Year: 2021

Categories : Diseases, Syndromes and Conditions Medical Research & TechnologyTags :

Researchers Study Enzyme Processes for New Drugs

On By ModernMedia

Traditional discovery has produced drugs that effectively target proteins directly involved with disease, but options are starting to run out and researchers are looking to more complex and obscure interactions for drug targets.

So far, drug discovery has used the ‘small molecule’ approach, where a specific protein is targetted in a cancer cell to shut it down and bring down the cancer cell as a whole. Up until this point, traditional drugs have only been able to target proteins that are involved in the disease that also have activities that are amenable to the small molecule approach, leaving a vast number of proteins unaddressed. Many of these other proteins may be involved in disease processes behind the scenes.

“It’s starting to get to the point where we’ve kind of taken traditional drug discovery as far as we can, and we really need something new,” explained University of Nevada, Las Vegas biochemist Gary Kleiger.

“Cancer cells are clever,” Kleiger said. “They can evolve very, very quickly. So, a drug might be working at first—targeting an enzyme and telling that enzyme, ‘stop doing your activity,’ which can stop the cancer cells from growing. Those cancer cells appear to lie dormant, but all the while there are still little things that happen that eventually enable those cancer cells to bypass that drug.” Therefore, in order to stay ahead of cancer’s capacity to evolve drug resistance, it is necessary to target many additional disease-causing proteins, and thus, limiting the landscape of druggable proteins is a serious disadvantage.

The new approach by investigated by Kleiger and collaborators uses a family of human enzymes called ubiquitin ligases found in human cells. Of about 20 000 known proteins in the human body, some 5-10% are enzymes.

Kleiger’s team uses cutting edge cryo electron microscopes that can image the ubiquitin ligases when they’re at work. To test their hypotheses, Kleiger and collaborators measure the activity of ‘mutated’ enzymes that should now be defective in their activities.

Kleiger compared the process to how a 50 000 year old society might view a bicycle. They could identify its purpose and general properties, but could test the importance of a certain gear; if it was bent, the bicycle would no longer function. “We can do that at the molecular level with the enzymes,” he said.

Source: Medical Xpress

Journal information: Daniel Horn-Ghetko et al, Ubiquitin ligation to F-box protein targets by SCF–RBR E3–E3 super-assembly, Nature (2021). DOI: 10.1038/s41586-021-03197-9

Categories : Hospitals Medical Research & TechnologyTags :

Battery Backups Can Protect People Dependent on Medical Equipment

On By ModernMedia
A battery. Photo by Danilo Alvesd on Unsplash.

In countries prone to blackouts from extreme weather events (and in some cases solar flares) battery backups could provide a viable alternative to keep the medical support systems for vulnerable family members functioning. As climate change is set to increase the frequency and severity of weather-related blackouts, a study from the Columbia University Mailman School of Public Health examined the value of battery backups.

Millions of people are reliant on home medical equipment – the elderly, ill people, many of whom are poor or otherwise vulnerable. Medical equipment such as oxygen concentrators, nebulisers, ventilators, and dialysis and sleep apnoea machines often have no backup power in case of an outage.

In a 2019 wildfire which caused power outages, many vulnerable residents reported complications, such as one man who awoke, unable to breathe when his sleep apnoea breathing machine stopped functioning.
Community centres such as schools are often turned to for services when power fails, such as using their refrigerators to store food, but many do not have backup power.

“Climate change coupled with aging energy infrastructure is driving extreme weather-related power outages, as we’ve seen recently in Texas,” said study co-author Diana Hernández, PhD, Associate Professor of Sociomedical Sciences, Columbia University, “The technology to improve resiliency and energy independence exists, and it needs to be made more accessible to those who could most benefit. Battery storage units, particularly those powered by the sun, are a critical tool to help vulnerable individuals and communities survive the climate crisis.”

In the US territory of Puerto Rico, following the widespread destruction of the electrical grid by Hurricane Maria, many residents used solar panels instead of diesel generators due to ease of use, low cost, and not emitting fumes that exacerbate asthma and other lung conditions

A review of literature showed that blackouts can result in negative health consequences ranging from carbon monoxide poisoning, temperature-related illness, gastrointestinal illness, and mortality to cardiovascular, respiratory, and hospitalisations for kidney disease, especially for individuals dependent on electrically powered medical equipment.

