Publisher Health

Researchers have discovered a new approach for using visible-light to structurally modify bioactive molecules in chemical reactions, providing a possible sustainable alternative to traditional methods that could be used in the design and production of new medicines.
Scientists from the University of Nottingham’s School of Chemistry, based at the GSK Carbon Neutral Laboratory are exploring the development of new sustainable ways to make chemicals by exploiting the green and inexhaustible energy of visible-light, as an alternative to traditional chemical methodologies requiring the use of toxic reagents and heavy metals. Their latest research ‘Visible Light-driven conjunctive olefination’ has been published today in Nature Chemistry.
The invention of novel drugs and agrochemicals often involves investigation of several structural analogues to refine their bioactivity or other key chemical properties. Chemists often access these analogues through chemical modification of complex bioactive molecules, a process defined as “late-stage functionalisation.” However, only a fraction of the possible analogues is accessible through traditional chemical methods, which often use toxic or expensive reagents and catalysts. Many catalysts rely on using heavy metals which are well-known environmental pollutantsdue to their toxicity, persistence in the environment, and bioaccumulative nature.
Late-stage functionalisation is an important tool for drug design. This research offers a new approach that is very modular, practical and sustainable. This new approach will significantly expand the structures available to scientists and has the potential for extensive application in the design and production of new drugs.
Dr Mattia Silvi led the research and said: “We have now discovered a fundamentally new approach to structurally modify bioactive molecules handling them as practically as if they were Lego building blocks. Our approach exploits the sustainable energy of visible light, avoids the use of heavy metals and has general applicability, thereby opening access to exceptional room for the design of new derivatives. The results of our study could significantly impact the way scientists design new analogues of complex bioactive molecules, providing a new a new powerful tool for the development of the medicines of tomorrow.”
“This research also further demonstrates the exceptional potential of the use of visible-light energy in organic synthesis, that has impressively grown in the last decade, and is expected to continue to grow in the future, thereby opening new avenues for sustainable chemistry.”
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A House committee has requested documents related to the firm’s advice to drug makers and potential conflicts of interest with the F.D.A.In a new assault on the global consulting giant McKinsey & Company, Congress on Friday started an investigation into the firm’s role in the opioid crisis, sending a letter demanding records related to its “business practices, conflicts of interest and management standards.”The 12-page letter, which was sent by the House Committee on Oversight and Reform, asked for names of McKinsey clients in the health care industry as well as documents connected to its work with opioid manufacturers, distributors and retailers. The committee is also looking at how McKinsey’s consulting for drugmakers may conflict with work it has done for the Food and Drug Administration.By advising opioid makers and “the federal agency regulating their conduct,” McKinsey “may have had a significant negative impact on Americans’ health,” the committee said.The letter was signed by the committee’s chairwoman, Representative Carolyn B. Maloney of New York, who requested that McKinsey produce the documents by Nov. 19. McKinsey has a policy of not identifying its clients or the advice it gives.A spokesman for the firm on Friday said McKinsey had “received the committee’s letter and will engage directly with the committee regarding their requests.”This year, McKinsey agreed to pay all 50 states more than $600 million to settle investigations into how it had helped “turbocharge” opioid sales, focusing mostly on its work with Purdue Pharma, the maker of OxyContin. McKinsey did not admit any wrongdoing.The request on Friday follows a narrower one on Aug. 23, from a bipartisan group of six U.S. senators seeking records from the F.D.A. on its work with McKinsey at the same time that it was regulating opioid manufacturers, calling that relationship “a potential conflict of interest.” The senators asked for more information about the firm’s work with the F.D.A. division that approved certain classes of drugs, including prescription opioids.Representative Carolyn B. Maloney of New York has called for scrutiny of McKinsey’s ties to the F.D.A.Pool photo by Bill ClarkOxyContin and similar painkillers can be addictive and prone to abuse. From 1999 to 2019, nearly 500,000 people in the United States died of opioid overdoses, according to the Centers for Disease Control and Prevention.The House panel is seeking information on McKinsey’s “apparent failure to monitor and prevent harmful practices,” Ms. Maloney, a Democrat, wrote in the letter, addressed to the firm’s managing partner, Bob Sternfels.In the past several years, McKinsey has come under scrutiny from both Republicans and Democrats for a wide range of its consulting projects. In October 2018, Senator Elizabeth Warren, a Massachusetts Democrat, asked the firm for more information about its work in Saudi Arabia. Last year, Senator Marco Rubio, a Florida Republican, asked McKinsey to disclose the names of Chinese clients whose business might conflict with American national interests.The letter from Ms. Maloney was addressed to McKinsey’s managing partner, Bob Sternfels.no creditThe House committee is also seeking documents beyond McKinsey’s opioid work, citing instances when consultants may have helped companies increase drug prices or “block competition” from cheaper generic drugs.Also under scrutiny is McKinsey’s in-house hedge fund, the McKinsey Investment Office Partners, a pension fund and investment vehicle for partners that last year reported more than $31 billion in assets under management. The fund has held indirect investments in companies including its drugmaker clients. The committee wants an enumeration of all of the fund’s investments and a list of McKinsey employees who have done work with it since 2005.

