Non-drug therapies as good as or better than drugs for treating depression in people with dementia
Doctors should consider more “social” prescribing of non-drug approaches for depression and loneliness, say researchers
Non-drug therapies, such as exercise, appear to be as, or more, effective than drugs for reducing symptoms of depression in people with dementia, suggests research published online in The BMJ.
The findings suggest that people with dementia will derive a clinically meaningful benefit from non-drug interventions, and the researchers say doctors should consider more “social” prescribing of non-drug approaches to treat symptoms of depression and loneliness.
Fifty million people worldwide have a diagnosis of dementia. About 16% of these people also have a diagnosed major depressive disorder, and 32% will experience symptoms of depression without a formal diagnosis.
Previous trials have shown that non-drug approaches, such as exercise, alleviate symptoms of depression in people with dementia, but it’s not clear how effective they are compared with drugs to reduce symptoms of depression.

Women who experience a miscarriage appear to be more likely to die prematurely (before age 70), particularly from cardiovascular disease, than women with all other pregnancy outcomes, suggests research published by The BMJ today.
The association between miscarriage and premature death was particularly strong for women who had miscarriages early in their reproductive life or who had recurrent miscarriages, prompting the researchers to suggest that miscarriage could be “an “early marker of future health risk in women.”
Spontaneous abortion (the official term for a miscarriage) is one of the most common adverse outcomes of pregnancy, affecting an estimated 12-24% of known pregnancies.
Substantial evidence indicates that women with a history of miscarriage have a greater risk of high blood pressure, cardiovascular diseases, and type 2 diabetes, but evidence relating miscarriage to risk of early death is scant and inconsistent.
To explore this further, a team of US researchers set out to investigate the associations between miscarriage and risk of all cause and cause specific premature death.
Their findings are based on data for 101,681 female nurses taking part in the Nurses’ Health Study II — an ongoing study of US women of reproductive age at the beginning of the study (25-42 years) — whose pregnancies and health were followed over a 24-year period between 1993 and 2017.

Even small increases in nitrogen dioxide levels in the air may be linked to increases in cardiovascular and respiratory deaths, according to research published by The BMJ today.
The findings suggest a need to revise and tighten the current air quality guidelines, and to consider stricter regulatory limits for nitrogen dioxide concentrations.
Nitrogen dioxide (NO2) is a common air pollutant formed by burning fuel for things like transport, power and industrial processes.
It is measured in micrograms (one-millionth of a gram) per cubic meter of air or µg/m3. World Health Organization (WHO) air quality guidelines currently recommend that nitrogen dioxide levels should not exceed an annual average of 40 40 µg/m3.
Many studies have reported the effects of short term exposure to NO2 on health, but most have been based on small samples, covered limited geographical areas, or used different study designs, so results are inconsistent.
To address this uncertainty, a team of international researchers set out to investigate the short term associations between NO2 and total, cardiovascular, and respiratory deaths across multiple countries/regions worldwide.

When clinical trials were conducted to determine the immunogenicity — the ability to elicit an immune response — for the first two vaccines marshaled against SARS-CoV-2the virus that causes COVID-19, one group was not among those included: people who have received solid organ transplants and others (such as those with autoimmune disorders) who are immunocompromised.
Now, Johns Hopkins Medicine researchers have tried to rectify that inequity, taking one of the first looks at how people who are immunocompromised respond to their first dose of one of the two mRNA vaccines — Moderna and Pfizer-BioNTech — currently being administered worldwide. Their findings, as published March 15, 2021, in a research letter in the Journal of the American Medical Association, disappointingly show that only 17% produced detectable antibodies against the SARS-CoV-2 virus.
“This is in stark contrast to people with healthy immune systems who are vaccinated, nearly all of whom mount a sufficient antibody defense against COVID-19,” says study lead author Brian Boyarsky, M.D., a surgery resident at the Johns Hopkins University School of Medicine.
The study evaluated the vaccine immunogenic response for 436 transplant recipients, none of whom had a prior diagnosis of COVID-19 or tested positively for SARS-CoV-2 antibodies. The median age was 55.9 years and 61% were women. Fifty-two percent were administered a single dose of the Pfizer-BioNTech vaccine and 48% received one shot of the Moderna vaccine. The median time since transplant for the participants was 6.2 years.
