Publisher Health

Creating a mutation that inhibits how the bacterial pathogen Neisseria gonorrhoeae causes gonorrhea, a common sexually transmitted infection, could offer a new way to prevent and treat the disease, according to researchers in the Institute for Biomedical Sciences at Georgia State University.
The researchers found that generating a mutation in a key part of the outer membrane transporter that N. gonorrhoeae uses to hijack human immunity proteins and strip them of metals could help to prevent gonorrhea infection. The findings are published in the journal mBio.
Gonorrhea, which affects more than 80 million people worldwide each year, is a global threat to public health because of the increasing incidence of antimicrobial drug resistance, rising treatment costs and lack of a protective vaccine. Up to 80 percent of cases in women are asymptomatic, and if left untreated, gonorrhea can lead to serious health consequences, including pelvic inflammatory disease, ectopic pregnancy, infertility and even life-threatening endocarditis and meningitis.
Effective treatment options for gonorrhea are decreasing because of evolving antimicrobial resistance to existing drugs. Also, it’s challenging to identify suitable vaccine targets because N. gonorrhoeae alters expression of key surface molecules and dampens the immune response. To block invading pathogens from causing disease, humans rely on a process called nutritional immunity to limit the availability of critical nutrients such as iron and zinc and starve invaders. Metal-binding proteins sequester metals and limit the amount of free essential metal ions that pathogens need to flourish and cause disease.
To overcome host nutritional immunity efforts, N. gonorrhoeae deploys TonB-dependent transporters (TdTs) to its outer membrane to bind to host nutritional immunity proteins and strip them of their metals. TdTs often play key roles in establishing infections, making them promising vaccine targets.
One TdT named TdfJ recognizes human S100A7, a zinc-binding protein that inhibits the replication of pathogens by hiding zinc. N. gonorrhoeae uses TdfJ to extract zinc from S100A7 and internalize the metal. TdfJ contains an alpha-helix finger in extracellular loop 3. A similar alpha-helix in loop 3 of another gonococcal TdT, known as TbpA, plays a critical role in the interaction between TbpA and human transferrin, which is required for the uptake of iron. Based on this information, the researchers hypothesized the TdfJ loop 3 helix (L3H) participates in interactions with S100A7, and they generated a series of mutations in the TdfJ L3H to determine if they blocked theability of N. gonorrhoeae to acquire zinc and therefore to cause disease.
“The prospect of untreatable gonococcal infections has spurred efforts to identify targets for novel therapeutic and prevention strategies, and members of the family of outer membrane TonB-dependent metal transporters have emerged as promising candidates because they play a critical role in establishing infection,” said Dr. Cynthia Nau Cornelissen, senior author of the study, Distinguished University Professor and director of the Center for Translational Immunology in the Institute for Biomedical Sciences at Georgia State. “Our study revealed that mutagenesis of key residues within the TdfJ L3H reduced S100A7 binding and zinc piracy by the gonococcus, with the most profound effects seen with substitutions at residues K261 and R262. Taken together, these data suggest a key role for the TdfJ L3H in subverting host nutritional immunity.”
The study characterized the binding interaction between the zinc importer TdfJ and its human zinc source, S100A7, and it also identified a key region of TdfJ that mediates this interaction.
“We detailed for the first time, the binding interaction for gonococcal TdfJ and its human ligand S100A7. We also identified several mutations in TdfJ loop 3 that alter S100A7 binding and subsequent zinc extraction,” said Stavros A. Maurakis, first author of the study and a Ph.D. graduate of the Institute for Biomedical Sciences at Georgia State.”With a more thorough understanding of the intricate relationships between these bacterial nutrient receptors and their host nutrient sources, we may help pave the way toward identifying effective prophylaxis and/or treatment for an important human disease.”
Co-authors of the study include Stavros A. Maurakis, Julie L. Stoudenmire and Cynthia Nau Cornelissen of the Institute for Biomedical Sciences at Georgia State; and Jeffrey K. Rymer and Walter J. Chazin of Vanderbilt University.
