Tag: 15/7/22

Categories : COVIDTags :

Activities That Changed During the Pandemic – and Didn’t Change Back

On By ModernMedia
Photo by Julian Jagtenberg on Pexels

A new analysis describes how people in the UK shifted the amount of time they spent on various activities over various stages of pandemic restrictions and shifted to online versus in-person settings. The findings were published in the open-access journal PLOS ONE.

When the COVID pandemic began, the U.K. joined many countries in introducing restrictions on people’s movement and social activities to mitigate viral spread. A growing body of research reveals how such restrictions have affected people’s lifestyles worldwide. This study examined how UK residents’ habits changed over time as different restrictions were implemented and lifted.

The researchers conducted six online surveys of UK residents between April 2020 and July 2021 and were ultimately able to follow 203 people who responded to multiple surveys. The surveys included questions about 16 different types of activities respondents participated in during different phases of the pandemic, such as journalling, shopping, and getting active, and whether they participated online or in person.

Statistical analysis of the responses showed that the biggest changes in terms of amount of time spent – as well as the biggest changes in online versus in-person participation – occurred for cultural activities, spending time with others, and travelling. Changes were most pronounced in March to June 2020, corresponding with the first lockdown period, when participation in all 16 activities decreased. The biggest shift from in-person to online participation occurred from March to October 2020, which included the first lockdown followed by relaxation of restrictions.

Cultural activities, such as going to museums, and group activities were the two categories that fell the most, and did not recover to pre-pandemic levels when UK restrictions were lifted on July 19, 2021. During the restrictions, participation was mostly online in these activities. Spending time with family was among the most robust, and remained mostly in-person, though supplemented by online interaction.

These findings could help policymakers understand the impact of their pandemic restrictions. In the future, the researchers plan to investigate how demographic factors, such as age and employment, may have affected the results, as well as long-term mental health implications of the lifestyle changes.

Professor Patty Kostova, leader of the study, added: “This longitudinal research study illustrated citizens’ resilience throughout the stages of the pandemic.”

Lan Li adds: “This longitudinal study determines the frequency and way of people doing activities from Spring 2020 to Summer 2021 during different phases of the COVID pandemic in the UK. The findings provide an invaluable insight into understanding how people in the UK changed their lifestyle, including what activities they do, and how they accessed those activities in light of the COVID pandemic and related public health policy implemented to address the pandemic.”

Source: ScienceDaily

Categories : Cardiovascular Disease Lab Tests and ImagingTags :

AI Picks up Incidental Pulmonary Embolism on Chest CT

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Photo by Kanasi on Unsplash

According to a study published in the American Journal of Roentgenology, an AI tool for detection of incidental pulmonary embolus (iPE) on conventional contrast-enhanced chest CT examinations had high false negative and moderate false positive rates for detection, and was even able to pick up some iPEs missed by radiologists.

“Potential applications of the AI tool include serving as a second reader to help detect additional iPEs or as a worklist triage tool to allow earlier iPE detection and intervention,” wrote lead investigator Kiran Batra from the University of Texas Southwestern Medical Center in Dallas. “Various explanations of misclassifications by the AI tool (both false positives and false negatives) were identified, to provide targets for model improvement.”

Batra and colleagues’ retrospective study included 2,555 patients (1,340 women, 1,215 men; mean age, 53.6 years) who underwent 3,003 conventional contrast-enhanced chest CT examinations between September 2019 and February 2020 at Parkland Health in Dallas, TX. Using an FDA-approved, commercially available AI tool (Aidoc) to detect acute iPE on the images, a vendor-supplied natural language processing algorithm was then applied to the clinical reports to identify examinations interpreted as positive for iPE.

Ultimately, the commercial AI tool had NPV of 99.8% and PPV of 86.7% for detection of iPE on conventional contrast-enhanced chest CT examinations (ie, not using CT pulmonary angiography protocols). Of 40 iPEs present in the team’s study sample, 7 were detected only by the clinical reports, and 4 were detected only by AI.

Noting that both the AI tool and clinical reports detected iPEs missed by the other method, “the diagnostic performance of the AI tool did not show significant variation across study subgroups,” the authors added.

Source: American Roentgen Ray Society

Categories : Immune SystemTags :

Rare Immune Cells are Key in Mounting a Defence Against Candida

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The oral fungal pathogen Candida albicans (red) produce hyphae that allow attachment of another fungus Candida glabrata (green). Yeast cells of Candida glabrata (green) adhere to Candida albicans hyphae (red) both in static culture (left, scanning electron microscopy) and under biofilm conditions of flow (right, confocal fluorescence microscopy).
Credit: Edgerton Lab, State University of New York at Buffalo

Candida, a distant cousin of baker’s yeast is notorious for causing various types of thrush that can be a major nuisance, but it can also lead to an invasive and occasionally fatal infection. In a study in the journal Nature Immunology, a research team uncovered a previously unknown defense mechanism employed by the immune system in fighting Candida infections.

