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It is generally known that viruses, with their cell-invading capabilities, can be responsible for a number of different cancers. What is less broadly discussed are the cancer-causing capabilities of bacteria, or the processes by which they may cause malignancy.

In a review article appearing in the November 18 issue of Trends in Molecular Medicine, University of North Carolina at Charlotte, cancer biologists Pinku Mukherjee and Mukulika Bose discuss a mechanism that, they suggest, may implicate bacterial infections in a wide variety of cancers - a cause that science has yet to fully understood.

The article, "Microbe - MUC1 Crosstalk in Cancer-Associated Infections," makes the case for the likely implication of microbial (especially bacterial) interactions with the glycoprotein known as MUC1 in cancers involving epithelial cells, including cancers of the colon, lungs, stomach, liver and pancreas.

Epithelial cells are cells that are frequently specialized for absorption or secretion purposes, and to form linings or barriers in organs, including the intestines, lungs, stomach, liver and reproductive organs. MUC1 is a "transmembrane" protein - extending outside, through and inside the cell membrane to the cytoplasm - and is present in nearly all glandular epithelial cells. It is one of a group of proteins known as "mucins" for their involvement in protective mucous layers, whose gel-forming features are caused by sugar molecules coating part of the protein's length ("glycosolation"). The sugars, essentially, interact with water molecules, creating a slippery, slimy barrier, protecting cell layers against pathogens and environmental damage.

Mukherjee, Irwin Belk Distinguished Professor of Cancer Research and chair of UNC Charlotte's Department of Biological Sciences, has done considerable past research on the surprisingly negative roles MUC1 can play in a variety of cancers. The association of the protein with cancer is very strong -- as the article notes, "the National Cancer Institute ranked MUC1 as the second best target antigen for the development of cancer vaccines."

Mukherjee also does work on the interaction of cancer and pathogen infections. "Now it is known that about 20% of all malignancies, especially epithelial malignancies, are associated with some sort of infection, viral or bacterial, persistent inflammation being the root cause" she notes.

Mukherjee explains that a lot is now known about viruses and the biological mechanisms involved - the association of HPV with cervical cancer, for example.

"But there is very little known about what causes cancers associated with bacterial infections... not much is known about this. But when there are bacterial infections that have definitely been linked to cancer -- like H. pylori with stomach cancer and ulcers - that appears to have to do with the basic persistence of the bacteria," she said.

Persistent infections may be different because of the effects of their long-term attacks on cellular defense mechanisms.

"But if these persistent bacterial infections cause aberrations on the epithelial layers, mucins must be involved because every glandular epithelial cell has mucins and we know that mucins are the first protective layer in any bacterial infection."

Imbedded in the epithelial cell membrane, with its outside end coated with attached sugars and its inside end floating largely naked in the cell's cytoplasm, MUC1 serves a largely protective role, Mukherjee explains. Molecules on the surface of bacterial cells bind to the mucosal layer or to the glycosolated end of MUC1, but the cell is ready for the attack and responds.

"Attachment by the bacteria triggers MUC1 to shed its extracellular domain (the glycosolated section) with the bacteria attached, and the whole thing goes to the mucous layer, where the bacteria is removed," she said. "It thus works as an anti-inflammatory by pushing the attacking bacteria out and engulfing it into the sugary molecule."

However, the process can have side-effect, she explains: "That's mainly how MUC1 works, but what happens sometimes when MUC1 sheds, its remaining outside and cytoplasmic tail (the protein's inner segment) gets activated. A persistent bacterial barrage on a cell activates some cytoplasmic tail and we know that when the cytoplasmic tail is activated it can trigger signaling pathways that cause cancer."

MUC1 can thus play a dual role during infection, either being anti-inflammatory by staving off bacterial attack, or pro-inflammatory, triggering inflammation processes, which, in turn, can cause malignancy.

"The dual role of MUC1 as protective and oncogenic in the presence of microbial infection is, in a nutshell, what this article is about," she said. "There are pieces of research out there that point to this, but we are trying to pull them together."

The article surveys studies on a dozen common infections by bacteria and viruses that are known to involve MUC1 and notes a limited number of examples where the protein is known to play a pro-inflammatory role.

"The field has only looked at these mechanisms in small number of infection-associated cancers, and even fewer where bacteria are involved," she noted. "We hope our hypothesis leads to people looking at this in a more scientific manner."

Mukherjee's hypothesis stresses the central role of MUC1 and mucins in targeting future research. Because of strong connections between the protein and cancer processes in epithelial cells and the protein's strong involvement in combating microbial infections, it is an obvious, yet understudied connection between infection and cancer.

"The idea is that at some point we are going to have to start studying mucins more seriously," she said. "Rather than only studying mucins in already transformed cancer cells, we need to be studying them before the cells transform and see what is going on. The work being done on the cancer side needs to be connected with the work on the bacterial side, and the role of infection in triggering inflammation."

Adolescent binge drinking modifies gene expression in a fashion that increases susceptibility to anxiety and alcohol use disorders in adulthood, according to research in rats recently published in eNeuro. Targeting the microRNAs responsible could be a new route for undoing the damage of alcohol use caused during adolescence.

Previous researchers found that microRNA, small bits of RNA that modify how genes are expressed rather than coding for a protein, are involved in how early-life alcohol exposure changes the brain, but the exact mechanism was unknown.

