Tag: Research

1 in 5 older Canadian adults with diabetes developed functional limitations during the pandemic

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Researchers found that approximately 1 in 5 older Canadian adults with diabetes and no pre-pandemic functional limitations developed functional limitations for the first time during the COVID-19 pandemic. Functional limitations refer to difficulties with basic mobility-related tasks, such as walking two to three blocks, standing up from a chair, or climbing stairs. In comparison, only one in eight of their peers without diabetes developed functional limitations during the pandemic.

Functional status is an important predictor of longevity and quality of life among older adults, and individuals with diabetes face a higher risk of functional decline than the general population. Because the pandemic exacerbated many risk factors for functional decline, such as social isolation and physical inactivity, we wanted to examine changes in functional status among this population.”

Andie MacNeil, first author, research assistant at the Factor-Inwentash Faculty of Social Work (FIFSW) and the Institute for Life Course and Aging at the University of Toronto

The study’s sample came from the Canadian Longitudinal Study on Aging, a national longitudinal study of older Canadians. Respondents with diabetes were 53% more likely to develop at least one functional limitation during the pandemic compared to respondents without diabetes. Even after taking into account major risk factors for functional decline, such as such as physical activity, obesity, smoking, and other chronic health conditions, older adults with diabetes still faced a 28% higher risk of developing functional limitations.

“It is important for health professionals to encourage their older patients, particularly those with diabetes, to engage in behaviours that can help maintain their functional status, such as regular physical activity,” said co-author Susanna Abraham Cottagiri, doctoral candidate at the School of Medicine at Queens University.”

The study also found that socioeconomic factors were associated with functional limitations among older adults with and without diabetes. When compared to those with an annual household income of $100,000 or more, older adults with diabetes with an income of $20,000 or less had a 5-fold higher risk of developing at least one functional limitation. Even among those without diabetes, those with an income of $20,000 or less had double the risk of developing at least one functional limitation compared to those with an annual income of $100,000 or more.

“While socioeconomic status is an important predictor of functional decline among those both with and without diabetes, the magnitude of this relationship is much greater for respondents with diabetes,” said co-author Ying Jiang, a senior epidemiologist at the Public Health Agency of Canada.

The authors also examined the probabilities of functional limitations across various patient characteristics such as sex, diabetes status, and household income, and then stratified into several risk factors, such as age, physical activity level, smoking status, multimorbidity, and weight. Across various patient profiles, socioeconomic status was a consistent driver of functional status.

Co-author Professor Paul Villeneuve at the Department of Neuroscience and the CHAIM Research Centre, Carleton University, hypothesized the possible reason for this pattern: “People with low socioeconomic status face disproportionate stressors over their lifetime that may adversely impact their physical functioning in older age, such as working more physically demanding jobs, worse nutrition, and living in areas with less greenspace and walkability.”

The researchers hope these findings can be used to inform interventions to promote better physical functioning among middle age and older adults.

“Combining lifestyle approaches that integrate physical activity with nutrition interventions have been shown to improve physical function in older adults with diabetes” said co-author Margaret de Groh, scientific manager at the Public Health Agency of Canada.

“Poverty remains a major barrier to nutrition and food security,” said senior author Professor Esme Fuller-Thomson at the University of Toronto’s FIFSW and director of the Institute for Life Course & Aging. “It is important to think about broader strategies to decrease poverty and improve food access in Canada in order to promote better physical functioning among older adults.”

The study was published this week in the Canadian Journal of Diabetes. The study included 6,045 participants of the Canadian Longitudinal Study on Aging (CLSA) who were free from functional limitations in the 2015-2018 wave of data collection and who provided information on their functional status during the COVID-19 pandemic (September–December 2020). This research was supported, in part, by the Canadian Institutes of Health Research (CIHR) grant #172862 (PI Esme Fuller-Thomson).

Source:

Journal reference:

MacNeil, A., et al. (2024) Incident Functional Limitations Among Older Adults With Diabetes During the COVID-19 Pandemic: An Analysis of Prospective Data From the Canadian Longitudinal Study on Aging. Canadian Journal of Diabetes. doi.org/10.1016/j.jcjd.2024.02.005.

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April 17, 2024
Excessive internet use plus lack of sleep, exercise linked to teen truancy and school absence

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Spending too much time online to the point of compulsion and the neglect of other necessary activities, plus not sleeping or exercising enough, are linked to a heightened risk of both truancy and school absence due to illness among teens, finds research published online in the Archives of Disease in Childhood.

Teenage girls seem to be more vulnerable than teenage boys to excessive internet use, but getting the recommended quota of shut eye and exercise and having a trusting relationship with parents all seem to be protective, the findings indicate.

