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Osteoblasts act in a group to make bone over the course of several months. However, how osteoblasts cooperate with each other in vivo is still unknown. Now, researchers at Osaka University established an advanced high-resolution microscopy system to visualize extracellular vesicles secreted and captured by mature osteoblasts in vivo and identified a subset of osteoblast-derived vesicles limiting bone formation and stimulating bone-resorbing osteoclast differentiation through a microRNA (miRNA)-mediated mechanism. The osteoblast communication via extracellular vesicles controls the dynamic transition from bone-forming to bone-resorbing phases in vivo and could be a target for new treatments for bone diseases.
Bone remodeling occurs in different parts of the body throughout life to maintain bone architecture balance and systemic mineral homeostasis. During this “remodeling” process, osteoclasts remove mineralized bones, whereas osteoblasts form new bones. These resorption and formation phases are linked and balanced with intermittent coupling phases. “Functional coupling between these two cell types is critical for the maintenance of proper bone metabolism, and the mechanisms controlling the transition from bone-resorbing to bone-forming phases have been investigated. Nevertheless, the molecular and cellular mechanisms terminating osteoblastic bone formation and promoting osteoclastic bone resorption remain elusive,” explains senior author Masaru Ishii.
Intravital optical imaging using multiphoton microscopy can help dissect in vivo cellular dynamics in various intact tissues and organs. To understand the spatiotemporal dynamics of bone remodeling in vivo, the researchers have established an intravital imaging technique to visualize the intact bone tissues of living mice. Using this method, they explored the interplay between bone-destroying osteoclasts and bone-forming osteoblasts. However, the spatial resolution of intravital bone imaging was insufficient to visualize structures smaller than cells.
“In this study, we established an advanced high-resolution microscopy system to visualize extracellular vesicles secreted and captured by mature osteoblasts in vivo and identified a subset of osteoblast-derived vesicles limiting bone formation and stimulating osteoclast differentiation, thus regulating the switch from bone formation to bone resorption through a microRNA (miRNA)-mediated mechanism,” says Ishii.
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SharecloseShare pageCopy linkAbout sharingSickle cell patients have begun receiving the first new treatment for the blood disorder in over 20 years. The inherited condition can cause severe pain and organ failure, often requiring hospital admissions. Crizanlizumab is given as a monthly infusion and is thought to cut visits to A&E by 40%.Loury Mooruth, 62, received the treatment at Birmingham City Hospital, having suffered repeated periods of intense pain for decades.These are called sickle cell crises and are common in people with the condition.”To have a crisis is pain beyond what you could ever experience,” Loury says.”They give you a scale of one to 10 – but it is way beyond that.”Sickle cell disease causes red blood cells to distort and become sticky, blocking vessels and restricting oxygen supply, which triggers excruciating pain.Crizanlizumab, a monoclonal antibody, binds to a protein on blood cells, preventing them from clumping.Sickle cell mostly affects black people.During a crisis, patients often need powerful opioid painkillers but Loury, like many others, has faced suspicion when at A&E. “You know the protocol when you go in, which needles and so on. They think straight away you are a drug addict – they don’t believe you,” she says.She has refused to go to hospital during a crisis for the past two years because of her negative experiences. A report from MPs last year found “serious failings” in sickle cell care with some evidence of discrimination against patients.Dr Shivan Pancham, a consultant haematologist at Birmingham City Hospital, told the BBC: “Our patients often find the experience in emergency departments challenging with a lack of understanding of the severity of pain. “It is hoped with these new therapies if we reduce the likelihood of attending emergency departments, ultimately this will be much better for the patients.”‘Bright, new dawn’Ten specialist treatment centres have been set up across England which doctors hope will improve outcomes for sickle cell patients.Each vial of the drug costs £1,000 but NHS England has negotiated a confidential discount and hopes to treat up to 5,000 patients over the next three years. Loury is optimistic about the future, saying: “This is a bright new dawn.” “Hopefully this will take the crises and put them to one side, and I will see my haematologist a lot less.”Dr Bola Owolabi, NHS director of health inequalities, who also works as a GP in the Midlands, said: “It’s fantastic that our first NHS patients have been given this ground-breaking and historic new treatment for sickle cell disease – the first in over two decades.”This revolutionary treatment will allow patients to have a better quality of life, reduce trips to A&E by almost half and ultimately help to save lives.” Kye Gbagbo, chair of the Sickle Cell Society, said: “We are delighted to see the first sickle cell patients are now getting access to this life-changing new treatment. “We encourage others that are eligible to do similar. Sickle cell crises cause extreme pain and are a huge disruption to daily life. “We hope that this new treatment will bring a new lease of life to many living with sickle cell.”What is sickle cell disease?It is inherited from both parents, who pass on a particular geneIt is possible to carry the gene without having the diseaseNearly 300 babies are born with it each year in the UKA simple blood test will show whether someone has itChildren with sickle cell are at greater risk of strokeOther symptoms can include serious infections, anaemia and tirednessSource: Sickle Cell Society / NHS UKMore on this storyMPs find ‘serious failings’ in sickle cell careFirst new treatment for sickle cell in 20 yearsSickle cell disease – NHSSickle Cell Society – Supporting People Affected by Sickle Cell DisorderThe BBC is not responsible for the content of external sites.