Kyzar et al. exposed adolescent rats to alcohol and measured the resulting levels of miR-137, one type of microRNA, in the rats' amygdalae. The rats exposed to alcohol displayed increased levels of miR-137, resulting in lower expression of proteins necessary for healthy neuron growth and branching. In adulthood, the rats displayed higher levels of anxiety behaviors and a higher preference for alcohol compared to control rats. Inhibiting miR-137 in the amygdala reversed the anxiety and alcohol preference in the rats with an adolescent drinking history.

The drug ketamine decreases alcohol consumption in male, but not female, rats, according to new research published in eNeuro. The findings suggest that ketamine may be a viable treatment option for male patients with an alcohol use disorder.

Prior studies found that ketamine reduces alcohol use disorder symptoms in both rats and humans, but the drug was administered once, rather than over a more realistic treatment time period. Ketamine is itself an addictive drug, so it is critical to examine how it affects patients over extended use.

Strong et al. divided male and female rats into groups based on how much alcohol they were prone to consume. The rats were allowed unrestricted access to alcohol three times a week. Three weeks later, ketamine treatments began.

Ketamine administration reduced alcohol consumption in high-consumption male rats, and the effects lasted at least three weeks after the ketamine treatments ended. Ketamine did not affect the habits of high-consumption female rats and increased drinking in low-consumption females. The female rats also displayed a higher risk of abusing ketamine compared to the male rats.

Podcast permanent link: https://soundcloud.com/cmajpodcasts/190355-res

The overall rate of new cancer cases is decreasing in men but increasing in women younger than 80 years, and obesity-related cancers are increasing in young people, according to a study on cancer trends in Canada from 1971 to 2015 published in CMAJ (Canadian Medical Association). http://www.cmaj.ca/lookup/doi/10.1503/cmaj.190355.

"The most striking results from these analyses relate to increasing incidence trends among younger adults for breast, colorectal, pancreatic, endometrial and kidney cancers," writes Dr. Darren Brenner, Cumming School of Medicine, University of Calgary, with coauthors. "Obesity is a risk factor for these cancer sites, and the rising incidence runs parallel to the growing prevalence of obesity in recent decades."

The study, which included almost 5.2 million cancer cases diagnosed in Canada between 1971 and 2015, looked at cancer trends by age and birth cohort (patients grouped by year/decade of birth). Cancer incidence -- the rate of new cases -- is well documented in Canada, but less is known about trends by age groups.

"The trend among younger adults is of greater concern because they are ineligible for most cancer screening programs," write the authors.

Other key findings:

There has been an overall increase in cancers not normally occurring at younger ages, particularly breast and colorectal cancer.

The highest increase in cancer incidence is for women aged 30-39 years.

Cancer incidence has decreased in women aged 80-89 years.

The most recent trends show statistically significant decreases in the incidence of cervical, lung, bladder and prostate cancer, across most age categories.

The overall recent decrease in cancer incidence is due to declines in cancer in people older than 50 years.

The reductions in cancer incidence across age groups for several cancer types are most likely the result of primary and secondary prevention activities, including smoking cessation programs, which have decreased lung cancer, and sun safety behaviours, which have led to lower rates of melanoma in women younger than 40 and in men younger than 50 years. Endoscopy and fecal-based screening programs for colorectal cancer and screening for cervical cancer have contributed to declining rates in these cancers.

However, a rise in the use of prostate-specific antigen (PSA) testing resulted in sharp increases in prostate cancer diagnoses between 1990 and 2007, and thyroid cancer has also been over-diagnosed.

Age-specific cancer rates over time help identify the impact of changes in practice such as screening programs, better diagnosis and changing risk factors. Further efforts to reduce obesity, promote additional cancer prevention programs and further research into risk factors that may be causing cancer in younger age groups are essential.

ANN ARBOR, Mich. -- Telling the difference between a teen's normal ups and downs and something bigger is among top challenges parents face in identifying youth depression, a new national poll suggests.

Though the majority of parents say they are confident they would recognize depression in their middle or high school aged child, two thirds acknowledge barriers to spotting specific signs and symptoms, according to the C.S. Mott Children's Hospital National Poll on Children's Health at the University of Michigan.

Forty percent of parents struggle to differentiate between normal mood swings and signs of depression, while 30% say their child is good at hiding feelings.

"In many families, the preteen and teen years bring dramatic changes both in youth behavior and in the dynamic between parents and children," says poll co-director Sarah Clark. "These transitions can make it particularly challenging to get a read on children's emotional state and whether there is possible depression."

Still, a third of parents polled said nothing would interfere with their ability to recognize signs of depression in their child.

"Some parents may be overestimating their ability to recognize depression in the mood and behavior of their own child," Clark says. "An overconfident parent may fail to pick up on the subtle signals that something is amiss."

The poll also suggests that the topic of depression is all too familiar for middle and high school students. One in four parents say their child knows a peer or classmate with depression, and 1 in 10 say their child knows a peer or classmate who has died by suicide.

Indeed, rates of youth suicide continue to rise. Among people ages 10 to 24 years old, the suicide rate climbed 56% between 2007 and 2017, according to the Centers for Disease Control and Prevention.

"Our report reinforces that depression is not an abstract concept for today's teens and preteens, or their parents," Clark says.

"This level of familiarity with depression and suicide is consistent with recent statistics showing a dramatic increase in suicide among U.S. youth over the past decade. Rising rates of suicide highlight the importance of recognizing depression in youth."