The study is funded by the National Institutes of Health (NIH).
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Only 48% of people age 50 to 80 who take blood pressure medications or have a health condition that’s affected by hypertension regularly check their blood pressure at home or other places, a new study finds.
A somewhat higher number — but still only 62% — say a health care provider encouraged them to perform such checks. Poll respondents whose providers had recommended they check their blood pressure at home were three and a half times more likely to do so than those who didn’t recall getting such a recommendation.
The findings underscore the importance of exploring the reasons why at-risk patients aren’t checking their blood pressure, and why providers aren’t recommending they check — as well as finding ways to prompt more people with these health conditions to check their blood pressure regularly. This could play an important role in helping patients live longer and maintain heart and brain health, the study’s authors say.
Past research has shown that regular home monitoring can help with blood pressure control, and that better control can mean reduced risk of death; of cardiovascular events including strokes and heart attacks; and of cognitive impairment and dementia.
The findings are published in JAMA Network Open by a team from Michigan Medicine, the University of Michigan’s academic medical center. The data come from the National Poll on Healthy Aging and build on a report issued last year.
The poll, based at the U-M Institute for Healthcare Policy and Innovation and supported by Michigan Medicine and AARP, asked adults aged 50 to 80 about their chronic health conditions, blood pressure monitoring outside of clinic settings, and interactions with health providers about blood pressure. Study authors Mellanie V. Springer, M.D., M.S., of the Michigan Medicine Department of Neurology, and Deborah Levine, M.D., M.P.H., of the Department of Internal Medicine, worked with the NPHA team to develop the poll questions and analyze the findings.
The data in the new paper come from the 1,247 respondents who said they were either taking a medication to control their blood pressure or had a chronic health condition that requires blood pressure control — specifically, a history of stroke, coronary heart disease, congestive heart failure, diabetes, chronic kidney disease or hypertension.
Of them, 55% said they own a blood pressure monitor, though some said they don’t ever use it. Among those who do use it, there was wide variation in how often they checked their pressure — and only about half said they share their readings with a health provider. But those who own a monitor were more than 10 times more likely to check their blood pressure outside of health care settings than those who don’t own one.
The authors note that blood pressure monitoring is associated with lower blood pressure and is cost-effective. They say that the results suggest that protocols should be developed to educate patients about the importance of self blood pressure monitoring and sharing readings with clinicians.
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Each year, more than one billion people contract a fungal infection. Although they are harmless to most people, over 1.5 million patients die each year as a result of infections of this kind. While more and more fungal strains are being detected that are resistant to one or more of the available drugs, the development of new drugs has come to a virtual standstill in recent years. Today, only around a dozen clinical trials are underway with new active agents for the treatment of fungal infections. “In comparison with more than a thousand cancer drugs that are currently being tested on human subjects, this is an exceptionally small number,” explains Dr. Angelo Frei of the Department of Chemistry, Biochemistry and Pharmacy at the University of Bern, lead author of the study. The results have been published in the journal JACS Au.
Boosting antibiotics research with crowd sourcing
To encourage the development of anti-fungal and antibacterial agents, researchers at the University of Queensland in Australia have founded the Community for Open Antimicrobial Drug Discovery, or CO-ADD. The ambitious goal of the initiative is to find new antimicrobial active agents by offering chemists worldwide the opportunity to test any chemical compound against bacteria and fungi at no cost. As Frei explains, the initial focus of CO-ADD has been on “organic” molecules, which mainly consist of the elements of carbon, hydrogen, oxygen and nitrogen, and do not contain any metals.
However, Frei, who is trying to develop new metal-based antibiotics with his research group at the University of Bern, has found that over 1,000 of the more than 300,000 compounds tested by CO-ADD contained metals. “For most folks, when used in connection with the word ‘people’, the word metal triggers a feeling of unease. The opinion that metals are fundamentally harmful to us is widespread. However, this is only partially true. The decisive factor is which metal is used and in which form,” explains Frei, who is responsible for all the metal compounds in the CO-ADD database.