In healthy individuals, Candida is present in the microbiome in the gut and on the skin. Normally, Candida is held in check by the immune system, but it can occasionally grow excessively, invading the lining of the mouth, the vagina, the skin or other parts of the body. In severe cases, it can spread to the bloodstream and from there to the kidneys. Such life-threating infections may occur in weakened immune systems. Antibiotics can also unleash local or invasive Candida eruptions by wiping out competing, beneficial bacteria.

Until now, the immune cells that got most of the credit for defending the body against Candida were the small, round lymphocytes of the T cell type, called TH17. These cells were also the ones to take the blame when this defence failed.

In the new study, postdoctoral fellow Dr Jan Dobeš, working together with colleagues in Abramson’s lab, discovered that a powerful commando unit of TH17 cells capable of fighting Candida cannot be generated without crucial early support from an entirely different contingent: a subset of rare lymphoid cells known as type-3 innate lymphoid cells, or ILC3, that express a gene called the autoimmune regulator, or Aire

The two groups of cells belong to the two different arms of the immune system, which, like normal soldiers and specialised ‘commando’ units, join forces against a common enemy. The Aire-ILC3s – part of the more ancient, innate arm – spring into action almost immediately upon encountering a threat – in this case, a Candida infection. The TH17s belong to the immune system’s more recent, adaptive arm, which takes several days or even weeks to respond, but which launches a much more targeted and potent attack than the innate one.

The scientists found that as soon as Candida starts infecting tissues, the Aire-ILC3s engulf the yeast whole, chop them up and display some of the yeast pieces on their surfaces. In this way, the bits are presented to the TH17s, a few of which are generally on call in the lymph nodes, ready for an infection alert. This kind of presentation instructs the specialised T cells to start dividing rapidly, soaring in number from a few lone commandos to several hundred or even thousands of Candida-specific fighters, capable of destroying the yeast at the sites of infection.

“We have identified a previously unrecognised immune system weapon that is indispensable for orchestrating an effective response against the fungal infection,” Abramson said.

Abramson became intrigued by Candida because it commonly leads to severe, chronic infections in people with a rare autoimmune syndrome caused by defects in the Aire gene. Abramson’s lab had conducted extensive studies of this gene, helping to clarify its role in preventing autoimmune disorders. That research, as well as studies by other scientists, had shown that Aire-expressing cells in the thymus instruct developing T cells to refrain from attacking the body’s own tissues. When Aire is defective, T cells fail to receive proper instructions, consequently causing widespread autoimmunity that wreaks havoc in multiple body organs. But one puzzle remained: Why would Aire-deficient patients suffering from a devastating autoimmune syndrome also develop chronic Candida infections?

While trying to complete the Aire puzzle, Dobeš and colleagues found that outside the thymus, Aire is also expressed in a small subset of ILC3s in the lymph nodes. The researchers then genetically engineered two groups of mice: One lacked Aire in the thymus, and the other group lacked it in the ILC3s in the lymph nodes. The first group developed autoimmunity but was able to successfully fight off Candida. In contrast, those in the second group, the ones lacking Aire in ILC3s, were without autoimmunity, but were unable to generate numerous Candida-specific TH17s. Consequently, they failed to effectively eliminate Candida infections. In other words, without Aire-expressing ILC3s, the specialised T cells needed for fighting Candida were not produced in sufficient numbers.

“We found an entirely new role for Aire, one that it plays in the lymph nodes – turning on a mechanism that increases the numbers of Candida-fighting T cells,” Dr Dobeš explained.

An Aire-ILC3 cell (green) “kisses” a Candida-fighting TH17 cell (red), telling it to start dividing (top row), but it ignores other T cells that do not specialize in fighting Candida (bottom row)

These findings open up new directions of research that in the future may help develop new treatments for severe Candida, and possibly for other fungal infections. The newly discovered mechanism might, for example, help produce large numbers of Candida-fighting T cells to be used in cell therapy. If scientists one day decode the signals by which Aire-ILC3s boost T cell proliferation, they might serve as the basis for new therapies.

Source: Weizmann Institute of Science

Categories : Medical Research & TechnologyTags :

Lasers Turn Neutrophils into Medical Microbots

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Streptococcus pyrogenese bound to human neutrophil
Streptococcus pyogenese bound to a human neutrophil. Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

Bordering on science fiction, medicinal microrobots could help physicians better treat and prevent diseases. But a serious problem is the synthetic materials they are made of trigger immune responses. Now, for the first time, researchers report in ACS Central Science that they achieved precise control neutrophils as a natural, biocompatible microrobot by using lasers. By getting the ‘neutrobots’ to perform multiple tasks, the researchers demonstrated they could one day deliver drugs to precise locations in the body.

Microrobots being developed for medical applications would need to be administered in injections or oral capsules to get them inside the body. But these microscopic objects are often found to trigger immune reactions in small animals, resulting in the the microrobots being ejected from the body before they can carry out their tasks. By using the body’s own cells, such as neutrophils, drugs could be delivered less invasively without provoking an immune response.

