Tag: Muscle

Groundbreaking study unveils new insights into neurodegenerative disorder symptoms

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In a recent study published in Nature Medicine, researchers developed a method for rapidly gathering and integrating clinical (CD) and neuropathological diagnoses (ND) data by examining medical record summaries from donors at the Netherlands Brain Bank (NBB) to detect disease trajectories.

Study: Identification of clinical disease trajectories in neurodegenerative disorders with natural language processing. Image Credit: Natali _ Mis/Shutterstock.com

Background

Neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies, are a worldwide health issue due to their wide range of clinical symptoms and complicated comorbidities.

Current research struggles to acquire complete clinical data, which limits statistical designs. Innovative data-driven strategies that use large autopsy cohorts are required to improve diagnosis.

Brain banks give vital information on neurodegenerative illnesses, but drawbacks such as limited clinical data and binary case-control designs impede development.

About the study

In the present study, researchers created a computer pipeline to translate medical record summaries from Netherlands Brain Bank (NBB) donors into clinical illness trajectories, which included 84 neuropsychiatric symptoms and signs recognized using natural language processing.

They scanned NBB donor files, defined and predicted clinical features in the recorded history, translated predicted symptoms and signs into clinical illness trajectories, and applied them for downstream analysis.

The researchers developed a novel cross-disorder clinical classification system including 90 neuropsychiatric symptoms and signs related to brain illnesses and general well-being. One scorer evaluated 18,917 phrases from a randomly selected group of 293 contributors to build a dataset for refining, validating, and testing various Natural Language Processing (NLP) models.

The researchers optimized five model designs [support vector machine (SVM), bag of words (BOW), T5, PubMedBERT, and Bio_ClinicalBERT] and chose the best one based on microprecision.

The team developed the clinical illness trajectories, including several neuropsychiatric symptoms and signs, duration, and more donors than previously published. They then ran an enrichment assessment to investigate whether the estimated clinical features were more prevalent in each disease than expected.

To assess the diagnostic accuracy of this brain autopsy cohort, the researchers cleaned and matched CD descriptions to the human disease ontology and compared the generated clinical diagnosis labels to the neurodegenerative diagnoses.

The researchers incorporated machine-learning algorithms into healthcare practices to consistently predict neuropathological diagnoses from clinical illness trajectories.

They included 3,042 donors who provided 199,901 words of clinical history data and were diagnosed with different neuropathologically characterized brain illnesses.

The team chose symptoms and signs based on their medical-scientific importance, existence in the clinical history, and definition clarity.

The team used a gated recurrent unit (GRU-D) to assess the accuracy of forecasting ND from clinical illness trajectories, emphasizing the apolipoprotein E4 genotype associated with early AD and severe neurodegeneration.

The team used clinical illness trajectories to conduct temporal profiling of specific neuropsychiatric signs and symptoms across various disorders.

They also performed a survival analysis to determine whether there were differences in the overall survival rate after the first observation of a sign or symptom between donors with different neuropathological diagnoses.

Results

The researchers identified indications and symptoms that differ between often misdiagnosed illnesses and clinical subgroups of diverse brain disorders, indicating that neuronal substructures are affected differently.

The inter-annotator agreement for model reliability was high, with 269 signs and symptoms considerably enriched in particular diagnoses, 148 of which were pre-defined to be of diagnostic value.

All neuropsychiatric features showed significant enrichment in one or more brain conditions, indicating they were related to a subcategory of diseases.

As predicted, dementia and memory impairment were much more prevalent in dementias such as AD, frontotemporal dementia (FTD), vascular dementia (VD), dementia with Lewy bodies (DLB), and pervasive development disorders (PDDs), a finding not observed in Parkinson’s disease without dementia.

Likewise, multiple sclerosis (MS) demonstrated significant enrichment for mobility impairment, muscle weakness, and fatigue, consistent with the debilitating disease of the central nervous system.

Progressive supranuclear palsy (PSP), multiple system atrophy (MSA), PD, MS, PDD, and ATAXIA showed increased enrichment for reduced mobility.

In contrast, MND, VD, PSP, MS, and MSA showed higher enrichment for muscle weakness, indicating that the approach may identify a distinct set of disease-specific symptoms.

The researchers found specific indications and symptoms increased in specific subtypes of dementia, such as paranoia and façade behavior in Alzheimer’s disease and hearing issues and muscular weakness in vascular dementia.

Eighty-four percent of neuropathologically identified Alzheimer’s disease donors and 83% of neuropathologically defined FTD donors were clinically diagnosed with Alzheimer’s disease or frontotemporal dementia, respectively.

MSA was commonly clinically diagnosed as Parkinson’s disease, whereas vascular dementia and PSP were classified clinically as several different conditions, indicating that NBB brain donors frequently receive a misdiagnosis.

Conclusion

The study findings highlighted NLP usage to identify the clinical trajectories of neurodegenerative diseases. The findings indicate that many brain illnesses have largely overlapping symptoms, which might indicate disturbed neuronal substructures.

The findings can help epidemiologists, molecular biologists, and computational researchers investigate the clinical symptoms of neurodegenerative disorders and build prediction models to identify new data-driven clinical subgroups for diseases such as dementia, Parkinson’s disease, and multiple sclerosis.