At a median time of 20 days after the first dose of vaccine, the researchers report that only 76 of the 436 participants (17%) had detectable antibodies to the SARS-CoV-2 virus. The researchers also found that among the 76 transplant recipients, the most likely to develop an antibody response were those younger than age 60 who did not take anti-metabolites for immunosuppression and who received the Moderna vaccine.
“Given these observations, we feel that the U.S. Centers for Disease Control and Prevention should update their new guidelines for vaccinated individuals to warn immunocompromised people that they still may be susceptible to COVID-19 after vaccination,” says study senior author Dorry Segev, M.D., Ph.D., the Marjory K. and Thomas Pozefsky Professor of Surgery and Epidemiology and director of the Epidemiology Research Group in Organ Transplantation at the Johns Hopkins University School of Medicine. “As the guidelines are currently written, people assume that vaccination means immunity.”
Segev says that upcoming studies will define the immunogenic response of organ transplant recipients and other immunocompromised patients after a second vaccine dose. Other studies will look at the impact of more extensive immune system profiling — including characterizing the immune cells that remember SARS-CoV-2 after vaccination and produce antibodies, or directly attack the virus in response to the presence of the virus — to help guide vaccination strategies for this population.
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Materials provided by Johns Hopkins Medicine. Note: Content may be edited for style and length.

Bobby Wayne, a retired reverend, called the state seeking help getting the vaccine. He said he was told there was no evidence the vaccine was effective.Bobby Wayne, a retired reverend with prostate cancer and leukemia, had spent a week calling health agencies around his county in Mississippi, trying to find out where to get the Covid-19 vaccine.But when Mr. Wayne, 64, called the state’s hotline on Monday, he said an operator, whose job was to help residents schedule vaccine appointments, gave him unnerving and incorrect information.“This is the way she put it to me: They had no documentation that the vaccine was effective,” Mr. Wayne said. “And then she asked me did I still want to take it.”When he told her “yes,” he said the operator replied that there were no appointments available and that he should call again the next morning.Bobby Wayne said he was anxious to get the vaccine and baffled when a state hotline operator told him there was no proof it would work. Elizabeth WayneThe confusion was the result of “miscommunication” over a misleading script that the hotline operators had been given, according to the State Department of Health.The script referred to pregnant women, women who were lactating and people with compromised immune systems.It asked: “Do you still want to be vaccinated with an understanding there are currently no available data on the safety or effectiveness of Covid-19 vaccines, including Moderna Covid-19 vaccine, in pregnant people, lactating people, or immunocompromised people?”Most experts agree that the risks to pregnant women from Covid-19 are far greater than any theoretical harm from the vaccines. Doctors have said they believe that the vaccines are safe for people with autoimmune conditions.Liz Sharlot, a spokeswoman for Mississippi’s State Department of Health, said that the wording in the script could be confusing “when read out of context.”“We are replacing this confusing and misleading language,” she said in a statementHowever, Ms. Sharlot said the operators were never told that there was no documented proof that the Moderna vaccine or any other vaccine authorized for use by the Food and Drug Administration worked.“Just the opposite is true,” she said. “Both Moderna and Pfizer have high efficacy rates.”Ms. Sharlot added, “I think the gentleman misunderstood.”Mr. Wayne said he understood perfectly.“I’m not confused at all,” he said. “I may be 64 years old and handicapped, but my brain is still functioning and my ears are, too.”Mr. Wayne said it was unsettling to think people calling for information about getting vaccinated could be discouraged by the very people who are meant to help them get a shot.“I wouldn’t want anybody else going through that,” he said.Mississippi has administered at least one dose of a Covid-19 vaccine to 22 percent of its population, according to a New York Times database, putting it among the states that have had a slower rollout. Just over 12 percent of state residents have been fully vaccinated.Mr. Wayne’s daughter, Elizabeth Wayne, an assistant professor of biomedical engineering at Carnegie Mellon University, complained on Twitter about her father’s conversation with the state hotline operator and called it a “violence.”“It’s dangerous,” Dr. Wayne said. “There is a therapy available. There is a way to treat something, and you’re making it difficult for them to have access to that treatment so it’s increasing the likelihood they may become sick.”The Mississippi Free Press reported the story after Dr. Wayne wrote about her father’s experience on Twitter.Dr. Thomas E. Dobbs III, the state health officer, responded to her post on Twitter, sharing a link to a study in the New England Journal of Medicine that showed the Moderna vaccine was 94.1 percent effective at preventing Covid-19 and that “no safety concerns were identified.”Dr. Wayne said she was pleased that the health department appeared to take her concerns, and her father’s, seriously.“I think it was a really good example of the State Health Department trying to reach out because they actually want to restore faith” in the vaccine, she said.Mr. Wayne said he got his shot on Wednesday morning.“I feel a whole lot better,” he said.