Neutrophils already naturally pick up nanoparticles and dead red blood cells and can migrate through blood vessels into adjacent tissues, so they are good candidates for becoming microrobots. Previously, researchers have guided neutrophils with lasers in lab dishes, moving them around as ‘neutrobots’. However, this had not been tried in living animals. So, researchers set out to demonstrate the feasibility of light-driven neutrobots in animals using live zebrafish.

The researchers manipulated and moved neutrophils in zebrafish tails, using focused laser beams as optical tweezers. The ‘neutrobots’ could be moved up to a velocity of 1.3 µm/s, three times faster than a neutrophil’s natural speed. The optical tweezers were able to precisely and actively control the functions that neutrophils conduct as part of the immune system. For example, moving through a blood vessel wall into the surrounding tissue; carrying a plastic nanoparticle, showing potential for delivering medicine; and pushed towards red blood cell debris, a neutrophil engulfed the pieces. Surprisingly, at the same time, a different neutrophil, which wasn’t controlled by a laser, tried to naturally remove the cellular debris. Because they successfully controlled neutrobots in vivo, the researchers say this study advances the possibilities for targeted drug delivery and precise treatment of diseases.

Source: American Chemical Society

Categories : Diseases, Syndromes and ConditionsTags :

Findings May Lead to Paradigm Shift in Psoriasis Treatment

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Source: CC0

About a third of people with psoriasis develop inflammation in their joints (psoriatic arthritis) as a result of the chronic skin condition. Research published in Annals of the Rheumatic Diseases has now discovered a key starting point for inhibiting inflammation in both psoriasis and psoriatic arthritis. These findings may lead to major new developments for treatment, diagnostic and prevention strategies.

The study conducted by the research group led by Erwin Wagner at the Medical University of Vienna focused on the S100A9 gene. The team has discovered that the severity of psoriasis (Ps) and psoriatic arthritis (PsA) can be reduced by inhibiting S100A9 systemically throughout the whole body rather than locally on the skin.

With this finding, the researchers are laying the foundation for a paradigm shift in the treatment of Ps and PsA: “Our study is an important step towards the development of targeted therapeutic options in the form of drugs that act systemically rather than locally on the skin,” affirms Erwin Wagner. New diagnostic and prevention strategies can also build on the study.

Psoriasis, typically an adult-onset disease, have triggers such as stress and UV radiation. There can also be a genetic predisposition to developing Ps. S100A9 activation in skin and immune cells has been identified as a risk factor for the development of Ps and/or PsA.

Previous work by Erwin Wagner’s team showed that the symptoms of psoriasis disappear when the S100A9 gene is deactivated in all of the body’s cells. Their recent preclinical experiments highlighted the particular influence that those skin and immune cells in which S100A9 is produced have on disease severity. “We now know that the inflammatory responses in psoriasis and psoriatic arthritis are enhanced when S100A9 is only inhibited in skin cells,” Erwin Wagner explained. Therefore drugs inhibiting S100A9 would have to be administered systemically in the form of tablets or drips

Source: Medical University of Vienna

Categories : Diseases, Syndromes and ConditionsTags :

2-Drug Combo Boosts Spinal Muscular Atrophy Treatment

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Woman using lab equipment
Source: NCI on Unsplash

In 2016, Spinraza® became the by the first FDA-approved treatment for spinal muscular atrophy (SMA). This neurodegenerative disease is the leading genetic cause of infant death. The drug was conceived and developed by Cold Spring Harbor Laboratory (CSHL) Professor Adrian Krainer and collaborators. But Prof Krainer’s lab continued to try and improve Spinraza® could be improved, in collaboration with Alberto Kornblihtt at Universidad de Buenos Aires. They discovered pairing Spinraza® with a second FDA-approved drug called valproic acid (VPA) could be a new way to boost its therapeutic effects, without increasing toxic side effects.

Prof Krainer explained: “Sometimes you don’t want to use a ton of a drug. If you have a condition that allows you to use less drug, then you may have fewer toxicities. So the idea is to combine these two drugs to get maximal effects.”

In SMA, the body produces insufficient amounts of a protein called SMN. Spinraza® is a type of molecule called an antisense oligonucleotide (ASO) that helps cells make more SMN protein from a gene called SMN2. Roadblocks were discovered on the SMN2 gene when using Spinraza®, slowing down the cellular machine producing SMN protein. The drug VPA helps remove these roadblocks, allowing Spinraza® to further increase the SMN protein output. When mice with SMA were treated with both VPA and a Spinraza®-like ASO used for research, the mice survived longer, with improved muscle function.

To date, more than 11 000 SMA patients have been treated with Spinraza® in more than 50 countries. Prof Krainer’s latest research shows that there’s always room for improvement. He hopes the team’s findings will help optimize the efficacy of Spinraza® treatments, and hopes their work will help the development of treatments for other neurodegenerative diseases.

Source: Cold Spring Harbor Laboratory