Culture

Oncotarget Volume 11, Issue 10 reported that the statistically associated Cp G sites were analyzed in blood samples from two separate atherothrombotic stroke cohorts, ischemic stroke-cohort 1: 37 atherothrombotic patients and 6 controls, ischemic stroke-cohort 2: 80 atherothrombotic patients and 184 controls.

The results suggest different DNAm status of MMP24 between stable and unstable atherothrombotic carotid plaques, and between atherothrombotic stroke and controls in blood samples.

Dr. Israel Fernandez-Cadenas from Stroke Pharmacogenomics and Genetics, Sant Pau Research Institute, Barcelona, Spain, Dr. Jerzy Krupinski from the Neurology, Hospital Universitari Mútua de Terrassa/Fundacio Docència i Recerca MútuaTerrassa, Terrassa, Spain as well as the Centre for Biomedicine, Manchester Metropolitan University, Manchester, UK & Dr. Cristina Gallego-Fabrega also from the Neurology, Hospital Universitari Mútua de Terrassa/Fundacio Docència i Recerca MútuaTerrassa, Terrassa, Spain as well as the Stroke Pharmacogenomics and Genetics, Sant Pau Research Institute, Barcelona, Spain said, "Arteriosclerosis is the underlying pathology in most cases of cardiovascular disease (CVD), including ischemic stroke (IS), contributing to major mortality in Western countries."

"Arteriosclerosis is the underlying pathology in most cases of cardiovascular disease (CVD), including ischemic stroke (IS), contributing to major mortality in Western countries"

- Dr. Israel Fernandez-Cadenas, Stroke Pharmacogenomics and Genetics, Sant Pau Research Institute & Dr. Jerzy Krupinski from the Neurology, Hospital Universitari Mútua de Terrassa/Fundacio Docència i Recerca MútuaTerrass and the Centre for Biomedicine, Manchester Metropolitan University & Dr. Cristina Gallego-Fabrega also from the Neurology, Hospital Universitari Mútua de Terrassa/Fundacio Docència i Recerca MútuaTerrassa and the Stroke Pharmacogenomics and Genetics, Sant Pau Research Institute

MMPs and TIMPs have raised considerable interest within atherosclerosis and IS research community, as they represent an attractive target for the use of current drugs and the development of novel ones, aimed at blocking MMP activity.

Some studies have observed associations between protein plasma levels of MMPs, TIMPs, atheromatous plaque instability, stroke progression.

Here, the authors present a characterization of DNAm status of the MMP and TIMP gene families in donor-matched stable and ulcerated carotid artery atherosclerotic plaques and whole blood in atherothrombotic stroke patients and controls.

The Fernandez-Cadenas/Krupinski/Gallego-Fabrega Research Team concluded, in their Oncotarget Research Article, "we characterized MMPs and TIMPs DNAm patterns in atheromatous plaque, which led us to observe significant differences between stable and ulcerated portions in plaque tissue for MMP24 and TIMP2. Differences in MMP24 were also observed in blood samples between atherothrombotic stroke patients and healthy controls. The generalized hypermethylation found in ulcerated portions and samples from healthy controls is in line with other methylation studies. Functional analysis of the implications of methylation levels changes in MMP24 and TIMP2 have in their expression levels are needed to link this finding with the biopathology of plaque destabilization. Studies with larger sample size, to confirm our results."

Oncotarget Volume 11, Issue 10 reported that dysregulation of noncoding micro RNA molecules has been associated with immune cell activation in the context of Helicobacter pylori-induced gastric inflammation as well as carcinogenesis, but also with downregulation of mismatch repair genes, and may interfere with immune checkpoint proteins that lead to the overexpression of antigens on gastric tumor cells.

Among the many micro RNAs involved in gastric inflammation, adenocarcinoma development and immune checkpoint regulation, mi R-155 is notable in that its upregulation is considered a key marker of chronic gastric inflammation that predisposes a patient to gastric carcinogenesis.

Dr. Christian Prinz from the Lehrstuhl für Innere Medizin1, University of Witten gGmbH, Helios Universitätsklinikum said, "Increasing evidence suggests that microRNA (miRNA) dysregulation has critical impacts on development, as well as inflammation and cancer development"

"Increasing evidence suggests that microRNA (miRNA) dysregulation has critical impacts on development, as well as inflammation and cancer development"

- Dr. Christian Prinz, Lehrstuhl für Innere Medizin1, University of Witten gGmbH, Helios Universitätsklinikum

Notably, it seems that human gastrointestinal cancer can be better classified using mi RNA expression profiles than mRNA or protein expression profiles.

