Month: January 2021

New Study Reveals T-Cell Role in Periodontitis and Bone Loss

There are mechanisms involved in diseases of bone loss, such as periodontitis that are still not well understood, but an unexpected behaviour of a type of T-cell may shed new light on the matter.

Looking at periodontal disease in mice, scientists found that regulatory T (Treg) cells start behaving unexpectedly. They lose their ability to regulate bone loss and begin to promote inflammation instead.

“That is important because, in many therapies analyzed in in-vivo models, researchers usually check if the number of regulatory T cells has increased. But they should check if these cells are indeed functioning,” said lead author Dr Carla Alvarez, a postdoctoral researcher at the Forsyth Institute.

In periodontal disease, bone loss occurs because the immune system responds disproportionately, destroying tissue through inflammation. The Treg cells normally suppress the immune system but lose the ability to do so during periodontal disease.

Understanding this falls into the field of osteoimmunology, which is about understanding the interaction of bone metabolism and the immune system. “This is an interesting mechanism highlighting how the bone loss is taking place in periodontal disease,” said Dr Alpdogan Kantarci, at Forsyth and co-author of the paper.

A potential treatment for periodontal disease would involve reactivating the Treg cell’s immunosuppression function, but this is a complex, nonlinear task complicated by the fact that periodontal disease is initiated by oral microbes.

“The relationship between immune response and bone is not so straightforward,” said Alvarez. “There are multiple components. You have to imagine a complex network of signaling and cells that participate.”
The researchers’ next step is to examine the process in humans.

Source:Medical Xpress

Journal information: Alvarez, C., Suliman, S., Almarhoumi, R. et al. Regulatory T cell phenotype and anti-osteoclastogenic function in experimental periodontitis. Sci Rep 10, 19018 (2020). doi.org/10.1038/s41598-020-76038-w

Ebola Vaccine Stockpile Being Created

The International Coordinating Group (ICG) announced on Monday that it was creating a stockpile of the Ebola vaccine in Switzerland, to help contain future outbreaks. Between 2014 and 2016, the haemorrhagic fever claimed 11 300 lives, with a fatality rate of 90%.

The single dose Ebola vaccine was trialled with 350 000 in Guinea and in the 2018-2020 DRC outbreak under “compassionate use”. The vaccine was jointly developed by the World Health Organization (WHO), UNICEF, the International Federation of Red Cross and Red Crescent Societies (IFRC) and Médecins Sans Frontières (MSF), with Gavi, the Vaccine Alliance, providing financial support.Countries requesting a vaccine will be able to receive a response in 48 hours, with a goal for a seven day delivery time.Unlike COVID, Ebola is a rare and unpredictable disease, and thus there is the need to create a reserve for the vaccine as opposed there being a “natural market” for it.

“We are proud to be part of this unprecedented effort to help bring potential Ebola outbreaks quickly under control,” said Henrietta Fore, UNICEF executive director, in a press release, saying that when it comes to dealing with disease outbreaks, “preparedness is key.”

She said the vaccine stash is a “remarkable achievement” that will allow vaccines to be delivered to those who need them in a timely manner. 
Assembling the required 500 000 doses for the stockpile will take some to three years, with 6890 doses currently available for outbreak response. The WHO, UNICEF, Gavi, and vaccine manufacturers are in the meantime are ready to escalate production if needed.

Source: Voice of America News

Link Found Between Telomeres and COVID Lung Damage

Researchers developing a therapy to regenerate lung tissue damaged by severe COVID have postulated that shortened telomeres are associated with the damage.

Telomeres are structures at the ends of chromosomes that maintain their integrity, and a small portion of them are lost with each cell division, such as when regenerating damaged tissue. As the telomere sections shorten, they eventually become unable to divide and are senescent. The team was already working on a way to regenerate lung tissue in pulmonary fibrosis, and adapted their research to the COVID pandemic. In pulmonary fibrosis, lung tissue becomes scarred and rigid, resulting in reduced lung capacity. In previous research, they had shown that telomere damage to the alveolar type II pneumocytes – which happen to be the same cells targeted by SARS-CoV-2.

Maria A Blasco, a researcher at CNIO said, “When I read that type II alveolar pneumocytes were involved in COVID-19, I immediately thought that telomeres might be involved.” The researchers believe short telomeres hinder tissue regeneration after severe COVID.

Blasco explained, “we know that the virus infects alveolar type II pneumocytes and that these cells are involved in lung regeneration; we also know that if they have telomeric damage they cannot regenerate, which induces fibrosis. This is what is seen in patients with lung lesions after COVID-19: we think they develop pulmonary fibrosis because they have shorter telomeres, which limits the regenerative capacity of their lungs.”

