Publisher Health

Researchers from the National Eye Institute (NEI) have identified a new disease that affects the macula, a small part of the light-sensing retina needed for sharp, central vision. Scientists report their findings on the novel macular dystrophy, which is yet to be named, in JAMA Ophthalmology. NEI is part of the National Institutes of Health.
Macular dystrophies are disorders that usually cause central visual loss because of mutations in several genes, including ABCA4, BEST1, PRPH2, and TIMP3.
For example, patients with Sorsby Fundus Dystrophy, a genetic eye disease specifically linked to TIMP3 variants, usually develop symptoms in adulthood. They often have sudden changes in visual acuity due to choroidal neovascularization- new, abnormal blood vessels that grow under the retina, leaking fluid and affecting vision.
TIMP3 is a protein that helps regulate retinal blood flow and is secreted from the retinal pigment epithelium (RPE), a layer of tissue that nourishes and supports the retina’s light-sensing photoreceptors. All TIMP3 gene mutations reported are in the mature protein after it has been “cut” from RPE cells in a process called cleavage.
“We found it surprising that two patients had TIMP3 variants not in the mature protein, but in the short signal sequence the gene uses to ‘cut’ the protein from the cells. We showed these variants prevent cleavage, causing the protein to be stuck in the cell, likely leading to retinal pigment epithelium toxicity,” said Bin Guan, Ph.D., lead author.
The research team followed these findings with clinical evaluations and genetic testing of family members to verify that the two new TIMP3 variants are connected to this atypical maculopathy.
“Affected individuals had scotomas, or blind spots, and changes in their maculas indicative of disease, but, for now, they have preserved central vision and no choroidal neovascularization, unlike typical Sorsby Fundus Dystrophy,” said Cathy Cukras, M.D., Ph.D., a Lasker tenure-track investigator and medical retina specialist who clinically evaluated the patients.
NEI’s Ophthalmic Genomics Laboratory gathers and manages specimens and diagnostic data from patients who have been recruited into multiple studies within the NEI clinical program to facilitate research of rare eye diseases, including Sorsby Fundus Dystrophy.
“Discovering novel disease mechanisms, even in known genes like TIMP3, may help patients that have been looking for the correct diagnosis, and will hopefully lead to new therapies for them,” said Rob Hufnagel, M.D., Ph.D., senior author and director of the Ophthalmic Genomics Laboratory at NEI.
The study was funded by the NEI Intramural Research Program.
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In biology, getting rid of stuff can be just as important as making it. A buildup of cells, proteins, or other molecules that are no longer needed can cause problems, so living things have evolved several ways to clean house.
A prime example is the RNA exosome. RNA molecules perform many roles in cells. Some of them are translated into proteins; others form a cell’s protein-building machinery. The RNA exosome is a cellular machine that degrades RNA molecules that are faulty, harmful, or no longer needed. Without this microscopic Marie Kondo to prune what doesn’t spark joy, our cells would become dysfunctional hoarders, unable to function.
“RNA surveillance and degradation pathways exist in all forms of life,” explains Christopher Lima, Chair of the Structural Biology Program in the Sloan Kettering Institute. “From bacteria to humans, all living things have mechanisms to monitor the quality of RNA and to purposely degrade it.”
For a long time, Dr. Lima says, these pathways were considered, like housework, kind of boring. But it turns out that these degradation pathways are highly regulated and control everything from embryonic development to the progression of the cell cycle.
What’s more, errors in these pathways can lead to many types of disease, from cancer to neurodegeneration.
In a new paper published June 9, 2022 in Cell, Dr. Lima and M. Rhyan Puno, a postdoctoral fellow in the Lima lab, present findings that help explain how the RNA exosome locates the RNA that needs to be degraded. With the help of cryogenic-electron microscopy (cryo-EM), an advanced type of imaging technology, the scientists were able to decipher the structure of a protein assembly called Nuclear Exosome Targeting (NEXT) Complex, which is a key part of the degradation machinery.

One of the hallmarks of Parkinson’s disease (PD) is the accumulation in the brain of a protein known as alpha-synuclein. For more than two decades, alpha-synuclein has been a focal point of attention for researchers, clinicians and drug makers interested in PD. But alpha-synuclein’s function is not well understood. A new study led by investigators at Brigham and Women’s Hospital, Harvard Stem Cell Institute and the Broad Institute of Harvard and MIT shines new light on the role of alpha-synuclein, uncovering a new function for the protein with relevance for PD and related conditions. Findings are published in Cell.
