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Hysteroscopic sterilization, a nonincisional procedure, was found to be as effective as minimally invasive laparoscopic sterilization in preventing pregnancy, but both methods had higher than expected failure rates, according to a new study led by an investigator at Weill Cornell Medicine.
The comparative study, published April 12 in Fertility and Sterility, found that both methods had failure rates of five to six percent at 5 years post-procedure. Dr. Aileen Gariepy conducted the investigation while at Yale School of Medicine; she is now director of complex family planning in the Department of Obstetrics and Gynecology at Weill Cornell Medicine. Co-investigators included Dr. Eleanor Bimla Schwarz from the University of California, San Francisco and University of California, Davis, and Dr. Diana Zuckerman from the National Center for Health Research.
“The rate we found is five to six times higher than the sterilization failure rate of one percent that’s often cited by physicians when counseling patients,” Dr. Gariepy said. The one percent figure, she noted, is based on decades-old data from the U.S. Collaborative Review of Sterilization study.
With 219 million women and their partners relying on female sterilization, considered a permanent way to prevent pregnancy, it is the most commonly used contraceptive method worldwide. In the United States, sterilization is more commonly used by women insured by Medicaid than those with private health insurance, according to researchers.
The goal of the study was to compare the effectiveness of hysteroscopic and laparoscopic sterilization procedures. For laparoscopic sterilization, a surgeon makes a small incision near the belly button and can use an array of methods to cut or close off the fallopian tubes.
Hysteroscopic sterilization uses a medical device known by the trade name Essure to block the fallopian tubes. The implanted metal coils generate scar tissue over time, which prevents pregnancy.

Doctors typically treat people with nonsmall cell lung cancer, a prevalent and typically incurable type of cancer that makes up 80%-85% of lung cancers, with tyrosine kinase inhibitors, specifically epidermal growth factor receptor inhibitors. About 15%-20% of these patients will become resistant to these standard treatments, resulting in their eventual death.
Researchers understand part of the reason for this: The cells develop a mutation that leads to resistance. But about half of those resistant patients remain unexplained.
Andrea Kasinski, a cellular biologist, and her lab have discovered that some of the explanation is epigenetic. When cells lose the histone methyltransferase (KMT5C), genes that KMT5C were repressing instead become expressed, leading to resistance to epidermal growth factor receptor inhibitors. This understanding lays the groundwork for future therapeutics and gives researchers and doctors a deeper insight into the biology and progression of cancers, especially the role that epigenetic-modifying proteins play in drug resistance, a phenomenon that is not well understood.
“For the majority of genes that contribute to cancer, we’re not sure how they work yet,” Kasinski said. “And for many, we don’t have a way to therapeutically target them. Research like this, that helps us understand how those genes work to determine cancer outcomes, adds to our understanding of the network. This knowledge will ultimately lead us to better therapeutics.”
Purdue professor’s expertise
Kasinski is an expert in how epigenetic factors, especially noncoding RNAs, affect cancer outcomes, including resistance to therapeutics. She is the William and Patty Miller Associate Professor in the Department of Biological Sciences in Purdue’s College of Science, as well as a researcher studying cell identity and signaling with the Purdue Center for Cancer Research. She is an expert in target discovery and characterization, delivery and formulations and in vivo disease models with the Purdue Institute for Drug Discovery.
Brief summary of methods
Kasinski and her team identified the KMT5C gene using a global CRISPR-Cas9 screen after challenging the cells with an epidermal growth factor receptor inhibitor. They selected cells that grew out and then identified the mutations, finding that KMT5C was the most significantly mutated gene in the screen. They validated the results in other cell lines using genetic knockdown and chemical inhibition of KMT5C, leading them to discover that the gene MET, a prominent cancer gene, was upregulated. They used chromatin immunoprecipitation with an antibody for the methylation mark made by KMT5C to determine that an RNA that enhances MET expression is normally methylated and, thus, not expressed. When cells lose KMT5C, the RNA is expressed, leading to MET expression and the subsequent resistance to therapeutics.
This study was funded in part by the National Institutes of Health, as well as grants from the Purdue Research Foundation, the Purdue Center for Cancer Research and Purdue University.
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Materials provided by Purdue University. Original written by Brittany Steff. Note: Content may be edited for style and length.