The Times is hosting a live chat with reporters about the coronavirus vaccine and children. We’d like to hear your questions.Administering a Pfizer-BioNTech shot to a 13-year-old at a clinic in Orange, Calif., in August.Jae C. Hong/Associated PressThe Times is hosting a live audio conversation on Twitter about the coronavirus vaccine and children at 5 p.m. ET on Monday, Nov. 8. To tune in, follow @nytimes and look for a notification at the top of the Twitter app at that time. We also plan to share a recording of the conversation.Submit your questions below, and our reporters Apoorva Mandavilli and Tara Parker-Pope may address them during the chat.

Keen to do your bit for the environment? Cut back on sweets, pastries, fried foods and processed meat. According to a new study published this month, reducing these foods in our diet is not only better for our health but also the planet.
Australia and New Zealand households eat more discretionary and junk foods than recommended by dietary guidelines, contributing to food-related greenhouse gas emissions (GHGe) and other environmental impacts.
University of South Australia (UniSA) dietitian Sara Forbes, who led a review examining 20 studies on the environmental impacts of food consumption in both countries, says the findings highlight the need for more sustainable dietary choices.
According to a Federal Government report released in 2020, Australia emitted an estimated 510 metric tonnes of carbon dioxide, with food-related emissions accounting for 14.2 per cent of this total. The report found that the average Australian produces the equivalent of 19.7kg of carbon dioxide each day via their diets.
Another report from 2017 found that food waste comprises approximately six per cent of Australia’s GHGe, considering the water, energy and pesticides used in food production and packaging that ends up in landfill, where it releases even more methane as it decomposes.
Unlike New Zealand, current Australian Dietary Guidelines (ADG) do not consider environmental impacts of food and need to be updated, researchers say.

Blending experts from molecular genetics, chemistry and health sciences, researchers at the University of California San Diego have created a rapid diagnostic technology that detects SARS-CoV-2, the coronavirus that causes COVID-19.
The new SENSR (sensitive enzymatic nucleic acid sequence reporter), described in a paper published in the journal ACS Sensors, is based on CRISPR gene-editing technology that allows speedy detection of pathogens by identifying genetic sequences in their DNA or RNA.
Currently, many human pathogens are detected using a method known as real-time polymerase chain reaction. While highly accurate and sensitive, such diagnostics are time consuming and require specialized laboratory equipment, limiting their use to health and specialized facilities. SENSR is designed to simplify the SARS-CoV-2 detection process with a goal of eventual adaptation for in-home use.
While the Cas9 enzyme has been used extensively in CRISPR genetic engineering research, scientists have recently employed other enzymes such as the Cas12a and Cas13a for the development of highly accurate CRISPR-based diagnostics. Developed in a similar vein, SENSR is the first SARS-CoV-2 diagnostic to leverage the Cas13d enzyme (specifically a ribonuclease effector called “CasRx”).
The researchers believe that in order to maximize CRISPR’s capabilities and expand the genetics-based diagnostics pipeline, any Cas enzymes that can complement or supplement existing systems should be explored.
“CRISPR has significantly advanced our capabilities for rapid identification of infected individuals and offers point-of-care testing in low-resource settings that previously wasn’t possible,” said UC San Diego Biological Sciences Professor Omar Akbari, the study’s senior author. “SENSR further opens the toolbox for CRISPR diagnostic systems and will help detect emerging pathogens before they become pandemics.”
In developing SENSR, Akbari’s molecular genetics lab worked in conjunction with Professor Elizabeth Komives’ lab in the Department of Chemistry and Biochemistry (Division of Physical Sciences) to purify SENSR proteins and Rob Knight’s lab in the Department of Pediatrics (School of Medicine and Center for Microbiome Innovation) to test SARS-CoV-2 samples.