Beyond electrical backup, in the US, older adults, poorer families, and individuals of non-Hispanic Black and Hispanic race/ethnicity are also less likely to have emergency supplies of food, water and medicine in the event of disaster.

Overall, the researchers found that more work is needed to better define and capture the relevant exposures and outcomes. “There is urgent need for data to inform disaster mitigation, preparedness, and response policies (and budgets) in an increasingly energy-reliant world,” said first author Joan Casey, PhD, assistant professor of environmental health sciences at Columbia Mailman School.

Eskom in South Africa is already facing a shortfall due to users abandoning its services for solar power generation, forcing tariff changes and increases. An uptake of battery backups to complement the solar panels may greatly alleviate vulnerabilities of people dependent on medical equipment in an uncertain power supply environment, as well as improving resilience to natural disasters, without the health hazards of generators.

Source: News-Medical.Net

Journal information: Mango, M., et al. (2021) Resilient Power: Battery storage as a home-based solution to address climate-related power outages for medically vulnerable populations. Futures. doi.org/10.1016/j.futures.2021.102707.

Categories : COVID General InterestTags :

Pope Appoints New Personal Doctor After Predecessor Died of COVID

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The 84 year-old Pope Francis today appointed a new personal doctor to replace his previous one, 78 year-old Fabrizio Soccorsi, who passed away on January 9 from COVID related complications. He had served in the role since 2015.

Dr Soccorsi had been admitted to Rome’s Gemelli hospital on 26 December because of cancer, but died due to “pulmonary complications” caused by COVID. Pope Francis had held a funeral service on 26 January for the late Dr Soccorsi.

During his medical career, he had been head physician of the hepatology ward in Rome’s San Camillo-Forlanini hospital and director of its department of liver diseases, the digestive system and nutrition; he also taught immunology at medical schools.

His replacement, Roberto Bernabei, is an expert in health care for the elderly. Dr Bernabei, 69, leads the geriatrics and rehabilitative medicine department at Rome’s Gemelli, which is the Catholic hospital where popes traditionally go to be treated.

It is believed the pontiff remains in good health, despite having had part of his lung removed after developing pleurisy as a young man. He received a COVID vaccine in early January alongside former pope Benedict.

Source: Eyewitness News

Categories : Diet and NutritionTags :

Researchers Lower Salt in Parmigiano Reggiano But Keep Flavour

On By ModernMedia

Aged cheeses like Parmigiano Reggiano are prized for their strong, sharp flavours, but their production process creates a high salt content. Now, researchers have come up with a new process that reduces the salt content, a boon for people who have to manage their salt content, such as those with hypertension.

In the production process, aged cheeses are either coated in wax or submerged in brine for a number of weeks to create a rind. Parmigiano Reggiano is produced only in certain Italian provinces, and is subject to strict regulations. Made from skimmed cow’s milk, it is aged for at least one year and is lactose free. The flavours come from conversion of milk compounds during the ripening process, in which salt plays a role by hardening the cheese and regulating microbe and enzyme activity. Parmigiano Reggiano has a sodium content of 650mg per 100g. Reducing sodium in the diet reduces hypertension and also cardiovascular disease mortality and morbidity.

A key chemical process is lipolysis, where triglycerides from milk break down into free fatty acids and diacylglycerides. Free fatty acids add to the taste of the cheese and also serve as precursors to other flavour molecules. Lipolysis also takes place in the body when adipose triglycerides are broken down for energy.

To see if salt content could be reduced without compromising flavour, the researchers submerged wheels of the cheese in brine for 18 days or a shorter 12 day period before a 15 month ripening period. Salt content was 9% lower in the cheese brined for a shorter time. The researchers were surprised to find no difference in the moisture level, cholesterol, and total fat in the two sets of cheeses.

No major variations in compounds involved in the flavour profile were seen, as most of the free fatty acids overlapped in concentration ranges.

Yet in the cheeses with the shorter brining time, overall, the total free fatty acids and the total diacylglycerides concentration ranges were 260% and 100% higher, respectively, than the traditionally brined version. It is possible that the lower salt to moisture ratio made more water available for lipolysis reactions and more rapid enzymatic triglycerides breakdown. The cheese still needs to be assessed for texture.

