Tag: 29/1/21

Categories : Cancer GeneticsTags :

New Method to Pick up Mutations Behind Colorectal Cancer Risks

On By ModernMedia

University of Michigan researchers have developed a method to detect mutations which give rise to colorectal cancer.

Colorectal cancer is the third most common cancer type, and the second most common cause of cancer-related deaths in the United States. Although most cases occur sporadically, some 5 to 10% of cases are hereditary, the most common cause of which is Lynch syndrome. Lynch syndrome results in an 80% increase in the lifetime risk of developing colorectal cancer. Those with a family history of colorectal cancer are advised to start screening before age 45. However, genetic testing for cancer risk does not always provide useful information for those with family history.  

To address this, a new method of genetic testing was developed by Jacob Kitzman, PhD, of the Department of Human Genetics at Michigan Medicine plus together with other colleagues. Since mutations are rare in the human population, determining which one is responsible is difficult, and simply studying one in the lab is too time consuming to be practical.
With deep mutational scanning, the researchers measured the effect of MSH2 mutations, which is one major cause of Lynch syndrome

They deleted the normal copy of MSH2 from human cells with CRISPR-Cas, replacing it with a library of every possible mutation in the MSH2 gene. Each cell in the mix then carried a unique MSH2 mutation. Chemotherapy then killed off only the cells that had a functional variant of MSH2.

The counterintuitive idea, noted Kitzman, is that the surviving cells do not have functioning MSH2—which have mutations that are most likely to cause disease.

“We were basically trying to sit down and make the mutations we could so they could serve as a reference for ones that are newly seen or are amongst the thousands of variants of unknown significance identified in people from clinical testing,” says Kitzman. “Until now, geneticists could not be sure whether these are benign or pathogenic.”

It is hoped that with other patient-specific information, some of these variants could be reclassified, and those individuals advised to undergo more intense screening.

Kitzman said: “One of the next areas that will need some focus in the field of human genetics is to create these sorts of maps for many different genes where there is a clinical connection, so we can be more predictive when variants are found in an individual.”

Source: Medical Xpress

Journal information: Xiaoyan Jia et al, Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk, The American Journal of Human Genetics (2020). DOI: 10.1016/j.ajhg.2020.12.003

Categories : Diet and Nutrition GastrointestinalTags :

Underweight and Gastrointestinal Distress – A Bidirectional Relationship?

On By ModernMedia

An Asian cross-sectional study found that underweight was linked to functional dyspepsia (FD), regardless of the presence of anxiety, although anxiety was additionally associated with FD.

The study by Kee Huat Chuah, MD, of the University of Malaysia in Kuala Lumpur, and colleagues, also found no link between high body mass index (BMI) and other functional gastrointestinal disorders (FGIDs). People with FGIDs often have irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, two-thirds will have chronic, fluctuating symptoms. The questionnaire-based study recruited 1002 adult individuals with a median age of 32, with 20.7% having FGID according to the Rome III criteria.

Across different FGIDs, including irritable bowel syndrome (IBS) and functional diarrhea and constipation, FD affected more underweight adults (defined as BMI less than 18.5) compared with a non-FGID control group (13.3% vs 3.5%, P=0.002). Multivariate analysis showed that underweight maintained an independent association with FD, at an odds ratio (OR) of 3.648 (95% CI 1.494-8.905, P=0.004).

The results of a large population study from France were consistent with these findings, which also found that being underweight was independently associated with FD in females.  Diarrhoea may also have been associated with central obesity, but there were too few individuals with diarrhoea to draw conclusions, although a large US population study from 2019 showed that obesity was associated with chronic diarrhoea.

A bidirectional association has been observed in eating disorders (often linked with anxiety disorders) with both a low BMI and FD.  Anxiety and/or eating disorders may have caused FD subjects to have a low BMI.

William D Chey, MD, of Michigan Medicine, who was not involved with the research, said the results were interesting and that they could be applicable to the US population since obesity rates are comparable to those in Malaysia.

“But I do agree it’s important to consider whether these observations are cause or effect,” Chey commented. “In other words, FD might cause people to lose weight or thin people might be more prone to developing FD. I do think there’s face validity to these observations. Remember that patients with functional dyspepsia that have meal-related symptoms of fullness and early satiety are unable to eat very much without feeling ill.”

Patients with postprandial distress syndrome often lose weight as a result, Chey continued. “On the other hand, patients with anorexia often have measurable abnormalities in gastric emptying, but that’s not to say all FD patients have eating disorders. My point is that certain non-GI conditions associated with weight loss can also be associated with abnormal GI function.”

The team called for further studies of longitudinal design to explore whether anxiety causes a low BMI in FD or vice versa. Limitations included not being population based, with the cohort being mostly hospital and university staff members. In addition, the data on psychological disorders came from a subgroup of original participants in the study’s second phase; the number of participants with functional diarrhoea was low; the cross-sectional design did not allow for causality; and the questionnaire only asked about dietary habits.

Source: MedPage Today

Journal information: Beh KH, et al “The association of body mass index with functional dyspepsia is independent of psychological morbidity: a cross-sectional study” PloS One 2021; doi: 10.1371/journal.pone.0245511.

Categories : Ageing Neurodegenerative DiseasesTags :

Obesity Adds to Alzheimer Severity

On By ModernMedia

In addition to it being a risk factor for many known chronic diseases, obesity is an additional burden on cerebral health and may also be associated with the progression of Alzheimer’s disease, according to a new study from the University of Sheffield and the University of Eastern Finland.  

The study used multimodal neural imaging and showed that obesity may contribute to the vulnerability of neural tissue, while maintaining a healthy weight helped to maintain brain structure in mid dementia Alzheimer’s disease.

