A major analysis of all relevant published studies indicates that poor periodontal health and tooth loss may increase the risk of both cognitive decline and dementia. The finding, published in the Journal of the American Geriatrics Society, affirms a long-suspected connection between dental and cognitive health.
The analysis included 47 studies. Poor periodontal health, reflected by having periodontitis, tooth loss, deep periodontal pockets, or alveolar bone loss, was linked to a 23% increase in risk for cognitive decline and a 21% higher risk of dementia. Tooth loss on its own was associated with a 23% higher odds of cognitive decline and a 13% higher risk of dementia. The overall quality of evidence was low, however.
“From a clinical perspective, our findings emphasise the importance of monitoring and management of periodontal health in the context of dementia prevention, although available evidence is not yet sufficient to point out clear ways for early identification of at-risk individuals, and the most efficient measures to prevent cognitive deterioration,” the authors wrote.
The majority of people who were likely infected with the Omicron variant were unaware they had the virus, according to a new study published in JAMA Network Open.
“More than one in every two people who were infected with Omicron didn’t know they had it,” said Susan Cheng, MD, MPH, corresponding author of the study. “Awareness will be key for allowing us to move beyond this pandemic.”
Previous work estimated that between 25% and 80% of people infected with SARS-CoV-2 may be asymptomatic. Compared to other variants, Omicron is associated with generally less severe symptoms that may include fatigue, cough, headache, sore throat or a runny nose.
“Our study findings add to evidence that undiagnosed infections can increase transmission of the virus,” said Sandy Y. Joung, MHDS, an investigator at Cedars-Sinai and first author of the study. “A low level of infection awareness has likely contributed to the fast spread of Omicron.”
As part of research into the effects of COVID and the impact of vaccines, the investigators began collecting blood samples from healthcare workers more than two years ago. In the second half of 2021, just before the start of the Omicron variant surge, the investigators were able to expand enrolment to include patients. Of the healthcare workers and patients who have participated in the research, investigators identified 2479 people who had contributed blood samples just prior to or after the start of the Omicron surge. The investigators identified 210 people who likely were infected with the Omicron variant based on newly positive levels of SARS-CoV-2 antibodies.
Study participants were invited to provide health status updates through surveys and interviews. Only 44% of study participants testing positive were aware of their infection. Of the 56% of study participants who were unaware, only 10% reported having any recent symptoms that they attributed to a common cold or other type of infection.
More studies involving larger numbers of people from diverse ethnicities and communities are needed to learn what specific factors are associated with a lack of infection awareness, according to the investigators.
Cheng and colleagues are also studying patterns and predictors of reinfections and their potential to offer long-lasting immunity to SARS-CoV-2. In addition to raising awareness, this information could help people manage their individual risk.
Dupilumab, a monoclonal antibody that suppresses interleukin-13 can improve survival rates for patients with moderate to severe COVID, according to the results of a small clinical trial published in the Open Forum of Infectious Diseases.
Dupilumab is most often prescribed for skin conditions such as atopic dermatitis, asthma, and sinus congestion and swelling. The treatment also proved safe in the small study, as expected, because dupilumab is already a safe and effective allergy medicine.
The small trial, designed and led by Dr Jennifer Sasson, found that dupilumab improved patient survival at 60 days and reduced the number of patients who needed intensive care. Almost 90% of patients who received dupilumab in the randomised trial were alive at 60 days, compared with 76% of patients who did not.
“Our clinical trial suggests that treatment with the anti-allergy medicine dupilumab may decrease deaths due to COVID,” said Dr Sasson, of the University of Virginia School of Medicine. “A large multi-institution study to validate these preliminary results is being designed. If successful, this multi-site trial will open a new window to treatment of COVID and potentially other viral pneumonias.”
Cytokine levels inspire trial
The researchers were inspired to launch the trial after discovering that COVID patients were at significantly greater risk of needing a ventilator if their blood contained high levels of the cytokine interleukin-13. Dupilumab, which received FDA approval in 2017, works by blocking the effects of IL-13 and reducing inflammation.
To see if dupilumab could improve the body’s immune response to COVID, Sasson and her collaborators enrolled 40 patients with moderate to severe cases in a clinical trial. The trial was double-blinded, meaning neither the patients nor the doctors knew whether the patient was receiving the antibody or a placebo. Both groups of trial participants otherwise received standard care.