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March 14, 2024
Could vitamin D levels be associated with lower back pain?
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In a recent study published in the journal Nutrients, researchers from Germany investigated a large cohort from the United Kingdom (U.K.) Biobank to examine the cross-sectional and longitudinal associations between vitamin D status or the use of vitamin D supplements and the incidence of lower back pain.

Study: Serum 25-Hydroxyvitamin D Status and Vitamin D Supplements Use Are Not Associated with Low Back Pain in the Large UK Biobank Cohort. Image Credit: FotoHelin / Shutterstock

Background

Vitamin D deficiency is a significant public health problem worldwide since vitamin D is essential for the health of the musculoskeletal system, muscle function, and bone mineralization. Studies have reported that over 90% of patients with disorders associated with the musculoskeletal system have low levels of 25-hydroxyvitamin D, which is the standard and most accurate method of measuring the concentration of vitamin D in the body. Vitamin D also plays an anti-inflammatory role and helps modulate pain. Therefore, individuals with low vitamin D levels in the serum often suffer from various conditions involving chronic pain.

Of the many chronic pain conditions, lower back pain is believed to be the one linked to the most years lived with disability across the world. Health statistics from 2017 indicate that close to 8% of the global population suffers from lower back pain, and the number is rapidly rising. While various factors such as injuries, sedentary lifestyles, genetics, occupational causes, and psychosocial issues can contribute to lower back pain, the role of vitamin D in alleviating lower back pain remains largely unexplored.

About the study

In the present study, the researchers used a substantial cohort from the U.K. Biobank to examine whether the levels of 25-hydroxyvitamin D or vitamin D supplementation were associated with lower back pain using longitudinal and cross-sectional data.

The participants consisted of adults between the ages of 40 and 69 who were recruited across centers in Scotland, England, and Wales. Their biomedical information was obtained through multiple methods, including questionnaires, interviews, functional and physical evaluations, and clinical analyses of saliva, urine, and blood samples.

Vitamin D status was decided based on the serum levels of 25-hydroxyvitamin D, with deficiency defined as 25-hydroxyvitamin D levels below 30 nmol per liter, while concentrations between 30 and 50 nmol per liter being considered as vitamin D insufficiency. Serum 25-hydroxyvitamin D levels above 50 nmol per liter were considered sufficient. Baseline visit questionnaires provided the researchers with data on the use of multivitamins and vitamin D supplements.

The primary care records were used to obtain information on lower back pain diagnoses and diagnosis dates. The baseline visit diagnoses were used for the cross-sectional analysis, while lower back pain cases diagnosed during follow-ups were used for the longitudinal analysis. Questionnaires were also used to determine self-reported lower back pain, and this data was combined with physicians’ diagnoses of lower back pain to determine the exposure variable.

A wide range of covariables that could have statistically significant associations with vitamin D deficiency were considered during the analysis. These included body mass index, sociodemographic factors, biomarkers, lifestyle characteristics, and disease. Covariables associated explicitly with vitamin D levels, such as seasonality and geographic latitude of the recruitment centers and the calendar month during which the blood samples were drawn, were also included in the analysis.

Results

The results showed that lower back pain showed no associations with serum levels of vitamin D or the use of vitamin D supplements. The researchers believe this lack of any significant association is perhaps due to the multi-factorial nature of lower back pain.

While the cross-sectional analysis indicated significant associations between lower back pain, serum vitamin D levels, and the use of vitamin D supplements, the significance of these associations did not hold after adjusting for the various confounding factors. The longitudinal analysis did not find any associations between the use of vitamin D supplements or vitamin D levels in the serum and the incidence of lower back pain.

The researchers stated that while vitamin D plays a vital role in musculoskeletal health and suppressing inflammation, lower back pain could arise from diverse factors such as sedentary habits, injuries, and occupations involving working in unhealthy postures. Other comorbidities and genetic reasons can also cause lower back pain. Therefore, the role of vitamin D in alleviating lower back pain needs to be investigated for specific etiologies of the condition.

Conclusions

In conclusion, the findings indicated that perhaps due to the multi-factorial nature of lower back pain, serum vitamin D levels or the use of vitamin D supplements were not found to be associated with lower back pain.
Journal reference:

Sha, S., Chen, L., Brenner, H. and Schöttker, B. (2024). Serum 25Hydroxyvitamin D Status and Vitamin D Supplements Use Are Not Associated with Low Back Pain in the Large UK Biobank Cohort. Nutrients, 16(6). DOI: 10.3390/nu16060806, https://www.mdpi.com/2072-6643/16/6/806
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March 14, 2024
Nutrition’s crucial role in Alzheimer’s progression revealed
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In a recent cross-sectional study published in the journal Frontiers in Nutrition, researchers used data from 266 participants along the cognitive impairment spectrum to investigate the association between nutrition and cognitive decline. Their study reveals that nutrition-related variables such as body composition and dietary patterns are significantly associated with the onset and progression of Alzheimer’s disease (AD), with malnutrition substantially increasing AD risk. Since malnutrition presents an easily adjustable, safe, and non-invasive health behavior, the early identification of at-risk populations and dietary interventions therein may substantially reduce the future global burden of AD and similar cognitive disabilities.