Low toxicity demonstrated
In their new study, the researchers turned their attention to the metal compounds which showed activity against fungal infections. Here, 21 highly-active metal compounds were tested against various resistant fungal strains. These contained the metals cobalt, nickel, rhodium, palladium, silver, europium, iridium, platinum, molybdenum and gold. “Many of the metal compounds demonstrated a good activity against all fungal strains and were up to 30,000 times more active against fungi than against human cells,” explains Frei. The most active compounds were then tested in a model organism, the larvae of the wax moth. The researchers observed that just one of the eleven tested metal compounds showed signs of toxicity, while the others were well tolerated by the larvae. In the next step, some metal compounds were tested in an infection model, and one compound was effective in reducing the fungal infection in larvae.
Considerable potential for broad application
Metal compounds are not new to the world of medicine: Cisplatin, for example, which contains platinum, is one of the most widely used anti-cancer drugs. Despite this, there is a long way to go before new antimicrobial drugs that contain metals can be approved. “Our hope is that our work will improve the reputation of metals in medical applications and motivate other research groups to further explore this large but relatively unexplored field,” says Frei. “If we exploit the full potential of the periodic table, we may be able to prevent a future where we don’t have any effective antibiotics and active agents to prevent and treat fungal infections.”
The study was supported by the Swiss National Science Foundation, the Wellcome Trust and the University of Queensland, among others.
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A study published in the journal Environmental Pollution has found an association, in children aged 9-12, between exposure to air pollutants in the womb and during the first 8.5 years of life and alterations in white matter structural connectivity in the brain. The greater the child’s exposure before age 5, the greater the brain structure alteration observed in preadolescence.The study was led by the Barcelona Institute for Global Health (ISGlobal), a research centre supported by the “la Caixa” Foundation.
Tracts or bundles of cerebral white matter ensure structural connectivity by interconnecting the different areas of the brain. Connectivity can be measured by studying the microstructure of this white matter, a marker of typical brain development. Abnormal white matter microstructure has been associated with psychiatric disorders (e.g., depressive symptoms, anxiety and autism spectrum disorders).
In addition to the association between air pollution and white matter microstructure, the study also found a link between specific exposure to fine particulate matter (PM2.5) and the volume of the putamen, a brain structure involved in motor function, learning processes and many other functions. As the putamen is a subcortical structure, it has broader and less specialised functions than cortical structures. The study found that the greater the exposure to PM2.5, especially during the first 2 years of life, the greater the volume of the putamen in preadolescence.
“A larger putamen has been associated with certain psychiatric disorders (schizophrenia, autism spectrum disorders, and obsessive-compulsive spectrum disorders),” says Anne-Claire Binter, ISGlobal researcher and first author of the study.
“The novel aspect of the present study is that it identified periods of susceptibility to air pollution” Binter goes on to explain. “We measured exposure using a finer time scale by analysing the data on a month-by-month basis, unlike previous studies in which data was analysed for trimesters of pregnancy or childhood years. In this study, we analysed the children’s exposure to air pollution from conception to 8.5 years of age on a monthly basis.
Effects Observed Even at Pollution Levels Complying With European Union Standards
Another strong point of this study is that the data analysed came from a large cohort of 3,515 children enrolled in the Generation R Study in Rotterdam (Netherlands).
To determine each participant’s exposure to air pollution during the study period, the researchers estimated the daily levels of nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM2.5 absorbance) at their homes during the mother’s pregnancy and until they reached 8.5 years of age. When participants were between 9 and 12 years analysed of age they underwent brain magnetic resonance imaging to examine the structural connectivity and the volumes of various brain structures at that time.
The levels of NO2 and PM2.5 recorded in the present study exceeded the annual thresholds limits specified in the current World Health Organization guidelines (10 µg/m3 and 5 µg/m3, respectively) but met European Union (EU) standards, an indication that brain development can be affected by exposure to air pollution at levels lower than the current EU air quality limit values.