After 28 days, no difference was seen between the two groups in ventilator-free survival or in adverse events. But by 60 days, there were only two deaths among the patients receiving dupilumab and five deaths among those receiving placebo.
Among the patients who were not already in the intensive care unit when they joined the trial, three receiving dupilumab were ultimately admitted to the ICU, compared to six receiving placebo.
A new study published in the journal Science reveals a unique form of cell communication that controls muscle repair, coordinated by hyaluronic acid. In damaged muscle, stem cells must work together with immune cells to complete the repair process, yet how these cells coordinate to ensure the efficient removal of dead tissue before making new muscle fibres has remained unknown.
“When muscles get damaged, it is important for immune cells to quickly enter the tissue and remove the damage before stem cells begin repair,” said Dr Jeffrey Dilworth, senior author on the study. “Our study shows that muscle stem cells are primed to start repair right away, but the immune cells maintain the stem cells in a resting state while they finish the cleanup job. After about 40 hours, once the cleanup job is finished, an internal alarm goes off in the muscle stem cells that allows them to wake up and start repair.”
Dr Dilworth and his team identified hyaluronic acid as the key ingredient in this internal alarm clock that rouses muscle stem cells from their slumber. When muscle damage occurs, stem cells start producing and coating themselves with hyaluronic acid, which, when thick enough, blocks the sleep signal from the immune cells, thereby causing the muscle stem cells to wake up.
Using mouse and human tissues, the researchers also discovered how muscle stem cells control the production of hyaluronic acid using epigenetic marks on the Has2 gene.
“Interestingly, ageing is associated with chronic inflammation, muscle weakness and a reduced ability of muscle stem cells to wake up and repair damage,” said lead author Dr Kiran Nakka. “If we could find a way to enhance hyaluronic acid production in the muscle stem cells of older people it might help with muscle repair.”
The regenerative effect of hyaluronic acid seems to depend on it being produced by the muscle stem cells, the authors noted. They are currently investigating if drugs could epigenetically stimulate muscle stem cells to increase their production of hyaluronic acid.
Patients with blood cancers have an impaired immune system due to their disease and its treatment, putting them at risk of severe COVID infection and a reduced COVID vaccination response. In a recent study published in CANCER, less than half of patients with haematologic malignancies including leukaemia, lymphoma, and multiple myeloma mounted detectable antibodies after initial COVID vaccination, but 56% of ‘nonresponders’ produced antibodies after receiving a booster dose.
For the study, Thomas Ollila, MD, and colleagues retrospectively analysed antibody responses to initial and booster COVID vaccination in 378 patients with hematologic malignancies.
Anti-SARS-CoV-2 antibodies were detected in the blood of 181 patients (48%) after initial vaccination with one of three FDA-authorised or approved COVID vaccines, and patients with active cancer or those recently treated with an immune cell–depleting therapy were least likely to produce these antibodies. Among patients who did not mount an antibody response following initial vaccination, responses were observed after a booster dose in 48 of 85 (56%) patients who were assessed.
By the end of February 2022, 33 patients (8.8%) developed a COVID infection, with three COVID-related deaths (0.8%). Although there was no significant link between post-vaccination antibody response and incidence of COVID infection, no patient with antibody responses died from COVID
Also, no patient who received tixagevimab plus cilgavimab was diagnosed with a COVID infection. Tixagevimab and cilgavimab are antibody therapies that bind to non-overlapping portions of the SARS-CoV-2 spike protein, preventing the virus from binding to and infecting cells. The FDA authorised the combination therapy for emergency use during the COVID pandemic as a way to help prevent COVID infection in certain individuals.
“Our findings build on the wealth of literature showing that patients with hematologic malignancies have an impaired response to COVID vaccination. Importantly, we show that many of these patients who did not respond initially will in fact have a response to booster vaccination,” said Dr Ollila. “Moreover, when we looked at outcomes, we found that deaths from COVID in the patient population we reviewed only occurred in those with undetectable antibodies, and nobody who received prophylactic antibody therapy was diagnosed with COVID. This suggests to us the importance of checking antibody levels in these patients and arranging prophylactic antibody therapy.”