Compared to the ratings of their own ability, parents polled were also less confident that their preteens or teens would recognize depression in themselves.

Clark says parents should stay vigilant on spotting any signs of potential depression in kids, which may vary from sadness and isolation to anger, irritability and acting out. Parents might also talk with their preteen or teen about identifying a "go to" adult who can be a trusted source if they are feeling blue, Clark says.

Most parents also believe schools should play a role in identifying potential depression, with seven in 10 supporting depression screening starting in middle school.

"The good news is that parents view schools as a valuable partner in recognizing youth depression," Clark says.The bad news is that too few schools have adequate resources to screen students for depression, and to offer counseling to students who need it."

Clark encourages parents to learn whether depression screening is taking place at their child's school and whether counseling is available for students who screen positive. Given the limited resources in many school districts, parents can be advocates of such efforts by talking to school administrators and school board members about the importance of offering mental health services in schools.

The nationally representative Mott Poll report is based on responses from 819 parents with at least one child in middle school, junior high, or high school.

Our expert's guide for parents on how to talk to children and teens about depression and suicide.

Opening Medicare to Americans aged 50 to 64 would lower health care premiums for the group, but also drive up costs for younger people who buy health insurance on exchanges created under the federal Affordable Care Act, according to a new RAND Corporation study.

Under most scenarios examined, the study estimates that the premium to buy into Medicare would be about $10,000 per year in 2022. For many potential enrollees, this amount is a good deal compared to the ACA-compliant individual insurance market, in which older adults are charged up to three times as much as younger adults.

While older exchange enrollees currently pay higher premiums, the analysis finds that, as a group, their care is less expensive relative to their high premiums. Younger people in the exchange tend to be less healthy and their care is more expensive than the premiums they pay.

As a result, the analysis finds that enabling adults aged 50 to 64 to move to Medicare could increase premiums for those remaining in the individual health insurance market by between 3% and 9%.

"Our findings suggest that Medicare buy-in could offer significantly more-affordable health care coverage to older adults, while potentially leading to higher premiums for the pool of people remaining on the individual market," said Christine Eibner, the study's lead author and the Paul O'Neill Alcoa Chair in Policy Analysis at RAND, a nonprofit research organization.

For a typical 50-year-old, buying into Medicare would cost about $2,500 less than buying a gold-level plan on the insurance exchanges, but be about $500 more than a bronze-level plan. Medicare offers significantly better coverage than bronze-level insurance plans, but unlike exchange plans, it does not have a maximum limit on the total amount of out-of-pocket spending a beneficiary might have to pay.

For a typical 60-year-old, the savings would be greater. For this group, buying into Medicare would cost about $8,000 less per year as compared to a gold-level plan on the insurance exchanges and $3,700 less than buying a bronze-level plan.

The analysis finds that opening Medicare to Americans aged 50 to 64 would not substantially change the number of Americans with health insurance. While such a move likely would increase the number of Americans aged 50 to 64 who have health insurance, the higher costs on insurance exchanges is likely to mean that fewer younger Americans would buy coverage.

Under all the scenarios studied, a Medicare buy-in for Americans aged 50 to 64 would have no effect on the Medicare Trust Fund or on outcomes for current Medicare beneficiaries.

Policymakers have long discussed allowing people under the age of 65 to buy into Medicare, primarily as a way to provide older adults with access to insurance without regard to coverage denial or preexisting condition exclusions.

Following the passage of the ACA and its requirement that coverage be offered regardless of health status, discussions about expanding Medicare eligibility have focused on creating alternative coverage options that include access to Medicare's provider payment rates, reducing premiums on the ACA's marketplaces by moving older people into a separate risk pool and increasing overall insurance enrollment.

The RAND study used a microsimulation model to estimate the effects of allowing older adults to buy into Medicare under a number of scenarios. Researchers assumed that eligible individuals can apply their marketplace advanced premium tax credits to the buy-in plan.

The study's finding that allowing 50- to 64-year-olds to buy into Medicare would drive up insurance costs for individuals in the marketplace runs counter to conventional wisdom, which argues that older adults drive up individual market premiums because they tend to have more medical problems.

The RAND model accounts for the fact that low-cost older adults are more likely to enroll in the insurance exchanges than low-cost young adults, and these healthy older people act as a stabilizing force. The model also accounts for the fact that Medicare payment rates are lower than commercial rates, and administrative costs are lower in Medicare than in private plans.

The report was developed with the support of funding by AARP. Any opinions, findings, conclusions and recommendations are those of the authors and do not necessarily reflect the views of AARP.

Given consumer concern that statins may be associated with memory or cognitive decline, a new study published today in the Journal of the American College of Cardiology may offer reassurance, as no difference was found in the rate of memory or cognitive decline of elderly statin-users compared to never-users.

"Not only are statins one of the most prescribed medications in the world, there is strong evidence that they reduce mortality in our patients with heart disease, stroke, diabetes, renal disease and other lipid disorders. Most importantly, statins aren't associated with a risk for major adverse health advents," said Katherine Samaras, MBBS, PhD, an endocrinologist at St. Vincent's Hospital in Australia and the study's lead author. "These findings will hopefully go a long way toward reducing consumers' concerns about memory and cognition from statins, so they don't stop taking these lifesaving medications."