“One of the important conclusions of this study” explains Binter “is that the infant’s brain is particularly susceptible to the effects of air pollution not only during pregnancy, as has been shown in earlier studies, but also during childhood.”
“We should follow up and continue to measure the same parameters in this cohort to investigate the possible long-term effects on the brain of exposure to air pollution” concludes Mònica Guxens, ISGlobal researcher and last author of the study.
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People who wear reusable contact lenses are nearly four times as likely as those wearing daily disposables to develop a rare sight-threatening eye infection, finds a study led by UCL and Moorfields researchers.
The case control study, published in Ophthalmology, identifies multiple factors that increase the risk of Acanthamoeba keratitis (AK), including reusing lenses or wearing them overnight or in the shower.
AK is one type of microbial keratitis (corneal infection) — a condition that results in inflammation of the cornea (the eye’s clear protective outer layer).
Lead author, Professor John Dart (UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust) said: “In recent years we have seen an increase of Acanthamoeba keratitis in the UK and Europe, and while the infection is still rare, it is preventable and warrants a public health response.
“Contact lenses are generally very safe but are associated with a small risk of microbial keratitis, most commonly caused by bacteria, and which is the only sight threatening complication of their use. Given that an estimated 300 million people across the globe wear contact lenses, it is important that people know how to minimise their risks for developing keratitis.”
Contact lens use is now the leading cause of microbial keratitis in patients with otherwise healthy eyes in countries in the global north. Sight loss resulting from microbial keratitis is uncommon but Acanthamoeba, although a rare cause, is one of the most severe and is responsible for about half of those contact lens users who develop sight loss after keratitis. 90% of AK cases are associated with avoidable risks, although the infection remains rare, affecting fewer than 1 in 20,000 contact lens wearers per year in the UK.

Taking a dip in cold water may cut ‘bad’ body fat in men and reduce the risk of disorders such as diabetes, suggests a major scientific review published in the peer-reviewed International Journal of Circumpolar Health.
The authors say many of the 104 studies they analysed demonstrated significant effects from cold water swimming including also on ‘good’ fat which helps burn calories. This may protect against obesity, cardiovascular disease, they add.
However, the review was inconclusive overall on the health benefits of cold-water bathing, an increasingly popular hobby.
Much of the available research involved small numbers of participants, often of one gender, and with differences water temperature and salt composition. In addition, it is unclear whether or not winter swimmers are naturally healthier, say the scientific expert team of review authors from UiT The Arctic University of Norway and from the University Hospital of North Norway.
“From this review, it is clear that there is increasing scientific support that voluntary exposure to cold water may have some beneficial health effects,” states lead author James Mercer, from UiT.
“Many of the studies demonstrated significant effects of cold-water immersion on various physiological and biochemical parameters. But the question as to whether these are beneficial or not for health is difficult to assess.

A newer-generation clot-busting drug called tenecteplase outperforms the traditional treatment for ischemic strokes in several key areas, including better health outcomes and lower costs, according to a new study published today in the American Stroke Association’s journal Stroke.
The study was led by a team of neurologists at Dell Medical School at The University of Texas at Austin and was carried out over a 15-month period at 10 Ascension Seton hospitals in Central Texas starting in September 2019.
“The Dell Med Neurology Stroke Program was one of the first in the United States to make this change,” said Steven Warach, M.D., lead author of the study and director of the Stroke Program for Dell Med and Ascension Texas. “Based on even the earliest results from this study, other experts across the country were convinced and made the switch from alteplase to tenecteplase at their own stroke centers, including at Ascension hospitals nationwide.”
Nearly 800,000 people in the United States have a stroke every year. The vast majority of those strokes (about 87%) are ischemic, meaning they occur when a vessel supplying blood to the brain is obstructed by a blood clot. This can result in a corresponding loss of neurologic function.