Study: An investigation into the potential association between nutrition and Alzheimer’s disease. Image Credit: Adisak Riwkratok / Shutterstock

Diet and cognitive health

One of humanity’s crowning achievements is longevity – modern medicine’s lengthening of natural human lifespans. An unfortunate side-effect of this achievement, however, is a slowly aging world, with more senior citizens alive today than ever before and a corresponding explosion in the incidence and prevalence of chronic, age-associated conditions such as cardiovascular diseases, cognitive declines, and some cancers. While initially presenting a ‘safer’ (lower mortality) pathology than cancers and cardiovascular diseases, cognitive declines are alarmingly debilitating conditions, resulting in substantial economic and mental trauma for patients and their families, even before accounting for their potentially lethal comorbidities.

Alzheimer’s disease (AD) is the most common cognitive disorder associated with old age. It is a chronic, progressive disease characterized by initial mild memory loss, which eventually declines into severely debilitating dementia. It is caused by the deposition of specific proteins, which results in the loss of neural connections. Despite substantial research in the field, a cure for the condition remains elusive, with clinical interventions focused on symptom management and progression delay.

Recently, studies have suggested a link between malnutrition and dementia. The European Society for Clinical Nutrition and Metabolism (ESPEN) has further classified malnutrition as the most common AD-associated comorbidity. Unfortunately, research has failed to establish an association between specific nutritional components and their impacts on the different stages of AD progression. Understanding the holistic relationship between multiple nutritional indices and their implications on various stages of AD would allow clinicians and dieticians the information needed to curb the prevalence of these cognitive disorders.

About the study

The present study aimed to investigate the relationship between various commonly used nutritional indices and their respective contributions to AD risk and progression. The sample cohort was recruited from the Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University.

Between April 2019 and April 202, 946 participants with mild cognitive impairment (MCI due to AD – ‘AD-MCI’) or dementia due to AD (‘AD-D’) without other neurological conditions relating to cognition (e.g., Parkinson’s disease) and non-diet-based malnutrition (prevalence of hematological tumors, liver cirrhosis) were enrolled. Of these, 266 participants presented completed demographic and medical information and were included in the final analyses. These comprised 73 controls (normal cognition – ‘NC’), 72 AD-MCI, and 121 AD-D samples.

Subject body composition metrics were measured using the Global Leadership Initiative on Malnutrition (GLIM) criteria. These included ‘reduced food intake,’ ‘non-volatile weight loss,’ ‘muscle mass,’ and ‘body mass index (BMI).’ Additionally, subjects’ dietary patterns (e.g., Mediterranean diet and Mediterranean-DASH diet intervention for neurodegenerative delay [MIND]) were recorded, and the nutritional composition of these diets was separately investigated.

Venous blood samples were used for the estimations of fasting blood glucose (FBG), hemoglobin A1c (HbA1c), blood urea nitrogen (BUN), hemoglobin, creatinine, total calcium, albumin, globulin, albumin/globulin (A/G), and other nutritional status determinants.

Study findings

The present study comprised 266 participants, 57.14% of whom were female, with a mean age of 64.89 years. Medical data revealed that 36.84% of participants carried the APOE ε4 allele, a common culprit in AD pathology. Body composition metrics showed that AD-D patients had, on average, substantially lower arm, waist, calf, and hip circumferences and lower BMIs compared to AD-MCI and NC cohorts. Surprisingly, all participants were found to follow some interpretation of either Mediterranean or MIND dietary patterns, which did not differ in their nutritional scores.

“…a smaller waist circumference was linked to lower level of β amyloid protein (Aβ) and higher levels of phosphorylated tau (P-tau) and total tau (T-tau) in the cerebrospinal fluid of AD patients. This phenomenon may be attributed to the utilization of skeletal muscle mass as a nutritional reservoir in response to a prolonged state of negative energy balance during disease. Consequently, the muscle mass of AD patients gradually decreases as the disease progresses in AD.”

Nutritional assessment scales present that the AD-D cohort fared worse than the NC and AD-MCI groups. Study data analyses show that BMI and AD occurrence are independently associated, validating previous research.

Investigations into specific nutritional variables revealed that body composition, nutritional assessment scales, and blood-based nutritional laboratory variables were significantly associated with the occurrence and progression of AD. Malnutrition was found to be most prevalent in the AD-D cohort, but prevalence in even the AD-MCI was shown to be substantially higher than in the NC group.

“Since malnutrition is a risk factor that can be intervened, early identification and intervention of individuals with nutritional risk or malnutrition are significantly beneficial for reducing the risk, development, and progression of AD.”
Journal reference:

He, M., Lian, T., Liu, Z., Li, J., Qi, J., Li, J., Guo, P., Zhang, Y., Luo, D., Guan, H., Zhang, W., Zheng, Z., Yue, H., Zhang, W., Wang, R., Zhang, F., & Zhang, W. (2024). An investigation into the potential association between nutrition and Alzheimer’s disease. In Frontiers in Nutrition (Vol. 11). Frontiers Media SA, DOI – 10.3389/fnut.2024.1306226, https://www.frontiersin.org/articles/10.3389/fnut.2024.1306226/full
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March 11, 2024
Can postbiotics improve athletic performance and recovery?
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A recent systematic review published in Nutrients describes the utility of postbiotics in improving exercise performance and recovery.

