Culture

Welcome to shopping during the coronavirus pandemic: customers clad in masks, slathered with sanitizer and surrounded by signage urging them to avoid close contact. Despite guidelines plastered on the walls and floors of grocery and retail stores encouraging customers to maintain six-feet of physical distance, many do not. A new study by researchers at the University of Houston Conrad N. Hilton College of Hotel and Restaurant Management identifies two key messaging components -- negativity and anthropomorphism, or attributing human characteristics to nonhuman objects -- could improve the persuasiveness of those appeals and trigger compliance.

Adjusting the messaging to stress the negative health outcomes associated with not following physical distancing guidelines, including the possibility of severe sickness or death, could more effectively persuade consumers to comply, according to the study co-authored by UH associate professor Priyanko Guchait and published in The Service Industries Journal. The study found that adding intimidating human attributes to the otherwise invisible coronavirus, such as a scary red face with long sharp teeth and tentacles, significantly strengthens that message.

"We don't know how the coronavirus looks because we can't see it, so how can people be afraid of it? Giving it human characteristics and making it look scary strengthens the effect when combined with the negative messaging," said Guchait.

The researchers applied the regulatory focus theory, a persuasion theory in the field of psychology which focuses on framing the information either negatively or positively. Based on a hypothetical supermarket scenario, survey respondents were presented with different physical distancing messages that either used preventive or promotive language - some included a "Mr. Deadly COVID-19" scary face.

The preventive messaging emphasized potential costs and negative outcomes: If you don't maintain physical distance, you could get infected and endanger your life. In contrast, promotive messaging highlighted potential benefits and positive outcomes: Maintaining physical distance protects you from infection and secures your life.

"Preventive language was significantly more effective in this study because people are persuaded by loss language, especially in high-risk, health-related situations. It's the same thing with traffic accidents where people follow the rules because they know they could die. They experience fear and that's why they follow traffic rules," said Guchait, who collaborated on the research with visiting scholar The Khoa Do and Chen-Ya Wang from National Tsing Hua University in Taiwan.

Despite a consistent rise in coronavirus cases and deaths, many customers underestimate the importance of complying with physical distancing. A survey of grocery and food workers conducted by the United Food and Commercial Workers International Union at the beginning of the pandemic last spring, found that up to 85% of customers at grocery and retail stores did not practice physical distancing. Other surveys have revealed that people consistently underrate the risk of getting infected themselves or transmitting the virus to others.

The researchers hope the service industry will adapt and change how they frame and present physical distancing appeals, particularly small retail and grocery businesses which lack the resources to fully implement expensive health and safety interventions.

"This is more about playing with the human mind, which we know is more impactful than actual devices such as partitions or physical barriers," said Guchait. "We encourage stores to add the picture of a scary coronavirus along with preventive messaging because it could save them money but, more importantly, it could save lives."

Cucurbit downy mildew is a devastating disease affecting economically important crops such as cucumber, cantaloupe, squash, pumpkins, and watermelon. Previously effective fungicide have been failing in the United States and Europe, making accurate and early diagnosis critical for timely disease management.

As the disease is rapid, infectious, and hard-to-diagnose, a team of plant pathologists with North Carolina State University and Michigan State University put together a clear and summarized guide to cucurbit downy mildew for beginners and experts. Accorded to Andres Salcedo, "We realized the necessity to compile relevant and concise information about the causal agent of cucurbit downy mildew and developed a guide of multiple alternatives for its diagnosis and handling."

As cucurbit downy mildew is caused by Pseudoperonospora cubensis, an obligate pathogen that cannot be cultured using standard microbiological methods, this guide provides well-documented written and graphic material to help with diagnosis based on symptoms and the presence of the pathogen in the plant. The guide also covers diagnosis methods based on DNA testing and microscopy as well as methodologies for isolation, damage evaluation, multiplication, and storage under laboratory conditions.

The ability to quickly identify cucurbit downy mildew is crucial for cost-effective chemical or cultural control strategies. To help those who are trying to assess the efficacy of new disease management products, this guide also provides protocols for pathogen handling and evaluation. Parts of the guide are also being used to develop extension training videos to further inform a broader audience about cucurbit downy mildew.

To see the guide for yourself, read "Diagnostic Guide for Cucurbit Downy Mildew" published in Plant Health Progress.

JACKSONVILLE, Fla. -- Mayo Clinic researchers, along with national and global collaborators, have developed a potential test for Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3) ? a disease that has no cure. They also have clarified the role of a gene target associated with the disease.

The inherited disease is linked to a mutation in the ATXN3 gene. This mutation, which affects the central nervous system, appears between the ages of 40 and 70, and is characterized by an unsteady gait, loss of muscle control, and decline of motor and sensory nerves. Symptoms may resemble those of Parkinson's disease or multiple sclerosis. The researchers present their findings in Science Translational Medicine.

In the retrospective study, the researchers set out to find a molecular target to help assess potential treatments for SCA3 and the group of neurodegenerative diseases in which it's categorized. Guiding the researchers in this effort was previous work at Mayo Clinic on Lou Gehrig's disease ? also known as amyotrophic lateral sclerosis ? as well as frontotemporal dementia with mutations in the C9orf72 gene.

