Year: 2021

Categories : Allergies GastrointestinalTags :

Stomach Bugs Induce Irritable Bowel Syndrome

On By ModernMedia

Researchers have pinpointed a localised biological mechanism behind irritable bowel syndrome (IBS), a chronic gastrointestinal condition where eating certain foods causes subsequent abdominal pain or discomfort.

Around 20% of people experience IBS, and diets such as gluten-free ones provide some relief. However, the exact cause was unknown, as the patients did not have allergic responses nor did they have coeliac disease, causing many physicians to dismiss it as psychological.A healthy immune system tolerates foods, and the first link is understanding how the tolerance is removed. Previous work showed that there was a link between mast cells and food, and that blocking histamine in people with IBS relieved the symptoms.

People with IBS often report their symptoms begin following a gastrointestinal infection, so the researchers reasoned that an infection associated with a particular type of food in the guy might sensitise the immune system to that food.The team fed mice with ovalbumin (an egg protein) and then infected them with a stomach bug. The mice were then fed ovalbumin again, and the researchers recorded elevated mast cell activation, histamine levels and digestive intolerance. In control mice who were fed with ovalbumin but who were not infected with the stomach bug, there was no response.

Breaking down the chain of events leading to the sensitisation, the researchers discovered that there was a localised immune response in the part of the guy infected by the bacteria, but did not produce the more generalised symptoms of a food allergy.  

Lead author Prof Guy Boeckxstaens, a gastroenterologist at KU Leuven thinks this may point to a spectrum of food-related immune disorders. He said, “At one end of the spectrum, the immune response to a food antigen is very local, as in IBS. At the other end of the spectrum is food allergy, comprising a generalised condition of severe mast cell activation, with an impact on breathing, blood pressure, and so on.”

When researchers injected IBS-associated food antigens into the intestinal walls of IBS patients, they observed localised reactions similar to what they saw in the mice, and there were no reactions in healthy patients. Larger clinical trials will be needed to confirm these observations.

“This is further proof that the mechanism we have unraveled has clinical relevance,”  Prof Guy Boeckxstaens said. “But knowing the mechanism that leads to mast cell activation is crucial, and will lead to novel therapies for these patients,” he goes on. “Mast cells release many more compounds and mediators than just histamine, so if you can block the activation of these cells, I believe you will have a much more efficient therapy.”

Source: Medical Xpress

Journal information: Local immune response to food antigens drives meal-induced abdominal pain, Nature (2021). DOI: 10.1038/s41586-020-03118-2 , www.nature.com/articles/s41586-020-03118-2

Categories : Mental HealthTags :

Depression May be Influenced by Metabolism

On By ModernMedia

A study by researchers from University of California San Diego School of Medicine and from the Netherlands, has shown that major depressive disorder (MDD) may be predicted by metabolism, in the form of certain metabolites.

MDD is one of the most common disorders, with a lifetime prevalence of 20.6% in the United States. For those with recurrent major depressive disorder (rMDD), the risk is 80% over five years.

MDD is characterised by any combination of feelings of sadness or hopelessness, anger or frustration, loss of interest, sleep disturbances, anxiety, slowed or difficulty thinking, suicidal thoughts and unexplained pain such as backaches.

“This is evidence for a mitochondrial nexus at the heart of depression,” said senior author Prof Robert K Naviaux, at UC San Diego School of Medicine. “It’s a small study, but it is the first to show the potential of using metabolic markers as predictive clinical indicators of patients at greatest risk—and lower risk—for recurring bouts of major depressive symptoms.”

Recruiting 68 participants who were in remission for rMDD and not on antidepressants, the researchers found a range of molecules in participants’ blood that were up to 90% predictive of relapse in 30 months. The most predictive molecules consisted of certain lipids and purines.

Purines are produced from molecules such as ATP and ADP (major cellular energy storage molecules), and also have a role in signalling in stressed cells.The researchers found that in subjects with rMDD, certain metabolites in six metabolic pathways resulted in the alteration of key cellular activities.

“The findings revealed an underlying biochemical signature in remitted rMDD that set diagnosed patients apart from healthy controls,” Naviaux said. “These differences are not visible through ordinary clinical assessment, but suggest that the use of metabolomics—the biological study of metabolites—could be a new tool for predicting which patients are most vulnerable to a recurrence of depressive symptoms.”

Source: Medical Xpress

Journal information: Roel J. T. Mocking et al. Metabolic features of recurrent major depressive disorder in remission, and the risk of future recurrence, Translational Psychiatry (2021). DOI: 10.1038/s41398-020-01182-w

Categories : GastrointestinalTags :

Faecal Transplants Safe in the Long Term for C. Diff Treatment

On By ModernMedia

A new study from the Mayo Clinic has provided more evidence for the safety and efficacy of faecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI).

Recruiting 609 patients diagnosed with CDI, 20% of whom were overweight or obese and 22.8% had inflammatory bowel disease (IBD), FMT was performed with a stool product from a common donor. At a short term follow-up, >60% of patients had diarrhoea, <33% had constipation, and 9.5% reported additional CDI episodes after one year. At long-term follow up (median 3.7 years), there 73 new diagnoses out of 477 patients, 13% had gastrointestinal problems, 10% had weight gain, and 11.8% had new unrelated infections.