Testing shortages, long waits for results, and an over-taxed health care system have made headlines throughout the COVID-19 pandemic. These issues can be further exacerbated in small or rural communities in the US and globally. Additionally, respiratory symptoms of COVID-19 such as fever and cough are also associated with the flu, which complicates non-lab diagnoses during certain seasons. A new study by College of Health and Human Services researchers is designed to help identify which symptoms are more likely to indicate COVID during flu season. This is the first study to take seasonality into account.
Farrokh Alemi, principal investigator and professor of Health Administration and Policy, and other Mason researchers predict the probability that a patient has COVID-19, flu, or another respiratory illness prior to testing, depending on the season. This can help clinicians triage patients who are most suspected of having COVID-19.
“When access to reliable COVID testing is limited or test results are delayed, clinicians, especially those who are community-based, are more likely to rely on signs and symptoms than on laboratory findings to diagnose COVID-19,” said Alemi, who observed these challenges at points throughout the pandemic. “Our algorithm can help health care providers triage patient care while they are waiting on lab testing or help prioritize testing if there are testing shortages.”
The findings suggest that community-based health care providers should follow different signs and symptoms for diagnosing COVID depending on the time of year. Outside of flu season, fever is an even stronger predictor of COVID than during flu season. During flu season, a person with a cough is more likely to have the flu than COVID. The study showed that assuming anyone with a fever during flu season has COVID would be incorrect. The algorithm relied on different symptoms for patients in different age and gender. The study also showed that symptom clusters are more important in diagnosis of COVID-19 than symptoms alone.
The algorithms were created by analyzing the symptoms reported by 774 COVID patients in China and 273 COVID patients in the United States. The analysis also included 2,885 influenza and 884 influenza-like illnesses in US patients. “Modeling the Probability of COVID-19 Based on Symptom Screening and Prevalence of Influenza and Influenza-Like Illnesses” was published in Quality Management in Health Care’s April/June 2022 issue. The rest of the research team is also from Mason: Professor of Global Health and Epidemiology Health Amira Roess, Affiliate Faculty Jee Vang, and doctoral candidate Elina Guralnik.
“Though helpful, the algorithms are too complex to expect clinicians to perform these calculations while providing care. The next step is to create an AI, web-based, calculator that can be used in the field. This would allow clinicians to arrive at a presumed diagnosis prior to the visit,” said Alemi. From there, clinicians can make triage decisions on how to care for the patient while waiting for official lab results.
The study does not include any COVID-19 patients without respiratory symptoms, which includes asymptomatic people. Additionally, the study did not differentiate between the first and second week of onset of symptoms, which can vary.
This research was a prototype of how existing data can be used to find signature symptoms of a new disease. The methodology may have relevance beyond this pandemic.
“When there is a new outbreak, collecting data is time consuming. Rapid analysis of existing data can reduce the time to differentiate presentation of new diseases from illnesses with overlapping symptoms. The method in this paper is useful for rapid response to the next pandemic,” said Alemi.
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Materials provided by George Mason University. Original written by Mary Cunningham. Note: Content may be edited for style and length.

Maladaptive daydreaming (MD) may be a better diagnosis for some people than ADHD, according to a new study by Ben-Gurion University of the Negev researchers, in collaboration with the University of Haifa. MD is a condition whereby people slip into involved highly detailed and realistic daydreams that can last hours at the cost of normal functioning. It has not yet been recognized as a formal psychiatric syndrome. However, Dr. Nirit Soffer-Dudek of the Consciousness and Psychopathology Laboratory in the Department of Psychology at BGU is one of the foremost experts on the condition and is hoping to get MD added to the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM VI), by promoting rigorous research on the subject.
“Some individuals who become addicted to their fanciful daydreams experience great difficulty in concentrating and focusing their attention on academic and vocational tasks, yet they find that an ADHD diagnosis and the subsequent treatment plan does not necessarily help them. Formally classifying MD as a mental disorder would enable psychological practitioners to better assist many of their patients,” says Dr. Soffer-Dudek.
Previous studies had found high levels of ADHD in those also presenting with MD, thereby raising the question of whether MD was separate from ADHD. In the current study, published recently in the Journal of Clinical Psychology, doctoral candidate Ms. Nitzan Theodor-Katz, together with Dr. Soffer-Dudek and their colleagues from the University of Haifa, assessed 83 adults diagnosed with ADHD for inattention symptoms, MD, depression, loneliness, and self-esteem. Of those, about 20% met the proposed diagnostic criteria for MD, with significantly higher rates of depression, loneliness, and lowered self-esteem, compared to those with ADHD that did not meet criteria for MD.