SCA3 is defined by the characteristic accumulation of a mutant protein: polyQ ataxin-3. Researchers think this protein bunches up inside the cell and causes toxicity by interfering with cell actions in a number of ways. While there is no treatment for SCA3, the goal is to reduce protein accumulation.

"We were able to develop an immunoassay, or test, that can quantify the amount of mutant protein in human biofluids, such as cerebrospinal fluid and blood of patients with SCA3," says Mercedes Prudencio, Ph.D., first author of the study. "We can use the test to determine the effectiveness of new therapies aimed at decreasing the amount of mutant protein." Dr. Prudencio is an assistant professor of neuroscience, Mayo Clinic College of Medicine and Science.

"There is an unmet patient need for biomarkers for SCA3 that can tell us whether therapies targeting polyQ ATXN3 proteins are working," says Leonard Petrucelli, Ph.D., one of the senior authors on the paper. "If therapies can be more targeted toward decreasing the mutant protein, rather than the normal protein, this would have great implications for the field." Dr. Petrucelli is the Ralph B. and Ruth K. Abrams Professor of Neuroscience.

The researchers also clarified that a genetic alteration, called a single nucleotide polymorphism, previously identified and linked to SCA3, was strongly associated with the mutant ATXN3 gene among the study samples.

"While the mutant protein levels may serve as a marker to evaluate whether certain SCA3 therapies are working, the genetic alteration that is strongly associated with that mutant protein offers a new opportunity to develop therapies that specifically target it," says Dr. Prudencio. The results of the study pave the way for accelerated clinical trials involving SCA3 therapies.

Historically, SCA3 was more common in people from the Azores and Portugal. However, cases of the disorder have been found in people across Europe, Asia and the Americas. The study cohort included patient samples from around the globe, including Japan, Mexico, the Netherlands, Norway, Portugal, Sweden, and the U.S. The findings were validated through a collection of SCA3 samples from European countries over the course of many years by Ataxia Centre, which is affiliated with University College London.

"This was truly an international effort in team science," says Zbigniew Wszolek, M.D., a senior author on the paper. "SCA3 is a rare and complex disorder, and the collaboration on this work goes a long way in ultimately being able to help patients and their families who are suffering." Dr. Wszolek is a professor of neurology, Mayo Clinic College of Medicine and Science, and the Haworth Family Professor in Neurodegenerative Diseases.

Mayo Clinic researchers plan to follow patients with SCA3 through the Mayo Clinic Ataxia Program as a next step in furthering studies around this neurodegenerative disorder.

This research was funded by the National Institutes of Health; National Institute of Neurological Disorders and Stroke; Mayo Clinic; and the Donald G. and Jodi P. Heeringa family. University College London Queen Square Institute of Neurology was part of the research collaboration, with Professor Paola Giunti, M.D., a corresponding senior author on this paper. See the published paper for a full list of authors, funding sources and competing interests.

Approximately 30% of breast cancer patients who receive chemotherapy treatment gain weight, though it is unclear why this phenomenon occurs in some women but not in others. Beyond weight gain, chemotherapy is also known to increase the risk of high blood pressure and glucose intolerance, a prediabetes condition. Although this is a familiar phenomenon, the mechanisms underlying these processes have not yet been identified. A new study, just published in the journal BMC Medicine, suggests that gut bacteria are partially responsible for metabolic changes that lead to weight gain following chemotherapy treatment.

The research was initiated by Dr. Ayelet Shai, Director of Oncology at the Galilee Medical Center, who led the study with Prof. Omry Koren, an expert in gastrointestinal bacteria at the Azrieli Faculty of Medicine of Bar-Ilan University.

Dr. Shai says that symptoms she has witnessed as an oncologist led her to initiate the study: "In my clinical work with women recovering from breast and gynecological tumors, I have seen many of them gain weight following treatment and experience difficulty returning to their original weight. When I read in medical literature about the link between the microbiome and obesity in people without cancer, I thought it would be interesting to see if the microbiome of patients is one of the causes of obesity and other metabolic changes," she says.

The study conducted by Dr. Shai and Prof. Koren involved 33 women who were about to begin chemotherapy for breast cancer and gynecological cancer. The women were weighed once before the treatment, and once again approximately five weeks after treatment began. Prior to treatment, a stool sample was used to genetically characterize the microbiome of each of the women. Nine of the women were found to have gained weight to a degree that was defined as significant (3% or more). The microbiome of these women exhibited a smaller diversity of gut bacteria and different bacterial strains compared to that of the women who did not experience weight gain.

The study showed that the composition of intestinal bacteria may predict which women will gain weight as a result of chemotherapy. In addition when the gut microbiota of women who gained weight were transferred to germ-free mice, they developed glucose intolerance and signs of chronic inflammatory condition were detected in their blood. These findings suggest that bacteria are partially responsible for metabolic changes that lead to weight gain following chemotherapy treatment.

"We have shown for the first time that the pre-treatment microbiome of patients that gained weight following chemotherapy is different than the microbiome of patients that did not gain weight, and that fecal transplantation from patients that gained weight results in glucose intolerance, adverse lipid changes and inflammatory changes in germ-free mice," says Prof. Koren. These results suggest that the intestinal microbiome is mediating metabolic changes in women treated by chemotherapy. Moreover, the pre-chemotherapy composition of the intestinal microbiome can predict which patients will gain weight following treatment.