Although differences in how excessive internet use is assessed and categorized can make it difficult to quantify, digital media may be a factor tempting teens to stay home from school, and may also hinder learning through lack of sleep, suggest the researchers.

To try and gauge what impact excessive internet use might have on school attendance and what, if any, mitigating factors there might be, the researchers used data from the School Health Promotion study, a national biennial survey conducted in Finland and managed by the Institute for Health and Welfare.

They focused on 86,270 year 8 and 9 pupils aged 14 to 16. The teens were specifically asked about their relationship with their parents in terms of how often they shared concerns with them (often to fairly rarely), as well as how long they slept every night, and how many days of the week they had been on the move for at least an hour.

Excessive internet use was assessed using a validated (Excessive Internet Use; EIU) scale consisting of 5 components indicating compulsion; neglect of family, friends, and study; anxiety if not online; and failure to eat or sleep because of being online.

Respondents were asked to estimate how often they experienced each of these, scoring them from 1 (‘never’) to 4 (‘very often’) to provide an overall average.

And they provided information on how many times during the most recent school year they had played truant and/or had been absent due to illness, ranging from ‘not at all’ through to ‘daily or almost daily’.

The EIU scale average score was just under 2; and just over 2% (1881) of participants scored the maximum of 4. Girls spent more time online than boys: they were 96% more likely to fall into the excessive internet use category than boys (79%), possibly because they tend to use social media more than boys, suggest the researchers.

On average, the teens slept 8 hours on school nights, and 9 hours on weekend nights. But more than a third (35%) clocked up fewer than 8 hours on school nights, and 11% slept fewer than 8 hours at the weekend.

Participants reported physical activity for at least an hour on 4 days of the preceding week and vigorous physical activity for 2-3 hours a week. But a third reported low levels of physical activity—fewer than 3 days a week. Boys were more likely than girls to report no, or daily, physical activity.

Overall, 3-4% of respondents reported high rates of school absence. Boys reported more truancy than girls, who reported more medically explained absences than boys.

Older age was associated with a greater likelihood of truancy. But spending an excessive amount of time online was associated with an increased risk of both truancy (38% heightened risk) and medically explained school absences (24% heightened risk).

Good parental relations, longer nightly weekday sleep, and physical activity all emerged as significantly protective, with more of each factor associated with a steadily decreasing risk of both truancy and school absences due to illness.

Being able to talk about concerns with parents was most strongly associated with the lowest risk of either type of school absence. Teens who often felt able to share troubling issues with their parents were 59% less likely to play truant and 39% less likely to be absent from school due to illness.

This is an observational study, and as such, no firm conclusions can be drawn about causal factors, and the researchers acknowledge that the School Health Promotion study didn’t include information on the type of internet use teens engaged in.

“Despite the limitations, our results have important implications for promotion of health and educational attainment,” suggest the researchers.

“Our results are relevant for professionals organising and working in school health and wellbeing services, especially when professionals meet students whose school absences raise concern,” they add.

Source:

Journal reference:

Kosola, S., et al. (2024). Associations of excessive internet use, sleep duration and physical activity with school absences: a cross-sectional, population-based study of adolescents in years 8 and 9. Archives of Disease in Childhood. doi.org/10.1136/archdischild-2023-326331.

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April 17, 2024
AI techniques massively accelerate the search for Parkinson’s disease treatments

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Researchers have used artificial intelligence techniques to massively accelerate the search for Parkinson’s disease treatments.

The researchers, from the University of Cambridge, designed and used an AI-based strategy to identify compounds that block the clumping, or aggregation, of alpha-synuclein, the protein that characterises Parkinson’s.

The team used machine learning techniques to quickly screen a chemical library containing millions of entries, and identified five highly potent compounds for further investigation.

Parkinson’s affects more than six million people worldwide, with that number projected to triple by 2040. No disease-modifying treatments for the condition are currently available. The process of screening large chemical libraries for drug candidates – which needs to happen well before potential treatments can be tested on patients – is enormously time-consuming and expensive, and often unsuccessful.

Using machine learning, the researchers were able to speed up the initial screening process by ten-fold, and reduce the cost by a thousand-fold, which could mean that potential treatments for Parkinson’s reach patients much faster. The results are reported in the journal Nature Chemical Biology.

Parkinson’s is the fastest-growing neurological condition worldwide. In the UK, one in 37 people alive today will be diagnosed with Parkinson’s in their lifetime. In addition to motor symptoms, Parkinson’s can also affect the gastrointestinal system, nervous system, sleeping patterns, mood and cognition, and can contribute to a reduced quality of life and significant disability.

