Tag: 31/3/21

An Eye for Wine: Alcohol May Prevent Cataracts

Two people clinking wine glasses together. Photo by Jep Gambardella from Pexels

A study from the UK has shown that people who drink up to 14 units of alcohol a week have a reduced risk of developing cataracts, with red wine having an even more pronounced effect.

Drinking less than 14 units of alcohol (or about six pints of beer, or six glasses of wine) is in line with the British Chief Medical Officer’s low risk drinking guidelines.

Cataracts are a major cause of impaired eyesight and blindness, mainly in older people. Cataract removal is simple, and is the most common surgery carried out by the UK’s National Health Service. The NHS considers drinking to be a risk factor for cataracts.

Researchers from Moorfields eye hospital in London and University College London’s institute of ophthalmology studied the medical and lifestyle history of nearly half a million participants in either the UK Biobank or Epic-Norfolk longitudinal health studies.

The results showed that people who drank within the 14 units a week guideline were less likely to have cataract surgery. Wine drinkers were even less likely to have it, compared to those who consumed beer or spirits. In the Epic-Norfolk study, drinking wine at least five times a week meant a 23% reduced chance of cataract removal than non-drinkers, while those in the UK Biobank study were 14% less likely.

“Cataract development may be due to gradual damage from oxidative stress during ageing. The fact that our findings were particularly evident in wine drinkers may suggest a protective role of polyphenol antioxidants, which are especially abundant in red wine,” said first author Dr Sharon Chua.

Research leader Dr Anthony Khawaja added: “We observed a dose-response with our findings – in other words, there was evidence for reducing chance of requiring future cataract surgery with progressively higher alcohol intake, but only up to moderate levels within current guidelines.”

The authors emphasised that there was still not a causal link between alcohol consumption and reduced cataract surgeries despite the association.

Dr Sadie Boniface, research head at the Institute of Alcohol Studies thinktank, cast doubt on the findings. She said that longitudinal studies such as UK Biobank may not accurately represent health across the nation because many volunteers were often in good health.

“Comparing the health of moderate drinkers with that of non-drinkers also carries problems. Non-drinkers are a diverse group, including people who have stopped drinking because of health problems. This means moderate drinking can artificially look like it carries health benefits, because the moderate drinkers are compared to people on average in poor health,” said Dr Boniface.

“The bigger effect seen among wine drinkers may be because of other characteristics of this group to do with their cataract risk which weren’t accounted for. If the amount of alcohol or number of units somebody drinks was having a direct effect, you’d expect this to be similar regardless of drink type.”

Source: The Guardian

Osteoporosis Rates are Increasing in US Women

Osteoporosis is present in Almost one in five American women aged 50 and older, according to data from the National Health and Nutrition Examination Survey (NHANES), and the osteoporosis rates are increasing.

Neda Sarafrazi, PhD, of the National Center for Health Statistics (NCHS) in Hyattsville, Maryland, and colleagues reported the findings in an NCHS Data Brief.

Osteoporosis is defined as bone mineral density (BMD) value at least 2.5 standard deviations below young-adult average at the femoral neck or lumbar spine was present, and was measured in NHANES with dual x-ray absorption dosimetry.

In cross-sectional survey data from 2017-2018, 19.6% of women 50 and older had osteoporosis at the femoral neck, lumbar spine, or both. In men, the age-adjusted prevalence was only 4.4% of men 50 and older.

All in all, osteoporosis was present in 12.6% of all American adults 50 and older, which was defined as a bone mineral density (BMD) value at least 2.5 standard deviations below the average for young adults at the femoral neck or lumbar spine.

Osteoporosis, as to be expected, was far more common among older adults, affecting 17.7% of all men and women 65 and older, versus 8.4% of those ages 50-64. In women ages 65 and older, the prevalence was 27% and at ages 50-64 was 13.1%. In men, prevalence values were 5.7% in those 65 and older and 3.3% for those 50-64.

Sarafrazi’s team found that osteoporosis had become slightly more prevalent over the years. In 2007-2008, 9.4% of Americans 50 and older had osteoporosis. While rates remained steady throughout for men, a big uptick of 5 percentage points was seen for women.