Source: News-Medical.Net

Categories : COVID VaccinesTags :

Why It’s So Hard to Compare Vaccines

On By ModernMedia

While the world is looking to vaccinations to end the COVID pandemic, a MedPage Today article explains that even with vaccines that have high efficacy, ending transmission is not guaranteed, and there are a lot of differences between simple figures like 94% for Pfizer and 95% for Moderna vaccines.

Firstly, asymptomatic cases are not tracked, simply because assembling tens of thousands of people for a clinical trial is a monumental logistic task, and in the current pandemic, a race against time.

Internist Jeffrey Carson, MD, who managed the Johnson & Johnson COVID vaccine trial’s site at Rutgers University in New Jersey, explained to MedPage Today that it would be difficult but not impossible to create a vaccine trial that provided rapid data about asymptomatic cases.

“You might have people swab themselves every couple days, or every week. You’ll be picking up a lot of disease that way, and you’ll be able to see if the vaccine prevents asymptomatic disease,” Dr Carson said. The current Novavax trial, for example, only asks participants to test themselves for COVID with provided swabs if they believe they are developing symptoms. The Novavax vaccine had also prompted alarm as it was only 49.4% effective against the B501Y.V2 variant, its efficacy reduced by the low rate of protection for HIV positive participants.

The New York Times explained that efficacy is merely how well a vaccine did in a clinical trial, effectiveness is how well it performs in the real world.
Vaccine statistics are difficult even for medical experts to grasp. An infectious diseases expert wrote in a letter to the Lancet explaining that they had misunderstood what 94% to 95% efficacy means for Moderna and Pfizer vaccines and asymptomatic spread.

“It does not mean that 95% of people are protected from disease with the vaccine — a general misconception of vaccine protection.” Instead, it “means that in a population such as the one enrolled in the trials, with a cumulated COVID-19 attack rate over a period of 3 months of about 1% without a vaccine, we would expect roughly 0.05% of vaccinated people would get diseased [with symptomatic infections]. … Accurate description of effects is not hair-splitting; it is much-needed exactness to avoid adding confusion to an extraordinarily complicated and tense scientific and societal debate around COVID-19 vaccines.”

A further problem for scientists is that viral diseases can spread to people unaware that they are infected, something they are still working on understanding. “It makes a lot of sense for survival of the invaders, if you think about it. Humans who feel unwell are not going out to meet up with others, but ones who feel fine will continue along with their daily schedules, allowing the infection to spread,” Bryn Boslett, MD, an infectious disease physician at the University of California San Francisco, told MedPage Today.

Regardless of how well vaccines interrupt the transmission of COVID, it’s important that mask-wearing, social distancing and disinfecting habits are maintained.

“One major worry going forward is that vaccinated people will change their behaviour and stop taking COVID-19 precautions,” Dr Boslett said. “It’s very tempting to do so, very understandable. However, the stars are not yet aligned for us to go back to ‘normal.’ There is still a lot of COVID-19, and most of us are still vulnerable. We need to continue to focus on behavior to reduce new cases of COVID-19.”

Source: MedPage Today

Categories : Cardiovascular Disease Diet and NutritionTags :

High GI Carbohydrates Raise CVD Risk Across Countries

On By ModernMedia

A multinational study has shown that high consumption of high glycaemic index foods increases the risk of cardiovascular disease (CVD) events such as stroke or heart disease, regardless of pre-existing CVD.

The study examined low-, middle- and high-income countries, beginning in 2006, with a median follow-up of 9.5 years. Data was used from nearly 120 000 participants.

The glycaemic index was first introduced in the 1970s to compare the rise of blood glucose from a given carbohydrate food in a patient in comparison to their blood glucose curve from the same patient ingesting glucose. This ranges from 20 for fructose to 100 for barley. In comparison to individuals eating low glycaemic index foods, those eating high glycaemic index foods had a greater risk of CVD events (51%) if there was pre-existing CVD, and even without CVD (21%). 

The highest glycaemic index foods were eaten in China, followed by Africa and Southeast Asia. The highest glycaemic loads were seen in Southeast Asia, followed by Africa and China. Glycaemic load is a better measure of a food’s effect on blood sugar taking into account how quickly it enters the bloodstream and how much glucose can be delivered.

