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Researchers at Memorial Sloan Kettering Cancer Center (MSK) and Mount Sinai Hospital have discovered medicines that can help patients with multiple myeloma, a kind of blood cancer, who have tried the immunotherapy CAR-T but have had relapses.
CAR-T treatment, which stands for chimeric antigen receptor T-cell therapy, enlists immune cells called T cells to combat multiple myeloma by modifying them in the lab so that they can detect and destroy cancer cells. It has proven a game-changing treatment for this lethal malignancy, yet some patients relapse after getting CAR-T therapy and have no other alternatives.

The researchers analysed a large sample of multiple myeloma patients who relapsed after receiving a form of CAR-T cell treatment termed BCMA-directed CAR-T in a new study published in the journal Blood in November. In order to combat multiple myeloma, this form of CAR-T cell therapy targets the BCMA protein on malignant plasma cells.
Other treatments that engage T cells, such as bispecific antibodies and other forms of CAR-T cell therapy, tend to have the most significant effectiveness in bringing down these relapsed individuals’ malignancy for the longest period of time, according to the researchers.

“The findings of this study will serve as a benchmark for future prospective clinical studies that intend to improve the outcomes of patients who progress after CAR-T,” said Samir Parekh, MD, Director of Translational Research in Multiple Myeloma and co-leader of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. “This is the first research to report on the results of various treatment alternatives administered to a large cohort of patients who relapsed after receiving anti-BCMA CAR-T therapy. This is one of the most pressing and unmet demands in myeloma patients, and it piques the haematology community’s interest.”

The clinical features of 79 patients, the medications administered after recurrence, and the patients’ reactions to the therapies were all examined in this retrospective analysis. To far, the median overall survival for patients is around 18 months.
Stem cell transplantation were also effective in these individuals. Other medication combinations can also be employed with varying success depending on the features of each patient’s malignancy, according to the research.
The patients were treated at MSK and The Tisch Cancer Institute.
“We are excited that subsequent use of additional innovative immune treatments, such as a second CAR-T cell therapy or a bispecific antibody, was possible and resulted in sustained responses in patients,” said Sham Mailankody, MBBS, MSK Associate Attending Physician and senior author on the research.

“We are excited to continue this research and realise the full potential of immune treatments for patients with multiple myeloma.”

Trauma can result in dissociative symptoms such as an out-of-body experience or a sense of emotional numbness, which can be beneficial in the short term but harmful if they continue over an extended length of time.
McLean Hospital, the biggest psychiatric affiliate of Harvard Medical School and a component of Mass General Brigham, has uncovered locations within brain networks that communicate with one another when persons suffer dissociative symptoms. Their findings were published in the journal Neuropsychopharmacology recently.

“Dissociation and severe dissociative disorders like dissociative identity disorder or ‘DID’ remain at best unappreciated and, at worst, routinely go untreated or misdiagnosed,” said co-lead author and head of the Dissociative Disorders and Trauma Research Program Lauren A.M. Lebois, PhD.
“The cost of stigma and misdiagnosis is high: it has stopped people from receiving adequate and effective treatment, has caused extended suffering, and has stifled dissociation research. Furthermore, because DID affects women disproportionately, gender imbalance is a relevant issue in this setting.”
The study included 91 women with and without a history of childhood trauma, present post-traumatic stress disorder, and varied degrees of dissociative symptoms.

Participants underwent a functional magnetic resonance imaging scan so that researchers could learn more about their brain activity.
“The unique approaches we employed to analyse brain connections are crucial for understanding the role these network disruptions play in dissociative disorders,” stated co-senior author Lisa D. Nickerson, PhD, head of McLean Hospital’s Applied Neuroimaging Statistics Lab.
The researchers revealed that particular dissociation symptoms were linked to specific connections in the brain networks that govern cognitive and emotional processes. “We observed that dissociation important to DID and dissociation common to post-traumatic stress disorder are separately connected to unique brain signatures,” Lebois says.

The team is seeking to expand our understanding of the neurological correlates of dissociation in order to clarify historical misunderstandings about dissociation and DID, destigmatize these experiences, and help to lessening gender-related health inequalities.
“We also hope that it will raise awareness of dissociative symptoms,” said co-senior author Milissa Kaufman, MD, PhD, head of the Dissociative Disorders and Trauma Research Program.
According to the study’s authors, the different brain fingerprints of the various dissociative disorders may highlight the need for innovative therapies.