Study: It’s Dead! Can Postbiotics Really Help Performance and Recovery? A Systematic Review. Image Credit: Doucefleur / Shutterstock.com

Probiotics vs. postbiotics

Probiotics are live microorganisms that are associated with a wide variety of health benefits to the host when administered adequately. For example, probiotics can support gut health, improve mental health, prevent cardiometabolic diseases, improve sleep quality and duration, as well as reduce allergic reactions. Probiotics exert these health benefits through their effects on the immune system by reducing intestinal pH, maintaining intestinal barrier integrity, increasing gut microbial composition and diversity, reducing inflammation, and eliminating pathogens.

Recently, the International Society of Sports and Nutrition has stated that probiotics might be beneficial for improving exercise performance and recovery, in addition to supporting the training and competition demands of athletes.

In addition to probiotics, postbiotics have recently gained considerable attention in healthcare due to their potential ability to improve health. A significant advantage of using postbiotics for health purposes is their longer shelf-life and reduced susceptibility to degradation due to changes in ambient conditions.

According to the International Scientific Association of Probiotics and Prebiotics (ISAPP), a postbiotic is defined as a preparation of inanimate microorganisms and/or their components that confers health benefits. Existing evidence indicates that postbiotics can exert positive health effects on gastrointestinal, dermatological, and respiratory diseases.

Some of the different methods used to produce postbiotic preparations from live microorganisms include heat treatment, sonification, chemical treatment, and ultraviolet (UV) irradiation. Each method, as well as the processing condition, has a differential impact on the functionality of resulting postbiotics.

About the study

The authors systematically searched various electronic databases to identify studies that investigated the impact of postbiotic supplementation, specifically on exercise performance, recovery, as well as biomarkers related to muscle immune function, inflammation, and oxidative stress.

Only peer-reviewed, randomized, double-blind, and placebo-controlled trials involving healthy adults were included in the systematic analysis. Postbiotic supplements used in these studies included paraprobiotics, Tyndallized probiotics, ghost biotics, heat-killed probiotics, inactivated probiotics, and nonviable probiotics. The different outcomes measured in these studies included exercise, exercise performance, and recovery.

Systematic review findings

A total of 11 studies, including nine peer-reviewed papers and two conference abstracts, were included in the final review. These studies comprised a total of 477 participants and postbiotic supplementation periods ranging from 13 days to 12 weeks.

Three studies directly compared the probiotic and postbiotic preparations of the same strains, including Lactiplantibaccilus plantarum TWK10, Lacticaseibacillus paracasei PS23, and Weizmannia coagulans GBI-30 6086.

In one study investigating probiotic and postbiotic preparations of Weizmannia coagulans GBI-30 6086, none of the preparations were found to modulate the performance of healthy individuals participating in stressful lower-body exercises.

Another comparative study showed that both probiotic and postbiotic preparations of Lacticaseibacillus paracasei PS23 can reduce the rate of muscle damage caused by maximal vertical jump, facilitate faster recovery, and improve fatigue as compared to placebo. However, only the postbiotic preparation was associated with a greater ability than the probiotic preparation to improve strength recovery.

In one study investing probiotic and postbiotic preparations of Lactiplantibaccilus plantarum TWK10, both preparations similarly improved exercise performance. However, the probiotic preparation was superior than the postbiotic preparation in reducing glucose, lactate, and ammonia levels in response to exercise stimuli. This study also reported an increased inflammatory response to exercise in individuals supplemented with the postbiotic preparation.

Another study investigating the effects of a postbiotic preparation of Weizmannia coagulans GBI-30 6086 reported enhanced lower body power and anti-inflammatory profiles in soldiers. Similarly, one study investigating a postbiotic preparation of Lactiplantibaccilus plantarum TWK10 revealed improvements in endurance performance, grip strength, and muscle mass in healthy exercising males.

Regarding other health benefits, one study investigating a postbiotic preparation of Lactobacillus gasseri OLL2809 observed preservation of natural killer cell activity and improvements in mood during strenuous exercise. Likewise, another study highlighted the ability of a postbiotic preparation of Lactococcus lactis JCM 5805 in improving antiviral responses and reducing the number of days with upper respiratory tract infection symptoms in athletes performing high-intensity training. Immunomodulatory and anti-inflammatory activities were also reported for the postbiotic preparation of Lacticaseibacillus paracasei MCC1849.

Significance

Existing evidence suggests that postbiotics can be beneficial in improving mental health, reducing fatigue, and increasing the readiness of athletes across several weeks of exercise training. Thus, the current systematic review findings support the health and ergogenic benefits of postbiotic supplementation.
Journal reference:

Kerksick, C. M., Moon, J. M., & Jager, R. (2024). It’s Dead! Can Postbiotics Really Help Performance and Recovery? A Systematic Review. Nutrients. doi:10.3390/nu16050720
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March 6, 2024
Can the modulation of the gut microbiome using a prebiotic improve muscle function and cognition?