Proteins are responsible for important cell processes, but when people have Parkinson’s, these proteins go rogue and cause the death of nerve cells. When proteins misfold, they can form abnormal clusters called Lewy bodies, which build up within brain cells stopping them from functioning properly.

“One route to search for potential treatments for Parkinson’s requires the identification of small molecules that can inhibit the aggregation of alpha-synuclein, which is a protein closely associated with the disease,” said Professor Michele Vendruscolo from the Yusuf Hamied Department of Chemistry, who led the research. “But this is an extremely time-consuming process – just identifying a lead candidate for further testing can take months or even years.”

While there are currently clinical trials for Parkinson’s currently underway, no disease-modifying drug has been approved, reflecting the inability to directly target the molecular species that cause the disease.

This has been a major obstacle in Parkinson’s research, because of the lack of methods to identify the correct molecular targets and engage with them. This technological gap has severely hampered the development of effective treatments.

The Cambridge team developed a machine learning method in which chemical libraries containing millions of compounds are screened to identify small molecules that bind to the amyloid aggregates and block their proliferation.

A small number of top-ranking compounds were then tested experimentally to select the most potent inhibitors of aggregation. The information gained from these experimental assays was fed back into the machine learning model in an iterative manner, so that after few iterations, highly potent compounds were identified.

Instead of screening experimentally, we screen computationally. By using the knowledge we gained from the initial screening with our machine learning model, we were able to train the model to identify the specific regions on these small molecules responsible for binding, then we can re-screen and find more potent molecules.”

Professor Michele Vendruscolo, Co-Director of the Centre for Misfolding Diseases

Using this method, the Cambridge team developed compounds to target pockets on the surfaces of the aggregates, which are responsible for the exponential proliferation of the aggregates themselves. These compounds are hundreds of times more potent, and far cheaper to develop, than previously reported ones.

“Machine learning is having a real impact on the drug discovery process – it’s speeding up the whole process of identifying the most promising candidates,” said Vendruscolo. “For us this means we can start work on multiple drug discovery programmes – instead of just one. So much is possible due to the massive reduction in both time and cost – it’s an exciting time.”

The research was conducted in the Chemistry of Health Laboratory in Cambridge, which was established with the support of the UK Research Partnership Investment Fund (UKRPIF) to promote the translation of academic research into clinical programmes.

Source:

Journal reference:

Horne, R. I., et al. (2024). Discovery of potent inhibitors of α-synuclein aggregation using structure-based iterative learning. Nature Chemical Biology. doi.org/10.1038/s41589-024-01580-x.

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April 17, 2024
DASH diet may lower the risk of cardiovascular disease in breast cancer survivors

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A new paper in JNCI Cancer Spectrum, published by Oxford University Press, finds that following a healthy diet lowers the risk of cardiovascular disease in breast cancer survivors.

Cardiovascular disease is the top non-breast cancer related cause of death in women with breast cancer. There are more than 3.8 million female breast cancer survivors in the United States. These women are at higher risk for cardiovascular disease than women who have not had breast cancer. This is likely due to the cardiotoxic effects of breast cancer treatment, as well as common risk factors for both breast cancer and cardiovascular disease, such as aging, lack of exercise, and smoking. Dietary guidance for breast cancer survivors is limited and until recently has been based primarily on research related to cancer prevention.

Researchers used data from the Pathways Study, a prospective cohort study of women diagnosed with invasive breast cancer, to examine associations between diet quality and cardiovascular-related events. The analysis included 3,415 women diagnosed with invasive breast cancer at Kaiser Permanente Northern California between 2005 and 2013 and monitored through 2021.

To assess diet quality, researchers used a scoring system based on the Dietary Approaches to Stop Hypertension (DASH) diet which was developed in the 1990s to manage and treat hypertension. The diet emphasizes fruits, vegetables, whole grains, lean protein, and low-fat dairy. It also limits sodium, red and processed meats, and sugar sweetened beverages. The diet is similar to that recommended by the American Cancer Society, but also encourages consumption of low-fat dairy and nuts, and discourages sodium. The study evaluated heart health tied to these two diets as well as a plant-based diet, the 2020 Healthy Eating Index, and the alternate Mediterranean diet.

The researchers found that women whose diets were most similar to DASH at the time of their breast cancer diagnosis had a 47% lower risk of heart failure, a 23% lower risk of arrhythmia, a 23% lower risk of cardiac arrest, a 21% lower risk of valvular heart disease, and a 25% lower risk of venous thromboembolic disease than the women whose diets were least aligned with DASH.

