Day: July 19, 2023

Categories : Metabolic DisordersTags :

Earlier Breakfast Time Linked to Reduced Risk of Developing Diabetes

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Photo by Richard Bell on Unsplash

According to the findings of a study published in the International Journal of Epedmiology, eating breakfast after 9am increases the risk of developing type 2 diabetes by 59% compared to people who eat breakfast before 8am. This is the main conclusion of a study which followed more than 100 000 participants in a French cohort. The results show that people can reduce the risk of diabetes not only by changing what their diet, but also their mealtimes.

Type 2 diabetes is associated with modifiable risk factors, such as an unhealthy diet, physical inactivity and smoking. But another factor may be important: timing of meals. “We know that meal timing plays a key role in regulating circadian rhythms and glucose and lipid control, but few studies have investigated the relationship between meal timing or fasting and type 2 diabetes,” says Anna Palomar-Cros, ISGlobal researcher and first author of the study.

In this study, a team from ISGlobal joined at team from INSERM in France to investigate the association between meal frequency and timing and the incidence of type 2 diabetes among 103 312 adults (79% women) from the French NutriNet-Santé cohort. Participants filled in online dietary records of what they ate and drank over a 24-hour period on 3 non-consecutive days, as well as the timing of their meals. The research team averaged the dietary records for the first two years of follow-up and assessed the participants’ health over the following years (an average of seven years).

Early breakfast, early dinner

There were 963 new cases of type 2 diabetes during the study. The risk of developing the disease was significantly higher in the group of people who regularly ate breakfast after 9am, compared to those who ate breakfast before 8 am. “Biologically, this makes sense, as skipping breakfast is known to affect glucose and lipid control, as well as insulin levels,” explains Palomar-Cros. “This is consistent with two meta-analyses that conclude that skipping breakfast increases the risk of type 2 diabetes,” she adds.

The research team also found that a late dinner (after 10 pm) seemed to increase the risk, while eating more frequently (about five times a day) was associated with a lower disease incidence. In contrast, prolonged fasting is only beneficial if it is done by having an early breakfast (before 8am) and an early dinner.

“Our results suggest that a first meal before 8am and a last meal before 7pm may help reduce the incidence of type 2 diabetes,” concludes Manolis Kogevinas, ISGlobal researcher and co-author of the study. In fact, the same ISGlobal team had already provided evidence on the association between an early dinner and a lower risk of breast or prostate cancer.

Taken together, these results consolidate the use of chrononutrition (ie the association between diet, circadian rhythms and health) to prevent type 2 diabetes and other chronic diseases.

Source: Barcelona Institute for Global Health (ISGlobal)

Categories : AntibioticsTags :

Study Reveals Global Patterns of Antibiotic Resistance

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Proportion of third-generation cephalosporin resistance in Klebsiella pneumoniae, for blood infections, 2019 (data from ATLAS, Pfizer). Credit: Institut Pasteur, Eve Rahbé

To understand the main determinants behind worldwide antibiotic resistance dynamics, scientists developed a statistical model based on the ATLAS antimicrobial resistance surveillance database, the model revealed significant differences in trends and associated factors depending on bacterial species and resistance to certain antibiotics. For example, in some bacteria, resistance was strongly affected by global sales for those corresponding antibiotics, while national sales had minimal impact for most. The results of the study were published in the journal The Lancet Planetary Health.

For example, countries with high quality health systems were associated with low levels of antibiotic resistance among all the gram-negative bacteria investigated, while high temperatures were associated with high levels of antibiotic resistance in Enterobacteriaceae. Surprisingly, national antibiotic consumption levels were not correlated with resistance for the majority of the bacteria tested. The results suggest that antibiotic resistance control measures need to be adapted to the local context and to targeted bacteria-antibiotic combinations.

Antibiotic resistance (ABR) is currently one of the most urgent threats to global health. It is a natural phenomenon, but improper use of antibiotics is contributing to it by selecting resistance and complicating bacterial infection-control strategies. Worldwide surveillance of antibiotic resistance, especially under the aegis of WHO has been set up, and several databases have been created to record ABR worldwide, with the long-term aim of improving understanding of the causes to help tackle the phenomenon. Antibiotic resistance varies considerably depending on the bacterial species, but a recent Lancet study estimated that in 2019, 1.27 million deaths worldwide were attributable globally to ABR and ABR was associated with 4.95 million deaths.