There was less of an effect seen with glycaemic load only those with preexisting CVD showed an association between high glycaemic load diets and patient outcomes.

The participants were given a questionnaire, breaking foods down into seven categories based on glycaemic load and frequency, with a number of options each.

The broad geographic and economic scope of this study enabled the investigation of glycaemic index and load across a wide range of diets that would not be possible if it were restricted to sampling only Western-style diets.

“As expected, a higher glycaemic index was associated with an increased risk of adverse effects among the participants with a higher BMI, as reported previously,” the researchers wrote. “Although the glycaemic index of foods is independent of glucose-tolerance status, the overall postprandial glycaemic response to diet increases as the BMI increases.”

The authors acknowledge that economic development may have altered the mix of diets sampled over time, leading to an overestimation of glycaemic foods in China, for example. The findings nonetheless have important implications for primary and secondary prevention of CVD.

Source: MedPage Today

Journal information: Jenkins DJA, et al “Glycemic index, glycemic load, and cardiovascular disease and mortality” N Engl J Med 2021; DOI: 10.1056/NEJMoa2007123.

Categories : Ageing NeurologyTags :

Jump-Starting Neural Stem Cells in Aged Brains

On By ModernMedia

As we age, neural stem cells lose the ability to divide and create new neurons, resulting in a decline in memory. Now, research led by Sebastian Jessberger, a professor at the Brain Research Institute of the University of Zurich, explains why this happens.

The new neurons are used all over the brain, including the hippocampus which is responsible for memory. Declines here from age and Alzheimer’s mean fewer neurons are produced here, impacting memory functions.

“As we get older, stem cells throughout the body gradually lose their ability to proliferate. Using genetic engineering and cutting-edge microscope technology, we were able to identify a mechanism that is associated with this process,” explained doctoral candidate and first author Khadeesh bin Imtiaz. The results were published in the journal Cell Stem Cell.

The study used a mouse model to show that as organisms age, neurons’ ability to divide becomes impaired. Protein structures ensure that accumulated harmful proteins are laid out unequally among the two daughter neurons, important for the longevity of neurons. As the neurons age, the amount of nucleic proteins changes, resulting in impaired distribution of proteins, reducing the number of newly generated neurons in the brains of older mice.

The researchers identified a nuclear protein called lamin B1, levels of which decrease as people age. When lamin B1 was increased in aged mice, there was an improvement in stem cell division and the number of neurons increased.

The study was part of wider research into ageing and stem cells. “While our study was limited to brain stem cells, similar mechanisms are likely to play a key role when it comes to the ageing process of other stem cells,” said Prof Jessberger.

The latest findings represent an important step in understanding how brain stem cells change with age. “We now know that we can reactivate aging stem cells in the brain. Our hope is that these findings will one day help increase levels of neurogenesis, for example in older people or those suffering from degenerative diseases such as Alzheimer’s. Even if this may still be many years in the future,” concluded Prof Jessberger.

Source: Medical Xpress

Journal information: Cell Stem Cell, DOI: 10.1016/j.stem.2021.01.015

Categories : Diseases, Syndromes and ConditionsTags :

International Travellers at Risk of MDR Bacteria

On By ModernMedia

International travellers are at risk of picking up a number of drug-resistant pathogens, according to a new European study.

In the COVID pandemic, international travel has become a distant memory for most of those used to it. As restrictions are lifted and international travel resumes, travellers are still at risk from other dangerous pathogens. In recent years, the rise of intestinal multidrug resistant gram-negative (MDR-GN) bacteria around the world poses a serious health threat, with MDR clones of E.coli and Klebsiella pneumoniae threatening more antibiotic resistant infections around the world. The spread of MDR-GN is a known threat in long-term care facilities, with residents forming a reservoir for the microbes but is also common in international travel as well. It is well documented that international travel results in the spread of multidrug-resistant E. coli, with up to 80% of travellers returning from high-risk regions being colonised by MDR-GN bacteria for up to a year. However, the existing research only compared participants before and after travel. A group of researchers from Universities of Basel, Birmingham, Helsinki and Oslo, and the Wellcome Sanger Institute set out to investigate the spread of such bacteria on a day by day basis.