“Our findings suggest that there is a subgroup of those diagnosed with ADHD who would benefit more from a diagnosis of MD,” says Dr. Soffer-Dudek.
Additional researchers include Prof. Eli Somer and Dr. Rinatya Maaravi Hesseg of the University of Haifa.
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Scientists from the U.S., Europe and Russia are part of a team releasing the results of a large collaborative study involving the effects of long duration spaceflight on the brain. It appears in the Proceedings of the National Academy of Sciences.
The researchers found that while all of the astronauts and cosmonauts they studied had a similar level of cerebrospinal fluid buildup in the brain, along with reduced space between the brain and the surrounding membrane at the top of the head, there was a noteworthy difference when it came to the Americans. They had more enlargement in the perivascular spaces in the brain, passages that serve as a cleaning system during sleep. That’s something the researchers say warrants further investigation.
Donna Roberts, M.D., a neuroradiologist at the Medical University of South Carolina who helped lead the study, said a challenge when it comes to exploring the effects of spaceflight has been that there aren’t many people in the U.S. who have traveled to space. Combining information about NASA astronauts with that of Russian cosmonauts and astronauts from the European Space Agency gave the study depth.
“By putting all our data together, we have a larger subject number. That’s important when you do this type of study. When you’re looking for statistical significance, you need to have larger numbers of subjects.”
The study focused on 24 Americans, 13 Russians and a small, unspecified number of astronauts from the ESA. It used MRI scans of their brains before and after six months on the International Space Station to evaluate changes in the perivascular spaces.
Lead researcher Floris Wuyts, Ph.D., a professor at the University of Antwerp in Belgium, put the scope of the project in perspective. “I think it is one of the largest studies on space data, and for sure, one of the very few studies with NASA, ESA and Roscosmos data. It comprises data of almost 10% of all people who went into space.” Roscosmos is the Russian space corporation.
Fellow researcher and neuroscientist Giuseppe Barisano, M.D., Ph.D., who works at the University of Southern California, said they looked for differences between the crews. “And in this analysis, we found an increased volume of fluid-filled channels in the brain after spaceflight that was more prominent in the NASA crew than in the Roscosmos crew.”
Roberts explained what that might mean. “An important implication of our findings is that the volume of fluid-filled channels in the brain of astronauts is linked to the development of the spaceflight-associated neuro-ocular syndrome, a syndrome characterized by vision changes and whose mechanisms are still not completely clear.”
But space physiologist Elena Tomilovskaya, Ph.D., of the Russian Academy of Sciences, said further study is needed to determine if there are clinical implications for future flights. “We need to understand how specific microgravity-countermeasure usage, exercise regimes, diet and other factors may play a role in the differences we found between crews.”
Roberts agreed. “It is important not to speculate about pathology or brain health problems at this time. The observed effects are very small, but there are significant changes when we compare the post-flight scans with the preflight scans,” she said.
The idea for the large study came about as the scientists gathered at annual meetings held by NASA and ESA. “Independently, we had previously reported similar changes in space crews at post-flight brain MRI, including enlargement of the cerebral ventricles. We discussed our findings and realized how valuable it would be to perform a joint analysis of our data. I would like to point out that Dr. Wuyts, in particular, was instrumental in organizing our group, which met regularly for two years to carry out this analysis,” Roberts said.”I believe it highlights the importance of international cooperation in understanding the effects of long-term spaceflight on the human body. In fact, we believe international cooperation in space medicine research is essential to ensure the safety of our crews as we return to the Moon and on to Mars.”
The study, “The effect of prolonged spaceflight on cerebrospinal fluid and perivascular spaces of astronauts and cosmonauts,” was funded by the Russian Academy of Sciences, NASA, ESA, the Belgian Science Policy Prodex, FWO Flanders and the National Institute of Mental Health at the National Institutes of Health in the U.S.

A recent study by Kessler Foundation researchers demonstrated efficacy for the behavioral intervention, EMOPRINT, for treating deficits of facial recognition in individuals with multiple sclerosis (MS). The article, “Emotional processing intervention (EMOPRINT): A blinded randomized control trial to treat facial affect recognition deficits in multiple sclerosis,” was epublished on January 19, 2022, by Multiple Sclerosis and Related Disorders. The study is the first to provide Class I evidence supporting the efficacy of an intervention to treat these deficits in MS.
The authors are Helen M. Genova, PhD, Katie Lancaster, PhD, Zuzanna Myszko, Jimmy Morecraft, Jacqueline Leddy, Angela Smith, MA, Nancy Chiaravalloti, PhD, and Jean Lengenfelder, PhD, of Kessler Foundation.