To identify the main factors associated with worldwide antibiotic resistance dynamics, a multidisciplinary research team at the Institut Pasteur developed a statistical model and analysed antibiotic resistance data from the ATLAS database, which contains data collected since 2004 in more than 60 countries on every continent. The scientists analysed the data by testing a large number of determinants to reveal the main factors of antibiotic resistance and understand how they relate to the dynamics observed worldwide.

“Research teams study how antibiotic resistance emerges in a bacterium in a Petri dish or in an individual, but we are currently lacking a population-level, global overview that can be used to investigate links between resistance and specific factors like national health system quality for different species of pathogenic bacteria. To understand the dynamics of antibiotic resistance, it needs to be studied at every level. That is what this study sets out to do,” explains Eve Rahbé, PhD research student and first author of the study.

The first stage of the study was to select relevant factors that could influence antibiotic resistance dynamics. “Although some biological factors are known, it was also important for us to investigate hypotheses associated with socioeconomic and climate factors,” continues the scientist. A total of eleven independent factors were selected, including health system quality (based on the Global Health Security index), antibiotic consumption and national wealth (GDP per capita), as well as data on travel and climate variables. Statistical models were then developed to study potential associations between the ATLAS data and the selected factors.

The analysis of global data for the period 2006-2019 initially revealed an increase in resistance to carbapenems for several species, although global trends were stable for other resistances. The study also demonstrated that the dynamics and factors associated with antibiotic resistance depend on bacteria-antibiotic combinations. Surprisingly, however, national antibiotic consumption was not significantly associated with resistance for the majority of bacteria tested (except for quinolone consumption for fluoroquinolone-resistant Escherichia coli and Pseudomonas aeruginosa and carbapenem consumption for carbapenem-resistant Acinetobacter baumannii).

Conversely, high health system quality was associated with low levels of antibiotic resistance in all the gram-negative bacteria tested. High temperatures were associated with high levels of antibiotic resistance, but only for Enterobacteriaceae (Escherichia coli and Klebsiella pneumoniae).

“This study reveals the wide range of factors leading to antibiotic resistance among different pathogenic bacteria at global level, and the need to adapt resistance control approaches to the local context (country, transmission context) and the specific bacteria-antibiotic combination,” concludes Philippe Glaser, Head of the Institut Pasteur’s Ecology and Evolution of Antibiotic Resistance Unit and co-last author of the study.

Source: Institut Pasteur

Categories : Neurology PaediatricsTags :

Concussions don’t Lower Children’s IQs, Study Finds

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Photo by Anna Shvets on Pexels

The angst parents feel when their children sustain injuries is surely one of the universal conditions of parenthood. That anxiety is heightened greatly when those injuries involve concussions. But a new study led out of the University of Calgary, published today in the medical journal Pediatrics, may set worried parental minds slightly at ease.

Derived from data on emergency room visits in children’s hospitals in Canada and the US, the findings show that IQ and intelligence is not affected in a clinically meaningful way by paediatric concussions.

The study compares 566 children diagnosed with concussion to 300 with orthopaedic injuries. The children range in age from eight to 16 and they were recruited from two cohort studies. In the five Canadian hospitals that participated, patients completed IQ tests three months postinjury.

The US cohort was conducted at two children’s hospitals in Ohio, wherein patients completed IQ tests three to 18 days, postinjury.

“Obviously there’s been a lot of concern about the effects of concussion on children, and one of the biggest questions has been whether or not it affects a child’s overall intellectual functioning,” says Dr. Keith Yeates, PhD, a professor in UCalgary’s Department of Psychology and senior author of the Pediatrics paper. Yeates is a renowned expert on the outcomes of childhood brain disorders, including concussion and traumatic brain injuries.

“The data on this has been mixed and opinions have varied within the medical community,” says Yeates. “It’s hard to collect big enough samples to confirm a negative finding. The absence of a difference in IQ after concussion is harder to prove than the presence of a difference.”