However, this was marked by the appearance of additional medical conditions such as weight gain and irritable bowel syndrome, which the authors indicated should be investigated further. The study also did not use a standardised questionnaire for IBS, making those results harder to generalise, and there was no control group. However, administering questionnaires over an extended period to all participants instead of only a brief period shortly after FMT explains why there are fewer symptoms reported compared to other studies.  

A separate study with 207 patients receiving FMT showed 143 new diagnoses after the procedure, with a mean follow-up of 34 months. The researchers conducting this second study attribute the ability of FMT to reduce CDI to enhancements in CD4+ T cell and antibody-mediated immunity to C. difficile toxins such as TcdB.

“These results are important for the design of disease monitoring strategies and highlight that future study of how FMT influences pathogen specific immunity is warranted: specifically, determining if effectively restoring the TcdB specific cellular repertoire to healthy control proportions contributes to treatment success of FMT,” the researchers wrote.

These studies add to the growing body of evidence that show FMT combined with antibiotics is an effective way to treat CDI.

Source: MedPage Today

Journal information (first source): Saha S, et al. Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection, Gastroenterol 2021; DOI: 10.1053/j.gastro.2021.01.010. 

Journal information (second source): Cook L, et al. Fecal microbiota transplant treatment for recurrent Clostridioides difficile infection enhances adaptive immunity to TcdB, Gastroenterol 2021; DOI: 10.1101/2020.06.05.20114876.

Categories : COVIDTags :

SinoVac’s Vaccine 50.4% Effective in Brazilian Trial

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The vaccine from Chinese pharmaceutical company Sinovac is only 50.4% effective, according to updated data from a Brazilian trial.

Sinovac’s vaccine uses inactivated virus particles to trigger an immune response. Both the Sinovac vaccine and the Oxford vaccine have requests for emergency use in Brazil which are expected to soon to be granted.

This new number is lower than what was suggested last week by Butantan Institute, which distributes 65% of the vaccines in the country, and is running the trials. They had reported that the vaccine was 78% effective in “mild-to-severe” COVID cases, but reported on Tuesday that this number had not included cases with very mild COVID symptoms.
Interim results from late stage trials in Turkey and Indonesia reported that SinoVac was 91.25% effective and 65.3% effective, respectively. 

All of these discrepancies show just how hard to it is to compare the effectiveness of vaccines as measured by different trials in different countries. Other countries only count cases of COVID which generate obvious symptoms; including cases which are almost asymptomatic will lower the reported effectiveness.

However, there has been concern that the Chinese vaccine trials have not been subject to the same level of scrutiny and transparency as those in the West. Conversely, claims that the Russian Sputnik vaccine has a 95% effectiveness have been met with some suspicion, especially given its haphazard roll-out, which combined a trial (now cut short) with a release for emergency use. 

Source:BBC News

Categories : Obstetrics & GynaecologyTags :

Onset of Morning Sickness Narrowed Down

On By ModernMedia

The onset of “morning sickness”, the nausea and vomiting that often occurs near the beginning of pregnancy and normally resolves at 12-14 weeks, has been narrowed down in a new study from researchers at the University of Warwick.

The cause of nausea and vomiting of pregnancy (NVP) had historically been ascribed to psychological conditions, but currently is believed to have a multifactorial basis, involving various genetic, endocrine and gastrointestinal factors.

The study involved 256 women who became pregnant, keeping a diary recording the onset of nausea and vomiting, their last menstruation and date of ovulation as measured by a urine test.Determining the date of the start of pregnancy as determined by the date of their last ovulation, the first onset of NVP was 8 to 10 days, compared to 20 to 30 days as measured from the date of their last menstruation.

Lead author Prof Roger Gadsby, Warwick Medical School, said: “The precise course of pregnancy sickness is unknown, but this research shows that it occurs at a specific developmental stage, in a specific timeslot. For researchers it narrows our focus in terms of where we look for the cause. If we know that symptoms occur in a very narrow window 8-10 days after ovulation, researchers can concentrate their efforts on that particular stage of development to find the cause of the condition, both anatomically and biochemically.”

Knowing that the onset of NVP has such a tight timeframe will help future research narrow down a biological cause behind it, and help generate targets for treatment development.

An unexpected outcome of the study was a very high prevalence of NVP of 94%, compared to the 80% calculated in prior research. This is explained by the fact that data were regularly collected from participants from before they became pregnant to 60 days after their last menstruation, as opposed to most studies asking women to recall symptoms after they became pregnant.

Prof Gadsby added, “What we’ve shown is that more people get symptoms of pregnancy sickness than has ever been shown before, and one of the reasons for that is that this research has picked up mild early symptoms that tend to fade by 7-8 weeks. In other studies those symptoms would have faded by the time the research started.”

Source: News-Medical.Net

Categories : Diseases, Syndromes and Conditions T-cellsTags :

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

On By ModernMedia

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

Categories : EbolaTags : 1 Comment

Ebola Vaccine Stockpile Being Created

On By ModernMedia

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

Categories : COVID LungTags :

Link Found Between Telomeres and COVID Lung Damage

On By ModernMedia

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

Categories : Diseases, Syndromes and ConditionsTags :

A Growing Need to Expand Aneurysm Warnings for Fluoroquinolones

On By ModernMedia

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

Categories : COVIDTags :

Gauteng Doctors’ Struggle in COVID “Fever Tents”

On By ModernMedia

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