Scientists make pivotal discovery of method for wireless modulation of neurons with X-rays that could improve the lives of patients with brain disorders. The X-ray source only requires a machine like that found in a dentist’s office.
Many people worldwide suffer from movement-related brain disorders. Epilepsy accounts for more than 50 million; essential tremor, 40 million; and Parkinson’s disease, 10 million.
Relief for some brain disorder sufferers may one day be on the way in the form of a new treatment invented by researchers from the U.S. Department of Energy’s (DOE) Argonne National Laboratory and four universities. The treatment is based on breakthroughs in both optics and genetics. It would be applicable to not only movement-related brain disorders, but also chronic depression and pain.
This new treatment involves stimulation of neurons deep within the brain by means of injected nanoparticles that light up when exposed to X-rays (nanoscintillators) and would eliminate an invasive brain surgery currently in use.
“Our high-precision noninvasive approach could become routine with the use of a small X-ray machine, the kind commonly found in every dental office,” said Elena Rozhkova, a lead author and a nanoscientist in Argonne’s Center for Nanoscale Materials (CNM), a DOE Office of Science User Facility.
Traditional deep brain stimulation requires an invasive neurosurgical procedure for disorders when conventional drug therapy is not an option. In the traditional procedure, approved by the U.S. Food and Drug Administration, surgeons implant a calibrated pulse generator under the skin (similar to a pacemaker). They then connect it with an insulated extension cord to electrodes inserted into a specific area of the brain to stimulate the surrounding neurons and regulate abnormal impulses.

Sarcomeres are small repeating subunits of myofibrils, the long cylinders that bundle together to make the muscle fibres. Inside the sarcomeres, filaments of the proteins myosin and actin interact to generate muscle contraction and relaxation. So far, traditional experimental approaches to investigate the structure and function of muscle tissue were performed on reconstructed protein complexes or suffered from low resolution. “Electron cryo-tomography, instead, allows us to obtain detailed and artefact-free 3D images of the frozen muscle,” says Raunser.
Cryo-ET was for a long time an established yet niche methodology. But recent technical advances in electron cryo-microscopy (cryo-EM) as well as the new development of cryo focused ion beam (FIB) milling are pushing cryo-ET resolution. Similar to cryo-EM, researchers flash-freeze the biological sample at a very low temperature (- 175 °C). Through this process, the sample preserves its hydration and fine structure and remains close to its native state. FIB milling is then applied to shave away extra material and obtain an ideal thickness of around 100 nanometers for the transmission electron microscope, which acquires multiple images as the sample is tilted along an axis. Finally, computational methods reconstruct a three-dimensional picture at high resolution.
Raunser’s team performed cryo-ET on mouse myofibrils isolated at the King’s College, and obtained a resolution of one nanometer (a millionth of a millimetre, enough to see fine structures within a protein): “We can now look at a myofibril with details thought unimaginable only four years ago. It’s fascinating!,” says Raunser.
Fibres in their natural context
The calculated reconstruction of the myofibrils revealed the three-dimensional organisation of the sarcomere, including the sub regions M-, A-, and I- bands, and the Z-disc, which unexpectedly forms a more irregular mesh and adopts different conformations. The scientists used a sample with myosin strongly bound to actin, representing a stage of the contracting muscle that is called the rigor state. And indeed, they could visualise for the first time in the native cell how two heads of the same myosin bind to an actin filament. They also discovered that the double head not only interacts with the same actin filament but is also found split between two actin filaments. This has never been seen before and shows that proximity to the next actin filament is stronger than the cooperative effect between the neighbouring heads.
