Day: November 22, 2021

Gaps and Gender Differences in Diabetes Management

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A new study from the University of Eastern Finland revealed there are gaps and gender differences in diabetes management. Type 2 diabetes is often accompanied by elevated cholesterol levels, but many patients do not receive appropriate cholesterol-lowering treatment, according to the study, which appears in Scientific Reports.

Type 2 diabetes is a major risk factor of cardiovascular diseases, such as coronary artery disease and heart failure, as well as premature death. To prevent or at least delay complications, regular health care visits and good control of blood glucose, low-density lipoprotein cholesterol (LDL-C) and other risk factors are needed.

The present study shows that LDL-C control and statin prescriptions remain suboptimal in clinical practice – despite guidelines that consistently recommend treating elevated LDL-C with statins at moderate- to high-intensity. The study drew on electronic health records of 8592 type 2 diabetes patients between 2012 and 2017.

Analysing LDL-C values over time, researchers identified four groups with different trajectories. Most patients (86%) had relatively stable LDL-C values at moderate levels and only a few patients showed a significant increase (3%) or decrease (4%) during the follow-up. However, the second-largest group (8%) consisted of patients with alarmingly “high-stable” LDL-C levels at around 3.9 mmol/L.  

The “high-stable” LDL-C group had the lowest proportions of patients on moderate- and high-intensity treatment as well as any statin treatment. The proportion of patients receiving any statin treatment even decreased from 42% to 27% among men, and from 34% to 23% among women between 2012 and 2017.

“We observed significant gender differences in care processes and outcomes,” said Laura Inglin, Early Stage Researcher, University of Eastern Finland. “In all the trajectory groups, women had significantly higher average LDL-C levels and received any statin treatment and high-intensity treatment less frequently than men.”

Significant differences were seen in terms of longitudinal care processes, outcomes, and treatments, pointing out gaps in current diabetes management. Efforts to control LDL-C should be increased – especially in patients with continuously elevated levels – by initiating and intensifying statin treatment earlier and re-initiating the treatment after discontinuation if possible.

Source: University of Eastern Finland

Placental Cells Could Help Growth-restricted Babies

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Healthy placenta from mothers of healthy newborns could potentially reduce brain injury in growth-restricted babies, University of Queensland researchers suggest. UQ’s Dr Julie Wixey said the study found stem cells sourced from a healthy placenta may reduce damaging inflammation in these babies after only three days.

“There is currently no treatment to protect the brains of a growth-restricted baby,” Dr Wixey said. “Up to 50% of them have long term issues ranging from mild learning and behavioural disorders all the way through to cerebral palsy. We know there’s inflammation in the brain and it doesn’t cease once these babies are born.  

“Our study has shown we could reduce inflammation and ongoing brain injury by treating these newborns on the day they’re born using a combination of two types of stem cells – endothelial colony forming cells and mesenchymal stromal cells – isolated from a healthy human placenta.”

About 32 million growth-restricted babies are born around the world each year. Many of them did not receive enough nutrients and oxygen from the placenta.

“Our research has found after just three days, the combination stem cell therapy not only reduced inflammation but also, importantly, appeared to repair damaged blood vessels in the brain in animal models,” Dr Wixey said. “We’re really excited by the outcomes of this study and we hope it’ll improve these babies’ lives long term.”

Dr Jatin Patel, who co-invented the stem cell harvesting technology, said: “This has been a fantastic collaborative study and demonstrates the exciting potential of stem cell therapy in the near future in treating unwell babies.

“We are now working towards scaling up our patented stem cell technology, that will result in greater quantities of cells to drive and expand the preclinical animal studies with the aim of progressing towards a human trial.”

The study was published in npj Regenerative Medicine. The researchers will now investigate the longer-term outcomes of the combination stem cell treatment.

Source: University of Queensland

Is Malaria Behind Low COVID Burden in Sub-Saharan Africa?

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In both rural and urban areas of Mali, there was a high seroprevalence of COVID, but a low burden of symptomatic disease, a researcher said in a presentation at the American Society of Tropical Medicine & Hygiene (ASTMH) virtual meeting. This could be tentatively attributable to the prevalence of malaria.