Owning a pet, like a dog or cat, especially for five years or longer, may be linked to slower cognitive decline in older adults, according to a preliminary study released today, February 23, 2022
“Prior studies have suggested that the human-animal bond may have health benefits like decreasing blood pressure and stress,” said study author Tiffany Braley, MD, MS, of the University of Michigan Medical Center in Ann Arbor and a member of the American Academy of Neurology. “Our results suggest pet ownership may also be protective against cognitive decline.”
The study looked at cognitive data from 1,369 older adults with an average age of 65 who had normal cognitive skills at the start of the study. A total of 53% owned pets, and 32% were long-term pet owners, defined as those who owned pets for five years or more. Of study participants, 88% were white, 7% were Black, 2% were Hispanic and 3% were of another ethnicity or race.
Researchers used data from the Health and Retirement Study, a large study of Medicare beneficiaries. In that study, people were given multiple cognitive tests. Researchers used those cognitive tests to develop a composite cognitive score for each person, ranging from zero to 27. The composite score included common tests of subtraction, numeric counting and word recall. Researchers then used participants’ composite cognitive scores and estimated the associations between years of pet ownership and cognitive function.
Over six years, cognitive scores decreased at a slower rate in pet owners. This difference was strongest among long-term pet owners. Taking into account other factors known to affect cognitive function, the study showed that long-term pet owners, on average, had a cognitive composite score that was 1.2 points higher at six years compared to non-pet owners. The researchers also found that the cognitive benefits associated with longer pet ownership were stronger for Black adults, college-educated adults and men. Braley says more research is needed to further explore the possible reasons for these associations.
“As stress can negatively affect cognitive function, the potential stress-buffering effects of pet ownership could provide a plausible reason for our findings,” said Braley. “A companion animal can also increase physical activity, which could benefit cognitive health. That said, more research is needed to confirm our results and identify underlying mechanisms for this association.”
A limitation of the study was that length of pet ownership was assessed only at one time point, so information regarding ongoing pet ownership was unavailable.
The study will be presented at the American Academy of Neurology’s 74th Annual Meeting being held in person in Seattle, April 2 to 7, 2022 and virtually, April 24 to 26, 2022.
The study was supported by the National Institutes of Health, the National Heart, Lung, and Blood Institute and the National Institute on Aging.
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Eating meat five times or less per week is associated with a lower overall cancer risk, according to a study published in the open access journal BMC Medicine.
Cody Watling and colleagues from the University of Oxford, UK investigated the relationship between diet and cancer risk by analysing data collected from 472,377 British adults who were recruited to the UK Biobank between 2006 and 2010. Participants, who were aged between 40 and 70 years, reported how frequently they ate meat and fish and the researchers calculated the incidence of new cancers that developed over an average period of 11 years using health records. They accounted for diabetes status and sociodemographic, socioeconomic and lifestyle factors in their analyses. 247,571 (52%) of participants ate meat more than five times per week, 205,382 (44%) of participants ate meat five or less times per week, 10,696 (2%) ate fish but not meat, and 8,685 (2%) were vegetarian or vegan. 54,961 participants (12%) developed cancer during the study period.