Dr. Shai and Prof. Koren are currently in the midst of a follow-up study which aims to examine the results in a larger patient population and to examine the microbiome of women at the end of chemotherapy in order to understand the effect of the treatment on bacterial composition. The researchers also plan to study the effect of chemotherapy on obesity in germ-free mice following fecal transplantation.

If the results obtained in the initial study are repeated, it will be possible to consider a stool test for women before starting treatment, so that the patient knows if she is at risk of gaining weight. As October marks Breast Cancer Awareness Month, Dr. Shai says, "We hope that in the future we will be able to identify those women who are at risk for weight gain through a simple examination and perhaps even suggest ways to prevent this phenomenon."

Non-pharmaceutical interventions such as voluntary shelter-in-place, quarantines, and other steps taken to control the SARS-CoV-2 virus can reduce the peak number of infections, daily infection rates, cumulative infections, and overall deaths, a new study published in the journal PLOS ONE has found.

"High compliance with voluntary quarantine - where the entire household stays home if there is a person with symptoms or risk of exposure in the household - has a significant impact on reducing the spread," said Pinar Keskinocak, the William W. George Chair and professor in the H. Milton Stewart School of Industrial and Systems Engineering (ISyE) and director of the Center for Health and Humanitarian Systems at the Georgia Institute of Technology. "Shelter-in-place (SIP) puts the brakes on the spread for some time, but if people go back to 'business as usual' after SIP, the significant impact is lost, so it needs to be followed up by voluntary quarantine and other physical distancing measures."

Utilizing data from the state of Georgia, the study determined that a combination of non-pharmaceutical interventions, with various levels of compliance that change over time, could in some instances cut cumulative infections in half and reduce the peak number of infections to about a third of what could have been seen, "flattening the peak" to avoid overwhelming a state's healthcare system.

The study compared actual statistics to revised models of what could have happened in the state during the past seven and a half months without the physical distancing. As Covid-19 cases increase toward what may be a new peak this fall, the study could help public health officials evaluate the benefits of potential intervention strategies, for example, in the debate around K-12 school closure.

The study modeled the number of Covid-19 infections and resulting severe outcomes, and the need for hospital capacity under social distancing, particularly, school closures, shelter-in-place, and voluntary quarantine.

"As one would expect, there is variation across the state in the observed data, which depends in large part on people's behaviors," said Nicoleta Serban, who is the Joseph C. Mello chair and professor in ISyE. "For example, mobility increased faster in some counties compared to others, which is likely to be correlated with increased physical and social interactions, and therefore faster spread of the coronavirus."

The team, including Georgia Tech ISyE Ph.D. students Buse Eylul Oruc and Arden Baxter, developed and used an agent-based simulation model to project the infection spread. "This is a sophisticated mathematical model which mimics what might happen in practice - under different scenarios - by capturing the progression of the disease in an individual, as well as the interactions between people in the household, in peer groups such as schools or workplaces, or in community groups such as grocery stores," Oruc said.

The model utilizes parameters specific to Covid-19 and data from Georgia on population interactions and demographics. The study covered a period starting February 18, evaluating different social distancing scenarios, including baselines in which no intervention would have taken place or the only intervention would have been K-12 school closure, comparing them to combinations of shelter-in-place and voluntary quarantine with different timelines and compliance levels.

Outcomes were compared at the state and community level for the number and percentage of cumulative and daily new symptomatic and asymptomatic infections, hospitalizations, and deaths; Covid-19-related demand for hospital beds, ICU beds, and ventilators.

The number of hospitalizations in Georgia turned out to be fewer than models last spring had forecast, but "models accurately predicted which hospital regions of the state that would have the largest gaps between number of people with severe outcomes and available care capacity - and therefore face potential shortages of ICU beds, hospital beds, and ventilators," Baxter said.

The results suggest that shelter-in place followed by voluntary quarantine reduced peak infections to less than a third of what we would have seen if no intervention had taken place and to less than a half if only schools had been closed. The models predicted correctly that the interventions would delay the peak from April to sometime between late July to mid-September, reducing the daily strain on health care systems.

According to the study, increasing shelter-in-place duration from four to five weeks yielded between 2% to 9% and 3% to 11% decrease in cumulative infection and deaths, respectively. Regardless of the shelter-in-place duration, increasing voluntary quarantine compliance decreased daily new infections and cumulative infections by about 50%. The cumulative number of deaths ranged from 6,660 to 19,430 under different scenarios.

As infection rates rise in the United States during late October, the study could help public health officials select the best techniques for addressing the viral threat. Georgia's total population is approximately 10.5 million, and Covid-19 related deaths have exceeded 7,600.

"The study further highlighted and quantified the impact of how compliance with public health measures impact infectious disease spread," Keskinocak said. "The takeaway message is that each of us have the power to control our health by making the right choices."

"As individuals and as a nation, we often expect technological or medical fixes or cures to health problems, whereas many of these problems, whether they are at the individual level or the public health level, are caused by or exacerbated by our choices and behaviors," Keskinocak said. "For many of them, we don't need a new fancy device, drug, or technology to make things better. As individuals, or households, or communities, we have the power and the responsibility to impact and improve our own health, and the public health, by making healthy choices."

University of Minnesota Medical School physician researchers studied hydroxychloroquine as a treatment to prevent COVID-19 for those with high-risk for exposure to the virus - health care workers.