From spring to autumn (northern hemisphere) 2020, the seropositivity rate among those with self-reported symptoms jumped from 20.8% to 48.6%, while those reporting symptoms but were seronegative also increased from 9.8% to 49.3% in the cohort, reported John Woodford, MD, of the National Institute of Allergy and Infectious Diseases (NIAID).

However, he said that during March to July, the COVID-attributable fraction was 11%, and from August to December, the COVID-attributable fraction was 0%.

In addition, the percentage of seropositive people with symptomatic illness over the background illness reporting rate was 0%-11%, well below the age-adjusted 33% of cases expected, based on the US case rate.

Only three hospitalisations occurred throughout spring and autumn 2020, also far below the expected 11-30 hospitalisations, and no deaths.

Dr Woodford pointed to “a lot of anecdotal reports that there was a limited disease burden in Mali.”

“It was repeated over and over again for a variety of sub-Saharan African settings, but there’s very limited data to back this up,” he clarified.

His group performed a serosurvey of urban and rural areas of Mali, using two-antigen ELISA qualified for use in that country. Participants were also given a questionnaire asking about self-reported symptoms, medical, and social history.

Overall, they obtained serosurvey data from 3671 participants at four sites, who were a median age of 15. They noted the dates of the symptom questionnaires were March to July 2020 and August to December 2020.

No symptoms were independently associated with seropositivity, Dr Woodford said. There was no greater change of seropositive people being absent from work, seeking medical care, or being hospitalised compared to seronegative people in the cohort during spring. However they were more likely to seek medical care in the autumn than seronegative people (63.4% vs 45.9%, respectively).
The second follow-up visit was during the malaria season, when there was a high percentage of seropositivity, but the proportion of those with self-reported symptoms was comparable with background illness. MedPage Today asked Dr Woodford as to whether malaria infection might have a protective effect, to which he responded: “That is a question much larger than me, and much larger than COVID.” He added that the rural areas in their study had higher rates of malaria than the urban sites, while the reverse was true for COVID.

“What that means, I’m not sure, but there’s certainly a blunt association there,” Dr Woodford noted.

He referenced a recent study of hospitalised patients in Uganda, which found that patients with low previous malaria exposure had higher risk of severe or critical COVID clinical presentation compared to those with high previous exposure, even among patients with no comorbidities.

However, Dr Woodford explained that without a much larger sample size and more accurate tests such as PCR, there was no way to tease out asymptomatic versus symptomatic infections.
“You’d need a very large population to look at symptomatic versus asymptomatic in seropositive patients,” he said. “Logistically, it’s a very challenging study to put together.”

Source: MedPage Today

Psychedelic Treatments for Mental Illness a Step Closer

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To find better solutions to mental illness, a Virginia Tech researcher has found that long-banned psychedelic drugs can treat several forms of mental illness and, in mice, have achieved long-lasting results from just one dose.

Using a process his lab developed in 2015, Professor Chang Lu is helping his collaborators study the epigenomic effects of serotonergic hallucinogens, commonly known as psychedelics.

Their findings, published in Cell Reports, give insight into how psychedelic substances like psilocybin, mescaline, LSD, and similar drugs may relieve symptoms of addiction, anxiety, depression, and post-traumatic stress disorder. The drugs seem to work faster and last longer than current medications, all with fewer side effects.

Prof Lu’s genomic analysis allows researchers to use very small samples of tissue, down to hundreds to thousands of cells, and draw meaningful conclusions from them. Older processes require much larger sample sizes, so Prof Lu’s approach enables the studies using just a small quantity of material from a specific region of a mouse brain.

And looking at the effects of psychedelics on brain tissues is especially important.

While researchers can do human clinical trials with them, taking blood and urine samples and observing behaviours, Prof Lu said. “But the thing is, the behavioural data will tell you the result, but it doesn’t tell you why it works in a certain way,” he said.