To support this, the team analysed the telomeres of 89 COVID patients. Although it might be expected that older patients had shorter telomeres, the researchers found that all of those with severe COVID had shorter telomeres – regardless of age.

The researchers wrote: “These findings demonstrate that molecular hallmarks of aging, such as the presence of short telomeres, can influence the severity of COVID-19 pathologies.”The involvement of shorter telomeres opens up the possibility of using telomerase to lengthen them again, as a potential treatment.The team will now move to an experimental mouse model, infecting mice with short telomeres and no telomerase with COVID, giving telomerase to some to see if the lung tissue can regenerate after severe COVID.

Source:News-Medical.Net

Journal information: Sanchez-Vazquez R, Guío-Carrión A, Zapatero-Gaviria A, Martínez P, Blasco M. Shorter telomere lengths in patients with severe COVID-19 disease. Aging (Albany NY). 2021. doi:10.18632/aging.202463

A Growing Need to Expand Aneurysm Warnings for Fluoroquinolones

New research suggests that the fluoroquinolone class of antibiotics may increase the risk of aortic aneurysm (AA).

In 2018 the US Food and Drug Administration added warnings for people at risk of aortic disease, based on data from its reporting system plus four epidemiological studies in other countries. According to a study by a team led by Melina Kibbe, MD at the University of North Carolina at Chapel Hill, cases of AA formation or dissection were 7.5 per 10 000 prescription fills for fluoroquinolones at 90 days compared with 4.6 per 10 000 fills for comparison antibiotics.

Fluoroquinolones include ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, and ofloxacin. The FDA had already warned that fluoroquinolones could cause tendon damage and rupture, peripheral nerve damage, mental health disturbance, hypoglycaemic coma and that they are associated with Clostridium difficile infection.

Using a database of health insurance claims for almost 28 million individuals aged 18 to 64,  the researchers searched for associations between fluoroquinolone prescriptions and aneurysms, compared to other antibiotic types.

Fluoroquinolones were associated with excess abdominal AAs (HR 1.31, 95% CI 1.25-1.37) and iliac artery aneurysms (HR 1.60, 95% CI 1.33-1.91), though associations with aortic dissection  or thoracic aortic aneurysm did not reach significance.

“As such, regional differences in the etiology, incidence, and clinical management of aortic disease in the thoracic vs abdominal aorta should be carefully considered,” wrote the researchers.

Adults over 35 also had a greater risk of AA with fluoroquinolones compared to younger cohorts. Limitations of the study included not controlling for the possibility of pre-existing aneurysms, or for the presence of risk factors such as smoking.

However, the researchers believe the results are significant enough to warrant attention. “Almost regardless, this large cohort study of a U.S. population suggests it is time once again to rethink the use of this class of antibiotics for patients with or without aortic disease,” they wrote.

Source: MedPage Today

Journal information: Newton E, Akerman A, Strassle P, Kibbe M. Association of Fluoroquinolone Use With Short-term Risk of Development of Aortic Aneurysm. JAMA Surg. 2021. doi:10.1001/jamasurg.2020.6165

Gauteng Doctors’ Struggle in COVID “Fever Tents”

Angry doctors have opened up concerning recent images of severely ill patients at Steve Biko Academic Hospital (SBAH) being treated in tents amid pouring rain. These images came as David Makhura and MEC for Health Dr Nomathemba Mokgethi visited the hospital on Monday.

Speaking on condition of anonymity, two doctors at SBAH spoke to Daily Maverick about the reality of the situation. The doctors described a desperate situation of overwhelmed facilities, with patients possibly dying as much from the cold and rain as from untreated COVID – or indeed, a condition that presents similarly to COVID.

The image presented to the public by the government is “smoke and mirrors”, said Dr Felicia (not her real name). “This is a show. They [health officials] are lying to you people. They are lying. They are covering it up,” she said.”Fever tents” have been set up outside the Emergency Department, where patients remain while they are being screened for COVID. If they test negative, they are admitted to SBAH If they test positive, they are sent to Tshwane District Hospital.”

According to Dr Felicia, conditions in the tents are abysmal. “There is no nursing, there is no oxygen or beds in these tents. There is no oxygen in the tanks, we actually just do 10 minutes of CPR and many times we don’t have PPE to do it in.”

As infections continue to rise in South Africa, approaching 250 000 active cases, hospitals are buckling under the pressure, and doctors are expecting the worst to come.

Dr Monica (not her real name) spoke of her feelings of the situation. “I don’t feel like I am being protected by our hospital right now. I am running around like a chicken without a head. I feel very hopeless. I feel like I should not care anymore. Caring is actually just hurting me and the patients because instead of me doing what I said I was going to do when I left medicine, I am treating these people like numbers. Someone dies and you have to shrug your shoulders and move on to the next. There is not even a minute to mourn a person or to figure out what went wrong. I feel completely hopeless,” she said.