Using a new bead-based flow cytometric mi RNA expression profiling method, they performed a systematic expression analysis of 217 mammalian mi RNAs from 334 samples, including multiple human cancers.

Furthermore, they successfully identified poorly differentiated tumors based on mi RNA expression profiles, whereas the classification of the same samples using messenger RNA profiles was highly inaccurate.

Many mi RNAs exhibit differential regulation in cancer, for example, mi R-34a is involved in p53-mediated apoptosis in pancreatic cancer, and nine mi RNAs are upregulated in primary breast cancer, including mi R-21, mi R-181b, and mi R-155.

The Prinz Research Team concluded in their Oncotarget Research Perspective, "clinical strategies aiming to prevent miR-155 overexpression (i. e., via silencer RNAs) may thus represent a promising method of controlling cancer growth (e. g., by allowing DNA repair), especially in pre-malignant lesions or during the early stages of gastric cancer."

A sperm enters an egg, an embryo develops and eventually a baby is born. But back up a second -- how does the mother's half-genome actually merge with the father's half-genome to form one new human genome? Turns out researchers don't really know that much about these relatively brief, yet crucial, incipient moments in fertilization.

Researchers at University of California San Diego School of Medicine have discovered that the enzyme SPRK1 leads the first step in untangling a sperm's genome, kicking out special packing proteins, which opens up the paternal DNA and allows for major reorganization -- all in a matter of hours.

The study published March 12, 2020 in Cell.

"In this study, we were simply interested in answering a fundamental question about the beginning of life," said senior author Xiang-Dong Fu, PhD, Distinguished Professor in the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine. "But in the process we've uncovered a step that might malfunction for some people, and contribute to a couple's difficulty conceiving. Now that we know SPRK1 plays a role here, its potential part in infertility can be further explored."

Sperm can be up to 20 times smaller than a normal cell in the body. And while sperm carry only half as much genetic material as a regular cell, it needs to be folded and packaged in a special way in order to fit. One way nature does this is by replacing histones -- proteins around which DNA is wound, like beads on a necklace -- with a different type of protein called protamines.

Fu's team has long studied SPRK1 for a completely different reason: its ability to splice RNA, an important step that enables the translation of genes to proteins. They previously showed that SPRK1 is over-activated in colon cancer, and they developed inhibitors to dampen the enzyme.

But back in 1999, shortly after Fu published a paper that first described the enzyme's role in RNA splicing, a research group in Greece noted similarities in the sequence of amino acid building blocks that make up SPRK1 substrates (the proteins upon which the enzyme acts) and protamine. Fu thought about it for years, but didn't have the expertise and tools to study sperm development. In 2015, Lan-Tao Gou, PhD, was interviewing for a position as postdoctoral researcher when Fu realized that with Gou's experience in spermatogenesis, he finally had the right person for the job.

"I said to Lan-Tao, let's do something nobody else is doing. I have a theory and you have the expertise," Fu said. "So we borrowed the equipment we needed and leveraged the core facilities we have here at UC San Diego.

"And, surprisingly, everything we tried supported our hypothesis -- SRPK1 leads a double life, swapping protamines for histones once sperm meets egg."

According to Fu, SPRK1 most likely started out playing this role in early embryogenesis, then later evolved the ability to splice RNA. In this way, SPRK1 gets to stick around even when it's no longer needed for embryogenesis.

Fu, Gou and team next want to determine the signals that instruct sperm to synchronize with the maternal genome.

"We have a ton of new ideas now," Fu said. "And the better we understand every step in the process of spermatogenesis, fertilization and embryogenesis, the more likely we are to be able to intervene when systems malfunction for couples struggling with reproductive issues."

Editor's Note: This release has been removed upon request of the submitting institution. For more information please contact Jenny Lavey, Jenny.lavey@mso.umt.edu.

Journal

Conservation Biology

DOI

10.1111/cobi.13450

Oncotarget Volume 11, Issue 10 reported that there are not standardized predictive biomarkers able to identify patients who benefit most from treatments.

The aim of this review is to provide an overview of prognostic and predictive markers used in clinical practice and to explore the most promising fields of research in terms of treatment selection and tailored therapy in pancreatic cancer.

Dr. Fabrizio Citarella from the Department of Medical Oncology, University Campus Bio-Medico, Rome 00128, Italy said, "Pancreatic ductal adenocarcinoma (PDAC) is the 12th most frequent cancer in the world and it is the 4th cause of cancer-related death in Western Countries, with a mortality rate almost equal to its incidence and a 5-year survival rate of 5–7%."

"Pancreatic ductal adenocarcinoma (PDAC) is the 12th most frequent cancer in the world and it is the 4th cause of cancer-related death in Western Countries, with a mortality rate almost equal to its incidence and a 5-year survival rate of 5–7%."