The researchers examined changes in the memory and global cognition regarding statin-use over a six-year observation period and two years of brain volume studies using the Sydney Memory and Ageing Study, a longitudinal observation study of cognition of community-dwelling, non-demented elderly participants conducted at the Centre for Healthy Brain Ageing (CHeBA), University of New South Wales, Sydney, Australia. Data were collected every two years on four occasions over the six-year period by psychologists and nurses. Clinicians diagnosed the presence of heart disease, cerebrovascular disease, hypertension and Type 2 diabetes.

Participants' medications and duration of use were categorized as statin ever-use versus never-use; continuous statin-use during observation versus never-use; specific statins (simvastatin, pravastatin and atorvastatin) versus never-use; and statin initiation during observation period versus never-use.

The 1,037 participants were aged 70 to 90 years and were 98% Caucasian and Australian- (67%) or European- (18%) born. There were 395 statin never-users and 642 statin ever-users, which included ever-users at baseline and those who commenced taking statins during the study period. On average, participants had been on statins for nine years.

To measure their primary endpoints--memory and global cognition--a comprehensive assessment of global cognition and memory was developed. Five memory tests were employed by the researchers to assess new learning and short and long-term recall using verbal and visual memory tasks. Global cognition evaluated memory plus processing speed, language, visuospatial ability and executive function.

All participants were offered brain magnetic resonance imaging (MRI) at baseline, with 529 patients accepting and 408 undergoing a repeat MRI two years later. Statin ever-users and never-users were found to have similar total brain volume, hippocampal and parahippocampal brain volumes at baseline with no significant differences two years later.

Statin ever-users and never-users were similar at baseline for both memory and global cognition, the researchers found no significant difference in rate of decline in either memory or global cognition. Participants who took statins continuously over the study period had significantly higher baseline performance in memory and global cognition compared to never-users; the rate of decline in memory and global cognition for this subgroup was similar over the six-year observation period. When researchers compared the 99 participants who started statins during the study period, they found statin initiation was associated with a lessening in the rate of decline of memory. Overall, no associations between statin use and cognition were found between baseline and the six years of observation.

The researchers did find a protective interaction between statin ever-use, heart disease and the six-year change in the total learning memory test score. Among patients with heart disease, statin ever-users displayed a slower rate of decline on this test compared to never-users. However, in patients without heart disease, there was a comparable rate of decline between statin ever-users and never-users. The study also found a protective interaction between statin ever-use and the rate of decline in long-delayed recall performance for patients carrying the APOE-4 genotype. Carriers of this genotype are at high risk of Alzheimer's disease. In secondary analyses, male statin users did display a significantly faster logical memory decline compared to male never-users, but there was no significant difference between female statin users and never-users.

"We must acknowledge some limitations of the study, in particular the observational design and potential for selection and survivor bias," said Perminder Sachdev, MBBS, PhD, senior author who, along with Henry Brodaty, MBBS, MD, leads the Sydney Memory and Ageing Study. "Additionally, as participants with more advanced cognitive impairment were excluded from the study, no conclusions can be made for statin benefits in that group."

In an accompanying editorial, Costantino Iadecola, MD, and Neal S. Parikh, MD, MS, from Weill Cornell Medicine in New York City said, "These data support the view that worries about cognitive impairment should not limit statin use and raise the possibility that statins may favorably alter cognitive trajectories in a group of elders at high risk of Alzheimer's disease."

A parasitic wasp was recently discovered in Guanajuato, Mexico, where it was found to parasitize the eggs of an invasive stink bug, known as the bagrada bug, which is a major pest of cruciferous vegetables. A research team from Colegio de Postgraduados (Mexico), Agriculture and Agri-Food Canada (AAFC) and the Florida State Collection of Arthropods (FSCA) collaborated to publish a study on the biology this species, Idris elba, and describe it as a species new to science.

The genus Idris was described in 1856 and now contains over 300 species and many more species are still undescribed. Species of Idris were previously known to only parasitize spider eggs. It was thus very unexpected when specimens of Idris were found to emerge from eggs of the bagrada bug by Dr. Refugio Lomeli-Flores and his team in Guanajuato. Advanced methods in molecular forensics were used by Dr. Tara Gariepy (AAFC) to match the DNA of the adult wasp with DNA left behind in the stink bug egg from which it emerged, independently confirming the results. The specimens were then sent to taxonomist, Dr. Elijah Talamas (FSCA), who determined that it was an undescribed species.

The discovery of this wasp marks an important step toward the development of efficient and natural control of the stink bug species Bagrada hilaris in North America. Commonly known as the bagrada bug, it is native to Africa, but is already an established and important pest of over 74 plant species in India, southern Europe, southern Asia and the Middle East. Across the Atlantic, it has been known since 2008, when it was reported from Los Angeles, California (USA), followed by records from Coahuila state, Mexico, in 2014. Three years later, it was also found in the state of Guanajuato, which is responsible for over 70% of the country's broccoli production, as well as the major import of broccoli and cauliflower in the USA and Canada. So far, measures to halt the bug's invasion have proven largely ineffective, and its distribution is expected to reach new ecosystems of economical importance.

While not unheard of, it is uncommon for native parasitoids to attack an introduced host. Idris elba is exceptional because it demonstrates that these wasps can make the leap from parasitizing the eggs of spiders to the eggs of stink bugs. Having rejected the possibility of the species having been introduced alongside its host, the scientists note that the unexpected association could be either the result of a broad host range, or a case of lucky confusion, where the parasitoid tends to mistake the eggs of the stink bug for those of a spider.