According to co-author Kerry J. Ressler, MD, PhD, chief scientific officer for McLean, future study may focus on dissociation-related brain activity as a solo treatment.

In a recent study, researchers gave further information on the relationship between COVID-19 severity and immunotherapy for cancer patients.
A University of Cincinnati researcher conducted the study, and Trisha Wise-Draper, MD, PhD, of the University of Cincinnati is a co-corresponding author. The study’s findings were reported in JAMA Oncology. According to Wise-Draper, there have been inconsistent data on how immunotherapy for cancer treatment impacts COVID-19 outcomes before to this study. Immunotherapy was thought to predispose cancer patients to poorer COVID-19 illness since immunotherapy therapies damage and immunosuppress patients’ immune systems.

“The goal of this study was to better understand the effects of immunotherapy and immunosuppression on cancer patients with COVID-19 and COVID-19 outcomes,” said Wise-Draper, an associate professor of medicine in the Division of Hematology/Oncology, section head for Medical Oncology in UC’s College of Medicine, co-leader of the Head and Neck Center of Excellence, and a UC Health physician.
The researchers obtained data on 12,046 patients from the COVID-19 and Cancer Consortium registry, a multi-institution registry of people with COVID-19 and a current or previous invasive cancer diagnosis. This was the COVID-19 and cancer patient cohort with the greatest data available at the time.
“We assessed individuals with cancer, those with baseline immunosuppression, and those who underwent immunotherapy prior to receiving COVID-19,” Wise-Draper explained.

Wise-Draper added that the study team evaluated the severity of COVID-19 disease using criteria such as whether patients required oxygen, were admitted to the hospital, or required intensive care unit therapy, in addition to mortality rates.
“The most relevant finding is that, while immunotherapy alone had no influence on COVID-19 illness outcomes, individuals who had baseline immunosuppression and were treated with immunotherapy had poorer COVID-19 outcomes,” Wise-Draper said.
Patients who underwent nonimmunotherapy medications, such as chemotherapy, had worse COVID-19 results than those who received immunotherapy, but to a lesser amount. These patients were immunocompromised at the start. COVID-19 was shown to be less severe in individuals who had received COVID-19 vaccinations.

Immunotherapy therapies, according to the research, are typically safe for those who do not already have immunosuppression to utilise, even when the pandemic is at its worst. According to the study’s authors, future research comparing patient outcomes based on different immunotherapy regimens might offer more information.

A research conducted by Washington State University discovered that women’s satisfaction and feelings about succeeding in their jobs were impacted by their sleep quality. It’s possible that it has no influence on men’s goals.
This discovery was made by the researchers during a two-week survey of 135 workers in the United States. Each day, participants recorded how well they had rested and the quality of their current mood, and then later in the day, how they felt about pursuing more status and responsibility at work.

“When women have a good night’s sleep and their mood improves, they are more likely to be oriented in their daily intents toward obtaining status and responsibility at work,” said lead author Leah Sheppard, an associate professor in Washington State University’s Carson College of Business. “If their sleep is poor and lowers their good mood, we found that they were less focused on their goals.”
Sheppard and co-authors Julie Kmec of WSU and Teng Iat Loi of the University of Minnesota-Duluth polled full-time employees twice a day for two consecutive work weeks for the study, which was published in the journal Sex Roles.

Every day around midday, the participants responded questions about their previous night’s sleep and present mood, and in the evenings they answered questions about their aspirations to pursue more responsibility, status, and influence at work.
Over the course of the trial, both men and women reported good and terrible sleep quality, with no gender difference in reported sleep quality. Women, on the other hand, indicated decreased intentions to pursue higher status at work on days following a night of bad sleep.
The researchers can only conjecture on why sleep affects women’s goals but not men’s, but they assume it has something to do with gender variations in emotion management as well as cultural expectations—or some combination of these variables.