“This is just the beginning. Cryo-ET is moving from niche to widespread technology in structural biology,” says Raunser. “Soon we will be able to investigate muscle diseases at molecular and even atomic level.” Mouse muscles are very similar to those of humans, yet scientists plan to investigate muscle tissue from biopsies or derived from pluripotent stem cells.
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Materials provided by Max Planck Institute of Molecular Physiology. Note: Content may be edited for style and length.

Businesses across the United States and beyond are offering free stuff to people who have been vaccinated. The perks include movie popcorn, alcohol and even marijuana.The benefits of getting vaccinated against Covid-19 — namely, protection against a dangerous virus — should be obvious by this stage in the pandemic.If that isn’t sufficient motivation, consider the swag.Businesses across the United States and beyond are offering free merchandise and other stuff to people who receive Covid shots. The perks include free rides, doughnuts, money, arcade tokens and even marijuana.Experts in behavioral motivation say that offering incentives is not necessarily the most effective or cost-efficient way to increase vaccine uptake. But that hasn’t stopped the freebies from piling up.In Cleveland, the Market Garden Brewery is offering 10-cent beers to the first 2021 people who show a Covid-19 vaccine certificate. “Yes, you read that right,” the brewery says on its website. “Ten Cents.”At the Greenhouse of Walled Lake, a medical marijuana dispensary in Michigan, anyone 21 and over who gets a Covid vaccine can pick up a prerolled joint until the end of the month.Chobani provides free yogurt at some vaccination sites. And Krispy Kreme said on Monday that for the rest of the year, it would give one glazed doughnut per day to anyone who provides proof of a Covid-19 vaccination.As vaccinations accelerated across the United States, “We made the decision that said, ‘Hey, we can support the next act of joy,’ which is, if you come by, show us a vaccine card, get a doughnut any time, any day, every day if you choose to,” the company’s chief executive, Michael Tattersfield, told Fox News.The Krispy Kreme initiative is no relation to the “vaccinated doughnuts” that were sold last month by a bakery in Germany, garnished with plastic syringes that dispense a sweet, lemony-ginger amuse-bouche. It also does not entitle vaccinated Americans to endless doughnuts, as Mr. Tattersfield seemed to imply in his Fox News interview — just one per day, as the company notes on its website.In a promotion it is calling “Tokens for Poke’ns,” Up-Down, a chain of bars featuring vintage arcade games, is offering $5 in free tokens to guests who present a completed vaccination card. Up-Down, which has six locations in five Midwestern states, is extending the offer to guests who visit within three weeks of their final dose.David Hayden, Up-Down’s communications manager, said he came up with the idea while sitting in an observation room after receiving his own vaccine.“It’s something we anticipated for so long,” he said, adding that the token giveaway was a way of giving customers something else to look forward to after being vaccinated.Cleveland Cinemas, a movie-theater chain in Ohio, is offering a free 44-ounce popcorn at two of its locations to anyone who presents a vaccination card through April 30.A woman was inoculated in February as part of an initiative in Tel Aviv offering a free drink at a bar to people getting the Covid vaccine.Corinna Kern/ReutersTo encourage younger people to get vaccinated, the city of Tel Aviv set up a mobile vaccination clinic at a bar last month, and offered free beer and shots of nonalcoholic peach juice to those who received a shot, The Times of Israel reported.Presenting cards for so many promotions might cause some wear and tear. To protect the cards from damage, Staples is offering to laminate them at no charge after customers have received their final dose. The promotion runs through May 1.Some vaccine perks flow from corporations to their employees. Tyson Foods, Trader Joe’s and others pay for the time it takes them to get vaccinated, while Kroger pays them a $100 bonus.Other incentives target people in vulnerable groups. Uber, for instance, has agreed to provide 10 million free or discounted rides to seniors, essential workers and others in countries across North America, Europe and Asia to help them get to vaccination centers.“Governments like these initiatives because they help them to get more vaccines in more arms,” said Chris Brummitt, a spokesman for the company in Singapore.That may be true, but the science of motivating people to get vaccinated is complex.