Researchers compared 21 individuals with MS with 15 placebo controls in this double-blinded, placebo-controlled, randomized clinical trial of EMOPRINT, a five-week, 12-session behavioral intervention for teaching facial recognition of the six universal emotions — happiness, sadness, fear, surprise, anger, and disgust. Participants underwent baseline and follow-up neuropsychological assessments of facial affect recognition, as well as assessments of quality of life and emotional functioning. At follow up, facial affect recognition skills significantly improved in the MS group compared with the placebo group.
The efficacy of EMOPRINT has important implications for individuals with MS, as well as for other populations that experience deficits of facial recognition, including autism, traumatic brain injury, and schizophrenia. Deficits in facial recognition, which are known to hinder social functioning, are often associated with mood disorders and reduced quality of life, according to lead author Dr. Genova, the Foundation’s associate director of the Center for Autism Research and an expert in the study of social cognition.
“Improving facial recognition may improve interpersonal relationships and lead to better outcomes at home and in the workplace,” she added. “The success of EMOPRINT in this MS study is an important first step toward the larger-scale, longer-term studies of social cognition we need to study these potential effects.”
Funding: National Multiple Sclerosis Society (RG-1507-05353)
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Materials provided by Kessler Foundation. Note: Content may be edited for style and length.

The diameter of the thoracic aorta is a biomarker for heart attacks and other adverse cardiovascular events in women and men, according to a new study published in the journal Radiology.
The aorta is a large artery that carries oxygenated blood to the heart and other parts of the body. The portion that passes through the chest, known as the thoracic aorta, is divided into an ascending aorta that rises from the left ventricle of the heart and a descending aorta in the back of the chest.
The thoracic aorta grows as we age, but changes of vessel size and structure, a phenomenon known as vascular remodeling, have a systemic nature involving hemodynamic — basic measures of cardiovascular function and blood circulation — and biological processes that are also linked to cardiovascular disease.
“While enlargement of the thoracic aorta is a frequent finding in clinical practice, few longitudinal data regarding its long-term prognosis for major cardiovascular disease outcomes at the population level exist,” said study senior author Maryam Kavousi M.D., Ph.D., from the Department of Epidemiology at Erasmus MC, University Medical Center Rotterdam in Rotterdam, the Netherlands.
Dr. Kavousi and colleagues assessed these associations in 2,178 participants from the population-based Rotterdam Study. Participants underwent multi-detector CT scans between 2003 and 2006 and were followed for nine years, on average. Thoracic aorta diameters were indexed for body mass index (BMI).
Larger BMI-indexed ascending and descending thoracic aortic diameters were significantly associated with increased risk of adverse cardiovascular outcomes like stroke and death in both women and men.

Researchers at The University of Texas MD Anderson Cancer Center have developed a new bioinformatics platform that predicts optimal treatment combinations for a given group of patients based on co-occurring tumor alterations. In retrospective validation studies, the tool selected combinations that resulted in improved patient outcomes across both pre-clinical and clinical studies.
The findings were presented today at the American Association for Cancer Research (AACR) Annual Meeting 2022 by principal investigator Anil Korkut, Ph.D., assistant professor of Bioinformatics and Computational Biology. The study results also were published today in Cancer Discovery.
The platform, called REcurrent Features LEveraged for Combination Therapy (REFLECT), integrates machine learning and cancer informatics algorithms to analyze biological tumor features — including genetic mutations, copy number changes, gene expression and protein expression aberrations — and identify frequent co-occurring alterations that could be targeted by multiple drugs.
“Our ultimate goal is to make precision oncology more effective and create meaningful patient benefit,” Korkut said. “We believe REFLECT may be one of the tools that can help overcome some of the current challenges in the field by facilitating both the discovery and the selection of combination therapies matched to the molecular composition of tumors.”
Targeted therapies have improved clinical outcomes for many patients with cancer, but monotherapies against a single target often lead to treatment resistance. Cancer cells frequently rely on co-occurring alterations, such as mutations in two signaling pathways, to drive tumor progression. Increasing evidence suggests that identifying and targeting both alterations simultaneously could increase durable responses, Korkut explained.
Led by Korkut and postdoctoral fellow Xubin Li, Ph.D., the researchers built and used the REFLECT tool to develop a systematic and unbiased approach to match patients with optimal combination therapies.

In genomic studies, researchers examine the DNA of a population to understand the influence of genetics on health and disease. Though genomic studies have been common for more than a decade, most participants in these studies have been of European descent.
