon, PhD, Dorothy J. Dunn, PhD, and Julie A. Baldwin, PhD

Local Efforts to Support People Living With Dementia and Encourage Brain Health Among Older Adults, by Beth Blair, MPP, Meredith Hanley, MSW, Sandy Markwood, MA, Greg Link, MA, Nirav R. Shah, MD, MPH, and Vijeth Iyengar, PhD

WILMINGTON, Del. (November 2, 2020) - Nemours Children's Health System increased patient immunizations by 4.6% from January - September 2020, compared with the same period in 2019, through an innovative hybrid approach to care using both in-person and telemedicine, according to new data presented today at the Children's Hospital Association's 2020 Annual Leadership Conference.

Between March and May, COVID-19 forced the cancellation of 48% of primary care visits and 28.5% of immunizations, but the multi-state health system was able to ensure the health needs of its 180,000 primary care patients by assembling a multidisciplinary team to improvise new methods to assure delivery of this crucial preventive care.

"Children's well-care has an enormous impact on their growth and development, and staying on track with their immunizations keeps us all safe from vaccine-preventable illnesses," said Jonathan Miller, MD, an author of the study and medical director of Nemours' Value-Based Service Organization. "The immunization rates we are seeing are a great sign of the impact we're having, especially considering the overall national declines that have been reported in immunizations among adolescents and children since the pandemic began."

After experiencing the sharp post-COVID decline, Nemours brought together a multi-disciplinary team representing expertise in population health, data analytics, and medical management to develop rapid, innovative changes to the health system's primary care sites in Delaware, Pennsylvania, and Florida. The team used four primary strategies:

1. Cohorting patients and practices to separate sick and well children to limit exposure to illnesses;

2. Harnessing telemedicine to meet immediate needs;

3. Using tents for immunizations and limited physical exams;

4. Calling families' homes to screen for social determinants of health that may be impacting their overall well-being.

As a result of these changes, Nemours increased overall child immunizations by 4.6% over 2019 rates, provided more than 36,000 primary care telemedicine visits, and cared for nearly 10,000 children using "tele-well" visits that used telemedicine and limited in-person care. Of nearly 20,000 physicals cancelled due to the pandemic, 85% have been completed or rescheduled.

"Given all of the hurdles children and families have faced in receiving preventative care this year, we are heartened by the level of care we were able to bring to our communities," said Thomas Lacy, MD, an author of the study and division chief for Nemours Primary Care and Urgent Care in Florida. "COVID-19 presented enormous obstacles that have required ingenuity to continue to meet the needs of children."