- Dr. Fabrizio Citarella, Department of Medical Oncology, University Campus Bio-Medico

This review covers:

HISTOPATHOLOGICAL CHARACTERISTICS
MOLECULAR FACTORS
MICROSATELLITE INSTABILITY
GLYPICAN-1 (GPC1)-EXPRESSING CIRCULATING EXOSOMES
microRNA AND LONG NON-CODING RNA
CIRCURLATING TUMOR DNA AND CIRCULATING TUMOR CELLS
CA19-9
INFLAMMATORY MARKERS
NOMOGRAMS AND PROGNOSTIC SCORES
MECHANISMS OF DRUG RESISTANCE, and
BRCA 1 AND 2

The Citarella Research Team concluded, in their Oncotarget Research Article, "In a changing landscape consisting of new chemotherapy regimens, immunotherapy, and target therapies, the identification of prognostic and predictive factors is needed in view of personalized medicine which aim to choose the best therapy for the right patient. Further studies are needed to better understand pancreatic cancer biology and to identify prognostic and predictive factors, which could help clinicians to stratify pancreatic cancer patients and improve their prognosis."

It is already hard to believe that there is ice on Mercury, where daytime temperatures reach 400 degrees Celsius, or 750 degrees Fahrenheit. Now an upcoming study says that the Vulcan heat on the planet closest to the sun likely helps make some of that ice.

As with Earth, asteroids delivered most of Mercury's water, the scientific consensus holds. But the extreme daytime heat could be combining with the minus 200-degree Celsius cold in nooks of polar craters that never see sunlight to act as a gigantic ice-making chemistry lab, say researchers at the Georgia Institute of Technology.

The chemistry is not too complicated. But the new study models it onto complex conditions on Mercury, including solar winds that pelt the planet with charged particles, many of which are protons key to that chemistry. The model presents a feasible path for water to arise and collect as ice on a planet rife with all the necessary components.

"This is not some strange, out of left field idea. The basic chemical mechanism has been observed dozens of times in studies since the late 1960s," said Brant Jones, a researcher in Georgia Tech's School of Chemistry and Biochemistry and the paper's first author. "But that was on well-defined surfaces. Applying that chemistry to complicated surfaces like those on a planet is groundbreaking research."

Hot, simple chemistry

Minerals in Mercury's surface soil contain what are called hydroxyl groups (OH), which are generated mainly by the protons. In the model, the extreme heat helps to free up the hydroxyl groups then energizes them to smash into each other to produce water molecules and hydrogen that lift off from the surface and drift around the planet.

Some water molecules are broken down by sunlight or rise far above the planet's surface, but other molecules land near Mercury's poles in permanent shadows of craters that shield the ice from the sun. Mercury does not have an atmosphere and thus no air that would conduct heat, so the molecules become a part of the permanent glacial ice housed in the shadows.

"It's a little like the song Hotel California. The water molecules can check in to the shadows but they can never leave," said Thomas Orlando, a professor in Georgia Tech's School of Chemistry and Biochemistry and the study's principal investigator. Orlando co-founded the Georgia Tech Center for Space Technology and Research.

"The total amount that we postulate that would become ice is 1013 kilograms (10,000,000,000,000 kg or 11,023,110,000 tons) over a period of about 3 million years," Jones said. "The process could easily account for up to 10 percent of Mercury's total ice."

The researchers will publish their results in Astrophysical Journal Letters on Monday, March 16, 2020. The research was funded by the NASA Solar System Exploration Research Virtual Institute (SSERVI) program and the NASA Planetary Atmospheres program.

Spacecraft confirms ice

In 2011, a NASA probe began orbiting Mercury and confirmed signals typical of glacial ice near the poles. The MESSENGER (MErcury Surface, Space ENvironment, GEochemistry, and Ranging) spacecraft sent back images and data that corroborated previous signatures for ice picked up years earlier by Earth-based radar.

The ice was dingy and lurked in permanent shadows in polar craters on Mercury, which is pocked by meteorite and asteroid scars much like Earth's moon. In fact, similarities between the two orbs, including their sizes, have led to many comparisons, including the probability of water ice on both.

Humans have found faint signs of possible ice on the moon but have found ice with near absolute certainty and in comparative abundance on Mercury. That has triggered some head-scratching: If asteroids, comets, and meteorites pummeled Mercury and the moon with water, what accounts for the difference in ice present? Did Mercury receive some water in a way that wouldn't work on the moon?

"The process in our model would not be anywhere near as productive on the moon. For one, there's not enough heat to significantly activate the chemistry," Jones said.

In a separate project, Orlando's lab is engineering a system based on the same chemistry to create water on the moon for future astronaut stations to be located there.