Combining the Canadian and U.S. cohorts gave the Pediatrics study an abundant sample and it allowed Yeates and his co-authors to test patients with a wide range of demographics and clinical characteristics.

“We looked at socioeconomic status, patient sex, severity of injuries, concussion history, and whether there was a loss of consciousness at the time of injury,” says Yeates. “None of these factors made a difference. Across the board, concussion was not associated with lower IQ.”

The children with concussion were compared to children with orthopaedic injuries other than concussion to control for other factors that that might affect IQ, such as demographic background and the experience of trauma and pain. This allowed the researchers to determine whether the children’s IQs were different than what would be expected minus the concussion.

The findings of the study are important to share with parents, says Dr Ashley Ware, PhD, a professor at Georgia State University and lead author of the paper.

“Understandably, there’s been a lot of fear among parents when dealing with their children’s concussions,” Ware says. “These new findings provide really good news, and we need to get the message to parents.”

Dr Stephen Freedman, PhD, co-author of the paper and a professor of paediatrics and emergency medicine, agrees. “It’s something doctors can tell children who have sustained a concussion, and their parents, to help reduce their fears and concerns,” says Freedman. “It is certainly reassuring to know that concussions do not lead to alterations in IQ or intelligence.”

Another strength of the Pediatrics research is that incorporates the two cohort studies, one testing patients within days of their concussions and the other after three months.

“That makes our claim even stronger,” says Ware. “We can demonstrate that even in those first days and weeks after concussion, when children do show symptoms such as a pain and slow processing speed, there’s no hit to their IQs. Then it’s the same story three months out, when most children have recovered from their concussion symptoms. Thanks to this study we can say that, consistently, we would not expect IQ to be diminished from when children are symptomatic to when they’ve recovered.”

She adds: “It’s a nice ‘rest easy’ message for the parents.”

Source: University of Calgary

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

Third Alzheimer’s Drug is ‘Opening a Chapter in a New Era’

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With yet a third new Alzheimer’s drug, the monoclonal antibody donanemab, expected to be approved by the Food and Drug Administration (FDA), the field is beginning to show progress in the fight to slow the disease. But the drugs work best for those in the earliest stages of Alzheimer’s, and other therapies will be needed to help those with advanced disease, according to Gil Rabinovici, MD, director of the UCSF Alzheimer’s Disease Research Center.

This is likely “just the opening chapter in a new era of molecular therapies for Alzheimer’s disease and related neurodegenerative disorders,” Rabinovici wrote in an editorial that is being published along with the results of the latest drug, donanemab, in JAMA. Rabinovici was not involved in the trial.

Donanemab is a monoclonal antibody, like the two earlier Alzheimer’s drugs, aducanumab (Aduhelm) and lecanemab (Leqembi). These drugs attack plaques in the brain that are made of a protein called amyloid. They disrupt cell function and lead to the rapid spread of another protein called tau. Both amyloid and tau contribute to the development of Alzheimer’s disease.

The trial showed donanemab slowed cognitive decline by 35% compared with placebo in patients with low-to-intermediate levels of tau in the brain. These results are similar to those reported with Leqembi, which received FDA approval earlier this month. In the donanemab trial, patients also experienced a 40% lower risk of progressing from mild cognitive impairment to mild dementia, or from mild-to-moderate dementia.

Donanemab was better at removing amyloid plaques compared to Aduhelm and Leqembi. It reduced tau concentrations in the blood, but not in a key area of the brain.

While these results are encouraging, Rabinovici said an in-depth analysis still is needed to understand how these findings affect patient outcomes.

Limited benefit in advanced disease

Patients with more advanced disease showed little to no benefit compared to those who received the placebo. Together with the drug’s potentially serious side effects, this should push experts to “aim higher in developing more impactful and safer treatments,” wrote Rabinovici, who is affiliated with the UCSF Memory and Aging Center, departments of Neurology, Radiology and Biomedical Imaging, as well as the Weill Institute for Neurosciences.

Donanemab should be restricted to patients with low-to-intermediate levels of tau, which indicates mild disease. Other trials are evaluating how well monoclonal antibodies work in the earliest phase of the disease before symptoms appear.