The pre-exposure prophylaxis trial results, which were published in Clinical Infectious Diseases, determined that taking 400mg of hydroxychloroquine once or twice weekly did not prevent the development of COVID-19 in health care workers better than the placebo.

"This randomized placebo-controlled trial launched on April 6, with the objective of evaluating whether or not hydroxychloroquine taken once or twice weekly in health care workers at high risk for COVID-19 exposure could prevent COVID-19 infection," said principal investigator Radha Rajasingham, MD, an infectious diseases physician and researcher at the U of M Medical School.

The double-blind trial enrolled 1,483 health care workers and first responders from across the U.S. and Canada. Participants were randomly assigned to receive once-weekly hydroxychloroquine, twice-weekly hydroxychloroquine or placebo. Participants were followed for a minimum of four weeks and up to twelve weeks to evaluate who developed COVID-19.

Overall, 7.9% assigned the placebo developed COVID-19, while 5.9% assigned hydroxychloroquine developed COVID-19. Those results were not statistically significant, meaning there was not a meaningful difference between hydroxychloroquine and the placebo. Side effects were reported in 21% of participants assigned the placebo; 31% in the once-weekly hydroxychloroquine group and 36% in the twice-weekly hydroxychloroquine group. The most common side effects were nausea, upset stomach and diarrhea. There was no increased risk of serious side effects or cardiac complications from taking hydroxychloroquine compared to the placebo.

Non-Cancerous Tissue from Nephrectomy Specimens: A Window into Kidney Pathology

Kidney pathology from non-cancerous portions of the kidney from patients undergoing nephrectomy can offer insight into the spectrum of kidney histopathological findings in humans. Researchers reviewed pathology reports from 1,347 patients who underwent nephrectomy between 1999-2018, examining the association between the degree of scarring in the glomerulus, tubules/interstitium, and vessels, with kidney function at the time of kidney removal. They also looked at the relationship between age and kidney function among each category of scarring. The researchers found that more scarring in the glomerulus, tubules/interstitium, and the vessels was associated with worse kidney function. They also found that though older individuals were more likely to have more scarring in the glomerulus and tubules/interstitium, and that taking into account age did not change these findings.

CLEVELAND--Brain cell dysfunction in low oxygen is, surprisingly, caused by the very same responder system that is intended to be protective, according to a new published study by a team of researchers at the Case Western Reserve University School of Medicine.

"These powerful protein responders initially protect brain cells from low oxygen as expected, but we find that their prolonged activity leads to unintended collateral damage that ultimately impairs brain cell function," said the study's principal investigator Paul Tesar, a professor in the Department of Genetics and Genome Sciences at the Case Western Reserve School of Medicine and the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics.

Defining the mechanism of brain-cell damage in low oxygen conditions provides an opportunity to develop effective therapies, including a class of drugs studied in their research that could inform future clinical approaches for many neurological diseases caused by low oxygen. The work also clarifies how the response to low oxygen causes disease in other tissues outside the brain.

Their research was published online Oct. 21 in the journal Cell Stem Cell.

The body's response to low oxygen

With the dawn of an oxygenated atmosphere, a burst of multicellular life was possible, as oxygen could be used to produce the energy needed to support complex life functions. Given the requirement of oxygen for life, nearly all organisms evolved a mechanism to rapidly respond to low oxygen--a condition called hypoxia. The Noble Prize in Physiology or Medicine was awarded in 2019 for discoveries of how cells in our body sense low oxygen levels and respond to stay alive.

At the core of this ancient response are proteins called hypoxia-inducible factors (HIFs), which instruct the cell to minimize oxygen consumption and maximize their access to oxygen. In this way, HIFs can be thought of as valiant heroes attempting to protect and resuscitate cells in the immediate response to low oxygen.

Prolonged hypoxia causes dysfunction in many tissues. In particular, stem cells in the brain are impaired by hypoxia in many diseases, including stroke, cerebral palsy related to premature birth, respiratory distress syndromes, multiple sclerosis and vascular dementia. Even the significant neurological damage caused by COVID-19 is attributed to hypoxia.

Until now, the precise causes of cell malfunction due to low oxygen were unknown.

The dark side of the hypoxia response

In this study, researchers developed a new approach to closely study how the hypoxia responder proteins function. By comparing how they work in brain-stem cells with other tissues, such as heart and skin, the scientists confirmed that the hypoxia responder proteins perform a beneficial function to promote cell survival in low oxygen in all tissues. However, these same hypoxia responder proteins had a previously unappreciated dark side, as they also switched on other cellular processes outside of the core beneficial response.

The team then demonstrated that this additional--and previously unknown--response is what impaired brain-stem cell function. This suggests that, while hypoxia responder proteins evolved to promote cell survival in all tissues of the body in low-oxygen conditions, their powerful effects can also have unintended consequences to disrupt cell function.

New opportunities for treating hypoxia damage

The authors tested thousands of drugs to try to restore brain-stem cell function to overcome the damaging effects of the hypoxia responder proteins. They discovered a group of drugs that specifically overcome the damage-inducing response, while leaving the beneficial response intact.