The researchers found that the overall cancer risk was 2% lower among those who ate meat five times or less per week, 10% lower among those who ate fish but not meat, and 14% lower among vegetarians and vegans, compared to those who ate meat more than five times per week. When comparing the incidence of specific cancers with participants’ diet, the authors found that those who ate meat five times or less per week had a 9% lower risk of colorectal cancer, compared to those who ate meat more than five times per week. They also found that the risk of prostate cancer was 20% lower among men who ate fish but not meat and 31% lower among men who followed a vegetarian diet, compared to those who ate meat more than five times per week. Post-menopausal women who followed a vegetarian diet had an 18% lower risk of breast cancer than those who ate meat more than five times per week. However, the findings suggest that this was due to vegetarian women tending to have a lower body mass index (BMI) than women who ate meat.
The researchers caution that the observational nature of their study does not allow for conclusions about a causal relationship between diet and cancer risk. Additionally, as UK Biobank dietary data was collected at a single time-point, rather than over a continuous period of time, it may not be representative of participants’ lifetime diets.
The authors suggest that future research could investigate the associations between diets containing little or no meat and the risk of individual cancers in larger populations with longer follow-up periods.
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Some people getting their initial shots of the Pfizer-BioNTech and Moderna coronavirus vaccines should consider waiting longer for their second dose, according to guidance the Centers for Disease Control and Prevention updated on Tuesday. The agency now suggests an eight-week interval between the first and second shots of those vaccines for some people older than 12, especially boys and men between 12 to 39 years.The new change, which does not affect those who have already been vaccinated, applies to about 33 million unvaccinated people. And the C.D.C. still recommends the original intervals — three weeks for Pfizer-BioNTech and four for Moderna — for certain people including those whose immune systems are moderately to severely immunocompromised, are 65 years or older, or are at risk of severe Covid.The change comes in light of research showing the longer interval between doses can increase vaccine effectiveness and reduce the risk of a serious but uncommon side effect called myocarditis, or inflammation of the heart. The overall incidence of post-vaccine myocarditis is low. A study conducted in Israel estimated that nearly 11 of every 100,000 males between 16 and 29 developed myocarditis.Earlier this month, an independent panel of scientific advisers to the C.D.C. reviewed research on myocarditis that supported an extended interval between doses. Research has shown that adolescent boys and young adult men have an increased risk of developing these heart problems after receiving their second dose of a Pfizer-BioNTech or Moderna vaccine.Still, the absolute risk of myocarditis is very small, most cases are mild and short-lived, and research shows a coronavirus infection is much more likely to cause heart problems than a Covid-19 vaccine. Patients of all ages infected with the virus had nearly 16 times the risk for myocarditis than uninfected patients, according to a C.D.C. report.People who waited six to 14 weeks between the first two doses of Pfizer-BioNTech or Moderna vaccines had higher antibody responses than those who waited a standard three or four weeks, according to a C.D.C. report presentation from the meeting. And the vaccines’ effectiveness against infection and hospitalization was also higher with an interval of six to eight weeks between the doses.When the vaccines first rolled out, the priority was to fully vaccinate people as quickly as possible, according to the presentation. Now, more than a year into the U.S. vaccination campaign, more data has become available to guide vaccination schedules, the presentation noted.Public health experts say a longer interval between doses means there is a risk of people getting infected after just one shot. But they say this change could sway some unvaccinated people and parents who are concerned about the potential risk of myocarditis.At the panel’s meeting, Dr. Matthew Daley, a senior investigator at Kaiser Permanente in Colorado and a member of the advisory committee, said that “If the message is, ‘We already have a highly effective and highly safe vaccine or vaccines, and this is an approach to make them even safer,’ that might convince some folks.”Benjamin Mueller

Babies born with congenital Zika syndrome (CZS), due to infection with the Zika virus during pregnancy, are at more than 11x greater risk of dying during the first three years of life than those born without the syndrome, according to a new study published in The New England Journal of Medicine.
