Tag: 12/5/22

Reduce Blood Sugar ASAP After Diabetes Diagnosis, Study Suggests

Image source: Pixabay CC0

Findings from new research published in Diabetes, Obesity and Metablism suggest that people with type 2 diabetes may need to reduce their blood sugar levels sooner after diagnosis than previously thought, to prevent major cardiovascular events such as heart attacks.

The University of Surrey study Surrey suggests that achieving glycaemic control within the first year of diagnosis reduces the incidence of major cardiovascular events. Additionally, the team found that the greater the variation in blood levels 12-months after diagnosis, the more likely a patient was to experience dangerous cardiovascular events.

Dr Martin Whyte, co-author of the study and Reader in Metabolic Medicine at the University of Surrey, said: “The conventional wisdom has been to slowly and steadily treat type 2 diabetes with diet and medicine dose-escalation over years – the period over which it took people to reduce their sugar levels after diagnosis was thought less important for major vascular protection. However, our observational study suggests that getting blood levels under control quickly — within the first 12 months after diagnosis — will significantly help reduce cardiovascular events.”

Type 2 diabetes is a common condition that results in the level of sugar in the blood becoming too high. The condition is linked to obesity or a family history of type 2 diabetes and can increase a person’s risk of getting serious health conditions.

The University of Surrey’s study used Royal College of General Practitioners’ Research and Surveillance Centre database to perform a comprehensive examination of glycaemic control achieved within the first year of diagnosis and subsequent blood sugar level variability with cardiovascular disease incidents.

Source: University of Surrey

How Do You Do, Fellow Kids? Making Anti-vaping Messaging Work

Vaping with an e-cigarette
Photo by Toan Nguyen on Unsplash

Effective anti-vaping advertisements geared to teens have the greatest impact when they emphasise the adverse consequences and harms of vaping e-cigarettes, use negative imagery, and avoid memes, hashtags and other ‘teen-centric’ communication styles, according to a first-of-its-kind study by researchers in the journal Tobacco Control.

The researchers also found that certain messaging content currently being used, especially sweets and flavour-related imagery, increases the appeal of vaping and should be avoided when designing prevention messages.

“E-cigarettes and vaping have become a major public health concern, with nicotine addiction and other harmful outcomes looming large for youth,” said Seth M. Noar, PhD, the paper’s corresponding author and UNC Lineberger professor. “The percentage of teens vaping increased from about 5% in 2011 to over 25% in 2019,” Prof Noar said. “That is an alarming trend, making an understanding of effective vaping prevention messages especially urgent.”

Since the introduction of e-cigarettes, numerous US health departments have created their own anti-vaping messaging geared to teens, as have national health organisations such as the US Food and Drug Administration and Centers for Disease Control and Prevention.

The online study asked 1501 teens to rate seven randomly selected vaping prevention ads from a pool of more than 200 ads. Vaping prevention ads that clearly communicated the health harms of vaping, or compared vaping to cigarette smoking, were comparatively more effective. Neutral or less personally relevant content, such as referencing the environmental impact of vaping or the targeting of youth by the tobacco industry, was less impactful.

“Although we anticipated that vaping prevention ads with neutral or pleasant imagery would not be as effective, we were alarmed to find that flavour-related messages actually heightened the attractiveness of vaping,” said Marcella H. Boynton, PhD, first author

“In retrospect, it stands to reason that by reminding teens about pleasurable aspects of e-cigarettes, even within the context of a prevention ad, we run the risk of doing harm. Notably, we found that flavour-related prevention ad content was associated with vaping appeal among both users and non-users of e-cigarettes, which is a good reminder of how much candy and fruit flavours in e-cigarettes have driven the youth vaping epidemic.”

The researchers hope to next investigate the effects of other types of anti-vaping ads on a wide range of audiences. They also are developing a series of messages and a companion website to test the ability of a text message-driven intervention to reduce youth vaping. In that regard, Prof Noar noted that “We have been developing our own evidence-based messages based on the latest science about the harms of vaping. Our messaging approach has been greatly influenced by the insights generated by this study.”

The study used UNC’s Vaping Prevention Resource, a website designed to provide practitioners, researchers and communities with vaping prevention media content from around the world, as well as strategies and resources for youth vaping prevention. It is the largest repository of free, open-access vaping prevention materials, all available for download at https://vapingprevention.org/.

Source: UNC Lineberger Comprehensive Cancer Center

Steroids after Severe COVID Reduces One-year Mortality by 51%

Photo by Stephen Andrews on Unsplash

Researchers have shown that severe inflammation during hospitalisation for COVID increases post-recovery mortality risk by 61% – but this risk is reduced again by 51% if anti-inflammatory steroids are prescribed upon discharge. We need to think of COVID as a potentially chronic disease that requires long-term management, argue the authors, whose results are published in Frontiers in Medicine.