“Monitoring the prevalence of osteoporosis and low bone mass may inform public health programs that focus on reducing or preventing osteoporosis and its consequences,” suggested Sarafrazi’s group. “Healthy People 2020 has a goal of 5.3% or less for the prevalence of osteoporosis at the femur neck for adults aged 50 and over.”

“In the United States, the prevalence of osteoporosis among adults aged 50 and over at the femur neck only was 6.3% and has not met the 2020 goal,” they stressed.

The data also revealed high rates of low bone mass, a precursor of osteoporosis, defined as BMD of 1 to 2.5 standard deviations below the average for young adults.

Among all adults ages 50 and older, 43.1% had low bone mass at the femoral neck, lumbar spine, or both. Among women, prevalence was 51.5% and among men 33.5% .

The overall rate reached 47.5% in those 65 and older. However, older age seemed to be less of a factor for women, with almost no difference between the 50-64 and 65-plus age groups.

However, the prevalence rates of low bone mass in both sexes held steady during the decade between 2007-2008 and 2017-2018.  

Source: MedPage Today

Journal information: Sarafrazi N, et al “Osteoporosis or low bone mass in older adults: United States, 2017–2018” NCHS Data Brief 2021; No 405.

New X-Ray Tool to Spy into Virus’ Cellular Subversion

A new X-Ray tool called the Compact Cell-Imaging Device (CoCID) will seek to answer the questions of how viruses penetrate cells, and disrupt and subvert cellular processes to produce more virus copies.

In order to advance research into viral diseases, the aim of the project is to develop a particularly suitable cell-imaging method – which has so far been of limited access to researchers – for extensive application in medical research.

A particularly high-performance method of cell-imaging is soft X-ray microscopy (SXM), explained Dr Venera Weinhardt from the Centre for Organismal Studies of Heidelberg University. A physicist specialising in innovative X-ray procedures, she is head of the Molecular Virology division at the Department of Infectious Diseases of Heidelberg University Hospital. “SXM makes use of the special properties of the soft X-ray spectrum in order to look into the interior of a single intact cell and generate three-dimensional images of its whole internal structure. That also reveals the changes induced by viral infections,” explained Dr Weinhardt. 
Thus, soft X-ray microscopy is distinct from methods like electron microscopy, which can visualise individual parts of a cell but not the whole interior.

Professor Ralf Bartenschlager, a Molecular Virologist at the Ruprecht-Karls-Universität Heidelberg commented, “As a virologist working on how SARS-CoV-2 interacts with and alters its host cell, we will greatly benefit from the development of a soft X-ray microscope that allows us to gain unprecedented insights into this intimate interaction. We have previously used several imaging technologies to address the question of host cell reprogramming by viruses, but each technique has its limitations.”

Since the illumination required for this type of microscopy comes from huge particle accelerators called synchrotrons, currently SXM can only be performed at five research stations in the entire world. The main feature of CoCID therefore lies in further developing a miniaturised soft X-ray approach which has been patented by SiriusXT, a spin-out company from University College Dublin. The breakthrough technology will reduce the size of the X-ray source from a football-field sized synchrotron, instead using a laser-produced plasma (LPP) device that can fit on a bench.

“The SXM microscope developed by SiriusXT performs just as well but is many times smaller, less expensive, and still very fast.” said Dr Weinhardt.

Heidelberg researchers are particularly interested in the potential of the new technology in researching SARS-CoV-2. Prof Bartenschlager’s working group is mainly concerned with how the virus reprograms its host cells. He said that SXM images created under the leadership of Dr Weinhardt at Lawrence Berkeley National Laboratory in California are already promising in this respect.

Three-dimensional images of cells infected with SARS-CoV-2 were generated thanks to a cooperation agreement with the European Molecular Biology Laboratory (EMBL) in Heidelberg.

“Through working with these images we have a pretty good idea of what factors play a role with imaging in connection with the virus-infected cells and we can pass these findings on to the CoCID consortium. As soon as the soft X-ray prototype from Dublin is up and running we will also deliver samples of infected cells, enable a direct comparison with available images and provide support in interpreting data,” said Prof Bartenschlager.

According to the Heidelberg researchers, a soft X-ray microscopy available for daily use should have distinct advantages over current techniques, such as being much faster. Prof Bartenschlager said: “We can’t afford long waits or a time-intensive method when it comes to novel viruses such as SARS-CoV-2, which we learn something new about and which changes on a daily basis.”