Of nearly 11.5 million live births in Brazil, 3,308 babies were born with confirmed or probable CZS — of which 12% (398) died during the study period. In comparison, of the over 11.4 million babies born without CZS, 1% (120,629) babies died during the study period.
The study was carried out by a joint team from the London School of Hygiene & Tropical Medicine (LSHTM), the Center of Data and Knowledge Integration for Health (CIDAS-Fiocruz) and the Federal University of Bahia (UFBA), funded by Wellcome and the Brazilian Ministry of Health.
The study found the mortality rate among live births with CZS was over 11x higher than among live births without CZS up to the age of 36 months.
Normally babies who are born prematurely or small are at greater risk of death. In contrast, in babies born with CZS, the highest risk was found to be for children who were carried to full term or at normal birth weight (over 5.5lbs) — 14.3x higher and 12.9x higher than babies in that group born without CZS, respectively.
The main causes of death amongst babies born with CZS were infectious diseases, diseases of the nervous systems, and congenital abnormalities — mainly sepsis, cerebral palsy and microcephaly, respectively.

A new “cocktail” drug being developed at the University of Alberta could provide an effective and economical treatment to lessen symptoms for up to 45 per cent of patients with Duchenne muscular dystrophy (DMD), a chronic muscle-wasting disease.
A team led by researcher Toshifumi Yokota, a professor of medical genetics in the Faculty of Medicine & Dentistry, created — and is now testing — a cocktail of six treatments which would mean nearly half of patients with DMD could be treated with just one drug.
DMD affects six of every 100,000 people — usually boys. People with DMD have various mutations in the body’s largest gene, dystrophin, which is a protein that cells need to stay intact. Dystrophin has 79 sections, or exons, and if even one is missing the body cannot produce the protein and the muscles degenerate.
There is no cure for DMD, but a new class of drugs uses an approach called “exon skipping.” It acts as a Band-Aid over the missing exons, so the body can skip over the damaged instructions and produce the protein needed to rebuild muscle tissue.
The U.S Food and Drug Administration has already approved other similar treatments, including viltolarsen, which is based on Yokota’s research. Each, however, has limited applicability. This new “cocktail” treatment could help many more patients.
“Each of the previously developed exon-skipping molecules has been able to treat only around 10 per cent of DMD patients because they have different mutations to their exons in different locations within the gene,” said Yokota, who is also the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair.
“Our approach is to skip over 11 exons all at once, which would allow us to treat approximately 45 per cent of patients,” he explained.
The research was published this week in the Proceedings of the National Academy of Sciences.
Yokota’s team tested the new synthetic drug in patient-derived muscle tissue in test tubes and in mice. They found signs of dystrophin production, muscle building and improved heart function.
DMD often leads to extreme skeletal body weakness, yet most patients actually die from heart failure. Existing exon-skipping treatments do not penetrate the heart muscle — a limitation this new cocktail addresses, according to Yokota.
“Our cocktail combines the antisense oligonucleotides with a new peptide which allows the drug to penetrate the heart muscle,” he said.
The cocktail still needs to undertake toxicology testing and go through the regulatory steps to conduct clinical trials. Yokota and his colleagues recently launched a company to help commercialize the drug.
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Among people with no memory or thinking problems, having a poor score on a simple memory test may be linked to biomarkers in the brain associated with Alzheimer’s disease as well as very early signs of memory impairment that precede dementia by several years, according to a study published in the February 23, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“These findings suggest that this test can be used to improve our ability to detect cognitive decline in the stage before people are diagnosed with Alzheimer’s disease,” said study author Ellen Grober, PhD, of Albert Einstein College of Medicine in the Bronx, New York. “This could be helpful in determining who to enroll in clinical trials for prevention of cognitive decline. It could also help by narrowing down those who already have signs of Alzheimer’s in the brain with a simple test rather than expensive or invasive scans or lumbar punctures.”
For the test, people are shown pictures of items and given cues about the item’s category, such as a picture of grapes with the cue of “fruit.” Then participants are asked to remember the items, first on their own, then with the category cues for any items they did not remember. This type of controlled learning helps with the mild memory retrieval problems that occur in many healthy elderly people but does not have much impact on memory for people with dementia, Grober said.