Evidence continues to gather that ‘long COVID’, that is, continued negative health impacts months after apparent recovery from severe COVID, is an important risk for some patients. For example, researchers showed last December that hospitalised patients who seemingly recovered from severe COVID run more than double the risk of dying within the next year, compared to those with only mild COVID or who never had COVID.

Now, the same research team shows that among patients hospitalised for COVID who seemingly recovered, severe systemic inflammation during their hospitalisation is a risk factor for death within one year.

“Here we show that the stronger the inflammation during the initial hospitalisation, the greater the probability that the patient will die within 12 months after seemingly ‘recovering’ from COVID.”

Professor Arch G Mainous III

“COVID is known to create inflammation, particularly during the first, acute episode. Our study is the first to examine the relationship between inflammation during hospitalisation for COVID and mortality after the patient has ‘recovered’,” said first author Professor Arch G Mainous III at the University of Florida Gainesville.

“Here we show that the stronger the inflammation during the initial hospitalisation, the greater the probability that the patient will die within 12 months after seemingly ‘recovering’ from COVID.”

Prof Mainous and colleagues analysed electronic health records of 1207 adults hospitalised with COVID in 2020 or 2021 within the University of Florida health system, with at least a one year follow-up after discharge. As a proxy for the severity of systemic inflammation during hospitalisation, they used a common and validated measure: C-reactive protein (CRP), secreted by the liver in response to a signal by active immune cells.

Widespread inflammation in the body

As expected, the blood concentration of CRP during hospitalisation was strongly correlated with the severity of COVID: 59.4mg/L for patients not needing supplemental oxygen, 126.9 mg/L for those who needed extra oxygen without mechanical ventilation, and 201.2 mg/L for the most severe cases, who required ventilation through a ventilator or through ECMO.

After correcting for risk factors, patients with the highest CRP concentration measured their during their hospital stay had a 61% greater risk of all-cause mortality within one year of discharge than patients with the lowest CRP concentration.

Prof Mainous said: “Many infectious diseases are accompanied by an increase in inflammation. Most times the inflammation is focused or specific to where the infection is. COVID is different because it creates inflammation in many places besides the airways, for example in the heart, brain, and kidneys. High degrees of inflammation can lead to tissue damage.”

Importantly, the authors showed that the increased all-cause mortality risk associated with severe inflammation was reduced again by 51% if the patient was prescribed anti-inflammatory steroids after their hospitalisation.

These results mean that the severity of inflammation during hospitalisation for COVID can predict the risk of subsequent serious health problems, including death, from ‘long COVID’. They also imply that current recommendations for best practice may need to be changed, to include more widespread prescription of orally taken steroids to COVID patients upon their discharge.

COVID as a chronic disease?

The authors propose that COVID should be seen as a potentially chronic disease.

“When someone has a cold or even pneumonia, we usually think of the illness being over once the patient recovers. This is different from a chronic disease, like congestive heart failure or diabetes, which continue to affect patients after an acute episode. We may similarly need to start thinking of COVID as having ongoing effects in many parts of the body after patients have recovered from the initial episode,” said Prof Mainous.

“Once we recognise the importance of ‘long Covid’ after seeming ‘recovery’, we need to focus on treatments to prevent later problems, such as strokes, brain dysfunction, and especially premature death.”

Source: Frontiers

A Blindness Gene That Also Increases Intelligence

DNA repair
Source: Pixabay/CC0

A new study published in Brain shows that a genetic mutation which causes blindness in humans also increases intelligence, possibly through an increase in synaptic activity between the very same neurons damaged by the mutation.

The present study came about when Professors Tobias Langenhan and Manfred Heckmann, came across a paper on a mutation that damages a synaptic protein. The mutation caused patients to go blind, but then doctors noticed that the patients were also of above-average intelligence, something which piqued the two neurobiologists’ interest. “It’s very rare for a mutation to lead to improvement rather than loss of function,” said Prof Langenhan.

The two neurobiologists have been using fruit flies to analyse synaptic functions for many years. “Our research project was designed to insert the patients’ mutation into the corresponding gene in the fly and use techniques such as electrophysiology to test what then happens to the synapses. It was our assumption that the mutation makes patients so clever because it improves communication between the neurons which involve the injured protein,” explained Prof Langenhan. “Of course, you can’t conduct these measurements on the synapses in the brains of human patients. You have to use animal models for that.”

“75 per cent of genes that cause diseases in humans also exist in fruit flies”

Professor Tobias Langenhan

First, in collaboration with Oxford researchers, the scientists showed that the fly protein called RIM looks molecularly identical to that of humans. This was essential in order to be able to study the changes in the human brain in the fly. In the next step, the neurobiologists inserted the genetic mutation into flies. They then took electrophysiological measurements of synaptic activity. “We actually observed that the animals with the mutation showed a much increased transmission of information at the synapses. This amazing effect on the fly synapses is probably found in the same or a similar way in human patients, and could explain their increased cognitive performance, but also their blindness,” concludes Professor Langenhan.