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In a recent study published in Nature Communications, researchers examined the efficacy of a prebiotic in improving muscular and cognitive performance vs. a placebo among elderly individuals.

Study: Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial. Image Credit: Tatiana Shepeleva/Shutterstock.com

Background

As the world’s population ages, age-related disorders such as muscle loss and cognitive impairment become more common. Researchers and physicians must acknowledge cognitive changes as part of healthy aging. Exercise can help reduce muscle loss, although elderly individuals may struggle. Interventions with physical and mental advantages are required.

According to recent studies, alterations in the gut microbiota might influence muscle physiology and cognitive function, potentially altering anabolic resistance in older muscles and cognition. Prebiotics are associated with improved health in older individuals.

About the study

In the present study, researchers explored the role of gut microbiota regulation in enhancing cognition and muscular function benefits from protein supplementation and exercise in elders.

The team conducted the PRebiotic and PrOtein on Muscle in Older Twins (PROMOTe) trial remotely using video visits, online surveys, cognitive tests, and the sending of equipment and biological samples. Participants were aged ≥60 years and had a low protein consumption of <1.0 g per kg weight per day, as established by the TwinsUK group.

The team excluded participants with severe food allergies, ongoing or recent antibiotic use, protein supplementation, prebiotics and probiotics, and advanced renal disease. They also excluded individuals with a weight reduction of ≥5.0% of body weight in the previous year, major surgery or injury that could alter physical functions, and current participation in other interventional trials.

The team randomized twin pairs to receive either a placebo (7.5g maltodextrin) or a prebiotic (intervention, 3.4 g inulin and 3.5 g fructo-oligosaccharides) daily for 12 weeks. They provided all individuals with 3.3g of branched-chain-type amino acid (BCAA) supplementation and resistance training. The primary objective was to reduce chair rise time (the time required to do five chair raises without using arms). Secondary outcomes included the cognitive battery factor score, the SPPB score (including chair rise time and gait speed), grip strength, gait speed, physical activity levels assessed using the International Physical Activity Questionnaire (IPAQ), and the Simplified Nutritional Assessment Questionnaire (SNAQ) appetite scale.

The participants completed the Short Physical Performance Battery (SPPB) remotely, including chair rise time and handgrip strength evaluations with a dynamometer with real-time instructions from a qualified researcher. The participants provided stool samples to extract microbial DNA for gut microbiota characterization by shotgun metagenomic sequencing. The CANTAB battery includes cognitive tests for executive function, spatial working memory, and memory. The team evaluated three days of food diary data. They conducted intention-to-treat (ITT), per-protocol (PP), and heritability analyses.

Results

Of 626 eligible individuals, 72 were successfully recruited (36 twin pairs). The participants had a mean age of 73 and were 78% female. There were more moderate adverse effects (like abdominal bloating) in the intervention group compared to the placebo group; however, the team found no compliance-related differences, indicating that the supplements were generally well accepted. In either arm, no participants stated gastrointestinal side effects as a cause for non-adherence to the research intervention. No critical adverse effects occurred.

There were no significant changes in findings between the PP and ITT models. The team found no significant differences between the study groups concerning primary or secondary outcomes. The intervention group outperformed the placebo group in terms of cognition first-factor scores. Furthermore, the specific cognition assessment paired associations learning showed considerably fewer errors in the intervention group than in the placebo group.

Using Bray-Curtis dissimilarity, twin pairs’ microbiotas were considerably more similar to the microbiota compositions of unrelated people at baseline and the conclusion of the research. The alpha and beta diversity assessments revealed no significant changes between the prebiotic and placebo groups. Compositional bias-adjusted linear modeling controlling for twin- and arm-pair-associated effects showed 144 microbiota characteristics, including 109 microbiome taxa, 33 microbe functions, richness, and Faith’s phylogenetic diversity strongly associated with chair rise time.

Correlation analysis of changes in microbiota characteristics and chair rise times throughout the research intervention period demonstrated a link between chair rise duration improvement and changes in richness, Shannon diversity, and Faith’s diversity. The study found 11 significant differences between the prebiotic and placebo groups, with the prebiotic group having higher levels of Bifidobacterium, Actinobacteria, Firmicutes, Bacteroidetes, and Phocea massiliensis. Eight microbiome traits were associated with cognitive capacity, including an increase in actinobacteria and improvements in cognition component scores.

Conclusion

Overall, the study found that gut microbiome manipulations can enhance cognition in elders, demonstrating the viability of remote trials for older adults. The prebiotic intervention, which was well tolerated and altered gut microbiota, increased the quantity of Bifidobacterium. However, there were no significant changes in chair rise times between the study groups. Future larger-scale research should explore the possibility of gut microbiome-targeted therapies to overcome age-related anabolic resistance.

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March 4, 2024
Does vitamin D have protective role against COVID-19?

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In a recent study published in Nutrients, researchers investigated whether vitamin D supplementation before the onset of coronavirus disease 2019 (COVID-19) could provide benefits.