“Our study offers new insights into a protein that is known to be at the center of the development of Parkinson’s disease and related disorders,” said corresponding author Vikram Khurana, MD, PhD, chief of the Division of Movement Disorders within the Department of Neurology at the Brigham and Harvard Medical School, and a principal investigator within the Ann Romney Center for Neurologic Diseases at the Brigham. “This is a protein that is being targeted by current therapeutics, but its function has been elusive. Traditionally, alpha-synuclein has been thought to play a role in binding to the cell membrane and transporting structures known as vesicles. But our study suggests alpha-synuclein is leading a double life.”
Khurana and colleagues’ initial leads came from yeast and fruit fly models of alpha-synuclein toxicity and were substantiated through studies of human cells, patient-derived neurons and human genetics. The team found that the very same part of the alpha-synuclein protein that interacts with vesicles also binds to “P-body” structures, machinery in the cell that regulates the expression of genes through messenger RNAs (mRNAs). In induced pluripotent stem cell-derived neurons generated from PD patients with alpha-synuclein gene mutations, the physiologic structure and function of the P-body was lost, and mRNAs were abnormally regulated. The same occurred in tissue samples from postmortem brains from patients. Human genetic analyses supported the disease-relevance of these findings: patients who accumulate mutations in P-body genes appeared to be at higher risk for PD.
The authors describe alpha-synuclein as a “toggle switch” that regulates two very distinct functions: transport of vesicles and gene expression. In disease states, the balance is broken. The findings have potential implications for development of treatments for PD. The authors note that more clarity is needed on which of the P-body machinery components might be the best targets for a therapeutic intervention. Ongoing genetic studies aim to identify which patients might be best suited for such an intervention, and how much this newly discovered pathway contributes to risk of the disease and disease progression in PD patients at large.
“If we want to be able to develop treatments that target alpha-synuclein, we need to understand what this protein does and the potential consequences of reducing its level or activity,” said lead author Erinc Hallacli, PhD, of the Department of Neurology and the Ann Romney Center for Neurologic Diseases at the Brigham. “This paper provides important information to fill our knowledge gaps about this protein, which may be beneficial for clinical translation.”
Disclosures: Khurana is a co-founder of and senior advisor to Dacapo Brainscience and Yumanity Therapeutics, companies focused on central nervous system diseases. Co-authors Chee Yeun Chung and Xin Jiang contributed to this work as employees of Yumanity Therapeutics.
Funding: Khurana is a NYSCF Stem Cell Robertson Investigator and an investigator of the Aligning Science Across Parkinson’s Initiative. He is a George C. Cotzias Fellow of the American Parkinson’s Disease Association. This work was also supported by the Brigham Research Institute Director’s Transformative Award, Department of Defense (W81XWH-19-1-0695), Human Frontier Science Program (LT000717/2015-L) and the National Institutes of Health (R21NS112858, R21NS112858 and R01NS109209). Additional funding support was provided by Alzheimer’s Research UK (ARUK), the Biomarkers Across Neurodegenerative Diseases Grant from the Alzheimer’s Association, Koerner New Scientist Program from the Koerner Family Foundation, Michael J. Fox Foundation for Parkinson’s Research (MJFF) and the Weston Brain Institute (Weston) (BAND-19-615151).