'Big magnetic tornados'

Protons from solar winds are more plentiful on Mercury than on Earth, where a mighty magnetic field whips solar wind particles, including protons, back out into space. Mercury's field is only about 1 percent as strong, and it swirls protons down onto the surface.

"These are like big magnetic tornados, and they cause huge proton migrations across most of the surface of Mercury over time," Orlando said.

The protons implant themselves into the soil all over the planet about 10 nanometers deep, forming in the minerals the hydroxyl groups (OH), which diffuse to the surface, where the heat does the rest.

"I would concede that plenty of the water on Mercury was delivered by impacting asteroids," Jones said. "But there's also the question of where asteroids laden with water got that water. Processes like these could have helped make it."

"A comet or asteroid actually doesn't need to carry water because the collision alone with a planet or moon can also make water," Orlando said. "Mercury and the moon are always being hit by small meteoroids, so this is happening all the time."

New Zealand should follow the UK and more than 30 other countries in introducing a tax on sugary drinks to tackle obesity and reduce deaths from chronic diseases, leading researchers say.

In a review of recent international and New Zealand research on the impact of food and beverage taxes, the researchers identify the strong level of scientific evidence showing such taxes work.

The lead author, Professor Nick Wilson from the University of Otago, Wellington, says the UK's Soft Drinks Industry Levy, known as the 'sugar tax', introduced in April 2018, has prompted manufacturers to significantly reduce the amount of sugar they add to soft drinks.

"Imposing a levy on soft drinks would be in line with the Government's priorities on improving well-being and protecting child health, and would be consistent with New Zealand's approach to taxing tobacco and alcohol to reduce the burden of harm from these products."

Another one of the authors, Professor Boyd Swinburn from the University of Auckland's School of Population Health, says dietary risk factors and high body mass index are leading causes of health loss in New Zealand, when death and disability are combined.

"In this country, around a third of adults are obese, and diet-related diseases, such as heart disease, cancer and diabetes are major causes of premature death."

Professor Swinburn says diet-related diseases are a particular burden for Māori and Pasifika and are a major cause of ethnic inequalities in health in New Zealand.

A sugar tax would help the government achieve its goals of preventing obesity in children and young people and reducing health inequities for Māori and Pacific peoples, he says.

"A tax could provide greater benefit to Māori and Pacific populations because of greater price sensitivity, and among children and young people because of their higher consumption of sugar-sweetened drinks."

The nutritional content of processed food is largely unregulated in New Zealand, with no limit to the amount of sugar, salt or saturated fat which can be added.

"None of the damage to the health of New Zealanders and the public health system costs associated with processed food are specifically paid for by the food industry, with the costs largely borne by the taxpayer-funded health system, and by the individuals and their families."

Professor Wilson says a 20 per cent tax on sugar-sweetened beverages would raise an estimated NZ$40 million a year, which could be recycled back into the community.

"The government could use the money to fund free fully-subsidised healthy breakfasts and lunches in all low-income schools and early childhood education centres, and ensure adequate drinking water fountains were provided in all public spaces."

The findings of this review form the basis of the position of the Health Coalition Aotearoa, a new non-governmental organisation which includes New Zealand health workers and researchers with expertise in nutrition.

Highlight

In a study of kidney transplant recipients, the composition of certain immune cells in the blood 1 year after kidney transplantation was linked with a patient's subsequent risk of kidney transplant failure.

Washington, DC (March 12, 2020) -- A newly discovered blood marker may help physicians predict which patients who recently underwent kidney transplantation are at risk of experiencing organ rejection several years later. The findings appear in an upcoming issue of JASN.

Immunosuppressive medications are essential for keeping a kidney transplant recipient's immune system from attacking the transplanted organ, but in many cases, rejection eventually occurs. Predicting kidney transplant failure may help clinicians intervene before it's too late, but this requires a better understanding of individual patients' immune responses.

By analyzing blood samples from 284 kidney transplant recipients who were followed for a median of 8.3 years, a team led by Nicolas Degauque, PhD (Université de Nantes and CHU Nantes, in France) found that the composition of immune cells called CD8+ memory T cells 1 year after kidney transplantation was linked with a patient's subsequent risk of kidney transplant failure. The investigators also found that specific CD8+ memory T cells called effector memory expressing CD45RA cells play a major role in initiating multiple immune-related processes that lead to kidney transplant failure.

"The identification of at-risk kidney transplants is based on clinical metrics already measured in the standard of care of patients and on the quantification of blood subsets of CD8+ cells that could be easily transferable in the routine monitoring of kidney transplant recipients," said Dr. Degauque. "The findings are important because early identification of at-risk kidney transplant recipients is critical to allow physicians to adapt their care by either increasing the frequency of patient monitoring or by introducing new therapeutics adapted to patients' own risks."