"One of the exciting avenues that stems from this work is identifying drugs that specifically target the damaging side of the hypoxia response while sparing the beneficial side," said first author Kevin Allan, a graduate student in Case Western's Medical Scientist Training Program. "This offers a new perspective on combating tissue damage due to hypoxia."

"Whether the damaging side of the hypoxia response is solely an unintended pathological effect or potentially a previously undiscovered normal process that goes awry in disease remains unknown," Tesar said. "Our work opens the door to a new way of thinking about how cells respond to low oxygen in health and disease."

Bottom Line: Among women participating in cervical cancer screening in Sweden, those with a diagnosis of invasive cervical cancer had an increased risk of iatrogenic injuries (as a consequence of medical intervention) and non-iatrogenic injuries (caused by accidents and self-harm) requiring hospitalization.

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research

Author: Qing Shen, PhD, researcher in the Department of Medical Epidemiology and Biostatistics at the Karolinska Institutet in Stockholm

Background: “Cervical cancer screening is one of the most successful cancer prevention programs which has greatly reduced cervical cancer incidence and mortality,” said Shen. “Despite these substantial benefits, our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic workup, although at a very low level.”

Previous work conducted by Shen and colleagues demonstrated an increased risk of injuries during the time period before and after a diagnosis of any cancer. “These injuries were likely a result of invasive procedures and the severe psychological distress experienced during the clinical evaluation of a potential cancer,” Shen explained. Whether there is a similar increase in risk among patients screened for cervical cancer, when an organized cancer screening program was largely accessible, was unknown, she added.

How the Study was Conducted: Using data from the Swedish Total Population Register, the researchers identified over 3 million women who participated in cervical cancer screening during 2001-2012. Cross-linkage with multiple Swedish registries allowed for the identification of women within this cohort who received a diagnosis of invasive cervical cancer, cervical cancer precursor lesions, or had a normal smear during follow-up. The final cohort included roughly 1.85 million women with a normal smear, roughly 22,000 women with cervical intraepithelial neoplasia (CIN) grade 1, roughly 21,000 women with CIN2, roughly 37,000 with CIN3/adenocarcinoma in situ (AIS), and roughly 5,000 women with invasive cervical cancer.

The researchers examined the incidence of injuries during the diagnostic workup of patients who participated in cervical cancer screening. Among women with precursor lesions or cervical cancer, the diagnostic workup was defined as the time interval between the first Pap smear or punch biopsy until surgical treatment, or two months after the last smear or punch biopsy, if not treated surgically. Among women with normal smear results, the diagnostic workup was defined as the two months following the smear.

The researchers calculated incidence rates of both iatrogenic injuries and non-iatrogenic injuries that occurred during the diagnostic workup. Iatrogenic injuries, which were mostly related to receipt of a punch biopsy, and which required at least two days of hospitalization, were included in this analysis. Non-iatrogenic injuries, which included accidents and intentional self-harm, and which required at least one day of hospitalization, were included. Incidence rate ratios for injuries that occurred during the diagnostic workup, which were calculated by comparing women with a diagnosis of cervical cancer or its precursor lesions with women with a normal smear, were adjusted for age, calendar period, screening adherence, education, income, and marital status.

Results: Compared with women with a normal smear, women with a diagnosis of invasive cervical cancer had eight times the incidence of iatrogenic injuries, and women with CIN3/AIS had three times the incidence of iatrogenic injuries. Women with CIN1-2 did not have a significantly increased rate of iatrogenic injuries compared with women with a normal smear.

“Women with invasive cancer can have greater vascularity due to tumor growth, which can lead to hemorrhage and hematoma following a biopsy,” Shen explained.

Compared with women with a normal smear, women with a diagnosis of invasive cervical cancer had about twice the incidence of non-iatrogenic injuries. Women with CIN1-2, CIN3, or AIS did not have a significantly increased rate of non-iatrogenic injuries compared with women with a normal smear. The most common type of non-iatrogenic injuries were unintentional falls, Shen said.

“An increase in non-iatrogenic injuries points to high levels of psychological distress in relation to receiving a diagnosis of cervical cancer,” said Shen.

Author’s Comments: “This study for the first time systematically examined the risks of injuries during the cervical diagnostic workup. Although the chance of having such injuries was rare, we found an increased risk of inpatient care for iatrogenic and non-iatrogenic injuries for women with invasive cervical cancer. It is important to emphasize, however, that cervical cancer screening is greatly beneficial for the early detection of cancer and is largely safe.”

Study Limitations: Limitations of the study include a lack of information on non-surgical treatments among women with invasive cervical cancer, such as palliative care, chemotherapy, and radiotherapy, which could have potential implications for injuries. Further, because the authors only included iatrogenic injuries that required at least two days of inpatient care, only the more severe forms of these injuries were captured in this analysis.

Funding & Disclosures: The study was sponsored by the Swedish Cancer Society; the Swedish Research Council for Health, Working Life and Welfare; a Karolinska Institutet Senior Researcher Award and Strategic Research Area in Epidemiology Award; and by the China Scholarship Council.

Shen declares no conflict of interest.

What The Study Did: Researchers examined the sociodemographic characteristics of patients associated with racial/ethnic differences in COVID-19 outcomes.

Authors: Bhramar Mukherjee, Ph.D., of the University of Michigan School of Public Health in Ann Arbor, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.25197)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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WEST LAFAYETTE, Ind. -- Getting run over by a car is not a near-death experience for the diabolical ironclad beetle.