Women have more emotional reactivity and less emotion regulation than males, according to neuroscience studies, and this is reinforced by societal preconceptions of women as more emotional. At the same time, preconceptions of males as more ambitious than women likely add greater pressure for them to climb the corporate ladder, thus poor sleep quality may be less likely to stop men from pursuing their professional goals.
However, Sheppard believes that these findings are encouraging for women who desire to grow in their jobs.

For example, they may take some practical efforts to enhance their job ambitions, such as practising meditation to aid with both sleep and emotion control, setting better work hours, and, of course, just aiming to get more sleep.
“It’s critical to be able to relate ambitions to something controllable happening outside of the work environment,” she added. “Anyone can do a variety of things to have a better night’s sleep and control their mood in general.”

According to a new study, the microbial community in the intestines of wild martens (Martes americana) living in relatively pure natural settings differs from the gut microbiome of wild martens living in places more strongly touched by human activities. The discovery reveals a new tool that will enable academics and wildlife managers to measure the health of natural habitats.
“Specifically, we discovered that wild martens in more undisturbed regions have more carnivorous diets than martens in human-affected areas,” explains Erin McKenney, co-lead author of the study and associate professor of applied ecology at North Carolina State University.

Marten are tiny animals that are closely related to weasels, ferrets, and mink. “This result, together with our earlier study on carnivore microbiomes, shows us that the microbial ecosystems in carnivore stomachs can vary greatly, reflecting a carnivore’s environment,” McKenney adds. “This means that we can identify how much people are harming a region by examining the gut microbiomes of carnivores who reside there, which can be done by testing wild animal excrement. In practise, this research reveals a useful tool for monitoring the health of natural ecosystems.”

“Our objective here was to investigate how, if at all, human disturbance of a landscape impacts the gut microbiota of American martens who reside in that area,” explains Diana Lafferty, co-lead author and assistant professor of biology at Northern Michigan University. “And the answers were quite plain here.”
The researchers obtained gut microbiota data from 21 martens for the study. During a lawful trapping season, sixteen martens were caught. The remaining five were successfully captured and released at the Huron Mountain Club in Michigan’s Upper Peninsula.
“The Huron Mountain Club is very relevant for our study because it’s relatively virgin – one of the biggest, primaeval forests in the eastern United States,” adds Lafferty.

“This makes it a wonderful contrast to the 16 martens gathered, which were obtained in areas more damaged by human activity.”
The researchers discovered that the gut microbiomes of marten captured in the Huron Mountain Club’s pristine forest were clearly unique from marten collected elsewhere.
“This reflects the fact that marten in relatively pure forest may graze at a higher trophic level, which means they hold a higher position in the food web,” Lafferty explains. “In other words, marten in relatively pristine forests have a more carnivorous diet, whereas marten in more populated regions are more omnivorous.”

Essentially, the data show that a disrupted environment causes a considerably altered diet, which is reflected in their gut microbiomes.”
“It’s also worth noting that we were able to trap and release the marten in Huron Mountain Club during the dead of winter because we designed and built custom box traps to protect them from the elements,” says Chris Kailing, a co-author of the paper and former Northern Michigan University student who worked on the project. “This is interesting since it allows for winter sampling for future animal studies even in difficult winter circumstances.”
“This is the most recent chapter in a collection of research that is assisting us in understanding carnivore gut microbiomes,” McKenney adds.

“Carnivore gut microbiomes are naturally more varied than other species’ gut microbiomes. This work adds to the developing understanding that all of this variation is not just noise. This variety is caused by the nutritional landscape that carnivores have access to, which in turn reflects the health of the ecosystem that carnivores occupy. This means that studying the gut microbiota of wild predators can provide us with valuable information about the environments in which they dwell.”

According to new study, one sort of muscular contraction is more successful at developing muscle strength and growth, and instead of lifting weights, the emphasis should be on lowering them.
According to new study from Edith Cowan University (ECU), one form of muscular contraction is more successful at building muscle strength and growth, and the emphasis should be on reducing weights rather than raising them. The team, which comprised researchers from Niigata University, Nishi Kyushu University, and Londrina State University in Brazil, had groups of participants practise three different types of dumbbell curl exercises and measured the effects.