Dr. Ollila encourages providing booster vaccines for patients and prioritising prophylactic antibody therapy when indicated. “This is real world evidence that these actions can save lives,” he said.
COVID restrictions have finally come to an end altogether in South Africa, as Health Minister Joe Phaahla gazetted a number of changes to the rules, as reported by BusinessTech. This means the end of mask use requirements, social gatherings restrictions and COVID border testing. Prof Shabir Madhi was welcoming of the move in a recent tweet, having criticised SA’s lockdowns as overly harsh and economically damaging. Around the world, many had questioned the widespread use of masks, or their use by some subset of the population, such as children – and even questioned locally by a scientist who argued that it didn’t and wouldn’t work in a South African setting, where people are less adherent to regulations.
Professor Salim Abdool Karim likened such a viewpoint to saying Africans with HIV can’t use ARVs because they didn’t have watches to take them at the right time, reminiscent of “a colonial mentality”.
The case for public mask use is well established. Experiments had shown that even simple cloth masks were moderately effective at hindering the transmission of SARS-CoV-2–containing aerosol particle from infected individuals, though they were less effective at protecting a wearer against infection. Predictably, N95 masks and others are better at doing the job than simple cloth face coverings.
There are no real-world studies for South Africa comparing mask use vs non-mask use as mask wearing was compulsory from the early stages of the outbreak. It would have been downright unethical to ask people to not wear masks, although some people may have had exemptions due to medical conditions or other important reasons. There is a country with good COVID surveillance and a distinct division in mask wearing – the United States. Implementation of mask mandates in the US was down to local authorities, which provides a basis for comparison.
One US study, published in Health Affairs, found that, compared to nonmasking counties, masking counties saw a daily case incidence decline by 25% at four weeks, 35% at six weeks after introduction of masking mandates. The reductions were strongest in Republican-leaning counties, which is notable since Republican voters were less in favour of lockdowns and mask mandates.
Another study found a 16.9% drop in cases four weeks after counties introduced masking mandates. Real-world data also show mask use was effective in preventing infection. A case-and-control study done in California by the CDC showed a 29% drop for surgical mask/respirator use “some of the time” and a 56% drop for “all of the time”.
While a direct comparison between a wealthy country like the US and South Africa as a middle-income country is impossible, it is easy to believe that masking mandates reduced cases by a significant percentage, perhaps saving tens of thousands of lives especially against the country’s possible true COVID death toll of 300 000.
The negative effects of beer on health have long been studied, but a new research suggests that beer – both alcoholic and nonalcoholic – has a positive impact on gut health. A lucky group of adult male volunteers drank moderate amounts of beer daily for a month, and the findings on their gut health biomarkers were published in the Journal of Agricultural and Food Chemistry.
Gut microbiota modulation might constitute a mechanism mediating the effects of beer on health. However, intestinal microorganisms can use compounds present in beer. Previous work has found beneficial effects on intestinal from moderate beer drinking, mostly from butyric acid and gut bacteria changes.
In this randomised, double-blinded, two-arm parallel trial, 22 healthy men were recruited to drink 330 mL of nonalcoholic beer (0.0% v/v) or alcoholic beer (5.2% v/v) daily during a 4-week follow-up period. Blood and faecal samples were collected before and after the intervention period. To measure diversity, gut microbiota were gene sequenced to identify strains.
Drinking nonalcoholic or alcoholic beer daily for 4 weeks did not increase body weight and body fat mass, an encouraging sign. The nonalcoholic beer had 26kcal of energy and 5.9g of carbohydrates per 100mL, but the alcoholic beer had more energy (38.5kcal/100mL) despite having fewer carbohydrates (2.8g/100mL). The researchers also found no significant effect on serum cardiometabolic biomarkers.
Both types of beer increased gut microbiota diversity, something which has been associated with positive health outcomes and tended to increase faecal alkaline phosphatase (ALP) activity, a marker of intestinal barrier function.
The increase in gut microbiota may be down to phenolic compounds in the beer, chiefly from the yeast, and other types of beer besides the Lager used may have higher levels of these beneficial compounds. This benefit appears to outperform the negative effect alcohol
These results suggest the effects of beer on gut microbiota modulation are independent of alcohol and may be mediated by beer polyphenols.