It is no coincidence that this wasp has the species name "elba". Dr. Talamas explained that explicitly naming the species after Idris Elba (the actor), also known as a patronym, would have to follow Latin grammar and become Idris elbai. By treating the second name as an arbitrary combination of letters, the grammar was avoided.

Four-time Golden Globe nominee for Best Actor, Idris Elba is a famous British actor, producer, writer, singer, DJ and producer, best known for a long list of blockbusters, including a good number of superhero movies, such as the Marvel series inspired by the myths of the Norse god Thor. There, Elba stars as Heimdall, whose almost namesake: Heimdallr, is a Norse deity believed to be the sole protector of the bridge linking the human world and the realm of the gods.

PHILADELPHIA -- Vaccine-preventable disease (VPD) outbreaks are increasing in frequency in the United States, but this trend is also met with an uptick in legislation aimed at increasing childhood vaccination in places where those epidemics occurred, according to findings published today in JAMA Pediatrics from researchers at the Dornsife School of Public Health at Drexel University.

The Drexel team found that as VPD outbreaks increased, so did introduction of state legislation intended to restrict laws that allow for skipping childhood vaccinations. The team looked at 2010-2016 state-level data on 12 different childhood VPDs reported to health departments, including Hepatitis A and B, flu, measles, whooping cough and others. They then probed state legislature data for bills introduced the year following the start of an outbreak, between 2011-2017, that would expand or reduce the criteria required to be vaccinated for these diseases.

The study found that each state reported an average of 25 VPDs per 100,000 people per year, with substantial variability year to year. Of the 175 related bills proposed during 2011-2017, 53 percent made it easier to exempt oneself from vaccine requirements while 47 percent made it more difficult to be skip vaccination.

Although there were more anti-vaccine bills than pro-vaccine bills introduced overall during this seven-year period, grouping the bills into these two categories paints a more public health-centered picture. Researchers found that increases in VPDs were actually positively associated with increases in the number of proposed pro-vaccine bills that restrict exemptions. They did not observe any statistical association between decreases in VPDs and proposed bills that would make it easier to bypass vaccination.

Legislation to increase vaccination is particularly needed in the United States. In 2000, the Centers for Disease Control and Prevention declared measles eliminated in the United States, but announced 695 measles cases in 22 states in April 2019. Two recent outbreaks in California (2015) and New York (2019), led state legislatures to remove all nonmedical exemptions.

"Vaccines are our best public health tool for controlling many childhood diseases," said lead author Neal D. Goldstein, PhD, an assistant research professor of epidemiology and biostatistics at Drexel's Dornsife School of Public Health. "Seeing an uptick in legislation aimed at cutting vaccine exemptions following disease outbreaks suggests that media coverage may raise public awareness and advocacy and response from legislators. While it is unfortunate it took outbreaks of preventable disease to spawn legislative action, it further affirms the widespread support of this life-saving intervention."

According to the Wellcome Global Monitor 2018 report, support for vaccination varies substantially between countries, with lower income regions reporting greater confidence than higher income regions do in vaccines. This distrust of vaccines in some wealthier countries makes "herd immunity" - vaccination of the vast majority of a population to prevent individuals from contracting a disease and spreading it to others - much more difficult to achieve, particularly in small, but vocal communities who are hesitant to vaccinate.

The latest report on the consensus among the scientific community in support of vaccines is summed up in The Salzburg Statement on Vaccination Acceptance, published by some public health experts in July 2019 in the Journal of Health Communication. In the text, the authors share their "unwavering commitment to universal childhood vaccination."

In November 2018, Goldstein and colleagues published a study in the American Journal of Public Health showing that, despite increasing numbers of anti-vaccine bills being introduced in state legislatures from 2011 to 2017, pro-vaccine legislation was more likely to become law.

After countless studies on how laws affect health, the Drexel team flips that model on its head to report data about how health affects laws.

"We believe this paradigm can be applied to many other public health areas, not just vaccination," said Goldstein, who also consults for Merck Sharp & Dohme Co., but noted that the company had no role in the study or its outcome.

Progeria is a very rare disease that affects about one in 18 million children and results in premature aging and death in adolescence from complications of cardiovascular disease. In a study on mice and human cells, researchers at Sweden's Karolinska Institute and IFOM, the FIRC Institute of Molecular Oncology in Italy, have identified how antisense oligonucleotide therapies could be used as a new possible treatment option for the disease. The results are published in the journal Nature Communications.

Progeria, or Hutchinson-Gilford progeria syndrome as the disease is also called, has genetic causes and is linked to progerin, a defect form of the lamin A protein found in the cell nucleus. The mutation, which inhibits cell division, was identified in 2003 by researcher Maria Eriksson, co-author in the current study. The affected children usually die in early adolescence from complications of cardiovascular disease.

So far, more than a dozen treatments of progeria have been tested in different ways, but when it comes to clinical trials conducted in patients with progeria, the results have been disappointing.

"We have seen positive effects in the treatment of mice, but in humans the effect has been too small. We therefore need to rethink and find new ways to treat the disease," says Maria Eriksson, professor at the Department of Biosciences and Nutrition at Karolinska Institutet.

In the now published study, the researchers used cell samples from children with progeria to show an impaired function in the telomeres at the far end of the chromosomes and the accumulation of so-called telomeric non-coding RNA. By adding antisense oligonucleotides, a treatment used to inactivate harmful genes, the researchers were able to reduce the level of telomeric non-coding RNA. This led to a more normalised cell division, which would likely improve patients' conditions and extend their lifespan.