Dr Monica said people need to stop politicising the pandemic, and get the hospitals the resources they need. She also implored the reporters to convey their message. “Tell the people out there, this is serious. They must wear masks, they must social distance,” she said, breaking off and running to attend to a patient.

Source: Daily Maverick

US Health Workers’ Vaccine Hesitancy Is Cause for Concern

Health care workers in various parts of the United States are showing extraordinarily high rates of COVID vaccine hesitancy: 20% to 40% of front line workers in Los Angeles, and 60% of nursing home workers said they would refuse to take the vaccine. This has generated great concern along with some instances of shaming, but failing to address these worries is potentially going to worsen the progression of the pandemic.

Fortunately, national surveys show that vaccine hesitancy is decreasing with some 60% of Americans now intending to receive a vaccine, but the high numbers among healthcare workers demands attention. Speaking to the Guardian, Dr Whitney Robinson, an epidemiologist at the University of North Carolina, said that if this is not addressed, “It could mean after all this work, after all this sacrifice, we could still be seeing outbreaks for years, not just 2021, maybe 2022, maybe 2023.”

In Atlanta, while hundreds of healthcare workers were on the list for vaccines, the doses were literally “sitting in the freezers” because no-one would take them.In one survey, up to 55% of New York firefighters said would not take the vaccines, so the Uniformed Firefighters Association president put together a 50 minute video with a virologist friend, addressing their concerns. Subsequent calls from firefighters showed the video had helped to change minds and increase vaccination numbers.

The concerns are varied. Some are concerned about possible side effects and long term consequences, or have read misinformation online. Others are worried about the effect it will have on pregnant and breastfeeding women. Still others believe that having the vaccine is unnecessary after having recovered it, as they have the antibodies in their system. A lot of the distrust may be from minority groups’ deep-rooted distrust of large-scale health programs such as vaccinations, according to Dr Nikhila Juvvadi, the chief clinical officer at Loretto hospital in Chicago. Many specifically mentioned the Tuskegee Study, where federal health officials studied African-American men with sexually transmitted diseases which were deliberately not treated.

“I’ve heard Tuskegee more times than I can count in the past month – and, you know, it’s a valid, valid concern,” said Juvvadi.
However, she said that individual conversations were effective in helping alleviate concerns about the vaccines.

Source: The Guardian

Withdrawal Symptoms of Discontinuing Medical Cannabis

A new study on the long terms effects of having used medical cannabis show that over half of people who used it experience withdrawal symptoms between use. And about one in ten experienced worsening alterations in sleep, mood, mental state, energy and appetite over two years.

Patients who use cannabis usually turn to it because of the failure of other pain medications, or to avoid the long-term risks of opioid use. However, the perception that it is “harmless” is incorrect, as it has cannabinoids that act on receptors in the brain, and from which the brain can experience withdrawal symptoms. This can even lead to cannabis use disorder.

Addiction psychologist Lara Coughlin, PhD, who led the analysis said, “Some people report experiencing significant benefits from medical cannabis, but our findings suggest a real need to increase awareness about the signs of withdrawal symptoms developing to decrease the potential downsides of cannabis use, especially among those who experience severe or worsening symptoms over time.”

After they had gone a significant time without cannabis, the 527 participants in the study were asked whether they had any one of 15 symptoms, ranging from irritability to nausea. Using an analytic method, they empirically grouped them into three groups ranging from mild or moderate symptoms to severe, with most of the symptoms. They then surveyed the patients again after one year and then again after two years. Those in the mild class showed the most stability in symptoms over time.

Younger participants were more likely to be in the severe group, and were more likely to have a worsening trajectory. Coughlin concluded that patients seeking cannabis use for pain need to discuss it with their health care providers, and seek psychosocial treatments such as cognitive behavioural therapy.

Source: Medical Express

Journal information: Coughlin, LN et al. Progression of cannabis withdrawal symptoms in people using medical cannabis for chronic pain. Addiction. 2021. DOI: 10.1111/add.15370

Autism Theory Treats its Characteristic Traits as Favoured by Society

For decades, scientists have fruitlessly sought a unifying aetiology for autism and an explanation for its prevalence, but now a new theoretical model describes the condition as a combination of traits that are common in autism and which are socially valued, combined with co-occurring disabilities.

An estimated 1 in 54 people have autism, which has been on the increase in developed countries. TA Meridian McDonald, PhD, a research instructor in Neurology at Vanderbilt University Medical Center, said: “Up until now there have been a lot of theories about the possible causes of autism but none of those theories account for the majority of autism cases. There are also a lot of theories as to why the prevalence of autism has been increasing in the population but, to date, there hasn’t been a theory that provides an explanatory model that accounts for all of those phenomena, including the genetics, social history, or characteristics of autism.”