Using bacteriophages, viruses which prey on bacteria, is an emerging alternative to antibiotic use but with limited evidence. Now, with a new paper published in Clinical Infectious Diseases, collaborators report 20 new case studies on the use of the experimental treatment in Mycobacterium infections, with successes in more than half of the patients.
This is the largest ever set of published case studies for bacteriophage (or ‘phage’) therapy, giving unprecedented detail on their use to treat dire infections while laying the groundwork for a future clinical trial.
“Some of those are spectacular outcomes, and others are complicated,” said Professor Graham Hatfull at the University of Pittsburgh. “But when we do 20 cases, it becomes much more compelling that the phages are contributing to favourable outcomes – and in patients who have no other alternatives.”
The patients in the study had an infection from one or more strains of Mycobacterium, a group of bacteria that can cause deadly, treatment-resistant infections in those with compromised immune systems or cystic fibrosis. In 2019, Prof Hatfull led a team showing the first successful use of phages to treat one of these infections.
“For clinicians, these are really a nightmare: They’re not as common as some other types of infections, but they’re amongst some of the most difficult to treat with antibiotics,” said Prof Hatfull. “And especially when you take these antibiotics over extended periods of time, they’re toxic or not very well-tolerated.”
Since 2019, Prof Hatfull and his lab have fielded requests from more than 200 clinicians looking for treatments for their patients, working with them to find phages that could be effective against the particular strain of bacteria infecting each patient.
This newest paper, with collaborators from 20 institutions, dramatically expands the body of published evidence on the effectiveness of the therapy.
“These are incredibly brave physicians, jumping off the ledge to do an experimental therapy to try to help patients who have no other options,” said Prof Hatfull. “And each of these collaborations represents a marker that can move the field forward.”
Going on patient health and presence of Mycobacterium in samples, the team found that the therapy was successful in 11 out of 20 cases. No patients showed any adverse reactions to the treatment.
In another five patients the results of the therapy were inconclusive, and four patients showed no improvement. According to Prof Hatfull, even these apparent failures are key to making the therapy available to more patients. “In some ways, those are the most interesting cases,” he said. “Understanding why they didn’t work is going to be important.”
Several unexpected patterns emerged from the case studies. In 11 cases, researchers were unable to find more than one kind of phage that could kill the patient’s infection, even though standard practice would be to inject a cocktail of different viruses so the bacteria would be less likely to evolve resistance.
“If you’d asked me whether that was a good idea three years ago, I would have had a fit,” Prof Hatfull said. “But we just didn’t observe resistance, and we didn’t see a failure of treatment from resistance even when using only a single phage.”
Additionally, the team saw that some patients’ immune systems attacked the viruses, but only in a few cases did that render the virus ineffective. And in some instances, the treatment was still successful despite such an immune reaction. The study paints an encouraging picture for the therapy, said Prof Hatfull, opening up the possibility for new phage regimens that clinicians could use to maximise the treatment’s chance of success.
Along with the study’s significance to patients facing Mycobacterium infections, it also represents a substantial advance for the wider field of phage therapy. One concern is that researchers may be only publishing case studies of successful phage therapy.
“A series of consecutive case studies, where we’re not cherry-picking, is a much more transparent way of looking to see what works and what doesn’t,” said Prof Hatfull. “This adds considerable weight to the sense that the therapy is safe.”
This is still a very early stage in the development of phage therapy, and phages have not even begun to be tailored for treatment, Prof Hatfull said.
The whistle-blowing paediatrician Dr Tim de Maayer who spoke out about appalling conditions at Rahima Moosa Mother and Child Hospital (RMMCH) was suspended yesterday, apparently in a retaliatory move.
In the widely-read open letter appearing on the Daily Maverick, he spoke of the preventable tragedy of babies dying due to lack of resources. This came shortly after a viral video showed pregnant mothers sleeping on the floor.
Presciently, the Daily Maverick, which broke the story, stated that there were two options: act to change the situation for the better, or “shoot the messenger”. As the newspaper wryly noted as it broke the news on Friday, 10 June, the option of shooting the messenger has been taken.
Although there appeared to be an initial positive response, Dr Maayer gave notice on Thursday evening that he was not able to come into work on Friday as he was being placed on suspension. RMMCH doctors then contacted the Daily Maverick.