Over a period of three weeks, the researchers monitored the health of a group of European travellers in the Lao People’s Democratic Republic by analysing daily information returns and stool samples. They found that by the end of the study period, 70% of the travellers had been colonised. The bacterial strains colonised travellers staying at the same hotel and spending time in one another’s company. In one case, a participant was colonised by taking a shower in another’s bathroom.

“International travel is strongly linked to the spread of MDR-GN bacteria, with transmission highest in India and Southeast Asia, Africa and South America,” said senior study author Professor Alan McNally, University of Birmingham. “Travellers visiting these high-risk regions are at substantial risk of acquiring the bacteria. Colonisation by MDR-GN bacteria is a highly dynamic process. We found constant ‘competition’ between circulating strains acquired by individual hosts and the travelers’ ‘native’ bacteria. Travellers can pick up the bacteria even during short visits and further spread the strains after returning home.”

All of the participants had acquired extended-spectrum beta-lactamases (ESBL) during their stay in Laos. ESBL enzymes create resistance within the body to most beta-lactam antibiotics, including penicillins, cephalosporins, and aztreonam. Infections with ESBL-producing organisms have proved difficult to treat. Also, all but one participant acquired multiple strains of bacteria with 83 unique strains identified (53 E. coli, 10 Klebsiella, 20 other ESBL-GN species), with up to four other participants sharing strains.

Study co-senior author, Professor Jukka Corander, at the University of Oslo and the Wellcome Sanger Institute, commented: “Our study reveals the true scale and complexity at which drug-resistant bacteria colonise the intestinal tract during travel, demonstrating that it has been seriously underestimated previously.

“In addition, several of our participants lost some of their travel-acquired ESBL-GN strains while still abroad – indicating that previous studies solely employing pre- and post-travel sampling have under-reported the extent to which travellers are colonised by ESBL-GN.”

Source: News-Medical.Net

Journal information: Kantele, A., et al. (2021) Dynamics of intestinal multidrug-resistant bacteria colonisation contracted by visitors to a high-endemic setting: a prospective, daily, real-time sampling study. The Lancet Microbe. doi.org/10.1016/S2666-5247(20)30224-X.

Categories : Diseases, Syndromes and Conditions Expert OpinionTags :

Microbes Develop Resistance to Disinfectant Too, Warns UFS Professor

On By ModernMedia

News-Medical.Net interviewed Professor Robert Bragg of the University of the Free State on the topic of pathogens, particularly bacteria, developing resistance to common disinfectants.

Professor Robert Bragg said that the control of diseases rests on three pillars: 1) vaccinations and vaccines, 2) treatment options (such as antibiotics for bacterial diseases), and 3) biosecurity.

Proff Brage explained that 10 to 15 years ago, there was an assumption that bacteria would not evolve resistance against disinfectants, but the COVID pandemic prompted a rethink. Now, disinfectant resistance is being looked at in the same light as antibiotic resistance. Biosecurity, he said, is ensuring that individuals do not come into contact with the pathogens in the first place. This is easily seen in the COVID pandemic, where face masks are worn (with a protection against contracting the disease of up to 70%), social distancing is enforced and hands and surfaces are sanitised. Though Prof Bragg’s main area of research is not antibiotic resistance, he notes that, “There are resistance mechanisms that are shared between antibiotics and disinfectants and we are looking at how these mechanisms increase resistance to disinfectants.” 

The protection of antibiotics is something taken for granted, but although mostly easily treatable (for now), bacteria can spread much faster than viruses, which require cells to reproduce in and whose re[plication rate is measured in days. “A common well-known bacterium such as Escherichia coli has a doubling time of around 20 min under ideal conditions. In other words, it only takes just 20 minutes for a population of E. coli to go from 1 million to 2 million and another 20 mins to reach 4 million, and so on,” Prof Bragg said. In the post-antibiotic era, there would be some treatment options such as bacteriophages, but for livestock the best protection would be biosecurity. However, disinfectant resistance would reduce the effectiveness of that option.

His research team has conducted a number of studies into the mechanisms of bacterial disinfectant resistance. “My research team has been working on various aspects of efficacy and resistance to disinfectants for quite some time and we have various projects that are currently underway,” he said. “Recently we identified a highly resistant strain of a Serratia species of bacteria. This strain was substantially more resistant to many different disinfectants than the reference strain. This great difference in the levels of susceptibility has allowed us to investigate various possible research mechanisms and also to look for possible novel resistance mechanisms.”