Both tenecteplase and alteplase are federally approved for use in dissolving clots in blocked heart arteries. But the newer drug tenecteplase is also being used by clinicians, off-label, to treat ischemic strokes, because clinical trials in stroke suggest that it may be at least as good as alteplase and it is easier to administer. Tenecteplase is administered by a single five- to 10-second intravenous injection. The researchers compared its performance with the standard drug for stroke, alteplase, which is injected over 60 minutes.
“When it comes to treating patients with a stroke, every second matters,” said Warach, who is also a professor of neurology at Dell Med. “The shorter preparation and injection time with tenecteplase not only eliminates a lot of dosing errors related to alteplase, but it’s also more efficient. We were able to deliver the clot-busting medicine more quickly after patients arrived in the emergency department, and for patients who needed to be transferred to another hospital for more advanced care after receiving the clot buster, we were able to initiate the transfer sooner in those treated with tenecteplase.”
For patients who come into the emergency department after a stroke, Warach’s study found that the “door-to-needle” time — the time between patients’ arrival and the moment they receive treatment — was on average six minutes quicker with tenecteplase. And for patients who also required a thrombectomy, the surgical removal of a blood clot causing the stroke, tenecteplase sped up the process of transferring the patient to a thrombectomy-capable stroke center by 25 minutes.
Researchers also saw improvements in clinical outcomes for patients given tenecteplase, including: A 5% increase in patients who were able to walk independently at time of hospital discharge to home. A 4% decrease in occurrences of bad events such as brain hemorrhages, discharge to hospice care or death.The third major improvement: cost. The research team found that tenecteplase treatment cost the hospitals about $2,500 less than alteplase per patient.
“If this price differential continues, the magnitude of savings could equate to in excess of $150 million every year in the U.S.,” said David Paydarfar, M.D., co-author of the study and chair of the Department of Neurology at Dell Med. “This is a great example of value-based care — better care for less money.”
The Dell Med Neurology Stroke Program is now working with colleagues in the state-funded Lone Star Stroke Research Consortium to disseminate its study findings across the state, helping more stroke centers make the switch to tenecteplase. Warach is also working with Lone Star Stroke colleagues to build a statewide database to further confirm their results and answer lingering questions.
“For example, we have such a large Latinx population in Texas. I’d like to know if we’re seeing the same advantages from tenecteplase in that community as we are in the larger population,” said Warach. “The more data we have, the more questions we can answer.”
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There are strong links between bacteria living in the gut and the levels of small molecules in the blood known as metabolites. Such is the finding of a new study led by researchers from Uppsala University and Lund University, which is now published in the journal Nature Communications.
A team of scientists coordinated by Uppsala University and Lund University has found strong links between certain bacteria living in the gut and small molecules found in the blood. The study is based on analyses of both fecal and blood samples from 8,583 participants in the Swedish CArdioPulmonary bioImage Study (SCAPIS). The findings have now been published for the first time in Nature Communications, and have further been made freely available to the research community through an online atlas. The aim of the project was to contribute to the expanding knowledge base concerning how gut microbiota influence human health.
“Earlier studies have shown that the large bacterial community in our digestive system produce a variety of molecules, with the potential to enter the bloodstream and to impact our health. Conversely, medication or dietary components may affect the microbiota composition before entering the circulation. Characterisation of these interactions is an important step towards understanding the effects of the gut microbiota on health,” says Tove Fall, Professor of Molecular Epidemiology at the Department of Medical Sciences and the Science for Life Laboratory, Uppsala University, who coordinated the study together with researchers from Lund University.
Recent technological advances have enabled large-scale deep characterisation of bacterial communities in biological samples. This is done by sequencing the DNA content of the samples and comparing the results to DNA sequences from known bacteria. Advances in chemistry have further enabled large simultaneous screens of blood samples in order to measure small molecules. The SCAPIS study represents one of the largest collections in the world of both of these kinds of data. In this study scientists investigated the links between the gut microbiota and the small molecules in the blood.
“The gut microbiota is a universe of its own and we have just started to understand how the human host and the bacterial community affect each other. Our results show that for certain blood metabolites, the bacteria you carry in the gut constitute a strong determinant,” notes Marju Orho-Melander, Professor of Genetic Epidemiology, Lund University, and one of the senior authors of the study.