In a closer examination the researchers found that higher consumption of low-fat dairy reduced the risk for cardiovascular disease-related death, after adjusting for all other food groups. They also found that the relationship between DASH and cardiovascular disease appeared to be modified by the type of chemotherapy treatment a woman received. For example, women whose treatment included an anthracycline and had diets closely aligned with the diet had a lower risk of cardiovascular disease than women least aligned with DASH, a relationship that was not apparent among women on other types of chemotherapy regimens.

Our findings suggest that we need to begin talking to breast cancer survivors about the potential heart benefits of the DASH diet. We know that breast cancer survivors have an elevated risk for cardiovascular disease, and the diet might be able to help improve the overall health of this population.”

Isaac J. Ergas, PhD, paper’s lead author, staff scientist at the Kaiser Permanente Division of Research

Source:

Oxford University Press USA

Journal reference:

Ergas, I. J., et al. (2024) Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study. JNCI Cancer Spectrum. doi.org/10.1093/jncics/pkae013.

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April 17, 2024

To stop fentanyl deaths in Philadelphia, knocking on doors and handing out overdose kits

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On a narrow street lined with row houses and an auto body shop in the Kensington neighborhood of North Philadelphia, Marsella Elie climbs a home’s front steps and knocks hard on the door.

A middle-aged man appears with a wary look on his face.

“Hello, sir, how are you doing today?” asked Elie, wearing a royal-blue jacket embroidered with the city government’s Liberty Bell logo. “My name is Marsella. I’m working with the city. You heard about the overdoses that are going around in the neighborhood, right?”

The man gives a cautious nod.

Elie gestures to the pamphlets she’s holding about drug overdoses and addiction treatment programs. She holds up a box of Narcan, a brand of naloxone, which can reverse an opioid overdose.

“What we’re trying to do is get this in everybody’s household. Have you ever heard of this before?” Elie asked before handing the man a tote bag filled with more pamphlets, fentanyl test strips, and the box of Narcan.

Elie and other part-time city workers and volunteers are part of a large-scale, citywide door-to-door campaign in Philadelphia that aims to equip homes with naloxone and other drug overdose prevention supplies.

City officials hope that this proactive approach will normalize naloxone as an everyday item in the medicine cabinet, and prevent people from dying of overdoses, especially Black residents.

In Philadelphia in 2022, a record 1,413 people died from drug overdoses, according to city data. Among Black residents, deaths were up 20% from the year before, with many happening in private homes.

“The best thing we can do to make these things more accessible is to just give them to people,” said Keli McLoyd, deputy director of the city’s Opioid Response Unit, speaking about the tote bag with naloxone and other supplies. “We’re not asking you if you’re using drugs. The goal here is really to build sort of a collective responsibility. As Black and brown folks, as we saw during the covid epidemic, nobody’s coming to save us. For us, this is a tool that we can use to save ourselves.”

The canvassing initiative aims to take prevention supplies directly to people who might not otherwise seek it out themselves, and to spread awareness about overdoses beyond Kensington, the epicenter of the city’s addiction epidemic. Canvassers plan to knock on more than 100,000 doors in Philadelphia’s “hot spots” — ZIP codes with escalating rates of opioid overdoses, many in minority communities.

Widening racial disparities in overdose deaths are among the long-term consequences of the war on drugs, McLoyd said. Policies from that national anti-drug campaign led to decades of aggressive police tactics, racial profiling, and lengthy prison sentences, disproportionately affecting people of color and their communities.

Research shows that Black Americans still account for a disproportionate number of drug arrests and child protective services.

“Because of that, it’s very clear why Black or brown people might be hesitant to raise their hand and say, ‘I’m a person who uses drugs, I need those resources,’” McLoyd said.

Other communities have distributed naloxone and other supplies, albeit on a smaller scale than Philadelphia.

What Philadelphia is doing could become a model for other densely populated places, said Daliah Heller, vice president of drug use initiatives at Vital Strategies, a public health organization working with local governments in seven states to address the opioid epidemic.

“There’s something intensely personal about a human engagement,” Heller said. “And somebody knocking at your door to talk about drug use and overdose risk and that there’s something that can be done, I think is really powerful.”

Over the years, naloxone has become more accessible than ever before, Heller pointed out. It can now be ordered online and through the mail, it’s available in specialized vending machines, and some drugstores now sell Narcan nasal spray over the counter.

But tens of thousands of Americans are still dying from opioid overdoses every year. That means prevention efforts and messaging about the crisis are still not reaching some people, Heller said. And to her, reaching people means meeting them where they are. “That means physically, that means in terms of what they know about something, what their perception is of something, and their beliefs,” she said. “We need to think like that when we think about naloxone distribution.”