The results also indicate that effector memory expressing CD45RA cells may be promising targets for new treatment or prevention strategies against organ rejection.

Rates of at-risk alcohol consumption are higher in the South and East of Germany, compared to the North and West, according to a study published in the open access journal BMC Public Health. However, compared to West Germany, people in East Germany eat more healthily, while rates of smoking and lack of physical activity appear to be similar across regions.

Josefine Atzendorf, the corresponding author said: "Previous studies on lifestyle risk factors generally focused on age- or gender-specific differences. However, there are indicators that smoking, nutrition, alcohol consumption and physical activity also vary across regions. We examined how these behaviours differed according to sociodemographic factors, and between North, South, East and West Germany."

Using data on 9,204 people living in Germany, the authors found that East Germany had the highest prevalence for at-risk alcohol consumption (18.3% of the population), followed by South Germany (16.7%), West Germany (14.6%) and North Germany (13.9%). At-risk alcohol consumption was defined as drinking 12 grams or more of ethanol per day for women and 24 grams or more for men. Women were less likely to drink alcohol at at-risk levels than men, but individuals with higher education were more likely to report at-risk alcohol consumption than individuals with lower education.

Unhealthy nutrition was most prevalent in West Germany (70.6%) and least prevalent in East Germany (66.7%), while prevalence of physical activity did not differ between regions. Women were more likely to report lower physical activity but less likely to report unhealthy nutrition than men. Individuals with higher education were more likely to report lower physical activity but less likely to report unhealthy nutrition than individuals with lower education.

Daily smoking, defined as having smoked at least one cigarette, cigar, pipe or cigarillo per day in the past 30 days, was equally distributed across all four regions. Women and individuals with higher education were less likely to smoke on a daily basis.

The authors used data on 5,090 women and 4,114 men aged 18 to 64 from the 2015 Epidemiological Survey of Substance Abuse, which assessed the substance use among the general population in Germany at regular intervals between 1980 and 2015. Participants were asked about their daily smoking, diet, alcohol consumption and physical activity.

The authors caution that the use of self-reported data may have introduced bias towards socially desirable answers. Hence, the prevalence of unhealthy behaviors may have been underestimated. The observational nature of the study does not allow for conclusions about cause and effect.

Josefine Atzendorf said: "Our results indicate that health-promoting strategies to reduce lifestyle risk factors in Germany are currently insufficient. Our findings could provide starting points for the development or adjustment of health policies, considering differences between regions. However, for smoking and low physical activity, where no regional differences exist, prevention and intervention measures should focus on Germany as a whole."

ANN ARBOR, Mich. -- Black, Hispanic and indigenous women are more likely to have gaps in insurance around the time of pregnancy than white women, a new study suggests.

Nearly half of all black, Hispanic, and Indigenous women had discontinuous insurance coverage between preconception and after delivering their babies compared to about a fourth of white women, according to the research in Obstetrics and Gynecology.

Spanish-speaking Hispanic women had the lowest rates of steady insurance, with nearly one in 10 not being insured at all between preconception and the postpartum period.

The study comes as women from racial and ethnic minority backgrounds face greater risks of maternal morbidity - unexpected outcomes of labor and delivery that negatively impact a woman's health - and mortality associated with childbirth. Black and indigenous women are two to four times more likely to die from pregnancy-related causes compared with white peers.

"Racial and ethnic disparities in maternal and child health outcomes are a national public health crisis," says senior author Lindsay Admon, M.D., M.Sc., an obstetrician-gynecologist at Michigan Medicine's Von Voigtlander Women's Hospital.

"We found that disruptions in insurance coverage disproportionately affect racial and ethnic minority women. In the United States, insurance coverage is an important prerequisite for accessing healthcare.

"Throughout the most critical periods of pregnancy, we identified wide racial-ethnic disparities related to women's ability to access to preconception, prenatal, and postpartum care."

Admon notes that the findings are especially relevant as the Centers for Disease Control and Prevention has identified lack of access to quality healthcare as a key contributor to pregnancy-related deaths.

Researchers analyzed data from 107,921 women in 40 states between 2015 to 2017 to establish insurance status at three at time points, including the month before conception, at the time of delivery and 60 days after birth.

Admon's previous research finds that women of color and those of Hispanic heritage had higher rates of severe birth-related health issues than non-Hispanic white women even if they were otherwise healthy.

Disparities in Insurance Access

Income gaps between white and black populations play a big factor in insurance disparities. Nearly half of black, non-Hispanic women in the study had household incomes below the federal poverty level, which were linked to higher rates of Medicaid coverage during pregnancy.