How the beetle survives could inspire the development of new materials with the same herculean toughness, engineers show in a paper published Wednesday (Oct. 21) in Nature.

These materials would be stiff but ductile like a paper clip, making machinery such as aircraft gas turbines safer and longer-lasting, the researchers said.

The study, led by engineers at the University of California, Irvine (UCI) and Purdue University, found that the diabolical ironclad beetle's super-toughness lies in its two armorlike "elytron" that meet at a line, called a suture, running the length of the abdomen.

In flying beetles, the elytra protect wings and facilitate flight. But the diabolical ironclad beetle doesn't have wings. Instead, the elytra and connective suture help to distribute an applied force more evenly throughout its body.

"The suture kind of acts like a jigsaw puzzle. It connects various exoskeletal blades - puzzle pieces - in the abdomen under the elytra," said Pablo Zavattieri, Purdue's Jerry M. and Lynda T. Engelhardt Professor of Civil Engineering.

This jigsaw puzzle comes to the rescue in several different ways depending on the amount of force applied, Zavattieri said. A video explaining these findings is available on YouTube at https://youtu.be/NS3AqJB5SfU.

To uncover these strategies, a team led by UCI professor David Kisailus first tested the limits of the beetle's exoskeleton and characterized the various structural components involved by looking at CT scans.

Using compressive steel plates, UCI researchers found that the diabolical ironclad beetle can take on an applied force of about 150 newtons - a load of at least 39,000 times its body weight - before the exoskeleton begins to fracture.

That's more impressive than sounds: A car tire would apply a force of about 100 newtons if running over the beetle on a dirt surface, the researchers estimate. Other terrestrial beetles the team tested couldn't handle even half the force that a diabolical ironclad can withstand.

Zavattieri's lab followed up these experiments with extensive computer simulations and 3D-printed models that isolated certain structures to better understand their role in saving the beetle's life.

All of these studies combined revealed that when under a compressive load such as a car tire, the diabolical ironclad beetle's jigsaw-like suture offers two lines of defense.

First, the interconnecting blades lock to prevent themselves from pulling out of the suture like puzzle pieces. Second, the suture and blades delaminate, which leads to a more graceful deformation that mitigates catastrophic failure of the exoskeleton. Each strategy dissipates energy to circumvent a fatal impact at the neck, where the beetle's exoskeleton is most likely to fracture.

Even if a maximum force is applied to the beetle's exoskeleton, delamination allows the interconnecting blades to pull out from the suture more gently. If the blades were to interlock too much or too little, the sudden release of energy would cause the beetle's neck to snap.

It's not yet known if the diabolical ironclad beetle has a way to heal itself after surviving a car "accident." But knowing about these strategies could already solve fatigue problems in various kinds of machinery.

"An active engineering challenge is joining together different materials without limiting their ability to support loads. The diabolical ironclad beetle has strategies to circumvent these limitations," said David Restrepo, an assistant professor at the University of Texas at San Antonio who worked on this project as a postdoctoral researcher in Zavattieri's group.

In the gas turbines of aircraft, for example, metals and composite materials are joined together with a mechanical fastener. This fastener adds weight and introduces stress that could lead to fractures and corrosion.

"These fasteners ultimately decrease the performance of the system and need to be replaced every so often. But the interfacial sutures of the diabolical ironclad beetle provide a robust and more predictable failure that could help solve these problems," said Maryam Hosseini, who worked on this project as a Ph.D. student and postdoctoral researcher in Zavattieri's group. Hosseini is now an engineering manager at Procter & Gamble Corp.

UCI researchers built a carbon fiber composite fastener mimicking a diabolical ironclad beetle's suture. Purdue researchers found through loading tests that this fastener is just as strong as a standard aerospace fastener, but significantly tougher.

"This work shows that we may be able to shift from using strong, brittle materials to ones that can be both strong and tough by dissipating energy as they break. That's what nature has enabled the diabolical ironclad beetle to do," Zavattieri said.

LOS ANGELES -- An estimated 5.5 million people in the United States live with Alzheimer's disease, which is the most common form of dementia.

Keck Medicine of USC is enrolling individuals in an international phase 3 clinical trial to examine the safety and effectiveness of deep brain stimulation to treat Alzheimer's. The study uses electrical impulses to stimulate the region of the brain known as the fornix, which is associated with memory and learning.

"Deep brain stimulation has successfully treated conditions such as Parkinson's disease by improving motor skills, and we are now investigating if this therapy can stabilize or improve cognitive function," says Darrin Lee, MD, PhD, a neurosurgeon with Keck Medicine of USC and the site's principal investigator of the study. "Based on the results of earlier phases of this clinical trial, the treatment offers a potential benefit for patients with mild Alzheimer's."

This randomized, double-blind study will last four years. Subjects will first take a standardized assessment test for Alzheimer's to be used as a baseline measure of cognitive ability throughout the study.

Next, researchers will implant electrodes into subjects' brains that connect to a battery pack, similar to a heart pacemaker, placed underneath the collarbone.

For the first year of the study, subjects will be given either low-frequency stimulation to the brain, high-frequency stimulation or a placebo -- no stimulation.