The Philadelphia canvassing project is funded in part by the city’s share of settlement payouts from national lawsuits against opioid manufacturers and distributors. The city is set to receive about $200 million over roughly 18 years from settlements with AmerisourceBergen, Cardinal Health, McKesson, and Johnson & Johnson.

The initiative is staffed by many of the same people who initially started canvassing as part of the 2020 census count.

Not everyone answers the door for the canvassers. Some aren’t home when they come around. In those cases, workers hang a flyer on the door handle that offers information about overdose risks and contacts for further resources. The teams of canvassers, often with language interpreters, later make a second sweep through a neighborhood to reach people they missed the first time.

On a recent Thursday, Philadelphia canvassers were knocking on doors in the Franklinville and Hunting Park neighborhoods. In this ZIP code, about 85 people died of drug overdoses in 2022, according to city data. That’s fewer than the 193 people who died of overdoses in Kensington in 2022, but much higher than the few deaths seen in the city’s most affluent neighborhoods.

The canvassers approached a resident, Katherine Camacho, on the sidewalk, as she came out of her garage. Camacho told the teams she was aware of the overdose problem in her community and then eagerly accepted a box of Narcan.

“I will carry this with me, because, like I said, sometimes you’re in the street driving somewhere and you could save a life,” Camacho told them. “And if you don’t have these things, it’s harder to do so, right?”

Camacho said she’s seen how the opioid crisis has caused suffering in her neighborhood and across the city. As for Philadelphia’s canvassing effort, she said she believes that “God is putting these people to help.”

As she headed into her house carrying the box of Narcan, Camacho said she wanted to do her part to help, too.

This article was reprinted from khn.org, a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

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April 17, 2024

Sugary beverages linked to higher risk of atrial fibrillation

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In a recent study published in the European Journal of Clinical Nutrition, researchers used Mendelian randomization (MR) to explore the associations between the intake of pure fruit juices (PFJ) and sugar-sweetened beverages (SSBs) with cardiovascular disease (CVD).

Study: Association between sugar-sweetened beverages and pure fruit juice with risk of six cardiovascular diseases: a Mendelian randomization study. Image Credit: Andrii Zastrozhnov/Shutterstock.com

Background

Cardiovascular illnesses are a major worldwide health problem, with risk factors including high body mass index (BMI), alcohol use, and smoking habits.

SSBs and PFJ are associated with CVD; however, the causative relationship is uncertain. SSBs may be an elastic dietary target for lowering the CVD risk among females; however, PFJ may be a primary predictor.

However, several investigations have found no direct link between SSBs and CVD. PFJ use can increase important nutrient intake; however, one should limit intake due to the high free sugar and energy content.

The health consequences of PFJ consumption are inconsistent, and dietary advice differs among nations. The link between PFJ use and CVD mortality is unclear.

About the study

The present study researchers investigated whether SSB and PFJ consumption increased CVD risk.

The researchers assessed genetically estimated causal relationships between sugar-sweetened beverages, pure fruit juices [obtained from genome-wide association studies (GWAS) of European individuals], and six CVDs [hypertension, angina pectoris, atrial fibrillation (AF), coronary atherosclerosis (CA), acute myocardial infarction (AMI), and heart failure (HF)] using mendelian randomization.

The team obtained dietary intake data from the United Kingdom Biobank based on the Oxford WebQ 24-hour diet recall questionnaires filled out by 85,852 individuals. GWAS data on atrial fibrillation included 3,818 cases, with 333,381 control individuals. Angina data included 10,083 patients and 452,927 disease-free individuals.

AMI data included 3,927 patients and 333,272 control individuals. Coronary atherosclerosis data included 14,334 patients with 346,860 controls. Heart failure GWAS data included 1,405 patients with 359,789 control individuals. GWAS data on hypertension included 54,358 patients with 408,652 controls.

The researchers used the inverse variance weighted (IVW) approach for analysis, supplemented by the Cochran Q test, weighted median, MR Egger regressions, MR pleiotropy, Bonferroni corrections, and funnel plots.

To ensure that the primary analysis findings were robust, they calculated F-values as complementary tests to establish looser cut-offs for exposing the instrumental variables (IVs) and selected IVs by detecting single nucleotide polymorphisms (SNPs) strongly associated with PFJ and SSBs.

They determined odds ratios (OR) for the associations between SSB, PFJ intake, and CVD.

Results and discussion

The MR analysis showed genetically causal positive associations between sugar-sweetened beverages and atrial fibrillation (OR, 1.02) and negative associations between pure fruit juice and angina pectoris (OR, 0.97).

However, there were no causal relationships between SSB and PFJ intake and other cardiovascular disease risks. Supplementary MR methods yielded similar results.