"In a gene altered mouse model of progeria treated in the same way, we saw a significant increase in both the maximum life expectancy, up 44 percent, and the average life expectancy, up 24 percent," says Agustin Sola-Carvajal, former postdoc in Eriksson's research group and co-author of the study. "These results are very promising."

Progerin is also found in healthy subjects and has been observed to increase with age, suggesting the results may also be important for normal aging and age-related disease.

"More research is needed to assess how the relatively low levels of progerin seen in healthy individuals contribute to ageing and age-related disease," says Eriksson. "It is interesting to note that antisense oligonucleotides are now included as drugs in advanced clinical trials, some of which are already approved by the FDA in the U.S."

SACRAMENTO, Calif.) - A study of over 6,300 Latinos of Dominican, Central American, Cuban, Mexican Puerto Rican and South American heritage estimates that nearly 10% of middle-age and older Latinos in the U.S. meet the criteria for mild cognitive impairment. MCI is a transitional stage between healthy aging and dementia characterized by a slight decline in memory and thinking skills.

The research, led by researchers at the University of California at Davis and San Diego, publishes Nov. 18 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. It is an important first step in understanding Alzheimer's and other dementias in understudied Latino populations.

"Latinos share regional forms of the Spanish language, but their cultural histories, genetic ancestries and health profiles are diverse," said Charles DeCarli, co-principal investigator of the study and director of the UC Davis Alzheimer's Disease Center. "This is the first study to estimate the overall prevalence of mild cognitive impairment among diverse populations of Latinos. It also identified factors - cardiovascular disease and depression - that can be treated to reduce the risk."

The researchers found 9.8% of participants had MCI. Older age, high cardiovascular disease risk and symptoms of depression increased with MCI prevalence. However, a major risk factor gene for developing Alzheimer's in some populations, APOE4, was not associated with increased MCI risk in the Latino groups studied. This result differs from prior studies of principally white, non-Hispanic populations.

"Our findings suggest that there are other biological factors that may contribute to MCI in Latinos," said Hector M. Gonzalez, first author and co-principal investigator of the study. He also is an associate professor of neurosciences at UC San Diego.

The researchers linked Puerto Rican heritage with the highest MCI prevalence (12.9%) and those with Cuban heritage with the lowest (8.0%). MCI prevalence for those with heritage in other parts of the world included, Central Americans (10.8%), Dominicans (9.7%), South Americans (9.6%) and Mexicans (9.5%).

While MCI rates varied by Latino backgrounds, the variation was not as wide as reported in previous studies, the researchers said.

For the study, Gonzalez and colleagues assessed detailed data on Latino health from SOL-INCA, a Study of Latinos-Investigation of Neurocognitive Aging, and its parent study, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Funded by the National Institutes of Health, SOL-INCA contained the results of cognitive tests given in English and Spanish with follow-up testing occurring seven years later on average. HCHS/SOL focused on cardiovascular risk factors.

"With the in-depth sociocultural, behavioral, biological and genetic data collected and careful study design, we were able to generalize our findings for diverse Latino populations," said Gonzalez, principal investigator of SOL-INCA. "We believe we are at the frontier of making new discoveries and more precisely understanding Latino cognitive aging and Alzheimer's disease-related dementias.

By identifying cardiovascular disease and depression as important risk factors for MCI among Latinos, the researchers believe there is a tremendous opportunity to intervene to improve health.

"Cardiovascular disease and depression can be treated to reduce MCI risk in this large, rapidly growing, but understudied population," Gonzalez said.

In a related Perspective article published in the same issue of the journal, González and colleagues suggest using SOL-INCA as a model research framework for advancing research on Latino Alzheimer's disease and other dementias.

Latinos represent nearly one-fifth of the U.S. population. In California and Texas, they represent 40% of the population. Preventing dementia and addressing cardiovascular disease in Latinos later in life begins with understanding and modifying cardiovascular health earlier in the lifespan.

Osaka, Japan - Arthritis is a common chronic disease in which joints become inflamed, leading to stiffness and pain that can often be debilitating. Rheumatoid arthritis (RA) is an autoimmune form of the disease, arising when immune cells attack the tissue that lines the joints. There is a need for new treatment options, as current therapies only alleviate symptoms or, at best, slow the disease. Now, in a study published in Nature Immunology, researchers at Osaka University have discovered a previously unknown type of RA-causing cell within arthritic joints that could someday be a target for new treatments.

There are two major cellular culprits that contribute to RA. The first are immune cells, which release inflammatory chemicals around the tissue of affected joints. The second are osteoclasts, specialized cells that secrete acids and enzymes to break down bone. Osteoclasts normally help to remodel healthy bone, but in RA their bone-dissolving ability goes into overdrive and damages joints.

"The disease-modifying anti-rheumatic drugs available today predominantly act against the inflammatory response of immune cells," says Masaru Ishii, professor at Osaka University Graduate School of Medicine and corresponding author of the study. "Therapies targeting osteoclasts are limited, largely because we don't know enough about the osteoclasts involved in RA. We were interested in understanding whether these cells are somehow different from the osteoclasts involved in normal physiological processes."