Among the biggest factors for disrupted care is Medicaid discontinuity, authors say. Pregnancy-related Medicaid coverage is only offered for up to 60 days after a baby's birth, but there are bipartisan federal and state efforts to extend the coverage to a year.

"Medicaid stability before and after pregnancy is critical for ensuring continuity of coverage and access to care for women of color," says lead author Jamie Daw, Ph.D., researcher with the Department of Health Policy and Management at Columbia University.

"Extending pregnancy Medicaid to one year after birth is likely to reduce racial disparities in insurance disruptions and ultimately, disparities in postpartum health."

Improving coverage before conception is also critical in identifying underlying health issues that may negatively affect a mother or baby's health.

"We know that complications associated with preexisting conditions chronic conditions such as heart disease, high blood pressure, and substance use are among the leading causes of maternal morbidity and mortality," says Admon, who is also a researcher at the University of Michigan Institute for Healthcare Policy and Innovation.

"It's important for women to have quality health coverage and care to manage these conditions to have the best chance of a healthy pregnancy."

"Medicaid stability before and after pregnancy is critical for ensuring continuity of coverage and access to care for women of color," says lead author Jamie Daw, Ph.D., researcher with the Department of Health Policy and Management at Columbia University.

"Extending pregnancy Medicaid to one year after birth is likely to reduce racial disparities in insurance disruptions and ultimately, disparities in postpartum health."

Improving coverage before conception is also critical in identifying underlying health issues that may negatively affect a mother or baby's health.

"We know that complications associated with preexisting conditions chronic conditions such as heart disease, high blood pressure, and substance use are among the leading causes of maternal morbidity and mortality," says Admon, who is also a researcher at the University of Michigan Institute for Healthcare Policy and Innovation.

"It's important for women to have quality health coverage and care to manage these conditions to have the best chance of a healthy pregnancy."

Around eight in every 100 children (8.4%; 673/7,994) aged 9-10 years in the USA report suicidal ideation (temporarily or regularly thinking about, considering, or planning suicide), according to a new nationally representative observational study of almost 8,000 children aged 9-10 years in the USA, published in The Lancet Psychiatry journal.

Importantly, less than two in every 100 (1.3%; 107/7,994) children aged 9-10 years reported a suicide attempt in the study, and around one in 100 (0.9%; 75/7,994) had past or current suicidal plans.

The study, which is the largest of its kind in the USA, identifies important risk and protective factors associated with childhood suicidal ideation which could be used to identify vulnerable children and plan interventions to promote mental health in school and at home.

"While a minority (around 8%) of 9-10 year olds express suicidal thoughts, the robust associations shown in this study with psychological problems (mostly anxiety and depressive problems) and family conflict provide practitioners with important information as to how they can intervene to help children and their families," says Dr Sophia Frangou from Icahn School of Medicine at Mount Sinai, USA, who co-led the research. "The same applies to the protective influences which involve higher parental supervision (ie, knowing where children are, what they are doing, and with whom) and positive school engagement, which are actionable and modifiable." [1]

She continues: "Although the best way of offering support to children is unclear, current evidence suggests that school-based programmes which aim to increase awareness, like the Mental Health Packs for Schools initiative in the UK, are likely to be successful public health interventions for reducing both suicidal behaviours and suicidal ideation." [1]

In the USA, suicide is the second leading cause of death in 10-14-year-olds, and the number of children's hospital admissions for suicidal thoughts or self-harm has more than doubled over the last decade, increasing from 0.67% in 2008 to 1.79% in 2015. However, suicidal thoughts and behaviours among children have to date received comparatively little attention compared to older age groups.

The researchers based their findings on data from 7,994 children (average age 9.9 years) taking part in the Adolescent Brain Cognitive Development (ABCD) study--which is following the largest nationally representative sample of 9-10 year-olds living in the USA [2].

To measure suicidal ideation for each child, caregivers and children were independently asked about current wellbeing and suicidal history as well as personal, family, and social characteristics using questionnaires.

Modelling was used to quantify the association between suicidal ideation and a wide array of personal, family, and social characteristics in children who had caregiver-reported (654 children) or child-reported (684 children) experiences of suicidal ideation (including 198 cases in which caregivers and children were in agreement on reports of suicide ideation), and those who had never expressed suicidal thoughts or behaviours according to caregiver and self-reports (6,854 children).

Although suicide planning and suicide attempts are relatively rare, the researchers found that factors associated with an increase in risk of suicidal thoughts included psychological problems (odds ratio [OR] 1?7-4?8, 95% CI 1?5-7?4) and exposure to child-reported family conflict (OR 1?4-1?8, 95% CI 1?1-2?5) [3].