Study: Preventive Vitamin D Supplementation and Risk for COVID-19 Infection: A Systematic Review and Meta-Analysis. Image Credit: FotoHelin/Shutterstock.com

Background

Vitamin D is fat-soluble and synthesized in the epidermis; metabolic processes are required for its activation. 1,25-hydroxyvitamin D is the primary end product of these processes.

It binds to the vitamin D receptor (VDR) that mediates a majority of the vitamin’s effects, promoting the expression of genes with specific sequences.

The interplay between VDR, vitamin D, and repressor/promoter proteins has a crucial impact on bone mineral density.

Around 3% of the human genome is controlled by 1,25-dihydroxyvitamin D; as such, vitamin D is speculated to regulate muscle function, metabolism, immune responses, and oncogenesis, among others. The effects of vitamin D in disease, including COVID-19, are under scrutiny.

Available data support that adequate vitamin serum levels may be protective against COVID-19 incidence and mortality; however, this has not been validated.

About the study

The present study examined whether prophylactic vitamin D supplementation pre-COVID-19 could yield beneficial outcomes.

They searched the MEDLINE/PubMed, Scopus, Google Scholar, and Cochrane databases for randomized controlled trials (RCTs) and quasi-experimental, case-control, cross-sectional, and cohort studies with relevant quantitative data on vitamin D supplementation before COVID-19 diagnosis and its role against the disease.

The study population comprised patients or healthcare workers (HCWs). The primary outcome was COVID-19 incidence; secondary outcomes were COVID-19-related admission to the intensive care unit (ICU) and mortality.

The researchers excluded studies with insufficient data and those that did not meet the population, intervention, comparison, outcome, and study design (PICOS) criteria. There were no restrictions on the language or year of publication.

Two authors screened the literature, and studies were included after a full-text review. Data on relevant parameters were extracted. The team computed odds ratios and corresponding 95% confidence intervals as effect measures.

Study quality and bias were evaluated using distinct assessment tools specific to the type of study. Statistical heterogeneity was assessed using χ² and I² statistics. Publication bias was assessed using funnel plots and Egger’s linear regression.

Findings

Overall, the team selected 16 publications for analysis. Seven studies were RCTs, and eight were analytical studies. Five RCTs included HCWs, and two included patients. RCTs compared vitamin D supplementation with no treatment or high- vs. low-dose regimens.

COVID-19 incidence was assessed in 13 studies, ICU admission in three, and mortality in 11. The frequency of supplementation varied across studies.

Fifteen studies reported the precise dose of vitamin D. Controls received a placebo, low-dose vitamin D, or none. In RCTs, vitamin D supplementation was associated with a lower risk of infection despite the substantial degree of heterogeneity.

In RCTs on HCWs, the risk reduction with supplementation was approximately 80%, with negligible heterogeneity. The prevalence of vitamin D insufficiency and deficiency was consistent across these studies.

In RCTs on non-HCW populations, vitamin D supplementation did not affect the COVID-19 infection rate. Notably, the treatment group received a lower-dose regimen compared to other studies.

The researchers speculate that the low dose and low prevalence of vitamin D deficiency might have contributed to the lack of an effect. There was a protective role of supplementation among analytical studies, albeit the heterogeneity was high.

Only one RCT evaluated COVID-19 mortality and reported that vitamin D recipients had significantly reduced mortality.

Further, no association was observed between vitamin D supplementation and COVID-19 mortality in analytical studies. Moreover, vitamin D supplementation was protective against COVID-19-related ICU admission.

Conclusions

The study assessed the protective effects of vitamin D supplemented before COVID-19 onset on disease incidence, ICU admission, and mortality.

RCTs and analytical studies reported a decline in COVID-19 in vitamin D recipients, especially in populations with increased incidence of vitamin D insufficiency and deficiency. Notably, the number of studies analyzed was smaller than prior meta-analyses.

However, unlike the current study, they focused on other aspects, viz., supplementation during COVID-19. Besides, several studies in this analysis lacked data on the prevalence of vitamin D insufficiency and deficiency and the vitamin D formulation, i.e., calcitriol, cholecalciferol, etc.

Overall, the findings support the use of vitamin D in preventing COVID-19 and associated complications, particularly in individuals with vitamin D deficiencies.

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March 1, 2024
Understanding giggle incontinence: Causes, symptoms, and management

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A recent review published in the journal Pediatric Research discusses the historical background and current understanding of giggle incontinence, which is a bladder storage disorder.

Study: Giggle incontinence: a scoping review. Image Credit: Pavlova Yuliia / Shutterstock.com

What is giggle incontinence?

Giggle incontinence is a type of daytime urinary incontinence characterized by uncontrollable episodes of urinary incontinence due to loud, powerful, or bursting laughter. Unlike enuresis, stress urinary incontinence, non-neurogenic voiding dysfunction, bladder and bowel dysfunction, or anatomical disorders causing incontinence, giggle incontinence lacks additional functional symptoms.

Historically, giggle incontinence has been mistaken for stress urinary incontinence and an overactive bladder. Moreover, giggle incontinence has been considered a particular type of laughter-induced daytime urinary incontinence that can be distinguished from laughter-induced stress urinary incontinence by its specific feature of complete emptying of the bladder.