“Behavioral nudges” that are based on scientific observations may be a more cost-effective way to persuade people to get vaccinated against Covid-19 than straight-up incentives, said Hengchen Dai, a professor of management at the University of California, Los Angeles.In a recent study, Ms. Dai and her colleagues found that text messages could boost uptake of influenza vaccinations. The most effective texts were framed as reminders to get shots that were already reserved for the patient. They also resembled the kind of communication that patients expect to receive from health care providers.Jon Bogard, a graduate student at U.C.L.A. who contributed to the study, said that policymakers should proceed with caution on incentives because they can sometimes backfire. One problem is that the campaigns are expensive, he said. Another is that people receiving shots could see a large incentive as a sign that “vaccines are riskier than they in fact are.”A better alternative, Mr. Bogard said, could be handing out “low-personal-value, high-social-value” objects — like stickers and badges — that tap into a larger sense of “social motivation and accountability.”There appears to be no shortage of such swag swirling around the world’s hospitals and vaccination clinics.“Protected!” says a button that patients receive at a vaccination site in Hong Kong. It shows a cartoon syringe fist bumping a masked doctor.At a minor-league baseball stadium in Hartford, Conn., people receiving shots can pick up an “I got my Covid-19 vaccination” sticker bearing the home team’s mascot, a goat.If you aren’t satisfied with the vaccine-related style accouterment at your local clinic, there are plenty of options available for purchase online.One badge — “I got my Fauci ouchi” — pays homage to America’s best-known doctor, Dr. Anthony S. Fauci.“Thanks, science,” says another.

Businesses across the United States and beyond are offering free stuff to people who have been vaccinated. The perks include movie popcorn, alcohol and even marijuana.The benefits of getting vaccinated against Covid-19 — namely, protection against a dangerous virus — should be obvious by this stage in the pandemic.If that isn’t sufficient motivation, consider the swag.Businesses across the United States and beyond are offering free merchandise and other stuff to people who receive Covid shots. The perks include free rides, doughnuts, money, arcade tokens and even marijuana.Experts in behavioral motivation say that offering incentives is not necessarily the most effective or cost-efficient way to increase vaccine uptake. But that hasn’t stopped the freebies from piling up.In Cleveland, the Market Garden Brewery is offering 10-cent beers to the first 2021 people who show a Covid-19 vaccine certificate. “Yes, you read that right,” the brewery says on its website. “Ten Cents.”At the Greenhouse of Walled Lake, a medical marijuana dispensary in Michigan, anyone 21 and over who gets a Covid vaccine can pick up a prerolled joint until the end of the month.Chobani provides free yogurt at some vaccination sites. And Krispy Kreme said on Monday that for the rest of the year, it would give one glazed doughnut per day to anyone who provides proof of a Covid-19 vaccination.As vaccinations accelerated across the United States, “We made the decision that said, ‘Hey, we can support the next act of joy,’ which is, if you come by, show us a vaccine card, get a doughnut any time, any day, every day if you choose to,” the company’s chief executive, Michael Tattersfield, told Fox News.The Krispy Kreme initiative is no relation to the “vaccinated doughnuts” that were sold last month by a bakery in Germany, garnished with plastic syringes that dispense a sweet, lemony-ginger amuse-bouche. It also does not entitle vaccinated Americans to endless doughnuts, as Mr. Tattersfield seemed to imply in his Fox News interview — just one per day, as the company notes on its website.In a promotion it is calling “Tokens for Poke’ns,” Up-Down, a chain of bars featuring vintage arcade games, is offering $5 in free tokens to guests who present a completed vaccination card. Up-Down, which has six locations in five Midwestern states, is extending the offer to guests who visit within three weeks of their final dose.David Hayden, Up-Down’s communications manager, said he came up with the idea while sitting in an observation room after receiving his own vaccine.“It’s something we anticipated for so long,” he said, adding that the token giveaway was a way of giving customers something else to look forward to after being vaccinated.Cleveland Cinemas, a movie-theater chain in Ohio, is offering a free 44-ounce popcorn at two of its locations to anyone who presents a vaccination card through April 30.A woman was inoculated in February as part of an initiative in Tel Aviv offering a free drink at a bar to people getting the Covid vaccine.Corinna Kern/ReutersTo encourage younger people to get vaccinated, the city of Tel Aviv set up a mobile vaccination clinic at a bar last month, and offered free beer and shots of nonalcoholic peach juice to those who received a shot, The Times of Israel reported.Presenting cards for so many promotions might cause some wear and tear. To protect the cards from damage, Staples is offering to laminate them at no charge after customers have received their final dose. The promotion runs through May 1.Some vaccine perks flow from corporations to their employees. Tyson Foods, Trader Joe’s and others pay for the time it takes them to get vaccinated, while Kroger pays them a $100 bonus.Other incentives target people in vulnerable groups. Uber, for instance, has agreed to provide 10 million free or discounted rides to seniors, essential workers and others in countries across North America, Europe and Asia to help them get to vaccination centers.