Source: News-Medical.Net

Duo of Existing Drugs Punishes Ravenous Cancer Cells

Preclinical research from VCU Massey Cancer Center published recently in the Proceedings of the National Academy of Sciences shows that the combination of two existing drugs can kill aggressive neuroblastoma cancer cells by exploiting their metabolic ‘hunger’.

A cancer of the nervous system, neuroblastomas are one of the deadliest childhood cancers, and if the MYCN gene is overexpressed, the prognosis is even worse. Although paediatric blood cancers are more treatable thanks to medical advancements, it has been much harder to treat neuroblastomas mostly due to the difficulty of targeting MYCN.

“MYCN is a transcription factor, and it’s very difficult to drug transcription factors,” said study senior author Anthony Faber, PhD, co-leader of the Developmental Therapeutics research programme and Natalie N and John R.Congdon, Sr. Endowed Chair of Cancer Research at VCU Massey Cancer Center and associate professor in the Philips Institute for Oral Health Research at the VCU School of Dentistry. “So, the next best thing is to target what MYCN does in the cell. One thing it does is to crank up metabolic activity – what it’s doing to keep the cell alive – and we can work that against itself.”

Since these ravenous cells burn cellular energy stores as quickly as they can be replenished Prof Faber’s team looked for a method to kick their metabolism over the edge without harming normal cells.

Screening 20 metabolic drug combinations in cancer cells originating from nearly 1000 different patients, the researchers found that neuroblastoma with high MYCN expression was particularly sensitive to a cocktail containing two drugs: phenformin and AZD3965..

Phenformin was developed in 1957 to treat diabetes. It blocks complex I on the surface of mitochondria, the organelle where energy production occurs.

Although phenformin was taken off the US market in the 1970s after a number of deaths, it’s still in use elsewhere in the world and is finding new application in the US as a cancer drug. Right now, phenformin is being tested in phase I clinical trial for melanoma.

Meanwhile, AZD3965 is a much newer type of drug under phase I clinical investigation. It works by blocking MCT1 rectors on the surface of cells, in this case as a cancer treatment. MCT1 receptors ferry lactate, another energy source, out of the cell. Blocking MCT1 causes lactate to accumulate, causing the cell to stop using it to make energy.

Simultaneously targeting energy production with the two different pathways used by the drugs should result in disruption of the cellular power supply, stressing and finally killing the cells.

This idea was put to the test by using mice seeded with MYCN-amplified neuroblastoma patient cells. Greater tumour reduction was seen from the cocktail than either drug given alone, with the cocktail being well tolerated.

“The data we got with AZD3965 in combination with phenformin might get people to reconsider phenformin,” said study lead author Krista Dalton, MEng, PhD Student, Virginia Commonwealth University Philips Institute for Oral Health Research. “In combination, where we can use lower doses, phenformin might have better tolerability than it previously did on its own.”

Source: News-Medical.Net

Journal information: Dalton, K. M., et al. (2021) Catastrophic ATP loss underlies a metabolic combination therapy tailored for MYCN-amplified neuroblastoma. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2009620118.

As Lockdowns Ease, Masks and Social Distancing are Still Needed

A new model suggests that as lockdowns ease, other control measures such as mask use must be enhanced in order to prevent additional COVID outbreaks.

The mathematical model, developed by scientists at the Universities of Cambridge and Liverpool, provides general insights about how COVID will spread under different potential control scenarios.

They considered ‘non spatial’ control measures involving facemasks, handwashing and metre-scale social distancing can all limit the number of virus particles being spread between people. The other, ‘spatial’ control measures included lockdown and travel restrictions, which reduce how far virus particles can spread. Different combinations of COVID control measures showed that non-spatial control needs to be ramped up as lockdown is lifted.

“More effective use of control measures like facemasks and handwashing would help us to stop the pandemic faster, or to get better results in halting transmission through the vaccination programme. This also means we could avoid another potential lockdown,” said Dr. Yevhen Suprunenko, a Research Associate in the University of Cambridge’s Department of Plant Sciences and first author of the paper. The authors stress that their predictions rely on such non-spatial control measures being implemented effectively.

Their model took into account the socio-economic impact of the measures. The costs of spatial measures of lockdown increased over time, while costs for non-spatial measures decreased due to falling prices and greater availability of items such as masks, and usage becoming a habit.