It discovered that individuals who merely reduced a weight showed the same benefits as those who raised and lowered weights, although doing half the amount of repetitions.
Professor Ken Nosaka of ECU stated the findings supported earlier studies demonstrating that focusing on “eccentric” muscular contractions (in which active muscles are stretched) is more significant for building muscle strength and growth than volume.
“We already know that doing one eccentric muscle contraction each day for five days a week – even for three seconds a day – may develop muscular strength, but concentric (lifting a weight) or isometric muscle contraction (holding a weight) does not,” Professor Nosaka explained.

“This recent study demonstrates that by focusing on eccentric muscle contractions, we may be significantly more efficient in the time we spend training while still seeing meaningful improvements.” Many people feel that the lifting movement gives the most advantage, or at least some benefit, in the instance of a dumbbell curl, however we discovered that concentric muscle contractions contributed little to the training benefits.”

Researchers at Memorial Sloan Kettering Cancer Center (MSK) and Mount Sinai Hospital have discovered medicines that can help patients with multiple myeloma, a kind of blood cancer, who have tried the immunotherapy CAR-T but have had relapses.
Chimeric antigen receptor T-cell therapy, or CAR-T for short, treats multiple myeloma by altering immune cells called T cells in the lab to recognise and eliminate cancer cells. Despite being a pioneering therapy for this lethal cancer, some patients who get CAR-T therapy relapse and are left with no other acceptable therapeutic alternatives.

According to a recent study published in the journal Blood in November, when multiple myeloma patients relapsed after BCMA-directed CAR-T, a type of CAR-T cell therapy that targets the BCMA protein on cancerous plasma cells to treat multiple myeloma, they were treated with a variety of different therapies.
Alternative T cell treatments, such as bispecific antibodies and various kinds of CAR-T cell therapy, tend to have the most pronounced efficiency in permanently eliminating the illness in these relapsed individuals, according to the researchers.

“The findings of this study will serve as a benchmark for future prospective clinical studies that intend to improve the outcomes of patients who progress after CAR-T,” said Samir Parekh, MD, Director of Translational Research in Multiple Myeloma and co-leader of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.
“This is the first research to report on the results of various treatment alternatives administered to a large cohort of patients who relapsed after receiving anti-BCMA CAR-T therapy. This is one of the most pressing and unmet demands in myeloma patients, and it piques the haematology community’s interest.”

This study looked at the disease characteristics, post-relapse medicines, and treatment responses of 79 individuals. Patients’ median overall survival is presently about 18 months.
Stem cell transplantation was also successful in these individuals. The study revealed that different treatment combinations may be delivered with variable degrees of efficacy based on the characteristics of each patient’s cancer.
The patients were cared for at the Tisch Cancer Institute and MSK.
“We are excited that subsequent use of additional innovative immune treatments, such as a second CAR-T cell therapy or a bispecific antibody, was possible and resulted in sustained responses in patients,” said Sham Mailankody, MBBS, MSK Associate Attending Physician and senior author on the research.

“We are excited to continue this research and realise the full potential of immune treatments for patients with multiple myeloma.”

Researchers from Trinity College Dublin unearthed a secret that may help to explain why some people are able to withstand viral infections after assessing the immune systems of women who were exposed to hepatitis C (HCV) through tainted anti-D infusions given more than 40 years ago in Ireland.
The new study, which was just published in the esteemed journal Cell Reports Medicine, has a wide range of implications, from improving our fundamental knowledge of viral resistance to the possible creation of therapeutics for infected patients. Between 1977 and 1979, thousands of women in Ireland were exposed to the hepatitis C virus by contaminated anti-D, a treatment given to Rhesus-negative mothers carrying Rhesus-positive foetuses. Anti-D is a therapy made from donated blood plasma.

The medication prevents the formation of potentially dangerous antibodies that might occur during subsequent pregnancies. Some anti-D used between 1977 and 1979 was contaminated with hepatitis C.

This outbreak produced three separate populations: those with a chronic infection, those cured of the sickness by an antibody response, and those who seemed immune to the disease but did not produce antibodies against hepatitis C.
The senior author of the study is Cliona O’Farrelly, Professor of Comparative Immunology at Trinity’s School of Biochemistry and Immunology.