She has worked on autism for 25 years, culminating in a theory called, “The Broader Autism Phenotype Constellation-Disability Matrix Paradigm (BAPCO-DMAP) Theory”, a focuses on the genetic basis of autism in line with current science but shifts the emphasis to positive traits selected for by events occurring over the past century.”The BAPCO-DMAP theory describes how people are attracted to other people who are very similar. They are attracted to certain traits that are very common in the population, and this leads to offspring who are more likely to have certain traits, as well as a greater intensity of traits,” said McDonald.

“The [BAPCO] traits are not what people expect. They expect the traits to be about challenges or difficulties, but instead there are six main traits—increased attention, increased memory, a preference for the object world vs. the social world and their environment, increased nonconformity, increased differences in sensory and perception, as well as systemising.”

These BAPCO traits are thus not necessarily negative, and can be combined with social skills. Counterintuitively, babies with increased memory and attention spans learn language later, because babies normally rely on their tiny attention span to break words down into their simplest sounds. With greater memory and attention spans, infants engage in echolalia, speaking long phrases without understanding them.

“You can often see children with autism engaging in sense-making activities, such as watching the same show over and over and memorising information,” McDonald said.The BAPCO traits are not by themselves significant impediments, but when combined with a disability such as an information processing disorder, then the combination leads to greater difficulties.

According to McDonald, the increased prevalence of autism in developed countries is due to men and women with BAPCO traits being able to pursue similar careers and passions, as opposed to being limited by circumstance, and results in relationships. This effectively concentrates BAPCO traits in any children they have.Since the BAPCO traits are socially valued, there simply is no “cure” for them, according to McDonald.”When we talk about autism we need to address the developmental disabilities that these individuals are experiencing but also find way to support and enhance their broader autism trait constellations,” she concluded.

Source: Medical Xpress

Journal information: T.A. Meridian McDonald, The broader autism phenotype constellations–disability matrix paradigm: Theoretical model for autism and the broader autism phenotype, Medical Hypotheses (2020). DOI: 10.1016/j.mehy.2020.110456

FDA Approves New Medication for the Treatment of Progeria

On Friday, the FDA gave approval for the first medication able to actually treat the rare disease, Hutchinson–Gilford progeria syndrome (HGPS), which causes premature aging. Prior to the development of this medication in 2007, only palliative care was available to treat the disease.  

HGPS is an extremely rare disease affecting only some 400 people worldwide, the disease is caused by a chance genetic mutation that causes the buildup of a protein called progerin in the cells of the afflicted person, giving the disease its name. The disorder causes stunted growth, alopecia, and aged skin appearance. Children who have the disease develop atherosclerosis, and most die of stroke. The average life expectancy for sufferers is 14 1/2 years. The medication blocks the buildup of progerin, impeding the premature aging effect. 

A clinical trial followed participants for 11 years, and the medication was found to extend life by 2 1/2 years. The oldest participant is 24, having taken the medication for 13 years.

The new medication, Zokinvy, also known as lonafarnib, is expected to be expensive due to the small number of patients but the manufacturer, Eiger, said that it will offer finance plans to make it affordable for all patients. Eiger also helped finance the research for the treatment, along with the Progeria Research Foundation.

“This is just the first. We’ll find more and better treatments,” said Dr Leslie Gordon, the foundation’s medical director.

Source: Medical Xpress

COVID Variants May Increase False Negative Results, FDA Warns

The UK variant of the SARS-CoV-2 virus, known as B.1.1.7 could affect the accuracy of certain molecular COVID tests, causing increased false negative results, the US Food and Drug Administration (FDA) has warned.

A false negative from the UK variant could happen if the variant’s mutation happened to be in a part of the virus’ genome that was assessed by that test. However, genetic tests that target multiple parts of the virus genome are less likely to be affected by the new variants, the FDA advises.

Although the possibility of false negative results are to be expected from almost all tests, the effect of the COVID variants could impact the ability to properly monitor the disease, as well as complicating diagnosis.  

The FDA issued an alert on Friday, saying that they monitor tests which have received an Emergency Use Authorisation (EUA). They highlight three tests as being affected, with potentially less sensitivity to the mutations:

  • Accula SARS-Cov-2 Test, from Mesa Biotech
  • TaqPath COVID-19 Combo Kit, from Thermo Fisher Scientific)
  • Linea COVID-19 Assay Kit, from Applied DNA Sciences

However, the warning for Accula test was a result of “an abundance of caution”, and the latter two assess multiple genetic targets, so they are not likely to be impacted. The FDA issued recommendations for the users of these devices.The FDA’s warning was prompted by computer simulations showing reduced efficacy in certain tests for the virus variant.

In their press release, the FDA did not specifically mention whether any tests may be affected by mutations in the South African virus variant.

Source: MedPage Today