“Governments like these initiatives because they help them to get more vaccines in more arms,” said Chris Brummitt, a spokesman for the company in Singapore.That may be true, but the science of motivating people to get vaccinated is complex.“Behavioral nudges” that are based on scientific observations may be a more cost-effective way to persuade people to get vaccinated against Covid-19 than straight-up incentives, said Hengchen Dai, a professor of management at the University of California, Los Angeles.In a recent study, Ms. Dai and her colleagues found that text messages could boost uptake of influenza vaccinations. The most effective texts were framed as reminders to get shots that were already reserved for the patient. They also resembled the kind of communication that patients expect to receive from health care providers.Jon Bogard, a graduate student at U.C.L.A. who contributed to the study, said that policymakers should proceed with caution on incentives because they can sometimes backfire. One problem is that the campaigns are expensive, he said. Another is that people receiving shots could see a large incentive as a sign that “vaccines are riskier than they in fact are.”A better alternative, Mr. Bogard said, could be handing out “low-personal-value, high-social-value” objects — like stickers and badges — that tap into a larger sense of “social motivation and accountability.”There appears to be no shortage of such swag swirling around the world’s hospitals and vaccination clinics.“Protected!” says a button that patients receive at a vaccination site in Hong Kong. It shows a cartoon syringe fist bumping a masked doctor.At a minor-league baseball stadium in Hartford, Conn., people receiving shots can pick up an “I got my Covid-19 vaccination” sticker bearing the home team’s mascot, a goat.If you aren’t satisfied with the vaccine-related style accouterment at your local clinic, there are plenty of options available for purchase online.One badge — “I got my Fauci ouchi” — pays homage to America’s best-known doctor, Dr. Anthony S. Fauci.“Thanks, science,” says another.

Despite continued improvements in antibiotics and hospital intensive care, staph sepsis — a bloodstream infection caused by Staphylococcus aureus bacteria — still causes severe illness or death in 20 to 30 percent of patients who contract it.
Rather than continue to throw more antibiotics at the problem, University of California San Diego researchers want to boost the other side of the equation: the patient’s own immune system.
The team recently discovered a battle that occurs between staph bacteria and platelets — blood cells known better for their role in clotting than in immune defense. In some sepsis cases, they found, the bacteria win out and platelet levels plummet. Patients with fewer platelets were more likely to die of staph sepsis than patients with higher platelet counts.
The researchers also determined that two currently available prescription medications, approved by the U.S. Food and Drug Administration (FDA) for other uses, protect platelets and improve survival in mouse models of staph sepsis. The two repurposed drugs were ticagrelor (Brilinta), a blood thinner commonly prescribed to prevent heart attack recurrence, and oseltamivir (Tamiflu), prescribed to treat the flu.
The study publishes March 24, 2021 in Science Translational Medicine.
“In many cases, the antibiotics we give these patients should be able to kill the bacteria, based on lab tests, yet a significant number of patients are not pulling through,” said senior author Victor Nizet, MD, Distinguished Professor at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. “If we can reduce mortality in staph sepsis by 10 or 20 percent by arming or protecting the immune system, we can likely save more lives than discovering an additional new antibiotic that may still not cure the sickest patients.”
The study started with a group of 49 University of Wisconsin patients with staph sepsis. The team collected the patients’ blood, bacteria samples, and demographic and health information. To their surprise, it wasn’t white blood cell counts (immune cells) that correlated with patient outcomes — it was the platelet count. Low platelet counts, defined in this case as fewer than 100,000 per mm3 blood, were associated with increased risk of death from staph sepsis. Approximately 31 percent of patients with low platelet counts died from the infection, compared to less than 6 percent of patients with platelets above the threshold.