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Most of the state abortion prohibitions that would go into effect if Roe v. Wade is overturned do not contain carve-outs that were once widely supported by abortion opponents.In the years before Roe v. Wade, some states that had outlawed abortion began permitting it in limited circumstances: in cases of rape or incest, or to save the life or health of the woman.And for decades after the Roe ruling guaranteed the right to abortion throughout the United States, abortion opponents from Ronald Reagan to Donald J. Trump generally supported those exceptions, even as they worked to undo Roe.Exceptions for rape, incest and life endangerment are codified in the Hyde Amendment as the only reasons the federal government will pay for abortions through Medicaid. For decades, surveys have shown that large majorities of Americans support these carve-outs, even in heavily Republican states.But if the Supreme Court overturns Roe, as expected, many state abortion bans would take effect that do not include most of the exceptions.There are no allowances for victims of rape or incest in Alabama, Arkansas, Florida, Kentucky, Louisiana, Missouri, Oklahoma, Ohio, South Dakota, Tennessee or Texas. Mississippi, whose law banning abortion after 15 weeks is at the center of the case the Supreme Court will rule on this month, permits an abortion in cases of rape but does not specify incest.While all bans allow an exception to save the life of the woman, those in some states, such as Idaho, South Dakota and Arkansas, do not also cite protection of her health.The state senator who sponsored the Arkansas legislation, Jason Rapert, a Republican who is president of the National Association of Christian Lawmakers, said that his faith drove his views on abortion. He said he had heard testimony from rape and incest victims who expressed “the mental anguish they went through when they dealt with the fact they terminated the life of their own baby,” and who now oppose abortion.Arkansas’s only abortion exception is to save the woman’s life in “a medical emergency.” Mr. Rapert called exceptions to protect a woman’s health “an open door you could drive a truck through. You could describe anything that way.”Anti-abortion signs outside the Jackson Women’s Health Organization in Mississippi.Rory Doyle for The New York TimesMany of the new bans are set up as so-called trigger laws in 13 Midwestern and Southern states, intended to take effect swiftly if Roe falls. At least nine more states are weighing similar bans — some of which have been paused by courts — or could revive pre-Roe abortion prohibitions. The outcomes will depend on the details of the Supreme Court’s decision and the politics of each state.“I think we are heading in a direction of increasing absolutism and punitiveness,” said Reva Siegel, a Yale Law School professor who is a co-author of an equal protection amicus brief in the Mississippi case before the Supreme Court. She noted that even as Mississippi legislators restricted abortion access, they refused to expand postpartum Medicaid coverage.The move away from exceptions reflects the Republican Party’s shift to the right, said Mary Ziegler, a legal historian at the University of California, Davis, Law School and author of “Dollars for Life,” a book to be published this month about the anti-abortion movement and the Republican Party.Candidates are increasingly jockeying for far-right support in primaries in Republican-dominated states, she said, aware not only that turnout typically consists of the most fervent voters but also that national anti-abortion groups are searching for local standard-bearers to fund.Much of that rightward shift has been propelled by Mr. Trump. But during the 2016 and 2020 campaigns, Mr. Trump said in tweets that he supported exceptions to allow abortion for pregnancies resulting from rape and incest, or to protect the life of the mother. A spokesman for Mr. Trump declined requests from The New York Times to describe the former president’s current position on exceptions, or his reaction to the state bans that don’t include them.Though embracing limited exceptions might have once seemed politically expedient, the aims of the anti-abortion movement have grown increasingly unconditional. As the composition of the Supreme Court became more conservative, Ms. Ziegler said, there has been “a sense that the movement could pretty much get whatever it wanted without alienating the court.”Now, anti-abortion groups are debating whether to accept any exception to a ban.Students for Life, an anti-abortion organization, distinguishes between exceptions for rape or incest, and one to save the life of the woman, said Kristan Hawkins, the group’s president. How a child was conceived, she said, is irrelevant to the value of that child’s life: “We see them as valuable, worthy of love, and welcome.”Kristan Hawkins of Students for Life speaking at the University of Virginia in Charlottesville in April.Julia Rendleman for The Washington Post, via Getty ImagesThe group does, however, support exceptions for a lifesaving abortion. “That is not an act of abortion,” she said, “as the intent of abortion is to end life, not intervene to save life if possible.”But some groups, like Pro-Life Wisconsin and those affiliated with the abortion abolition movement, reject all exceptions, as does Doug Mastriano, the Republican nominee for governor of Pennsylvania, who calls abortion “science-denying genocide.”Some abortion rights supporters argue that focusing on exceptions is misguided. When people express shock that the new laws do not allow exceptions for rape and incest, “they seem to suggest that if those exceptions are granted, the new restrictive laws are more reasonable,” said Leslie J. Reagan, a historian of American medicine and public health at the University of Illinois at Urbana-Champaign. Whether or not there are exceptions, some state bans include criminal penalties, which Dr. Reagan, author of “When Abortion Was a Crime,” called “a step backwards to