The study involved 4,484 people with no cognitive problems and an average age of 71. The participants were divided into five groups based on their scores on the test, or stages zero through four. Stages zero through two reflect increasing difficulty with retrieving memories or items learned and precede dementia by five to eight years. In these stages, people have increasing trouble remembering the items on their own, but they continue to be able to remember items when given cues. In the third and fourth stages, people cannot remember all of the items even after they are given cues. These stages precede dementia by one to three years.
The study participants also had brain scans to look for the beta-amyloid plaques in the brain that are markers of Alzheimer’s disease, as well as to measure the volume of areas of the brain associated with Alzheimer’s pathology.
Half of the participants had no memory issues. Half had retrieval issues, issues for storage of memories or both.
The researchers found that people who tested in the third and fourth stages were likely to have higher amounts of beta-amyloid in their brains than people in the lower stages. They were also more likely to have a lower volume in the hippocampus and other areas of the brain associated with Alzheimer’s pathology.
At stage zero, 30% of people had beta-amyloid plaques, compared to 31% at stage one, 35% at stage two, 40% at stage three and 44% at stage four.
Grober said, “This system allows us to distinguish between the following: the difficulty people have retrieving memories when they are still able to create and store memories in their brains, which occurs in the very early stages before dementia can be diagnosed; and the memory storage problems that occur later in this predementia phase when people can no longer store the memories in their brains.”
A limitation of the study was that the participants had a high level of education, so the results may not be applicable to the general population.
The study was supported by the National Institutes of Health, Alzheimer’s Association, Cure Alzheimer Fund and Leonard and Sylvia Marx Foundation using publicly available data from the A4 study.
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Patients with both a high lipoprotein(a) and high coronary artery calcium score (CAC) face a more than 20% risk of heart attack or stroke over the following 10 years, according to findings from a multicenter study led by preventive cardiologists at UT Southwestern Medical Center.
“We are hopeful that by making the connection between Lp(a) and CAC as dual risk drivers, we can raise awareness in the medical community and improve earlier heart attack prevention for these patients,” said cardiologist Parag Joshi, M.D., Associate Professor of Internal Medicine at UT Southwestern.
“Our data may also expedite the development of treatments designed specifically for this high-risk population,” said Dr. Joshi, a member of the Clinical Heart and Vascular Center at UT Southwestern.
Approximately one in six people in the U.S. have high Lp(a), a type of bad cholesterol whose levels are driven largely by one’s genes. Coronary artery calcium, known as CAC, is a marker of plaque deposits around the heart.
The team of researchers, which included researchers from Emory University, found that participants with combined high Lp(a) and high CAC had a 22% 10-year risk of heart attack or stroke, compared with a 10-15% 10-year risk in patients who had either risk factor alone.
Investigators identified three distinct risk-related trends: High Lp(a), high CAC: These individuals face the highest 10-year risk of heart attack or stroke. High Lp(a), zero CAC: 10-year heart attack and stroke risk is low when there is no CAC, even if Lp(a) is high. Low Lp(a), high CAC: 10-year heart attack or stroke risk is higher than average but lower than with high LP(a) and high CAC combined.The findings are online in the Journal of the American College of Cardiology (JACC) and will appear in the March print edition. Read more at “What Can Lp(a) Add to CAC for ASCVD Risk Prediction? New Insights” at TMTMD.
“Establishing the connection between Lp(a) and CAC means we can move to the important next phase of research, which will be defining and personalizing early screening protocols to identify patients at high risk of heart attack,” said Dr. Joshi, whose research focuses on assessing risk for heart attack and stroke, CAC, cholesterol, and coronary CT angiography. “With further research, this could mean selectively scanning patients with high Lp(a) for their CAC score, and studying therapies specifically designed to reduce Lp(a) among patients with high CAC.”
Cardiology researchers confirmed the Lp(a) and CAC connection by comparing data from two landmark cardiovascular trials: The Dallas Heart Study, an ongoing comprehensive study of 6,000 diverse and heart-healthy patients conducted by UT Southwestern from 2000 to present Multi-Ethnic Study of Atherosclerosis (MESA): A 6,000-participant study investigating early-stage atherosclerosis (hardening of the arteries).
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