His suspension leaves the hospital without its only paediatric gastroenterologist, according to an anxious doctor who got in touch with the Daily Maverick late Thursday night. The news has spread like wildfire across social media, with other doctors quick to come to Dr de Maayer’s defence.
A petition on Change.org to reinstate the paediatrician is being circulated by ordinary citizens and clinicians including Professor Shabir Madhi, who has been vocal in his support of Dr de Maayer.
The Progressive Health Forum (PHF) called for the suspension of Dr de Maayer to be overturned.
“Dr de Maayer has been suspended on the grounds that he has a voice, a conscience and a professional ethic and being a committed public health clinician. This pattern of victimisation has been repeatedly applied to clinicians who dare call out inadequacies of the administration and negative impact on clinicians and on the lives of patients,” the PHF said in a statement.
Pregnant mothers have the ability to confer greater immunity to the vulnerable developing foetus with ‘super antibodies’. Now, a far-reaching study published in Nature provides a surprising explanation of how this actually works, and what it could mean for preventing death and disability from a wide range of infectious diseases.
The findings suggest the amped-up antibodies that expecting mothers produce could be mimicked to create new drugs to treat diseases as well as improved vaccines to prevent them.
“For many years, scientists believed that antibodies cannot get inside cells. They don’t have the necessary machinery. And so, infections caused by pathogens that live exclusively inside cells were thought to be invisible to antibody-based therapies,” said Sing Sing Way, MD. “Our findings show that pregnancy changes the structure of certain sugars attached to the antibodies, which allows them to protect babies from infection by a much wider range of pathogens.”
“The maternal-infant dyad is so special. It’s the intimate connection between a mother and her baby,” says John Erickson, MD, PhD, first-author of the study.
Drs Way and Erickson are both part of Cincinnati Children’s Center for Inflammation and Tolerance and the Perinatal Institute, which strives to improve outcomes for all pregnant women and their newborns.
Erickson continues, “This special connection starts when babies are in the womb and continues after birth. I love seeing the closeness between mothers and their babies in our newborn care units. This discovery paves the way for pioneering new therapies that can specifically target infections in pregnant mothers and newborns babies. I believe these findings also will have far-reaching implications for antibody-based therapies in other fields.”
How mothers make super antibodies The new study identifies the specific change in the sugar. During pregnancy, the “acetylated” form of sialic acid (one of the sugars attached to antibodies) shifts to the “deacetylated” form. This subtle molecular shift lets immunoglobulin G (IgG) take on an expanded protective role by stimulating immunity through receptors that respond specifically to deacetylated sugars.
“This change is the light switch that allows maternal antibodies to protect babies against infection inside cells,” Dr Way said.
“Mothers always seem to know best,” Dr Erickson added.
Revved-up antibodies can be produced in the lab The research team pinned down the key biochemical differences between antibodies in virgin mice compared to pregnant ones. They also identified the enzyme naturally expressed during pregnancy responsible for driving this transformation.
Further, the team successfully restored lost immune protection by supplying lab-grown supplies of the antibodies from healthy pregnant mice to pups born to mothers that were gene-edited to lack the ability to remove acetylation from antibodies to enhance protection.
Hundreds of monoclonal antibodies have been produced as potential treatments for various disorders, including COVID, with a variety of results.
Dr Way said this molecular alteration can be replicated to change how antibodies stimulate the immune system to fine-tune their effects. This potentially could lead to improved treatments for infections caused by other intracellular pathogens including HIV and respiratory syncytial virus (RSV), a common virus that poses serious risks to infants.
Another reason to accelerate vaccine development “We’ve known for years the many far-reaching benefits of breastfeeding,” Dr Erickson said. “One major factor is the transfer of antibodies in breastmilk.”
The study shows that nursing mothers retain the molecular switch, passing through the antibodies to their newborns.
Additionally, Dr Way says the findings underscore the importance of receiving all available vaccines for women of reproductive age – as well as the need for researchers to develop even more vaccines against infections that which are especially prominent in women during pregnancy or in newborn babies.
“The immunity needs to exist within the mother for it to be transferred to her child,” Dr Way said. “Without natural exposures or immunity primed by vaccination, when that light switch flips during pregnancy, there’s no electricity behind it.”