The leave-one-out analysis showed that individual SNP removal did not alter the causal associations, indicating that the primary findings were reliable and robust.

SSB and PFJ intakes have distinct substance compositions, which can raise the chance of developing AF while decreasing the risk of angina. SSBs contain dietary additives such as sodium citrate, which may increase the risk of AF over time.

Excessive intake of SSBs can activate an inflammatory response, resulting in higher levels of circulating inflammatory markers such as interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor receptors 1 and 2 (TNF-r1, r2). Higher IL-6 levels are associated with an increase in AF burden and mortality.

PFJ, on the other hand, has high levels of polyphenols, some of which have anti-inflammatory properties. Pomegranate juice can lower inflammatory indicators such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and IL-6 due to its high concentration of hydrolyzable tannins.

PFJ’s anti-inflammatory properties may lower angina incidence by blocking platelet aggregation and preventing coronary plaque development.

Conclusions

The study findings revealed a positive relationship between sugar-sweetened beverages and atrial fibrillation, whereas pure fruit juice had a negative link with angina.

The findings should help us better understand the impact of long-term SSB/PFJ intake on cardiovascular disease (CVD) and recommend dietary choices for people who are at risk. Patients with AF should limit their SSB consumption to prevent potential pathogenic hazards, whereas individuals may incorporate PFJ into their diet as a protective factor against angina.

However, further clinical and fundamental research is required to confirm these findings. Future research should concentrate on non-European ancestry groups and study data on various types of SSBs/PFJ and consumption rates to better understand their impact on CVD.

Further research is needed to improve the understanding of their protective and pathogenic characteristics and assess their potential utility in clinical CVD prevention and therapy.

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April 17, 2024
ELRIG UK and SRG announce partnership to advance life science professionals in drug discovery

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The European Laboratory Research & Innovation Group (ELRIG) UK, a not-for-profit, volunteer-led organization for the drug discovery community, today entered into a partnership with SRG, leaders in life science recruitment, to support the advancement of science professionals in their careers.

The partnership offers the ELRIG community access to career opportunities and provides organizations of all sizes with SRG’s specialist talent solutions to help grow the life science sector. In particular, early career professionals (ECPs) in industry and academia can attend forums and networking events where they can meet, and learn the skills needed to help them advance their careers in drug discovery.

ELRIG brings together academic and biopharma industry experts and thought leaders to exchange ideas and information through the provision of free-to-attend scientific meetings and conferences. Its primary objective is to provide leading-edge knowledge to the life sciences community on an open-access basis. As part of the ELRIG events programme, there are a range of activities designed specifically for ECPs. SRG, powered by Impellam Group, are experts in finding the specialist skills needed to support biotech and pharmaceutical research. They help life science companies — from start-ups to big pharma — to find, attract and nurture emerging talent, and aim to ensure outstanding career prospects for candidates. Together ELRIG and SRG will provide support to life science professionals that will allow them to gain a deeper understanding of the industry, select the right career path, and develop the tools needed to progress, while helping the drug discovery industry to flourish.

ELRIG and SRG have a shared ambition to advance the careers of early-stage professionals in drug discovery. ELRIG will provide the opportunities for ECPs to connect, whilst SRG can help them to expand their skillset and progress in their careers. Building such networks is an imperative as they navigate the myriad of collaboration and career options ahead of them. We are delighted to be working with the team at SRG, who bring 30 years of industry experience supporting scientific endeavors to this exciting collaboration.”

Sanj Kumar, CEO, ELRIG UK

Andrew Turner, Managing Director, SRG, said: “As technological innovations accelerate, new fields emerge, and competition intensifies, the demand for professionals within STEM industries continues to outpace the available talent pool. Our partnership with ELRIG, an organization that shares our passion for innovation, will focus on talent enablement, and supporting the advancement of science professionals at each stage of their career. ELRIG’s commitment to enabling early talent aligns wonderfully with the work that we perform across the life sciences sector to create opportunities for future generations. Together, we are creating world-class communities that empower individuals and businesses to shape tomorrow’s world.”

ECPs are invited to attend the webinar “AI at the Frontier: Empowering Early Career Professionals in Drug Discovery” at 1pm BST on 24 April 2024: https://elrig.org/portfolio/webinar-april-2024-ai-at-the-frontier-empowering-ecps-in-drug-discovery/

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April 17, 2024
Exploring how gene variants affect brain cells in children with severe epilepsy

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Epilepsy is a brain disorder that causes recurring seizures.

It is one of the most common neurological diseases, and it affects approximately 50 million people worldwide, according to the World Health Organization. In 2023, nearly 450,000 children in the United States were diagnosed with the disease.