A new study led by Lindsay Fernández-Rhodes, assistant professor of biobehavioral health at Penn State, and Mariaelisa Graff, associate professor of epidemiology at University of North Carolina at Chapel Hill, has shown that increasing the diversity of genomic samples can improve researchers’ ability to identify important genetic markers for health conditions.
Precision Medicine
One of the goals of conducting genomic studies is to develop precision medicine, which is the delivery of the exact treatment or medication that a person needs exactly when they need it.
“Precision medicine is a great idea, but it only works if we study the full diversity of the populations that we may see in the clinic,” Fernández-Rhodes explained. “We cannot treat people with precision if we do not have the relevant data. Previous large-scale genomic studies have largely overlooked Hispanic/Latino people. Since the United States is becoming increasingly diverse, our ability to provide appropriate medical treatment will suffer if the gaps in our genomic data are not addressed.”
The Hispanic/Latino Anthropometry Consortium
Fernández-Rhodes and Graff were joined by more than 100 researchers from around the world to form the Hispanic/Latino Anthropometry Consortium. The consortium pools research expertise and genetic data on people of Hispanic/Latino ethnicity in order to bolster the diversity in genomic studies.

Researchers at the Paul Scherrer Institute PSI and the Italian Institute of Technology IIT have developed a novel substance that disables a protein in the cell skeleton, leading to cell death. In this way, substances of this type can prevent, for example, the growth of tumours. To accomplish this, the researchers combined a structural biological method with the computational design of active agents. The study appeared in the journal Angewandte Chemie International Edition.
The cell skeleton, also called the cytoskeleton, pervades all of our cells as a dynamic network of thread-like protein structures. It gives cells their form, aids in the transport of proteins and larger cell components, and plays a crucial role in cell division. The central building block is the protein tubulin. It arranges itself into tube-shaped structures, the microtubule filaments.
Active agents that attach to the cell skeleton are among the most effective drugs against cancer. They block tubulin, and thus prevent cell division in tumours. PSI researchers, in collaboration with the Italian Institute of Technology in Genoa, have now developed another potent substance that disables tubulin. The have dubbed it ‘Todalam’.
“Todalam prevents tubulin from arranging itself in the form of microtubule filaments,” explains first author Tobias Mühlethaler, who co-designed and studied the substance as part of his doctoral research at PSI. “The protein remains as if frozen in a structure that doesn’t fit into microtubules.”
Rationally designed
There are typically two different approaches for developing new drugs: Researchers can test an enormous number of molecules to fish out the ones that appear promising, or they can specifically design chemical molecules that achieve the desired effect. The PSI and IIT researchers chose the second path, which is often more difficult.
In doing this, they were able to build on their own groundwork, research in which they had already located places in tubulin where molecules can dock especially well. These are the so-called binding pockets, of which they found 27. In addition, the researchers identified 56 fragments that bind to these sites. This work, too, had been published earlier in Angewandte Chemie International Edition.
In the current study based on this prior work, the researchers initially selected a newly discovered binding pocket on tubulin. They used computational design to combine the structures of three molecular fragments, which preferentially dock at this point, into a single chemical compound, and then they synthesised it in the laboratory. “By combining the three fragments into one molecule, we hoped to enhance the effect, since the new molecule fills the binding pocket better,” says Michel Steinmetz, head of the Laboratory of Biomolecular Research at PSI.
Using measurements at the Swiss Light Source SLS, the researchers checked to see how well the molecule actually fits into the binding pocket. In two further cycles, they improved the substance until they arrived at Todalam. “With relatively simple chemistry, we managed to get to a potent compound,” proudly says Andrea Prota, a scientist in the Steinmetz group who collaborated closely with Mühlethaler.
Simple chemical structure
In cell cultures, the researchers demonstrated that Todalam kills cells. No wonder, since tubulin is essential for life. “The better a substance binds to a critical site in tubulin, the more toxic it is for the cells,” Steinmetz explains. That makes Todalam a promising starting point for developing a drug.
The cytoskeletal inhibitors currently in clinical use are natural substances with large, complex structures and are therefore difficult to synthesise. The newly developed compound Todalam, on the other hand, can be produced in a simple chemical synthesis in the laboratory. “That also means that the compound could be produced in large quantities relatively easily,” Steinmetz stresses.
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Materials provided by Paul Scherrer Institute. Original written by Brigitte Osterath. Note: Content may be edited for style and length.