Osteoclasts are elusive, residing along the surface of bone under layers of cartilage and tissue. This makes them difficult to isolate in the lab, even with tractable models like mice. To collect the cells, the research group had to develop a surgical technique that allowed them to extract osteoclasts from the femurs of arthritic mice. With osteoclasts securely in hand, they were then able to gather new insights into RA.

"We tracked precisely how arthritis-inducing osteoclasts develop from their undifferentiated precursor cells," explains Tetsuo Hasegawa, lead author of the study. "While normal osteoclasts are derived from stem cells in the bone marrow, we found that osteoclasts involved in RA come from blood-borne precursors. The circulating precursors enter the joint and differentiate into a unique sub-type of osteoclasts, which are larger and have distinct markers that aren't seen in other osteoclasts."

The newly discovered cells, dubbed "AtoMs" (Arthritis-associated osteoclastogenic Macrophages), have properties that could be exploitable in the search for new treatments. In one example highlighted by the study, the researchers found that AtoMs have high levels of a protein (called FoxM1) known to make cells invade nearby tissue. They speculated that by getting rid of this hallmark protein—splitting the AtoM, if you will—they could perhaps quell its arthritic tendencies. This is indeed what they found: when FoxM1 was chemically or genetically disrupted in AtoMs, arthritic mice showed reduced bone destructions in their joints.

"Our findings suggest that osteoclasts involved in RA have distinct properties that make them amenable to therapeutic targeting," says co-author Masaru Ishii. "While there is still a lot to learn about this class of cells, we believe the discovery could open the door to new avenues of treatment."

CHAMPAIGN, Ill. -- A new web tool speeds the discovery of drugs to kill Gram-negative bacteria, which are responsible for the overwhelming majority of antibiotic-resistant infections and deaths. The tool also offers insights into discrete chemical changes that can convert drugs that kill other bacteria into drugs to fight Gram-negative infections. The team proved the system works by modifying a Gram-positive drug and testing it against three different Gram-negative bacterial culprits in mouse sepsis. The drug was successful against each.

The researchers report their findings in the journal Nature Microbiology.

"It's really hard to find new antibiotics for Gram-negative pathogens, because these bacteria have an extra membrane, an outer membrane, that's very good at keeping antibiotics out," said University of Illinois chemistry professor Paul Hergenrother, who led the research.

The challenge is so profound that no new classes of drugs to fight Gram-negative bacteria have been approved by the Food and Drug Administration in 50 years, Hergenrother said.

"A few years ago, we discovered the molecular features that allowed an antibiotic compound to surpass this barrier," he said. "Now, we've developed a tool to help others do this as well."

The new app, called eNTRyway, can quickly evaluate potential drug compounds to determine if they have the molecular characteristics that will enable them to cross the membrane and accumulate inside Gram-negative bacteria.

Developed by graduate student Bryon Drown, the app also can point to ways of modifying existing drugs - for example, those known to work against Gram-positive bacteria - to convert them into potent killers of Gram-negative pathogens.

As a demonstration of this latter capability, postdoctoral researcher and study co-lead author Erica Parker used the tool to identify a drug already in use against Gram-positive infections that - with a basic chemical modification - could potentially be converted to fight Gram-negative bacteria. By adding a positively charged chemical group known as an amine to the drug, Parker created a compound that, further tests revealed, accumulated in Gram-negative bacteria and was effective against several types of Gram-negative infections in mice.

The process of identifying the compound and modifying it took only a few weeks, Hergenrother said.

"Keep in mind that before this, over 100 derivatives of this same compound had been made. We found them in patents and papers," he said. "And none of these other derivatives had notable Gram-negative activity."

Hergenrother and his colleagues have so far identified more than 60 antibiotics that are effective only against Gram-positive bacteria but can be converted into drugs to fight Gram-negative infections. These compounds kill bacteria in a variety of different ways. The newly created drug, known as Debio-1452-NH3, interferes with fatty acid synthesis in bacterial - but not mammalian - cells.

Hergenrother said the new tool will speed the process of drug discovery to fight the burgeoning problem of antibiotic-resistant infections.

"We can use this tool to rapidly identify compounds that accumulate in Gram-negative bacteria," he said.

Shrouded in mystery since their discovery, the phenomenon of black holes continues to be one of the most mind-boggling enigmas in our universe.

In recent years, many researchers have made strides in understanding black holes using observational astronomy and an emerging field known as gravitational wave astronomy, first hypothesized by Albert Einstein, which directly measures the gravitational waves emitted by black holes.

Through these findings on black hole gravitational waves, which were first observed in 2015 by the Laser Interferometer Gravitational-Wave Observatories (LIGO) in Louisiana and Washington, researchers have learned exciting details about these invisible objects and developed theories and projections on everything from their sizes to their physical properties.

Still, limitations in LIGO and other observation technologies have kept scientists from grasping a more complete picture of black holes, and one of the largest gaps in knowledge concerns a certain type of black hole: those of intermediate-mass, or black holes that fall somewhere between supermassive (at least a million times greater than our sun) and stellar (think: smaller, though still 5 to 50 times greater than the mass of our sun).

That could soon change thanks to new research out of Vanderbilt on what's next for gravitational wave astronomy. The study, led by Vanderbilt astrophysicist Karan Jani and featured today as a letter in Nature Astronomy, presents a compelling roadmap for capturing 4- to 10-year snapshots of intermediate-mass black hole activity.