The exact etiology of giggle incontinence is not fully understood. However, two main hypotheses indicate the involvement of the central nervous system and dysfunction of the detrusor and pelvic floor muscles.

The authors of the current review systematically searched various scientific databases and identified 26 studies on giggle incontinence published between 1959 and 2023. These studies were assessed to describe the historical background, current understanding, and challenges associated with giggle incontinence.

Different types of urinary incontinence in children

Various terminologies have been used to describe giggle incontinence, including micturition induced by giggling, ambivalent laughter micturition, and enuresis risoria. To better understand giggle incontinence and develop appropriate treatments, it is important to distinguish the clinical consequences of giggle incontinence from those associated with stress urinary incontinence and an overactive bladder.

According to the International Children’s Continence Society (ICCS), stress urinary incontinence is characterized by the involuntary loss of urine due to activities that increase intra-abdominal pressure, such as sneezing, coughing, or laughter. Current estimates indicate that stress urinary incontinence affects 8-19% of children.

An overactive bladder is characterized by minor and frequent micturition, as well as other symptoms, including urgency, pollakiuria, and incontinence. This condition affects 5-12% of children.

ICCS describes giggle incontinence as a rare disorder marked by significant voiding during or after laughter, while bladder function remains normal in its absence. The condition is characterized by laughter-induced uncontrollable urine loss that cannot be stopped until the bladder is completely emptied. However, the condition is not associated with any concurrent urological disorders.

By analyzing 26 studies that reported a total of 351 giggle incontinence cases since 1959, giggle incontinence primarily affects females, with some cases reporting a family history of this condition. Giggle incontinence primarily affects children over five years of age and often improves or disappears with age.

Pathophysiology

A widely accepted hypothesis on the pathogenesis of giggle incontinence indicates the involvement of the central nervous system, similar to cataplexy, which is the loss of voluntary muscle control. Laughter acts as a stimulus to induce hypotonia and relaxation of pelvic floor muscles, thereby leading to uncontrolled micturition.

Mechanistic evidence links cataplexy with type 1 narcolepsy-associated laughter-induced muscle weakness. Most patients with type 1 narcolepsy are positive for the human leukocyte antigen HLA-DQB1*06:02, which may contribute to the familial tendency observed in some giggle incontinence patients.

Attention-deficit hyperactivity disorder (ADHD) is a common condition observed in about 23% of giggle incontinence patients. Existing evidence also links giggle incontinence pathogenesis with pelvic floor muscle dysfunction, as the proper functioning of these muscles is required for the closing of vaginal, urethral, and anal sphincters in response to increased intra-abdominal pressure. It has also been hypothesized that laughter-induced instability of the detrusor muscle can lead to giggle incontinence.

Diagnosis

A detailed voiding history is crucial for diagnosing diverse forms of daytime urinary incontinence. This will typically include a detailed patient history, maintenance of a voiding diary, analysis of urinary tract infection history, evaluation of toileting positions, and thorough physical examination of the abdominal, genital, and lumbosacral regions.

These procedures should be combined with lower urinary tract ultrasound, voiding residual analysis, and electromyographic flowmetry for an accurate diagnosis of lower urinary tract dysfunction. However, these examinations often provide normal results in patients with giggle incontinence.

Existing evidence highlights a connection between giggle incontinence and overactive bladder waves. However, urodynamic studies have defined overactive bladder waves as sensitive hyperactive waves, whereas giggle incontinence waves are considered asymptomatic hyperactive waves. Laughter-induced asymptomatic hyperactive waves may justify the urgent and spontaneous urination in giggle incontinence patients and distinguish it from the sensitive hyperactivity waves observed in overactive bladder.

Treatment

Medications that are commonly used to treat neurodynamic lower urinary tract disorders include anticonvulsants, antidepressants, anticholinergics, α-adrenergic blockers, and electric shocks. Three therapies are currently being used to control incontinence, including standard urotherapy, biofeedback, and methylphenidate.

Previous studies have shown that six-month standard urotherapy can partially improve giggle incontinence in 33% of patients; however, this therapy failed to cure the condition. Patients who are unresponsive to standard urotherapy are typically advised to undergo specific urotherapy.

Studies using biofeedback for giggle incontinence patients have reported an efficacy rate of 73% after ten weeks of weekly sessions. Patients are often advised to continue biofeedback training alone or in combination with methylphenidate once continence is achieved.

Methylphenidate is a central nervous system stimulant that acts by influencing urethral smooth muscles and increasing dopamine activity in the brain. Methylphenidate has been found to completely resolve giggle incontinence symptoms in patients; however, the treatment may cause adverse side effects in some patients, including insomnia, tachycardia, hypertension, anorexia, weight loss, abdominal pain, headache, irritability, agitation, or anxiety.

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February 28, 2024
Identifying antiviral protein IFN-γ as a potential biomarker for Long COVID

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SARS-CoV-2 triggers the production of the antiviral protein IFN-γ, which is associated with fatigue, muscle ache and depression. New research shows that in Long COVID patients, IFN-y production persists until symptoms improve, highlighting a potential biomarker and a target for therapies.