The scientists also found out how the increased transmission at the synapses occurs: the molecular components in the transmitting nerve cell that trigger the synaptic impulses move closer together as a result of the mutation effect and lead to increased release of neurotransmitters. A novel method, super-resolution microscopy, was one of the techniques used in the study. “This gives us a tool to look at and even count individual molecules and confirms that the molecules in the firing cell are closer together than they normally are,” said Prof Langenhan.

“The project beautifully demonstrates how an extraordinary model animal like the fruit fly can be used to gain a very deep understanding of human brain disease. The animals are genetically highly similar to humans. It is estimated that 75% of the genes involving disease in humans are also found in the fruit fly,” explained Professor Langenhan, pointing to further research on the topic: “We have started several joint projects with human geneticists, pathologists and the team of the Integrated Research and Treatment Center (IFB) Adiposity Diseases; based at Leipzig University Hospital, they are studying developmental brain disorders, the development of malignant tumours and obesity. Here, too, we will insert disease-causing mutations into the fruit fly to replicate and better understand human disease.”

Source: Universität Leipzig

Tumours Use Lactate to Bully Surrounding Cells into Helping Them

Cancer-associated fibroblasts surrounding a prostate tumour. Credit: Moscat/Diaz-Meco labs.

Some tumours can force neighbouring cells into supporting cancer growth by releasing lactate into their local environment, according to a study published in Cell Reports. The findings could lead to drugs that target that defence mechanism to help cancer patients ؘ– and also boost a current class of cancer drugs.

In the study, the researchers determined how developing tumours recruit nearby cells called fibroblasts to work as their enablers. Fibroblasts form part of the stroma, organs’ connective tissue, and normally have important repair and maintenance functions. But cancer-associated fibroblasts (CAFs) acquire properties that allow them to assist tumours in ways that make the tumours more malignant and harder to kill.

The researchers also discovered that PARP-1 inhibitors, a widely used class of cancer drugs, mimic one of the key steps in CAF recruitment, and can hamstring their own effectiveness by inadvertently switching local fibroblasts to this cancer-enabling mode.

“Future therapeutics that block this cancer-associated state of fibroblasts might be useful on their own or as a way to improve the effectiveness of PARP-1 inhibitors,” said study co-senior author Dr Maria Diaz-Meco.

Dr Diaz-Meco collaborated in the study with the laboratory of co-senior author Dr Jorge Moscat.

Developing tumours are known to often modify their local environments for their own survival and growth. Cancer-associated fibroblasts are a central component of the tumour microenvironment in prostate, lung, colon and other cancer types. Targeting these cells is therefore seen as a promising complementary approach to standard cancer treatment—and one that could work very broadly against cancers of different cellular and genetic origins.

“Cancer-associated fibroblasts support tumour growth by providing growth factors and essential metabolites to the tumour, by fending-off anti-tumour immune cells, and in many other ways,” Dr. Dr Moscat said. “The result is a tumour that is more malignant and treatment-resistant.”

Several years ago, the researchers discovered that a protein called p62, produced in fibroblasts, normally suppresses the CAF state, though many tumours find a way to restore this state by reducing fibroblast p62 production. In the new study, they showed that tumours achieve this by secreting high levels of an organic compound called lactate, also known as lactic acid.

Lactate is a normal by-product of certain energy-production processes in cells, which are often hyperactive in tumours. In experiments with prostate cancer cells, the researchers detailed the molecular chain of events by which tumour-secreted lactate disrupts the normal metabolism of fibroblasts, leading to reduced p62 gene activity and the activation of the tumour-enabling CAF state.

The finding is significant because it illuminates a major cancer-promoting pathway, which in principle can be targeted with future drugs as a standalone or add-on treatment strategy.

A second, surprising finding was that a key step leading from tumour lactate secretion to fibroblast p62 suppression turned out to be the inhibition of a DNA-repair enzyme called PARP-1, which has the same effect as PARP-1 inhibitors – suggesting that these drugs might be working partly against themselves by creating a more tumour-friendly microenvironment.

In vitro and animal testing confirmed that the PARP1 inhibitor olaparib does reduce p62 in fibroblasts, and pushes them into the CAF state, in turn increase tumours’ resistance to the drug’s primary cancer-killing effect.

Thus, the researchers emphasised, future treatments that reprogram CAF cells to the non-cancer state or prevent their development might greatly enhance PARP1 inhibitors’ anti-tumour effectiveness.

“We’re now studying several potential CAF-blocking therapeutics in our labs,” Dr Moscat said.

Source: Weill Cornell Medical College