But looking at molecular changes in animal models, such as the brains of mice, allows scientists to peer into what Prof Lu calls the black box of neuroscience to understand the biological processes at work. While the brains of mice are very different from human brains, Prof Lu said there are enough similarities to make valid comparisons between the two.

VCU pharmacologist Javier González-Maeso has made a career of studying psychedelics, which had previously been banned since the 1960s.
Other research, primarily on psilocybin, a substance found in more than 200 species of fungi, González-Maeso said psychedelics have shown promise in alleviating major depression and anxiety disorders. “They induce profound effects in perception,” he said. “But I was interested in how these drugs actually induce behavioral effects in mice.”

To explore the genomic basis of those effects, he teamed up with Prof Lu.

In the joint study, González-Maeso’s team used 2,5-dimethoxy-4-iodoamphetamine, or DOI, a drug similar to LSD, administering it to mice that had been trained to fear certain triggers. Prof Lu’s lab then analysed brain samples. They discovered that the epigenomic variations were generally more long-lasting than the changes in gene expression, thus more likely to link with the long-term effects of a psychedelic.

After one dose of DOI, the mice that had reacted to fear triggers no longer responded to them with anxious behaviours. Their brains also showed effects, even after the substance was no longer detectable in the tissues, Prof Lu said.

As well as the science, it’s personal for him too, saying: “My older brother has had schizophrenia for the last 30 years, basically. So I’ve always been intrigued by mental health,” Lu said. “And then once I found that our approach can be applied to look at processes like that – that’s why I decided to do research in the field of brain neuroscience.”

González-Maeso said research on psychedelics is still in its early stages, and there’s much work to be done before treatments derived from them could be widely available.

Source: Virginia Tech

Effective Psoriasis Treatment Could be a ‘TWEAK’ Away

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A key protein called TWEAK damages skin cells in psoriasis patients, according to a new study in mice and with human skin cells, and targeting TWEAK may help control the disease.

Although there are effective treatments for psoriasis, an autoimmune disease that shows up as patches of red, inflamed skin and painful, scaly rashes, not everyone responds to these therapies – and for many, the relief is temporary.

“These therapies don’t reduce disease by 100 percent, and they don’t cure the disease” says La Jolla Institute for Immunology (LJI) Professor Michael Croft, PhD. “And if you take patients off those drugs, the disease almost always comes back.”

“We think TWEAK might be considered a potential target for the treatment of psoriasis,” said first author Rinkesh Gupta, PhD, a postdoctoral fellow at LJI. “It’s good to have this chance to develop a new therapeutic option.”

The findings build on the lab’s earlier research showing that TWEAK can interact with keratinocytes, the most common type of skin cell. By investigating TWEAK-deficient mice, the researchers found that TWEAK is a driver of inflammation in a model of psoriasis.
The new study, published in Science Immunology, shows that TWEAK does not work alone; it teams up with two other proteins, tumour necrosis factor (TNF) and interleukin-17 (IL-17), to trigger inflammation. These three seem to control inflammatory molecule production and the expression of additional inflammation-associated proteins in patients with psoriasis.

“The fact that they work together suggests the disease is essentially driven by all three of those particular proteins at the same time,” explained Prof Croft. “The primary implication is that TWEAK will also be a good drug target. as has already been proven for TNF and IL-17.”

The researchers tested this idea with a mouse model of psoriasis to compare how well a TWEAK-inhibitor measured up to therapies inhibiting IL-17 or TNF.

“If you inhibit TWEAK from working on its receptor on keratinocytes, you get the same therapeutic effect as when you inhibit TNF or IL-17,” said Dr Gupta. A particularly encouraging aspect of this finding since TNF and IL-17 are both FDA-approved drug targets for psoriasis.

Prof Croft thinks TWEAK inhibitors have potential as therapies for many types of skin diseases. “We think TWEAK is involved in skin inflammation in general,” he said.

His lab is now investigating the role of TWEAK in atopic dermatitis, and while a distinct disease from psoriasis, they do have a few things in common – and there are not as many good treatments for atopic dermatitis.

“There’s certainly a lot of room for improvement in treatment of atopic dermatitis patients,” he said.

Source: La Jolla Institute for Immunology