Like the two other new Alzheimer’s drugs, donanemab was associated with ARIA, amyloid-related imaging abnormalities that may include brain swelling and microbleeds. Serious ARIA occurred in 3.7% of patients, including three deaths. Risks were higher among patients with the APOE4 gene, which is related to an increased risk for Alzheimer’s. For that reason, Rabinovici said, genetic testing should be recommended prior to monoclonal antibody treatment.

While ARIA has generally been managed safely in clinical trials, Rabinovici urged caution as these drugs enter into real-world practice. He suggested limiting access to patients with normal pre-treatment MRIs, repeating MRIs at regular intervals and stopping or suspending treatment when ARIA occurs.

Lack of racial and ethnic diversity was a major limitation of the trial. Just 8.6% of the 1,251 U. S. participants were non-white. Rabinovici said this raises ethical concerns about the “generalisability of results to populations at highest risk,” noting studies that have shown higher rates of dementia in Black and Latino populations.

Given the anticipated high cost of donanemab and high patient demand, Rabinovici said it might make sense to limit the treatment duration to the time needed to clear amyloid plaques from the brain, which is the approach pioneered in the trial. He said this could “greatly enhance the feasibility of treatment for patients, clinicians, insurers and health systems.”

Source: University of California – San Francisco

Note: this article previously used an incorrectly attributed image. This has since been taken down and replaced.

Categories : Uncategorized

Antipsychotic Drugs Work Differently than Previously Believed, Study Finds

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Photo by Rodion Kutsaiev on Unsplash

Antipsychotic drugs, used to treat schizophrenia, have many unpleasant side effects and are also ineffective for many patients, so new drugs are needed. New research published in Nature Neuroscience has discovered that antipsychotic drugs, which inhibit the overactive dopamine causing the symptoms of schizophrenia, interact with a completely different neuron than originally believed.

This new finding from Northwestern Medicine scientists provides a new avenue to develop more effective drugs to treat the debilitating symptoms of schizophrenia. Traditionally, researchers have screened antipsychotic drug candidates by evaluating their effects on mouse behaviour, but the approach used by a Northwestern lab outperformed these traditional approaches in terms of predicting efficacy in patients.

“This is a landmark finding that completely revises our understanding of the neural basis for psychosis and charts a new path for developing new treatments for it,” said lead investigator Jones Parker, assistant professor of neuroscience at Northwestern University Feinberg School of Medicine. “It opens new options to develop drugs that have fewer adverse side effects than the current ones.”

Individuals with schizophrenia have increased levels of dopamine in a region of the brain called the striatum. This region has two primary types of neurons: those with either D1 or D2 dopamine receptors.

Dopamine is a key for both receptors, but antipsychotics only block the D2 receptor locks. Therefore, experts have assumed these drugs preferentially act on neurons that express the D2 receptor locks. But, in fact, it was the other brain cells – the neighbouring ones in the striatum with D1 receptors – that responded to antipsychotic drugs in a manner that predicted clinical effect.

“The dogma has been that antipsychotic drugs preferentially affect striatal neurons that express D2 dopamine receptors,” Parker said. “However, when our team tested this idea, we found that how a drug affects the activity of D2 receptor-expressing striatal neurons has little bearing on whether it is antipsychotic in humans. Instead, a drug’s effect on the other striatal neuron type, the one that expresses D1 dopamine receptors, is more predictive of whether they actually work.”

Schizophrenia is a debilitating brain disorder that affects approximately 1 in 100 people. While existing antipsychotics are effective for the hallmark symptoms of schizophrenia such as hallucinations and delusions, they are ineffective for the other symptoms of schizophrenia such as deficits in cognitive and social function.

Moreover, current antipsychotics are completely ineffective in more than 30% of patients with treatment-resistant schizophrenia. The use of these drugs also is limited by their adverse effects, including tardive dyskinesia and parkinsonism.

The new study for the first time determined how antipsychotic drugs modulate the region of the brain thought to cause psychosis in living animals.

“Our study exposed our lack of understanding for how these drugs work and uncovered new therapeutic strategies for developing more effective antipsychotics,” Parker said.

Source: EurekAlert!