the century of criminalized abortion that the U.S. has already lived through.”The history of exceptions stretches back decades. In 1959, the American Law Institute, an independent group of legal scholars, lawyers and judges, began drafting model legislation to modify the crime of abortion. It proposed that termination be permitted if a physician decided there was grave risk to the health of the woman, or to the fetus, or if the pregnancy was the result of rape or incest.Two threats to a fetus were then of profound concern. One was the morning sickness drug thalidomide, tested on American women in the 1950s, that could cause severe birth defects or stillbirths. Another was rubella, commonly known as German measles, that could result in stillbirth or in life-threatening effects on the baby (a vaccine was approved in 1969).Over the next 14 years, at least 13 states would adopt some of those exceptions. Ms. Ziegler said that abortion opponents saw the exceptions as a compromise, acknowledging these were “hard cases, a fight not worth having because the country wasn’t there yet.”The idea behind the rape and incest exceptions in particular, she added, “was that people who had been sexually assaulted had not chosen to have sex, so you could legalize abortion in those cases without encouraging promiscuity, which was something the authors were worried about.”A pin on the wall of Trust Women Clinic in Oklahoma City. Oklahoma is one of several states where trigger laws carry no allowances for victims of rape or incest.Evelyn Hockstein/ReutersAllowing an abortion to save the woman’s life was encoded in abortion bans throughout the country for nearly a century before the Roe ruling. Police enforcement of the bans waxed and waned over the decades, depending on local political, social and economic factors.By the 1940s, police were raiding offices of licensed physicians who performed abortions, compelling patients to testify against their doctors. To offer doctors criminal liability shields, hospitals set up committees to evaluate which cases qualified for “therapeutic” abortions. But though hospital-sanctioned abortions provided a legal alternative to back-alley abortions, they were expensive and rarely authorized by the committees.Although the exceptions in the new abortion bans are scant, states nonetheless require doctors as well as patients to supply substantial documentation to justify the need.Florida’s law banning abortion after 15 weeks of gestation, scheduled to take effect July 1, says doctors must record the medical necessity for an abortion to save the woman’s life or to “avert a serious risk of imminent substantial and irreversible physical impairment of a major bodily function of the pregnant woman other than a psychological condition, and another physician is not available for consultation.”Many doctors see the statutory language that only permits abortion to prevent death or severe injury as putting them in violation of their professional oaths to their patients. Though states are often vague about thresholds such as life or “medical emergency,” they often require extensive documentation to justify the procedure, including gestational age of the fetus, indication of cardiac activity and medical records attesting to, as Oklahoma says, “the medical condition of the pregnant woman that prevented compliance with this act.”Yet the impact of the documentation requirements can cut both ways. Some state laws suggest that ample records can serve to defend the doctor against criminal conviction.“If doctors in these states are going to perform abortions, they will be checking with a hospital lawyer first,” said Elizabeth Nash, a policy analyst at the Guttmacher Institute, a reproductive health rights group that supports abortion.In essence, abortion exceptions that, decades earlier, were an attempt by lawmakers to keep pace with medical practice, have now come full circle: “The physical health of the woman will become more of a legal question than a medical one,” Ms. Nash said.

Heart failure patients who are unvaccinated against SARS-CoV-2, the virus that causes COVID-19, are three times more likely to die if infected with the virus compared to fully boosted heart failure patients, according to new research out of Mount Sinai Heart. The study, published June 9 in the Journal of Cardiac Failure, is the first to look at COVID-19 vaccination status and outcomes in patients with this cardiovascular condition, and shows how dramatic the protective effects are in this high-risk patient population.
The research is important since many heart failure patients are hesitant to get the COVID-19 vaccine due to fear of myocarditis, or inflammation of the heart muscle. This condition is a rare side effect of the Pfizer-BioNTech and Moderna vaccines but a more common complication of COVID-19 infection. The results of this work can help heart failure patients better understand the benefits of being fully vaccinated and boosted against COVID-19, and the protection it offers.
“I launched this study because our heart failure patients often express fear of getting the COVID-19 vaccine after hearing reports of vaccine-related myocarditis, which would cause another cardiac setback for them. Until now, it has been difficult to explain to these patients how the cardiovascular benefits of vaccination substantially outweigh the risks of complications to them, because we didn’t have concrete evidence to show the substantial risks of being unvaccinated, as few studies have focused on this specific high-risk population and COVID-19 vaccinations,” says corresponding author Anurhada Lala, MD, Director of Heart Failure Research and an Associate Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai. “Having specific data showing patients with heart failure who don’t have their full vaccine series are at a much higher risk of death, intensive care unit (ICU) admission, and general hospitalization — even after accounting for factors that might be related to an individual’s decision to become vaccinated — is helpful.”