Virginia Tech researchers at the Fralin Biomedical Research Institute at VTC are exploring how gene variants identified in children with severe epilepsy can have an impact on neurons, leading to abnormal electrical activity in the brain and recurrent seizures.

With two recent grants totaling $2.4 million from the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, scientists led by Matthew Weston will use mouse models expressing these epilepsy-associated gene variants to understand how they alter neuron behavior to cause seizures.

The Weston lab is particularly interested in a gene called KCNT1. This specific segment of DNA carries the instructions for a protein that forms an ion channel that acts like a tiny gate embedded in the membrane of neurons to control the flow of potassium ions.

This flow is essential to help neurons communicate properly and regulate the electrical activity in our brain, according to Weston, an associate professor at the Fralin Biomedical Research Institute.

Changes in this gene affect normal nervous system function and can lead to seizures by causing a dysregulation of electrical stabilization in neurons that can spread across networks throughout regions of the brain. Earlier investigations by Weston’s team examined the influence of KCNT1 genetic abnormalities on the excitability of neurons, indicating their potential connection to epilepsy.

We’re using mouse models with the exact same KCNT1 mutations that cause severe and untreatable epilepsy in kids. By closely examining these models, we hope to discover a path to therapeutic intervention.”

Matthew Weston, associate professor, Virginia Tech’s School of Neuroscience in the College of Science

Weston is collaborating with Wayne Frankel, professor of Genetics and Development at Columbia University’s Institute for Genomic Medicine. Frankel recently designed new research models for this study: a model with the KCNT1 genetic mutation in all neurons and another model that allows the KCNT1 genetic mutation to be expressed only in a subpopulation of neurons to identify which neuron types are most important for the disease.

By looking at the neurons in the brains of these models, Weston aims to uncover fresh perspectives on the alterations in neuronal function induced by KCNT1 mutations, resulting in heightened excitability and seizure occurrence. More importantly, he hopes to pinpoint the neuron types most susceptible to these changes, potentially guiding the development of innovative treatment strategies.

“With these models, we’re hoping to find new mechanisms underlying the disease and point to new therapies,” Weston said.

Weston serves on the scientific advisory board for the KCNT1 Epilepsy Foundation, which supports research and drug development, with the ultimate goal of finding an eventual cure for KCNT1-related epilepsies.

Amy Shore, a research scientist in Weston’s lab, finds inspiration in the connection with the foundation.

“Engaging with parents, and hearing stories about the devastation of this disease on their children and their daily lives, motivates us to focus and do our best to find answers that can translate into hope,” she said.

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April 16, 2024
AI facilitates collaboration between physicians and nurses for improved patient care

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With large language models that take notes during patient visits and algorithms that identify disease, artificial intelligence has begun to prove its worth as an assistant for physicians. But a new study from Stanford Medicine shows the potential of AI as a facilitator -; one that helps doctors and nurses connect to achieve more efficient, effective patient care.

The study, which published in JAMA Internal Medicine last month, describes an AI-based model in use at Stanford Hospital that predicts when a patient is declining and flags the patient’s physicians and nurses. Ron Li, MD, a clinical associate professor of medicine and medical informatics director for digital health who is the senior author on the study, said the alert system helps clinicians connect more efficiently and effectively as well as intervene to prevent patients from deteriorating and landing in the intensive care unit.

Li, who worked with informatics postdoctoral scholar and lead author Robert Gallo, MD, on the evaluation, discussed their team’s approach to harnessing the algorithm and how it fosters clinician connection in a ceaselessly buzzing hospital environment. Lisa Shieh, MD, PhD, clinical professor of medicine; Margaret Smith, director of operations for primary care and population health; and Jerri Westphal, nursing informatics manager, also helped lead the study and the implementation of the AI system.

What is a deterioration model and how does AI fit in?

The algorithm is a prediction model that pulls data -; such as vital signs, information from electronic health records and lab results -; in near-real time to predict whether a patient in the hospital is about to suffer a health decline. Physicians aren’t able to monitor all of these data points for every patient all of the time, so the model runs in the background, looking at these values about every 15 minutes. It then uses artificial intelligence to calculate a risk score on the probability the patient is going to deteriorate, and if the patient seems like they might be declining, the model sends an alert to the care team.

What’s the benefit of having such a model run in a hospital?

The big question I want to answer is, “How do we use AI to build a more resilient health system in high-stakes situations?” There are many ways to do that, but one core characteristic for a resilient system is strong communication channels. This model is powered by AI, but the action it triggers, the intervention, is basically a conversation that otherwise may not have happened.