The scientific team believes that the breadth of findings may spur the interest of other international groups focusing on gut microbiota and host interactions, and has therefore opted to publish all the associations on a public website hosted by SciLife Data Centre in Uppsala (https://gutsyatlas.serve.scilifelab.se).
“The large number of samples containing high quality data allowed us to identify many novel associations. We have therefore chosen to publish all of our findings in an online open resource for the research community to use for their varying needs,” says Koen Dekkers, lead author from Uppsala University.
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Since May 2022, cases of monkeypox have increased globally, stirring fears of a new pandemic. A study published in the open-access journal PLOS Pathogens on September 22 by Professor Souha Kanj and colleagues at the American University of Beirut Medical Center, Beirut, Lebanon, presents synthesized descriptions of its clinical characteristics, risk factors, infection control and prevention measures, as well as potential treatments.
Historically, monkeypox was mostly confined to endemic areas in Western and Central Africa and was mostly transmitted through contact with infected animals. However, human-to-human transmission has recently become the primary mode of transmission, raising concerns for previous undetected community spread. To better understand the epidemiologic landscape of this emerging outbreak, the authors conducted a literature review of the available evidence on monkeypox. They found that during the current outbreak, confirmed, probable, and/or possible monkeypox cases have increased tenfold across more than seventy-six countries. The data suggest an increase in the disease incidence and possible improved surveillance. Current cases showed a rapid human-to-human transmission, raising concerns for rapid community spread, though not necessarily related to travel to endemic areas in Africa.
The literature review has several limitations, including the small sample size of case studies and the absence of randomized controlled trials on monkeypox therapy, both of which limit generalizability. Larger and more robust studies are needed to determine the specific risk factors, transmission modes, and potential therapeutics, as well as the scope of the current outbreak.
According to the authors, “Key gap information needs to be further studied to provide better answers such as the exact mode of transmission and the role of animal reservoirs. Sexual modes of transmission, genetic mutations, waning immunity from smallpox and previous undetected cases of monkeypox warrant further investigation. Doctors should also keep in mind the atypical presentations and rely on the WHO and CDC criteria to guide patients and help in containing outbreaks.”
Kanj and co-authors add, “Monkeypox has been declared as a public health emergency that warrants special attention and early diagnosis in view of its global widespread and atypical presentation.”
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A recently discovered virus in a Russian bat that is similar to SARS-CoV-2, the virus behind COVID-19, is likely capable of infecting humans and, if it were to spillover, is resistant to current vaccines.
A team lead by researchers in Washington State University’s Paul G. Allen School for Global Health found spike proteins from the bat virus, named Khosta-2, can infect human cells and is resistant to both the monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Both Khosta-2 and SARS- CoV-2 belong to the same sub-category of coronaviruses known as sarbecoviruses.
“Our research further demonstrates that sarbecoviruses circulating in wildlife outside of Asia — even in places like western Russia where the Khosta-2 virus was found — also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2,” said Michael Letko, WSU virologist and corresponding author of the study published in the journal PLoS Pathogens.
Letko said the discovery of Khosta-2 highlights the need to develop universal vaccines to protect against sarbecoviruses in general, rather than just against known variants of SARS-CoV-2.
“Right now, there are groups trying to come up with a vaccine that doesn’t just protect against the next variant of SARS-2 but actually protects us against the sarbecoviruses in general,” Letko said. “Unfortunately, many of our current vaccines are designed to specific viruses we know infect human cells or those that seem to pose the biggest risk to infect us. But that is a list that’s everchanging. We need to broaden the design of these vaccines to protect against all sarbecoviruses.”
While hundreds of sarbecoviruses have been discovered in recent years, predominantly in bats in Asia, the majority are not capable of infecting human cells. The Khosta-1 and Khosta-2 viruses were discovered in Russian bats in late 2020, and it initially appeared they were not a threat to humans.