Mount Sinai researchers conducted a retrospective study to analyze the impact of COVID-19 vaccination status in the heart failure patient population. They looked at electronic records of 7,094 patients from the Mount Sinai Health System with a heart failure diagnosis (not including heart transplant and left ventricular assist device patients) who had office visits, emergency department visits, or hospitalizations between January 1, 2021, and January 24, 2022.
Of that group, 2,200 (31 percent) were fully vaccinated with two doses, 1,053 (14.8 percent) were fully vaccinated and had also received one booster — the recommended guidance from Centers for Disease Control and Prevention at that time; 645 (9.1 percent) were partially vaccinated with only one dose, and 3,196 (45 percent) were unvaccinated. That unvaccinated proportion in this study is approximately double the proportion of unvaccinated adults in the general New York City population.
Researchers compared survival rates and numbers of admissions to the hospital and intensive care units between the groups, looking at both all-cause mortality and mortality associated with concurrent, documented SARS-CoV-2 infection. They found the unvaccinated and partially vaccinated patients were three times more likely to die from COVID-19-related illness than fully vaccinated and boosted patients. The study goes on to show that unvaccinated and partially vaccinated patients were 15 percent more likely to be hospitalized if infected with the virus and nearly twice as likely to be admitted to the ICU when compared to fully vaccinated and boosted patients.
“The findings further emphasize that heart failure patients need to take vaccines seriously, since they have worse outcomes if infected with COVID-19, and stresses the importance of receiving the full COVID-19 vaccination dosage, especially since our previous work shows those with heart failure are 2.5 times more likely to die from the virus,” Dr. Lala adds. “I have used these results to help educate reluctant patients and in many cases this has been effective in encouraging them and getting them to follow through with full vaccination. The hope is that cardiologists will use these results as a tool to help their patients and improve their chances of survival.”

NIMS has developed a hot-melt tissue adhesive (i.e., medical glue that is applied in a molten state) capable of healing operative wounds. This adhesive has excellent medical material properties in terms of its ease of use, adhesiveness to tissues, biocompatibility and ability to prevent postoperative complications.
Post-surgical complications (e.g., adhesions, bleeding, inflammation and infections) are major issues in clinical medicine. For example, post-surgical adhesion — the binding of wounded tissue to a neighboring organ as it heals — can cause ileus, infertility and pelvic pain. This complication also may negatively affect patients’ quality of life, prolong hospitalization and necessitate further corrective surgery. Existing medical materials designed to prevent postoperative adhesion are known to have a number of disadvantages, including poor adhesiveness to tissues, difficulty in handling during endoscopy, cumbersome preparation and difficulty in preparing a homogeneous liquid mixture. It is therefore highly desirable to develop medical materials capable of minimizing the risk of postoperative complications with high degrees of adhesiveness to tissues, biocompatibility and manipulability.
This research team recently developed a single-syringe hot-melt tissue adhesive with an adjustable sol-gel transition temperature. Porcine skin-derived gelatin — a commonly used medical material — was initially found to be unsuitable for use as a tissue adhesive because its sol-gel transition temperature was around 32°C, causing it to become a sol at body temperature (37°C). The team therefore used porcine tendon-derived gelatin instead and added a specific number of ureidopyrimidinone (UPy) groups to it, thereby adjusting the number and strength of intermolecular hydrogen bonds within it. Through this process, the team synthesized a new hot-melt tissue adhesive made of biopolymers (UPy gelatin) whose sol-gel transition temperature can be freely controlled. The team then designed it to melt to a sol above 40°C and solidify into a gel at body temperature.
This tissue adhesive is expected to be able to transform into a stable gel within the human body, strongly bind to tissues and eventually decompose and be absorbed by the body, thereby preventing postoperative adhesions from developing and eliminating the need for secondary surgery. In fact, animal testing using rat cecum-abdominal wall models demonstrated that the use of this adhesive caused no postoperative adhesion.
In future research, the team plans to conduct preclinical studies and biological safety testing with the goal of putting the tissue adhesive into practical use in clinical medicine.