Children, and particularly boys, who experienced suicidal ideation also reported on average spending around an hour longer using screen-based devices at weekends. However, the authors caution that more research is needed to understand whether the relationship between screen time and suicide ideation is causal (eg, the result of increased exposure to cyberbullying or negative social comparisons) or correlative (eg, linked with social withdrawal or avoidance).

Greater parental supervision (ie, knowing where children are, what they are doing, and with whom) and a child's positive view of school (ie, children who liked going to school) were identified as having a strong protective effect against suicide ideation, possibly because they can aid the development of identity, self-esteem, and resilience.

Importantly, the researchers only noted agreement between caregiver and child reports of suicide ideation in 17% of cases (198/1,140 children), indicating that suicidal thoughts and behaviours in children cannot be reliably assessed by parental report alone.

"Fears of stigmatisation, communication difficulties, and lack of social and family support may mean young children feel less comfortable talking about their mental health," explains senior co-author Dr Beatriz Luna from the University of Pittsburgh, USA. "This disconnect underscores the need for separate and independent assessment of suicide risk in children and parents." [1]

The authors note several limitations including that experience of suicidal thoughts and behaviours were based on self-reported data, which might not be accurate; and due to the cross-sectional nature of the ABCD data at this point, they are unable to address questions about the evolution of suicidal thoughts and behaviours over time. Additionally, because of the rarity of suicide attempts, it was not possible to distinguish between factors associated with suicidal thoughts and acts.

Writing in a linked Comment, lead author Dr Rory O'Connor (who was not involved in the study) from the University of Glasgow, UK, says, "If we are to develop effective suicide prevention interventions, it is essential that we identify and target these childhood risks. In particular, greater effort to protect children from early life adverse experiences is vital, given that family conflict was associated with between a 30% and 75% increased risk of suicidality, even when taking into account the effect of psychopathology...A key focus for future research should be factors that facilitate as well as impede the transition from suicidal thoughts to acts of suicide."

In December 2019, an outbreak of respiratory illness caused by a novel (new) coronavirus was identified in Wuhan, Hubei Province, China. Since then various organizations and media outlets have struggled to identify the respiratory illness correctly.

The AMA Manual of Style, written by editors of the JAMA Network and published by Oxford University Press, has released guidance on the terminology.

The AMA Manual of Style addresses coronavirus (CoV) in section 14.14.3, Virus Nomenclature, which includes information on Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV).

The International Committee on Taxonomy of Viruses (ICTV) Coronaviridae Study Group has determined that the new virus belongs to the existing species severe acute respiratory syndrome-related coronavirus. Thus, the new virus name recommended is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The World Health Organization has named the new disease coronavirus disease 2019 (COVID-19).

For more information contact:
stylemanual@jamanetwork.org

An important biological mechanism that is thought to protect brain cells from neurodegenerative diseases such as Alzheimer's and Parkinson's may also be involved in regulating sleep, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The researchers found that a signaling pathway that helps prevent the buildup of abnormal protein aggregates in brain cells is also required for sleep in both fruit flies and zebrafish. The fact that this mechanism is present in two evolutionarily distant species suggests that it may also be present in humans.

There have long been puzzling hints that sleep loss and sleep disorders are connected to neurodegenerative diseases, and the findings, published online today in Current Biology, reveal one possible explanation for the link. If the results were extended to humans, they would point the way to new strategies against both sleep disorders and neurodegenerative diseases.

"Sleep fragmentation, which is characterized by repetitive short sleep interruptions, is one of the most common triggers of excessive daytime tiredness, especially in older people," said principal investigator Nirinjini Naidoo, PhD, a research associate professor of Sleep and Chronobiology. "Now that we know a major pathway that is involved in sleep regulation, we can target it to potentially improve fragmented sleep."

Studies in recent years have suggested that chronic sleep loss increases the risk of Alzheimer's, while people with Alzheimer's have an elevated risk of sleep disturbances. Sleep disturbances are also common features of Parkinson's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and other neurodegenerative diseases.

How the processes underlying neurodegenerative disease might be connected to sleep disturbances has never been clear. But one hint comes from findings in lab animals that the brain during sleep dials up "proteostasis" processes that clear away abnormal and potentially harmful protein aggregates, such as those that clutter the brain in neurodegenerative disorders.

In the new study, Naidoo and her colleagues scrutinized an important proteostasis process called the PERK signaling pathway, which, in response to a buildup of unwanted protein aggregates, causes cells temporarily to stop their assembly of most proteins. The scientists found that when they suppressed PERK signaling in Drosophila fruit flies or in evolutionarily distant zebrafish, using small-molecule compounds that block a key component of the pathway, both sets of animals slept much less than normal. Blocking PERK with genetic techniques in Drosophila brought similar results, while doing the reverse -- forcing the overproduction of PERK -- made the flies sleep more.