Alzheimer’s disease is a neurodegenerative disease which accounts for two thirds of dementia in over 65s, is the sixth leading cause of death in the United States and there is no cure at present.  

Lead author Professor Annalena Venneri from the University of Sheffield’s Neuroscience Institute and NIHR Sheffield Biomedical Research Centre, said: “More than 50 million people are thought to be living with Alzheimer’s disease and despite decades of ground breaking studies and a huge global research effort we still don’t have a cure for this cruel disease.

“Prevention plays such an important role in the fight against the disease. It is important to stress this study does not show that obesity causes Alzheimer’s, but what it does show is that being overweight is an additional burden on brain health and it may exacerbate the disease.”

She added that it was important to educate people early on in their lives as it was too late to wait until the 60s to lose weight as the disease lurks in the backgrounds.

The researchers examined MRI scans of the brains of 47 patients diagnosed with mild Alzheimer’s disease dementia, 68 patients with mild cognitive impairment, and 57 individuals who were cognitively healthy. Using three complementary, computational techniques, they studied the brain’s anatomy, blood flow and also the brain’s fibres.

They compared gray matter volume, white matter integrity, cerebral blood flow and obesity. Grey matter volume decreases in Alzheimer’s. In patients with mild Alzheimer’s, an association was found with obesity and grey matter volume around the right temporoparietal junction, suggesting obesity creates a neural vulnerability in cognitively impaired patients. The study also found that maintaining a healthy weight may help preserve brain structure in structure in the presence of age and disease-related weight loss.

Joint author Dr Matteo De Marco from the University of Sheffield’s Neuroscience Institute, said: “Weight-loss is commonly one of the first symptoms in the early stages of Alzheimer’s disease as people forget to eat or begin to snack on easy-to-grab foods like biscuits or crisps, in place of more nutritional meals.

“We found that maintaining a healthy weight could help preserve brain structure in people who are already experiencing mild Alzheimer’s disease dementia. Unlike other diseases such as cardiovascular disease or diabetes, people don’t often think about the importance of nutrition in relation to neurological conditions, but these findings show it can help to preserve brain structure.”

Source: Medical Xpress

Journal information: Manmohi D. Dake et al, Obesity and Brain Vulnerability in Normal and Abnormal Aging: A Multimodal MRI Study, Journal of Alzheimer’s Disease Reports (2021). DOI: 10.3233/ADR-200267

Categories : COVIDTags : 1 Comment

Ivermectin Approved to Treat COVID in SA on Limited Basis

On By ModernMedia

Ivermectin, which has some reports of high effectiveness in limited studies, has received approval from the SA government to be used under strict control for compassionate use.  

Dr Boitumelo Semete-Makokotlela, head of the South African Health Products Regulatory Authority (SAHPRA), said that practitioners applying to use the drug will be considered case-by-case.

Ivermectin has a long history of use as an antiparasitic treatment in animals, while in humans it’s used as an anthelmintic drug that is usually indicated for filarial and resistant scabies infections. While the World Health Organization has suggested the drug has encouraging effects on coronavirus, although it hasn’t been properly evaluated yet.

“We absolutely share everyone’s desperation at this point,” said Helen Rees, SAHPRA chairwoman. “So the question about ivermectin and self-medication goes back to what everyone in the scientific community is saying. And that is, we don’t know if it works and we don’t know if it doesn’t work. That’s why we need to get data.”

Physicians in Zimbabwe are reportedly treating COVID with ivermectin in combination with silver nanoparticles – normally used as an algaecide – to great success.

Rees, however, warned South Africans that people self-medicating “need to be very careful because we don’t have any information about the quality of what you’re taking.”

Dr Semete-Makokotlela said that clear guidelines for the rollout would be given tomorrow. She added that SAHPRA granted the health department permission to distribute the Oxford/AstraZeneca COVID vaccine, the first one for SA. It is also currently reviewing applications from Johnson & Johnson and Pfizer, but has yet to receive an application from Moderna, she said.

Source: BusinessTech

Categories : COVID HIVTags :

Novavax COVID Vaccine only 49.4% Effective in SA

On By ModernMedia

On Thursday, Novavax announced that its vaccine was 89% effective, according to its UK trials which had 15 000 participants. However, its SA trials showed a much lower effectiveness of 49.4%, believed to be caused by the SA COVID variant B.1.351 (aka 501.V2). 

The company conveyed the information in a press release, with a detailed journal publication still to come. The SA trial had 4400 participants, and the observed protection varied depending on HIV status. In people who were HIV negative, the vaccine conferred 60% protection. If the vaccination trial included a representative proportion of HIV positive adult South Africans, it may mean that its effectiveness for this vulnerable segment is very low.

“The higher efficacy of the vaccine in the UK than in South Africa is because the variants circulating in SA are less sensitive to vaccine induced immune responses,” said Professor Shabir Madhi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits, and principal investigator in the Novavax COVID vaccine trial in SA.

“Nevertheless, the 60% reduced risk against Covid-19 illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally. This is the only Covid-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa.”

Novavax is pressing ahead with a trial involving 30 000 participants in the United States and Mexico, and has shared data with the UK’s pharmaceutical regulator. It is not clear whether the data from the US and Mexico trial will be required before the vaccine receives approval there. Meanwhile on Friday, the Johnson & Johnson vaccine developed by its subsidiary Janssen has been shown to be 66% effective. It is a single dose vaccine with minimal refrigeration requirements, making it very important for the logistical challenge of vaccinations in developing countries. Since Aspen would be producing some of the doses locally, the SA government had been in talks with Johnson & Johnson to secure some of those vaccines for SA use. However, there are signs that it too is less effective against the B.1.351 variant.

Source: Business Insider