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Unvaccinated children mount a rapid immune response to SARS-CoV-2 which may contribute to less severe symptoms, but which may also limit the development of an immune “memory” response to ward off future infections, a study led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) has found.
Published in Immunity, the study is among the first to analyse the immune response of children following infection with SARS-CoV-2, using new technologies and a group of more than 50 children from Melbourne and Los Angeles.
They found that unvaccinated children that developed antibodies against SARS-CoV-2 also produced memory killer T cells — the cells responsible for recognising and fighting off subsequent infections, even against other variants of concern. However, these memory T cells were fewer in number in children when compared to adults.
Lead author University of Melbourne Dr Louise Rowntree, a Research Fellow at the Doherty Institute said that children’s limited ability to generate strong memory killer T cell responses following natural infection may leave them vulnerable to future infections.
“Memory killer T cells are essential for protection against severe disease in the future and while we observed these T cells in children, they were at a lower frequency compared to adults” Dr Rowntree said.
“We also found that not all household contacts who were exposed to SARS-CoV-2 generated memory T cell responses” Dr Rowntree said.

Moderate drinkers who binge alcohol are at a significantly higher risk of developing alcohol problems than those who drink the same amount overall but don’t binge, according to a new study from researchers at The University of Texas at Austin appearing in the American Journal of Preventive Medicine, published by Elsevier.
After analyzing a national sample of US adults, UT Austin psychology professor Charles Holahan, PhD, and his collaborators found that moderate average drinkers with a pattern of binge drinking were almost five times more likely to experience multiple alcohol problems and were twice as likely to experience more alcohol problems nine years later. Moderate drinking is defined as having on average no more than one drink a day for women and two for men. Binge drinking is defined as consuming five or more drinks on the same occasion.
“What this means,” said Dr. Holahan, “is that an individual whose total consumption is seven drinks on Saturday night presents a greater risk profile than someone whose total consumption is a daily drink with dinner, even though their average drinking level is the same.”
This research supports a growing recognition that binge drinking among adults is a public health concern and calls for increased public health efforts to address such drinking.
Research on binge drinking tends to focus on adolescents and college students, but most binge drinking occurs among adults over 30, and the prevalence of binge drinking in adults is increasing. However, research on adult alcohol consumption and its effects usually focuses only on a person’s average level of drinking, which masks binge drinking patterns. As a result, the impact of binge drinking among low and moderate adult drinkers has not been well studied or understood.
“In both scientific and media discussions of moderate drinking, the pattern of drinking is generally overlooked,” said Rudolf Moos, PhD, one of the study’s co-authors and professor emeritus of psychiatry and behavioral sciences at Stanford University School of Medicine. “This leaves many drinkers mistakenly assuming that a moderate average level of consumption is safe, regardless of drinking pattern.”
To get a better understanding of the impact of drinking patterns, the researchers analyzed survey responses from 1,229 drinkers ages 30 and older. The data, taken from two waves of the Midlife Development in the United States study, allowed the researchers to see how respondents’ drinking patterns affected them over nine years. What the investigators found surprised them: Most cases of binge drinking — and of multiple alcohol problems — occurred among individuals who were average moderate drinkers.
“Much binge drinking among adults escapes public health scrutiny,” said Dr. Holahan, “because it occurs among individuals who drink at a moderate average level. These findings point to a need for alcohol interventions targeting moderate average level drinkers in addition to conventional strategies focusing on the higher risk, but smaller, population of habitually high-level drinkers.”
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The number of reported cases using viruses to treat deadly Mycobacteriuminfections just went up by a factor of five. In a new study, a team led by researchers from the University of Pittsburgh and the University of California San Diego report 20 new case studies on the use of the experimental treatment, showing the therapy’s success in more than half of the patients.
It’s the largest ever set of published case studies for therapy using bacteria-killing viruses known as bacteriophages, providing unprecedented detail on their use to treat dire infections while laying the groundwork for a future clinical trial.
“Some of those are spectacular outcomes, and others are complicated,” said Graham Hatfull, the Eberly Family Professor of Biotechnology in the Kenneth P. Dietrich School of Arts and Sciences at the University of Pittsburgh. “But when we do 20 cases, it becomes much more compelling that the phages are contributing to favorable outcomes — and in patients who have no other alternatives.”