"Like a symphony orchestra emits sound across an array of frequencies, the gravitational waves emitted by black holes occur at different frequencies and times," said Jani. "Some of these frequencies are extremely high-bandwidth, while some are low-bandwidth, and our goal in the next era of gravitational wave astronomy is to capture multiband observations of both of these frequencies in order to 'hear the entire song,' as it were, when it comes to black holes."

Jani, a self-proclaimed "black hole hunter" who Forbes named to its 2017 30 Under 30 list in Science, was part of the team that detected the very first gravitational waves. He joined Vanderbilt as a GRAVITY postdoctoral fellow in 2019.

Along with collaborators at Georgia Institute of Technology, California Institute of Technology and the Jet Propulsion Laboratory at NASA, the new paper, "Detectability of Intermediate-Mass Black Holes in Multiband Gravitational Wave Astronomy," looks at the future of LIGO detectors alongside the proposed Laser Interferometer Space Antenna (LISA) space-mission, which would help humans get a step closer to understanding what happens in and around black holes.

"The possibility that intermediate mass black holes exist but are currently hidden from our view is both tantalizing and frustrating," said Deidre Shoemaker, co-author of the paper and professor in Georgia Tech's School of Physics. "Fortunately, there is hope as these black holes are ideal sources for future multiband gravitational wave astronomy."

LISA, a mission jointly led by the European Space Agency and NASA and planned for launch in the year 2034, would improve detection sensitivity for low-frequency gravitational waves. As the first dedicated space-based gravitational wave detector, LISA would provide a critical measurement of a previously unattainable frequency and enable the more complete observation of intermediate-mass black holes. In 2018, Vanderbilt physics and astronomy professor Kelly Holley-Bockelmann was appointed by NASA as the inaugural chair of the LISA Study Team.

"Inside black holes, all known understanding of our universe breaks down," added Jani. "With the high frequency already being captured by LIGO detectors and the low frequency from future detectors and the LISA mission, we can bring these data points together to help fill in many gaps in our understanding of black holes."

As the extinction crisis escalates, and protest movements grow, some are calling for hugely ambitious conservation targets. Among the most prominent is sparing 50% of the Earth's surface for nature.

'Half Earth' and similar proposals have gained traction with conservationists and policy makers. However, little work has gone into identifying the social and economic implications for people.

Now, researchers have produced the first attempt to assess how many and who would be affected if half the planet was 'saved' in a way that secures the diversity of the world's habitats.

A team of scientists analysed global datasets to determine where conservation status could be added to provide 50% protection to every "ecoregion": large areas of distinct habitats such as Central African mangroves and Baltic mixed forests.

Even avoiding where possible "human footprints" such as cities and farmland, their findings suggest a "conservative" estimate for those directly affected by Half Earth would be over one billion people, primarily in middle-income countries.

Many wealthy and densely populated nations in the Global North would also need to see major expansions of land with conservation status to reach 50% - this could even include parts of London, for example.

The study's authors, led by University of Cambridge researchers, say that while radical action is urgently required for the future of life on Earth, issues of environmental justice and human wellbeing should be at the forefront of the conservation movement.

"People are the cause of the extinction crisis, but they are also the solution," said Dr Judith Schleicher, who led the new study, published today in the journal Nature Sustainability. "Social issues must play a more prominent role if we want to deliver effective conservation that works for both the biosphere and the people who inhabit it."

Towards the end of next year, the leaders of most of the world's nations will aim to agree global targets for the future of conservation at the Convention on Biological Diversity in Beijing.

"Goals that emerge from the Convention on Biological Diversity could define conservation for a generation," said Schleicher, who conducted the research while at the University of Cambridge's Conservation Research Institute and its Department of Geography.

"We need to be ambitious given the environmental crises. But it is vital that social and economic implications at local levels are considered if the drivers of biodiversity loss are to be tackled. The lives of many people and the existence of diverse species hang in the balance."

The idea of a 'Half Earth' for nature was popularised by famed biologist E.O. Wilson in his 2017 book of the same name. More recently, a 'Global Deal for Nature' - aiming for 30% protection by 2030 and 50% by 2050 - has been endorsed by a number of leading environmental organisations. However, these proposals have been ambiguous about "exact forms and location", say Schleicher and colleagues.

Based on their analyses, researchers cautiously estimate that an additional 760 million people would find themselves living in areas with new conservation status: a fourfold increase of the 247 million who currently reside inside protected areas.

The team call for proponents of Half Earth, and all supporters of area-based conservation, to "recognise and take seriously" the human consequences - both negative and positive - of their proposals.

"Living in areas rich in natural habitat can boost mental health and wellbeing. In some cases, protected areas can provide new jobs and income through ecotourism and sustainable production," said Schleicher.

"However, at the other extreme, certain forms of 'fortress' conservation can see people displaced from their ancestral home and denied access to resources they rely on for their survival."

While conservation coverage has been increasing, species numbers continue to plummet - suggesting a "disconnect" between international targets and implementation at local and regional levels, argue the team.

"Conservation needs strong action to protect life on earth, but this must be done in a way that takes account of people and their needs," said co-author Dr Chris Sandbrook from Cambridge's Department of Geography.

"Failing to consider social issues will lead to conservation policy that is harmful to human wellbeing and less likely to be implemented in the first place."

Conservation is not just a problem for people of the Global South. Recent reports on UK wildlife revealed devastating declines in iconic species. Yet the study reveals that achieving 50% ecoregion coverage could even see parts of central London become protected. "It highlights the absurdity of hitting arbitrary targets," Sandbrook said.