Titin is a “titanically large” protein — the largest in the human body — which enables elastic movements of our muscles, including the heart. Mutations in the titin gene (TTN) that impair this function are the most frequent cause of a heart muscle disease known as dilated cardiomyopathy (DCM), which is characterized by a weak pump function. However, it had not been known why TTN mutations cause the disease, that is, which pathomechanisms underlie DCM. A team of experts headed by Prof. Wolfgang Linke, Director of the Institute of Physiology II at the University of Münster, has gained ground-breaking insights into the pathomechanisms of DCM due to a TTN mutation, which have now been published in the journal Science Translational Medicine.
“DCM can have various causes but the most frequent one is a special type of TTN mutation called truncation” says project leader Wolfgang Linke. “In patients with such a TTN-truncating variant or TTNtv, one of the two TTN alleles is shortened, whereas the other allele usually is healthy.” Although TTNtv have been known to cause DCM for nearly a decade, it took until now to uncover the key pathomechanisms of the disease, “in what has easily been some six years of intense research on the topic,” Wolfgang Linke says.
Collaborating with the Heart and Diabetes Centre in Bad Oeynhausen, the team studied over 100 tissue samples from endstage failing human DCM hearts and discovered about 20% with a TTNtv. By measuring the content of normal titin proteins, the scientists found that patient hearts with a TTNtv contained less normal titin than both DCM hearts without a TTNtv and nonfailing hearts from organ donors. The loss of normal titin protein caused a reduction in the number of contractile units, explaining the reduced contractile force of TTNtv-DCM hearts. “Although the healthy TTN allele produces even more normal titin than usual, it cannot compensate for the lack of a second healthy allele,” Wolfgang Linke explains.
For the first time, the team was also able to demonstrate that TTNtv patient hearts contain truncated titin proteins. Wolfgang Linke adds: “We showed that these truncated proteins are useless, because they are not incorporated into the contractile units of the cardiac muscle cells.” Instead, the truncated proteins are collected in intracellular blobs or aggregates. “Just as in neurodegenerative diseases such as Alzheimer’s, these aggregated proteins could be toxic.” Fittingly, the research team also discovered that the heart muscle cells of patients with TTNtv-DCM have a problem with the intracellular protein quality-control system, which usually “cleans up” defective or aged proteins. This system appeared to be overwhelmed by the large amounts of truncated titin protein, and so did not function properly.
Wolfgang Linke is convinced that the “study breaks new ground in this field.” Next to elucidating the pathomechanisms, his team also suggested possible treatment strategies for affected patients. To this end, they used human cardiac muscle cell cultures obtained from TTNtv patient tissue reprogrammed into stem cells. “With the help of our collaborators in Göttingen, we could show that the cultured cells with a TTNtv displayed the same pathomechanisms as the TTNtv patient hearts, and that inhibition of the protein quality-control system worsened the situation. Importantly, cell cultures with a TTNtv developed less contractile force than healthy controls but gene editing using CRISPR-Cas9 repaired the mutation and rescued contractile force. Although genetic editing is not yet possible in this form in patients, our study shows that patients could, in principle, be cured using this approach,” Wolfgang Linke explains.
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A landmark study by Monash University researchers has found that moderate drinking of alcohol is associated with a reduced risk of cardiovascular disease and a lowering of mortality from all causes — when compared to zero alcohol consumption. The study in more than 18,000 people in the US and Australia over the age of 70 is the first to look at the heart health implications of alcohol intake.
Excess alcohol consumption is a leading contributor to the global burden of disease and a major risk factor for mortality. Yet, prior studies suggested that moderate alcohol consumption may be associated with a lower risk of cardiovascular disease (CVD) events.
This Monash University study, published in the European Journal of Preventive Cardiology is the first to investigate the risk of CVD events and mortality, from all causes, associated with alcohol consumption in initially healthy, older individuals.
Populations around the world are ageing. The Monash University- led ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial was a large-scale, long-term multi-centre, bi-national study of aspirin and health in older adults, with the purpose to discover ways to maintain health, quality of life and independence as we age.
This study, led by Dr Johannes Neumann, from the Monash University School of Public Health and Preventive Medicine, analysed data from almost 18,000 ASPREE participants — Australians and Americans mostly aged 70 years and older.
Participants in the study did not have prior CVD events, diagnosed dementia or independence-limiting physical disability. CVD events included coronary heart disease death, non-fatal myocardial infarction, fatal and non-fatal stroke, non-coronary cardiac or vascular death, and hospitalisation for heart failure. Information on alcohol consumption (days of drinking per week and average standard drinks per day) was assessed by self-reported questionnaire at baseline. The study excluded former alcohol consumers who may have stopped alcohol consumption for various health reasons, possibly introducing bias from reverse causality.