Each patient treated in the study was infected with one or more strains of Mycobacterium, a group of bacteria that can cause deadly, treatment-resistant infections in those with compromised immune systems or with the lung disorder cystic fibrosis. In 2019, Hatfull led a team showing the first successful use of phages to treat one of these infections.
“For clinicians, these are really a nightmare: They’re not as common as some other types of infections, but they’re amongst some of the most difficult to treat with antibiotics,” said Hatfull. “And especially when you take these antibiotics over extended periods of time, they’re toxic or not very well-tolerated.”
Last month, the University of Pittsburgh researchers were involved in two new case studies successfully treating patients in collaboration with colleagues at National Jewish Health and Harvard University. But those reports represent only a fraction of the cases the team has been involved in behind the scenes. Since 2019, Hatfull and his lab have fielded requests from more than 200 clinicians looking for treatments for their patients, working with them to find phages that could be effective against the particular strain of bacteria infecting each patient.

Eating higher levels of fish, including tuna and non-fried fish, appears to be associated with a greater risk of malignant melanoma, suggests a large study of US adults published in Cancer Causes & Control.
Eunyoung Cho, the corresponding author said: “Melanoma is the fifth most common cancer in the USA and the risk of developing melanoma over a lifetime is one in 38 for white people, one in 1,000 for Black people and one in 167 for Hispanic people1. Although fish intake has increased in the USA and Europe in recent decades, the results of previous studies investigating associations between fish intake and melanoma risk have been inconsistent. Our findings have identified an association that requires further investigation.”
Researchers from Brown University, USA found that, compared to those whose median daily fish intake was 3.2 grams, the risk of malignant melanoma was 22% higher among those whose median daily intake was 42.8 grams. They also found that those whose median daily intake was 42.8 grams of fish had a 28% increased risk of developing abnormal cells in the outer layer of the skin only — known as stage 0 melanoma or melanoma in situ — compared to those whose median daily intake was 3.2 grams of fish. A portion of fish is approximately 140 grams of cooked fish.
To examine the relationship between fish intake and melanoma risk, the authors analysed data collected from 491,367 adults who were recruited from across the USA to the NIH-AARP Diet and Health Study between 1995 and 1996. Participants, who were aged 62 years on average, reported how frequently they ate fried fish, non-fried fish, and tuna during the previous year as well as their portion sizes.
The researchers calculated the incidence of new melanomas that developed over a median period of 15 years using data obtained from cancer registries. They accounted for sociodemographic factors, as well as participants’ BMI, physical activity levels, smoking history, daily intake of alcohol, caffeine and calories, family history of cancer, and the average UV radiation levels in their local area. 5,034 participants (1.0%) developed malignant melanoma during the study period and 3,284 (0.7%) developed stage 0 melanoma.
The researchers found that higher intake of non-fried fish and tuna was associated with increased risks of malignant melanoma and stage 0 melanoma. Those whose median daily tuna intake was 14.2 grams had a 20% higher risk of malignant melanoma and a 17% higher risk of stage 0 melanoma, compared to those whose median daily tuna intake was 0.3 grams. A median intake of 17.8 grams of non-fried fish per day was associated with an 18% higher risk of malignant melanoma and a 25% higher risk of stage 0 melanoma, compared to a median intake of 0.3 grams of non-fried fish per day. The researchers did not identify significant associations between consumption of fried fish and the risk of malignant melanoma or stage 0 melanoma.
Eunyoung Cho said: “We speculate that our findings could possibly be attributed to contaminants in fish, such as polychlorinated biphenyls, dioxins, arsenic and mercury. Previous research has found that higher fish intake is associated with higher levels of these contaminants within the body and has identified associations between these contaminants and a higher risk of skin cancer. However, we note that our study did not investigate the concentrations of these contaminants in participants’ bodies and so further research is needed to confirm this relationship.”
The researchers caution that the observational nature of their study does not allow for conclusions about a causal relationship between fish intake and melanoma risk. They also did not account for some risk factors for melanoma, such as mole count, hair colour, history of severe sunburn and sun-related behaviours in their analyses. Additionally, as average daily fish intake was calculated at the beginning of the study, it may not be representative of participants’ lifetime diets.
The authors suggest that future research is needed to investigate the components of fish that could contribute to the observed association between fish intake and melanoma risk and any biological mechanisms underlying this. At present, they do not recommend any changes to fish consumption.
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