“We hypothesised that women who seemed to resist HCV infection must have an elevated innate immune response, which is the oldest element of the immune system that works as the first line of defence,” Cliona, who is based at the Trinity Biomedical Sciences Institute, stated.
“To test this, we needed to contact ladies who had been exposed to the virus over forty years ago and ask them to aid us by enabling us to analyse their immune systems in search of scientific evidence that might explain their disparate reactions,” she continued.
Following a countrywide campaign, over 100 women came forward, providing us with some unique and essential insights.

The fact that so many women, many of whom have long lived with medical issues, were eager to assist demonstrates how much people want to connect with science and contribute to research that has the potential to have meaningful, good impacts on society. We owe them a great debt of gratitude.”
In the end, the researchers recruited 90 previously infected women and roughly 40 resistant individuals.
The researchers next obtained blood samples from roughly 20 women in each group, in collaboration with the Institut Pasteur in Paris. They are triggered by chemicals that mimic a viral infection and activate the innate immune system.

The study’s first author is Jamie Sugrue, a PhD candidate in Trinity’s School of Biochemistry and Immunology. “We discovered that resistant donors had an elevated type I interferon response following stimulation by comparing the reaction of the resistant women to those who were sick,” he added. Type I interferons are an essential family of antiviral immune mediators that aid in the defence against viruses such as hepatitis C and SARS-CoV-2, or COVID-19.”
“We believe that the enhanced type I interferon production by our resistant donors, visible today over 40 years after the original hepatitis C exposure, is what protected them from infection,” she added.

“These findings are significant because resistance to infection is a frequently neglected outcome following a viral epidemic, largely because identifying resistant individuals is difficult – because they do not feel ill after viral exposure, they may not be aware that they were infected. That is why, despite their devastating character, cohorts like this one are so valuable: they present a unique opportunity to study the response to viral infections in an otherwise healthy population.”

McLean Hospital, the biggest psychiatric affiliate of Harvard Medical School and a component of Mass General Brigham, has uncovered locations within brain networks that communicate with one another when persons suffer dissociative symptoms. Their findings were published in the journal Neuropsychopharmacology recently.

Trauma can cause dissociative symptoms such as out-of-body experiences or emotional numbness, which can be useful in the short term but dangerous if they persist over an extended period of time.

“Dissociation and severe dissociative disorders like dissociative identity disorder or ‘DID’ remain at best underappreciated and, at worst, frequently go undiagnosed or misdiagnosed,” said co-lead author Lauren A.M. Lebois, PhD, director of the Dissociative Disorders and Trauma Research Program.

“The cost of this stigmatization and misdiagnosis is high–it has prevented people from accessing appropriate and effective treatment, caused prolonged suffering, and stunted research on dissociation. In addition, given that DID disproportionately affect women, gender disparity is an important issue in this context.”

91 women with and without histories of childhood trauma, current post-traumatic stress disorder, and varying degrees of dissociative symptoms participated in Lebois and colleagues’ study. A functional magnetic resonance imaging scan was done by participants so that researchers could learn more about their brain activity.

“The novel methods we used to study brain connectivity are critical for understanding the role these network disturbances play in dissociative disorders,” said co-senior author Lisa D. Nickerson, PhD, director of the Applied Neuroimaging Statistics Lab at McLean Hospital.

The researchers discovered that specific connections between regions in the brain networks that control cognition and emotional processes were connected with certain dissociation symptoms. According to Lebois, “We discovered that dissociation key to DID and dissociation common to post-traumatic stress disorder are each linked to specific brain signatures.”

In order to correct historical misconceptions regarding dissociation and DID, destigmatize these experiences, and contribute to lowering gender-related health disparities, the team is working to improve our understanding of the neural correlates of dissociation.

“We also hope it will increase awareness of dissociative symptoms–and that, ultimately, clinicians will be more likely to assess for and consider these symptoms, and to connect patients with timely and appropriate treatment,” said co-senior author Milissa Kaufman, MD, PhD, director of the Dissociative Disorders and Trauma Research Program.

It is significant to note that the various dissociative disorders’ distinct brain signatures may indicate the need for novel treatments, according to the study’s authors. Future research may focus on dissociation-related brain activity as a standalone treatment, according to co-author Kerry J. Ressler, MD, PhD, chief scientific officer for McLean.