One of his team’s discoveries was that this highly resistant bacteria strain could grow on disinfectant if it was the sole source of carbon. Other areas of research around the resistant strain include sequencing and analysis of its genome, the role of bacterial efflux pumps removing disinfectant, and the role of plasmids (vehicles of genetic transfer between bacteria) in resistance and whether they are transferrable.

With regard to viruses, there are two kinds of viruses, enveloped and naked, and disinfectant has different effects on them. Enveloped viruses such as SARS-CoV-2, have a lipid layer picked up from their host cell, and are easy to kill with simple disinfectants because they break up the lipid layer, killing the cell. Naked cells are much harder to kill, and the few disinfectants that work against them are thought to do so by somehow disrupting the virus’ receptors.

One sanitiser of concern is alcohol, where 70% is considered optimal. However, people believe that ‘more is better’, yet increasing the alcohol percentage actually makes it evaporate faster, reducing contact time and thus leaving more of the virus behind. Similarly, some sanitisers include low levels of other disinfectant substances which are below the minimum threshold to kill the pathogens. This can leave surviving bacteria to develop resistance against these other sanitisers.

Prof Bragg advised that the public should purchase and use sanitisers prudently, following their instructions for use appropriately, and preferably checking to see if they are registered. He also cautioned

Source: News-Medical.Net

Categories : Diseases, Syndromes and Conditions Paediatrics VaccinesTags :

Researchers Say New Vaccines Needed for Childhood Pneumonia

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Research in Australia on new pneumonia vaccines show that while pneumonia in children is being suppressed,  empyaema is increased.

The research, which was led by the University of New South Wales (UNSW), examined the impact of the new 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyaema.
Empyaema, which is the collection of pus in the lungs, occurs in about 1% of children with pneumonia. In children, empyaema is far less fatal than it is in adults, but it does extend hospitalisation, requiring antibiotics and surgery or installation of a drain.
The findings of the study showed that while 13vPCV resulted in a 21% drop in childhood pneumonia hospitalisations, there was a contemporaneous 25% rise in empyaema hospitalisations.

According to senior author Professor Adam Jaffe, Head of the School of Women’s and Children’s Health at UNSW Medicine & Health, said the findings suggested an emergence of non-vaccine serotypes—those which 13vPCV does not cover.

13vPCV was introduced to cover the 13 most common serotypes that cause invasive pneumococcal infection, adding six more serotypes over the seven serotypes covered by its predecessor, 7cPCV.

Prof Jaffe said: “Although we found a substantial reduction in serotype 1, serotype 3 is now the predominant organism which causes childhood empyema—in 76% of cases—so, efforts must be made to create a vaccine which is more effective against serotype 3.

“In fact, Australia recently changed the vaccination dosage schedule to try and improve the effectiveness of 13vPCV against serotype 3, but we need to continue monitoring patients using molecular techniques to see if this change has had an impact.

“Childhood bacterial pneumonia and empyema are potentially preventable diseases through vaccination. So, if Australia can develop an effective vaccine, we could prevent children from being hospitalized with pneumonia and empyema.”

The researchers conducted a similar study over four years during the 7vPCV era.   

“Our new study had two parts,” Prof Jaffe said. “We analysed national hospitalisations for childhood empyaema and childhood pneumonia, then we conducted an enhanced surveillance study on children with empyaema.”

The first part of the research used publicly available hospitalisations data to find out if the introduction of 13vPCV changed how many children were admitted to hospital with pneumonia and empyaema.

The enhanced surveillance study involved the collection of blood and lung fluid samples from 401 children  with empyaema, followed by molecular testing on these samples and comparing the results to their previous study undertaken during the period of 7vPCV.

Prof Jaffe said research with a larger sample was ongoing, and 13vPCV monitoring was needed.

Source: Medical Xpress

Journal information: Roxanne Strachan et al. Assessing the impact of the 13 valent pneumococcal vaccine on childhood empyema in Australia, Thorax (2021). DOI: 10.1136/thoraxjnl-2020-216032