"For those with Alzheimer's disease, certain parts of the brain become atrophied," Lee says. "We are testing to see if stimulating the brain's fornix can reawaken brain activity in this area and stop the progression of the disease."

During the first year, subjects will be given subsequent cognitive tests to check if their memory or learning skills have held steady or improved. At the end of the year, study researchers will examine data to determine which level of stimulation had the most impact on these skills.

For the next three years of the trial, all subjects in the study will receive what researchers have determined is the optimal frequency of deep brain stimulation, even those originally receiving the placebo. Patients will continue to be given cognitive assessments throughout the four-year period.

To qualify for the trial, patients must be 65 or older, have been diagnosed with mild Alzheimer's and take Alzheimer's medication, and have a caregiver or family member who can accompany them to doctor visits.

The clinical trial involves approximately 200 patients at some 20 sites in the United States, Canada and Germany. Keck Medicine plans to enroll 8-15 patients.

The trial is sponsored by Functional Neuromodulation, Inc.

Those interested in enrolling in the clinical trial with Keck Medicine can contact Amanda Romano at amanda.romano@med.usc.edu or 213-393-5640.

Opioid use disorder affects about 2 million Americans each year and is the No. 1 cause of accidental death. Between 50 to 90 percent of individuals with this disorder were exposed to a prescription opioid first. Opioid use disorder is likely underdiagnosed within the healthcare system setting, which may be due in part to the reticence of practitioners who lack the specialized training in addiction medicine.

A new, retrospective cross-sectional study by researchers from Florida Atlantic University's Schmidt College of Medicine in collaboration with Geisinger, the University of Pennsylvania Perelman School of Medicine, and Cooper Medical School of Rowan University, shows that information in electronic health records (EHRs) may help identify patients with opioid use disorder. EHRs provide significant patient information such as demographic features, prior health encounters and prescription history.

For the study, researchers analyzed individuals within Geisinger, a large, integrated health system in Pennsylvania, who were prescribed opioids between Dec. 31, 2000 and May 31, 2017, using a mixed-methods approach. The cohort was identified from 16,253 patients enrolled in a Geisinger-specific medication monitoring program for opioid use, including patients who maintained or violated contract terms, as well as a demographically matched control group of 16,253 patients who were prescribed opioids but not enrolled in the monitoring program. Substance use diagnoses and psychiatric comorbidities were assessed using automated EHR summaries. A manual medical record review procedure using the Diagnostic and Statistical Manual of Mental Disorders, DSM-5 (Fifth Edition) criteria for opioid use disorder was completed for a subset of patients.

Results of the study, published in JAMA Network Open, suggest that patients with opioid use disorder may be identified using information available in the EHR, even when diagnostic codes do not reflect this diagnosis. Furthermore, the study demonstrates the utility of proxies coding for DSM-5 criteria from medical records to generate a quantitative DSM-5 score that is associated with opioid use disorder severity. Methods used in the study are unique in deriving a severity score that aims to mirror severity scores from more traditional interview-based diagnostic procedures.

Among the 16,253 patients enrolled in the medication monitoring program, opioid use disorder diagnoses as defined by ICD-10 diagnostic codes in the EHRs were present at a much lower rate than expected from the published literature - 291 patients (2 percent) - indicating the necessity for alternative diagnostic strategies. Using proxy measurements from the EHR for the DSM-5 criteria to assess opioid use disorder, the manual review of 200 patients in the monitoring program and 200 control patients pinpointed a larger percentage of patients with moderate-to-severe opioid use disorder. In the monitoring program, researchers identified 145 of 200 (73 percent) and in the control group 27 of 200 (14 percent) compared with the lower prevalence of opioid use disorder assessed using diagnostic codes.

"We find that chart review of electronic health records enables us to identify more patients with probable opioid use disorder than relying on diagnostic codes alone," said Vanessa Troiani, Ph.D., senior author and an assistant professor at Geisinger, who directed the team of scientists involved in this research.

Typically, opioid use disorder is diagnosed during a patient-physician consultation during which the addiction trained practitioner uses dialogue with the patient or questionnaires to evaluate whether the patient exhibits symptoms of opioid use disorder based on the DSM-5 opioid use criteria. These criteria are based on the assessment of whether opioid use causes significant impairment in physical and social functioning, as well as aspects of craving and unsuccessful efforts to reduce or control use, with multiple DSM-5 criteria within a 12-month period warranting an opioid use disorder diagnosis. In addition, the practitioner often relies on the self-report of the patient but may consult a significant other or relative of the patient.

"Our study showed that proxy measures that rely on multiple sources of data, including prescription drug history and notes in the electronic health record, may help identify patients with opioid use disorder who have not received a diagnosis," said Janet Robishaw, Ph.D., co-author, senior associate dean for research and chair of the Department of Biomedical Sciences in FAU's Schmidt College of Medicine.

Sarah Palumbo, 21, first author and a second-year medical student in FAU's Schmidt College of Medicine played a lead role in the research. Palumbo, who works in Robishaw's laboratory, was one of the first students accepted into the "FAU High School M.D. Direct" program and graduated from college three months after graduating from FAU High School.

"Our findings that psychiatric and other substance use codes are increased in patients in the drug monitoring program suggest the potential for assessing psychiatric and other substance use codes as an associated factor to evaluate patient risk for opioid use disorder in the chronic pain setting," said Palumbo.