“Measures such as lockdowns that limit how far potentially infected people move can have a stronger impact on controlling the spread of disease, but methods that reduce the risk of transmission whenever people mix provide an inexpensive way to supplement them,” explained co-author Dr Stephen Cornell at the University of Liverpool.

The model was derived from identifying control strategies for plant diseases threatening staple crops. Instead of the usual computer simulation model, mathematical approach allowed the authors to identify insights on how to control newly emerging infectious diseases of plants and animals.

“Our new model will help us study how different infectious diseases can spread and become endemic. This will enable us to find better control strategies, and stop future epidemics faster and more efficiently,” said co-author Professor Chris Gilligan in the University of Cambridge’s Department of Plant Sciences.

Source: Medical Xpress

Journal information: Analytical approximation for invasion and endemic thresholds, and the optimal control of epidemics in spatially explicit individual-based models, Journal of the Royal Society Interface,rsif.royalsocietypublishing.or … .1098/rsif.2020.0966

Sunlight Vulnerability of SARS-CoV-2 not Just from UV-B

A team of researchers have found that the sunlight vulnerability of SARS-CoV-2 cannot be explained by the effect of UV-B rays alone.

Most of the COVID management concepts remain as true as in the first days of the pandemic, such as handwashing with soap and social distancing, though some have changed such as the notion of the virus mainly transmitted through droplets whereas evidence showed it can linger suspended in aerosol.

The researchers, from UC Santa Barbara, Oregon State University, University of Manchester and ETH Zurich. examined the well-known vulnerability of SARS-CoV-2 to sunlight. They concluded that exposure to UV-B radiation doesn’t completely account for its inactivation by sunlight.

The idea that an additional mechanism might be in play came when the team compared data from a July 2020 study that reported rapid sunlight inactivation of SARS-CoV-2 in a lab setting, with a theory of coronavirus inactivation by solar radiation that was published just a month earlier.

“The theory assumes that inactivation works by having UV-B hit the RNA of the virus, damaging it,” said lead author Paolo Luzzatto-Fegiz, UC Santa Barbara mechanical engineering professor. “Judging from the discrepancies between the experimental results and the predictions of the theoretical model, however, the research team felt that RNA inactivation by UV-B “might not be the whole story.”

Experimentation showed 10-20 minutes to reach virus inactivation—much faster than the theory’s predictions. Viruses in simulated saliva were inactivated over eight times faster when irradiated by UV-B lamps than would have been predicted by the theory, while those cultured in a complete growth medium before exposure to UV-B were inactivated over three times faster. In order to match theory, SARS-CoV-2 would then have greater UV-B sensitivity than any currently known virus.

“The theory predicts that inactivation should happen an order of magnitude slower,” Prof Luzzatto-Fegiz said.

There might be another mechanism involved besides UV-B effects on RNA; such as the synergistic effect of the less energetic UV-A rays.

“People think of UV-A as not having much of an effect, but it might be interacting with some of the molecules in the medium,” he said. Such reactive intermediate molecules could be hastening virus inactivation, a concept known in wastewater treatment and other environmental science fields.

“So, scientists don’t yet know what’s going on,” Luzzatto-Fegiz said. “Our analysis points to the need for additional experiments to separately test the effects of specific light wavelengths and medium composition.”

These findings could help develop ways to control the virus with widely available UV-A and UV-B sources. Sources which emit UV-C, which is otherwise blocked by the atmosphere, has proven effective in certain settings such as air filtration but its high energy limits applications and raises safety concerns.

“UV-C is great for hospitals,” said co-author Julie McMurry. “But in other environments—for instance kitchens or subways—UV-C would interact with the particulates to produce harmful ozone.”

Co-author and UCSB mechanical engineering professor Yangying Zhu added that UV-A’s possible effectiveness meant that inexpensive UV-A LEDs many times brighter than UV-A in normal sunlight could be used. UV-A could be used more for air filtration for example, but the specifics of each setting warrant consideration, said co-author Fernando Temprano-Coleto.

Source: Medical Xpress

Journal information: Paolo Luzzatto-Fegiz et al. UVB Radiation Alone May Not Explain Sunlight Inactivation of SARS-CoV-2, The Journal of Infectious Diseases (2021). DOI: 10.1093/infdis/jiab070