Nurses and physicians have conversations and handoffs when they change shifts, but it’s difficult to standardize these communication channels due to busy schedules and other hospital dynamics. The algorithm can help standardize it and draw clinicians’ attention to a patient who may need additional care. Once the alert comes into the nurse and physician simultaneously, it initiates a conversation about what the patient needs to ensure they don’t decline to the point of requiring a transfer to the ICU.

Tell me about how your team implemented and evaluated the model.

We integrated this model, which we did not create, into our workflow, but with a few tweaks. Originally, it sent an alert when the patient was already deteriorating, which we didn’t find very helpful. We adjusted the model to focus on predicting ICU transfers and other indicators of health decline.

We wanted to ensure the nursing team was heavily involved and felt empowered to initiate conversations with physicians about adjusting a patient’s care. When we evaluated the tool, which we had running for almost 10,000 patients, we saw a significant improvement in clinical outcomes -; a 10.4% decrease in deterioration events, which we defined as transfers to the ICU, rapid response team events, or codes -; among a subset of 963 patients with risk scores within a “regression discontinuity window,” which basically means they’re at the cusp of being high risk. These are patients whose clinical trajectory may not be as obvious to the medical team. For that group of patients, this model was especially helpful for encouraging physicians and nurses to collaborate to determine which patients need extra tending.

How have nurses and physicians responded to the integration of this new model?

The model is far from perfect. The reactions have overall been positive, but there is concern about alert fatigue, since not all alerts are flagging a real decline. When the model was validated on data from patients prior to implementation, we calculated that about 20% of patients flagged by the model did end up experiencing a deterioration event within six to 18 hours. At this point, even though it’s not a completely accurate model, it’s accurate enough to warrant a conversation. It shows that the algorithm doesn’t have to be perfect for it to be effective.

With that said, we want to improve the accuracy; you need to do that to improve trust. That’s what we’re working on now.

Source:

Journal reference:

Gallo, R. J., et al. (2024). Effectiveness of an Artificial Intelligence–Enabled Intervention for Detecting Clinical Deterioration. JAMA Internal Medicine. doi.org/10.1001/jamainternmed.2024.0084.

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April 16, 2024
Research unveils bispecific antibodies for B-cell lymphoma treatment

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A new research paper was published in Oncotarget’s Volume 15 on April 12, 2024, entitled, “Novel therapeutic bispecific antibodies for B-cell lymphoma targeting IgM and other antigens on the B-cell surface.”

The B-cell receptor regulates B-cell proliferation and apoptosis. Aberrations in BCR signaling are associated with the development and progression of B-cell malignancies, such as mantle cell lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia, many of which express the IgM type of BCR on their cellular surface.

Therefore, IgM is an attractive target for therapeutic antibodies against B-cell malignancies. However, soluble IgM competitively binds to anti-IgM antibodies in the serum, and these antibodies show insufficient cytotoxic activity. Thus, antibody therapy targeting IgM is hindered by the presence of soluble IgM in the blood. In this new study, researchers Takahiro Ohashi, Sayuri Terada, Shinsuke Hiramoto, Yuko Nagata, Hirokazu Suzuki, Hitoshi Miyashita, Tetsuo Sasaki, Yasukatsu Tsukada, and Keiko Fukushima from ZENOAQ (Zenyaku Kogyo Co., Ltd.) used a bispecific antibody to address this problem.

“In this study, we aimed to produce IgM-dependent bispecific antibodies targeting IgM and the other B-cell antigens such as CD20, CD32b (FcγRIIB), CD79b, and human leukocyte antigen (HLA)-DR using the Cys1m technology [10, 43–45]. Additionally, the correct IgG-like bispecific antibody structures were confirmed and their efficacies in the presence of soluble IgM were analyzed.”

The researchers generated bispecific antibodies bound to IgM and other B-cell antigens such as CD20 and HLA-DR using their own bispecific antibody-producing technology, Cys1m. These bispecific antibodies directly inhibited cell proliferation via cell-cycle arrest and apoptosis in vitro, although large amounts of soluble IgM were present. Additionally, a bispecific antibody bound to IgM and HLA-DR (BTA106) depleted B-cells in cynomolgus monkeys.

“These data suggest that anti-IgM/B-cell surface antigen-binding specific antibodies are promising therapeutic agents for B-cell malignancies. Moreover, the bispecific antibody modality can potentially overcome problems caused by soluble antigens.”

Source:

Journal reference:

Ohashi, T., et al. (2024). Novel therapeutic bispecific antibodies for B-cell lymphoma targeting IgM and other antigens on the B-cell surface. Oncotarget. doi.org/10.18632/oncotarget.28578.

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April 16, 2024

Tag: Research

Background

About the study

Results and discussion

Conclusions