According to the National Institute on Drug Abuse, roughly 21 to 29 percent of patients prescribed opioids for chronic pain misuse them and between 8 and 12 percent develop an opioid use disorder. An estimated 4 to 6 percent who misuse prescription opioids transition to heroin. This issue has become a public health crisis with devastating consequences including increases in opioid misuse and related overdoses, as well as the rising incidence of neonatal abstinence syndrome due to opioid use and misuse during pregnancy.

"Opioids continue to be used for the treatment of pain. Precision medicine within integrated health systems such as Geisinger could be a major associated factor in developing more efficient pain treatments with less risk for addiction, and studies of this potential could be helped by establishing more effective proxy measures for opioid use disorder using data from electronic health records," said Robishaw.

A gut hormone, ghrelin, is a key regulator of new nerve cells in the adult brain, a Swansea-led research team has discovered. It could help pave the way for new drugs to treat dementia in patients with Parkinson's Disease.

Blood-borne factors such as hormones regulate the process of brain cell formation - known as neurogenesis - and cognition in adult mammals.

The research team focused on the gut hormone acyl-ghrelin (AG), which is known to promote brain cell formation. A structure change to the hormone results in two distinct forms: AG and unacylated-ghrelin (UAG).

The team, led by Dr Jeff Davies of Swansea University Medical School, studied both AG and UAG to examine their respective influences over brain cell formation.

This research is relevant to Parkinson's as a large proportion of those with the disease experience dementia, which is linked to a loss of new nerve cells in the brain. This loss leads to a reduction in nerve cell connectivity, which plays a vital role in regulating memory function.

The team's key overall findings were:

the UAG form of ghrelin reduces nerve cell formation and impairs memory

Individuals diagnosed with Parkinson's disease dementia have a reduced AG:UAG ratio in their blood

Dr Jeff Davies of Swansea University Medical School, lead researcher, said:

"Our work highlights the crucial role of ghrelin as a regulator of new nerve cells in the adult brain, and the damaging effect of the UAG form specifically.

This hormone represents an important target for new drug research, which could lead ultimately to better treatment for people with Parkinson's.

Our findings show that the AG:UAG ratio could also serve as a biomarker, allowing earlier identification of dementia in people with Parkinson's disease."

The team included collaborators from Newcastle University (UK) and Monash University (Australia). They examined the role of AG and UAG in the brain, and also compared blood collected from Parkinson's disease patients diagnosed with dementia with cognitively intact PD patients and a control group.

They found:

Higher levels of UAG, using both pharmacological and genetic methods, reduced hippocampal neurogenesis and brain plasticity.

AG helped reverse spatial memory impairments

UAG blocks the process of brain cell formation prompted by AG

The Parkinson's patients with dementia were the only one of the three patient groups examined to show a reduced AG:UAG ratio in their blood.

The research was published in Cell Reports Medicine.

Marine fish species are migratory in nature and not respectful of human-made territorial boundaries, which represents a challenge for fisheries management as policies tend to focus at the national level. With an average catch of 48 million tonnes per year, and USD $77 billion in annual fishing revenue, these species support critical fisheries, and require international cooperation to manage, according to UBC research.

The researchers focused on fish species that cross the Exclusive Economic Zones (EEZs) of two or more coastal states which are most often targeted by fisheries operating within those EEZs. They identified over 633 exploited transboundary species worldwide and found that the catch and revenue from these fisheries had been severely underestimated and over-exploited.

"We found that some countries get over 80 per cent of their catch from transboundary species. These are not small numbers or small nations: these catches are specifically important in terms of revenue for Northern America and Eastern Asia," said Juliano Palacios Abrantes, a doctoral student in UBC's Institute for the Oceans and Fisheries, and lead author on the study. "Fishing nations such as China, the USA, Russia, Peru, and Japan alone are responsible for 41 per cent of the yearly global fisheries revenue from transboundary species."

"Fisheries that include transboundary fish species, such as anchoveta in Peru's transboundary area with Chile or pollock in the U.S., Russia and Japan transboundary Alaskan region, catch on average 48 million tonnes per year, or USD $77 billion in annual fishing revenue," said William Cheung, senior author and professor in in UBC's Institute for the Oceans and Fisheries. "The catch from these fish species are declining at a much higher rate than non-transboundary species."

There are agreements between countries in many of these EEZs. Peru and Chile recently signed an agreement towards standardizing stock assessments and management of the southern anchoveta stock. However, transboundary fisheries have led to some notorious fisheries-related conflicts, including those between those Canada, the USA, Russia, and the European Union. The EU, Norway, Iceland, and Denmark's Faroe Islands continue to be at odds over the allowable catch sizes for Atlantic mackerel, a transboundary fish species that has changed its distribution patterns due to climate change.

"Climate change is going to continue changing the distribution of fish stocks among countries, with some new transboundary species emerging and some disappearing," said Palacios Abrantes. "This can only lead to more difficulties if nations are not able to adapt and manage fisheries through effective international cooperation."

"Collaborations are going to be needed to maximize long?term ecological, social, and economic benefits of shared marine species, particularly as stocks decline due to overfishing, and as fish populations move about the ocean in different patterns due to climate change," said Cheung. "Nations will have to adapt to these anthropogenic changes in our world as quickly, if not quicker, than fish species are having to do."