PhD candidate Sarah Ly examined tiny groups of neurons that produce a key wakefulness-promoting hormone in Drosophila, and found that knocking down PERK at night, just in these neurons, was enough to make the flies sleep less, whereas overproducing PERK made them sleep more. In one subset of these neurons the researchers were able to verify that boosting or reducing PERK had the effect of suppressing or unleashing production of the wakefulness hormone. "This raises possibility that PERK regulation of sleep occurs within multiple brain circuits," Ly said.

This discovery marks the first time that scientists have identified a specific and bidirectional biological mechanism tying sleep to proteostasis. The findings also point to the possibility that wakefulness tends to increase protein-aggregate accumulation in brain cells, leading to more PERK signaling. This ultimately helps reverse the brain-cell stress by enforcing sleep and allowing effective protein housekeeping to take place.

"Our findings suggest that one of the conserved functions of sleep may be to mitigate cellular stress caused by wakefulness," said Naidoo.

The authors believe that further research into this nexus between sleep and proteostasis has the potential to uncover important new therapeutic strategies for improving sleep quality, reducing the risk of Alzheimer's and other neurodegenerative diseases, and effectively slowing the aging of the brain.

Ewa Strus also co-authored this study. The research was supported by the National Institute of General Medical Sciences (R01GM123783).

Substantial amounts of ammonium salts have been identified in the surface material of the comet 67P/Churyumov-Gerasimenko, researchers report, likely revealing the reservoir of nitrogen that was previously thought to be “missing” in comets. The chemical and isotopic composition of the Sun is thought to reflect that of the solar nebula from which it was born. Comets, which are thought to have condensed long ago in the cold outer reaches of the solar nebula, far from the heat of the forming Sun, should contain the same primordial material. However, the nitrogen-to-carbon ratio (N/C) measured in comets, including Comet 67P, is lower than for the Sun, when it should be the same. The reason for this nitrogen deficiency is unknown. Spectroscopic measurements of Comet 67P’s surface by the Rosetta spacecraft show a ubiquitous, yet unidentified, infrared absorption feature centered around 3.2 micrometers (μm). While several materials, including nitrogen-bearing molecules, have been suggested as the source of the unknown spectral feature, a lack of reference data for plausible compounds has prevented its attribution. Oliver Poch and colleagues used laboratory experiments to simulate various possible comet surface compositions and measured their resulting reflectance spectra, attempting to reproduce the 3.2 μm feature observed on Comet 67P. Among the candidate compounds the authors tested, several nitrogen-containing ammonium salts could reproduce the comet’s unidentified infrared absorption bands. Based on these new findings, Poch et al. conclude that the ammonium ions (NH4+) in these compounds are likely the source for the 3.2-μm feature. The authors identify the semi-volatile ammonium salts as a substantial reservoir of nitrogen, the abundance of which could be high enough to account for the observed N/C discrepancy between comets and the Sun.

Head and neck squamous cell carcinoma (HNSCC) – a group of cancers that affect the the mouth, nose and throat – is a disease driven by mutations in the NOTCH tumor suppressor signaling pathway, according to a new study. It reveals the identity of rare driver mutations in tumor-suppressing genes using a mouse-based in vivo CRISPR screen to evaluate the function of so-called “long tail” mutations. In humans, these mutations are present in 67% of HNSCC patients and converge on NOTCH inactivation, thus promoting tumor development. HNSCC is the 6th most common human cancer and, while curable, has a poor survival rate and claims the lives of roughly 350,000 people worldwide each year. Like other cancers, HNSCC is characterized by a few genes mutated at high frequency in many patients (including the NOTCH tumor suppressor gene), followed by a “long-tail” of hundreds of other individually rare mutations observed in only a few patients. The functional consequences and biological significance of recurrent but rare mutations are generally unknown, but these mutations could potentially shed light on cancer biology and tumor evolution and perhaps lead to novel treatment strategies. Sampath Loganathan and colleagues developed a reverse genetic CRISPR screen that allowed them to identify genes that, upon mutation, predispose mice to developing MNSCC. Through their analysis, Loganathan et al. identified 15 potent tumor suppressor genes that, when mutated, triggered rapid growth of HNSCC in the mice. These genes included ADAM10 and AJUBA, which are also mutated in human HNSCC. The wild type versions of ADAM10 and AJUBA promote NOTCH signaling. These results show that HNSCC-associated mutations converge on inactivation of the NOTCH tumor suppressor signaling pathway.