A new study in the Veterinary Record reveals that pets can be infected with the alpha variant of SARS-CoV-2, which was first detected in southeast England and is commonly known as the UK variant or B.1.1.7. This variant rapidly outcompeted pre-existing variants in England due to its increased transmissibility and infectivity.
The study describes the first identification of the SARS-CoV-2 alpha variant in domestic pets; two cats and one dog were positive on PCR test, while two additional cats and one dog displayed antibodies two to six weeks after they developed signs of cardiac disease. Many owners of these pets had developed respiratory symptoms several weeks before their pets became ill and had also tested positive for COVID-19.
All of these pets had an acute onset of cardiac disease, including severe myocarditis (inflammation of the heart muscle).
“Our study reports the first cases of cats and dogs affected by the COVID-19 alpha variant and highlights, more than ever, the risk that companion animals can become infected with SARS-CoV-2,” said lead author Luca Ferasin, DVM, PhD, of The Ralph Veterinary Referral Centre, in the UK. “We also reported the atypical clinical manifestations characterized by severe heart abnormalities, which is a well-recognised complication in people affected by COVID-19 but has never described in pets before. However, COVID-19 infection in pets remains a relatively rare condition and, based on our observations, it seems that the transmission occurs from humans to pets, rather than vice versa.”
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Allergists and pediatricians have recommended since 2017 that parents start to introduce peanut product around the time their child begins solid foods to prevent peanut allergy. A new study being presented at this year’s American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting reveals that early egg introduction is associated with decreased egg allergy.
“We examined infant feeding and food allergy data from birth to 6 years, collected by 2237 parent surveys in the Infant Feeding Practices Study II conducted by the CDC and US-FDA,” said Allergy and Immunology Fellow Giulia Martone, MD, ACAAI member and lead author of the study. 1379 participants had complete food allergy data to 6 years. “We found that children who hadn’t had egg introduced by 12 months were more likely to have egg allergy at 6 years.”
14 of 2237 surveys (0.6%) reported egg allergy at one year and 11 of 1379 surveys (0.8%) reported egg allergy at 6 years. Children with egg allergy at 1 year-old and 6 years-old had less frequent egg consumption at 5, 6, 7 and 10 months of age.
“Egg allergy is the second most common food allergy throughout the world,” said Xiaozhong Wen, MD, PhD, senior author and principal Investigator of the study. “Current evidence suggests that early introduction of egg during infancy, followed by consistent and frequent feedings, seems protective against development of egg allergy. We are still investigating optimal timing of infant egg introduction and frequency of feeding.”
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Using cutting-edge genetic engineering, researchers have developed a model to study hereditary kidney disease with the help of tropical frogs. The method allows them to collect large amounts of data on anomalies, which can then be analyzed using artificial intelligence. The research opens up new opportunities in the search for new treatment approaches for the hitherto incurable disease.
Frogs’ anatomy and organ function are strikingly similar to those of humans. An international team led by Soeren Lienkamp, professor at the Institute of Anatomy at UZH, has now exploited this similarity by using a tiny tropical frog called Xenopus tropicalis to model human genetic diseases. The researchers focused on polycystic kidney disease, a congenital and currently incurable form of progressive kidney deterioration, and replicated it in frogs.
Observing disease processes in real time
Using CRISPR/Cas9, a methodology for turning off gene function, the scientists targeted genes known to play a role in cystic kidney disease. “Our novel frog models develop cysts in the kidneys within only a few days, allowing us to observe these disease processes in real time for the first time,” says lead author Thomas Naert. While most genetic studies are performed on mice, frogs have features that make them well-suited for larger scale studies. “One frog couple can produce hundreds or even thousands of eggs,” says Naert. “That’s why you see such large numbers of tadpoles in the Swiss lakes in springtime.” Similarly, in the lab large numbers of Xenopus tropicalis tadpoles can be manipulated to develop cystic kidney diseases.
AI analyzes data from light-sheet microscopy
To analyze the data from such a large number of animals, the team employed a technique called light-sheet microscopy, which produced a 3D reconstruction of the entire tadpole and all its organs. Much like magnetic resonance imaging, light-sheet techniques make it possible to see through tissues in tadpoles to find disease-affected organs. The collected data was then processed using artificial intelligence to allow rapid, automated assessment of disease. “While it would normally take my team several days or even weeks to analyze data from hundreds of tadpoles, artificial intelligence can now do this task in a matter of hours,” says Lienkamp.
The findings from frog models analyzed in this way provide new insights into the early processes of polycystic kidney disease. These insights will form the basis for developing new treatment approaches for affected patients.
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