Woman sitting on sofa in the dark, placing a hand to her forehead. Image Credit: Annie Spratt via Unsplash

A University of Cambridge-led study identifies the protein interferon gamma (IFN-γ) as a potential biomarker for Long COVID fatigue and highlights an immunological mechanism underlying the disease, which could pave the way for the development of much needed therapies, and provide a head start in the event of a future coronavirus pandemic.

The study, published today in Science Advances, followed a group of patients with Long COVID fatigue for over 2.5 years, to understand why some recovered and others did not.

Long COVID continues to affect millions of people globally and is placing a major burden on health services. An estimated 1.9 million people in the UK alone (2.9% of the population) were experiencing self-reported Long COVID as of March 2023, according to the ONS. Fatigue remains by far the most common and debilitating symptom and patients are still waiting for an effective treatment.

The study shows that initial infection with SARS-CoV-2 triggers production of the antiviral protein IFN-γ, which is a normal reaction from the immune system. For most people, when their infection clears, COVID-19 symptoms cease and production of this protein stops, but the researchers found that high levels of IFN-γ persisted in some Long COVID patients for up to 31 months.

We have found a potential mechanism underlying Long COVID which could represent a biomarker – that is, a tell-tale signature of the condition. We hope that this could help to pave the way to develop therapies and give some patients a firm diagnosis.”

Dr Benjamin Krishna, Co-author, Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID).

The research began in 2020 when Dr Nyarie Sithole set up a Long COVID clinic in Cambridge’s Addenbrooke’s Hospital, where he started collecting blood samples from patients and set about studying their immunology. Sithole soon enlisted the support of Dr Benjamin Krishna and Dr Mark Wills from the University of Cambridge’s Dept. of Medicine.

“When the clinic started, a lot of people didn’t even believe Long COVID was real,” Dr Sithole said. “We are indebted to all the patients who volunteered for this study, without whose support and participation we would obviously not have accomplished this study.”

The team studied 111 COVID-confirmed patients admitted to Addenbrooke’s Hospital CUH, Royal Papworth Hospital and Cambridge and Peterborough NHS Foundation Trusts at 28 days, 90 days and 180 days following symptom onset. Between August 2020 and July 2021, they recruited 55 Long COVID patients – all experiencing severe symptoms at least 5 months after acute COVID-19 – attending the Long COVID clinic at Addenbrooke’s.

The researchers analysed blood samples for signs of cytokines, small proteins crucial to the functioning of immune system cells and blood cells. They found that the white blood cells of individuals infected with SARS-CoV-2 produced IFN-γ, a pro inflammatory molecule, and that this persisted in Long COVID patients.

Dr Krishna said: “Interferon gamma can be used to treat viral infections such as hepatitis C but it causes symptoms including fatigue, fever, headache, aching muscles and depression. These symptoms are all too familiar to Long COVID patients. For us, that was another smoking gun.”

By conducting ‘cell depletion assays’, the team managed to identify the precise cell types responsible for producing IFN-γ. They pinpointed immune cells known as CD8+ T cells but found that they required contact with another immune cell type: CD14+ monocytes.

Previous studies have identified IFN-γ signatures using different approaches and cohorts, but this study’s focus on fatigue revealed a much stronger influence. Also, while previous studies have noticed IFN-y levels rising, they have not followed patients long enough to observe when they might drop back down.

The Cambridge team followed its Long COVID cohort for up to 31 months post-infection. During this follow up period, over 60% of patients experienced resolution of some, if not all, of their symptoms which coincided with a drop in IFN- γ.

Vaccination helping Long COVID patients

The team measured IFN-γ release in Long COVID patients before and after vaccination and found a significant decrease in IFN-γ post vaccination in patients whose symptoms resolved.

“If SARS-CoV-2 continues to persist in people with Long COVID, triggering an IFN-γ response, then vaccination may be helping to clear this. But we still need to find effective therapies,” Dr Krishna said.

“The number of people with Long COVID is gradually falling, and vaccination seems to be playing a significant role in that. But new cases are still cropping up, and then there is the big question of what happens when the next coronavirus pandemic comes along. We could face another wave of Long COVID. Understanding what causes Long COVID now could give us a crucial head start.”

Microclotting

Some well-publicised previous studies have proposed microclotting as a principle cause of Long COVID.

While not ruling out a role of some kind, these new findings suggest that microclotting cannot be the only or the most significant cause.

Classifying long COVID

This study argues that the presence of IFN-γ could be used to classify Long COVID into subtypes which could be used to personalise treatment.

“It’s unlikely that all the different Long COVID symptoms are caused by the same thing. We need to differentiate between people and tailor treatments. Some patients are slowly recovering and there are those who are stuck in a cycle of fatigue for years on end. We need to know why,” Dr Krishna said.

Source:

Journal reference:

Krishna, B. A., et al. (2024) Spontaneous, persistent, T cell–dependent IFN-γ release in patients who progress to Long Covid. Science Advances. doi.org/10.1126/sciadv.adi9379.

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February 24, 2024
Unlocking vitamin B6’s role in pancreatic cancer and immune system battle

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Vitamin B6 is beneficial in many ways, notably for its role in maintaining a strong immune system. However, when pancreatic cancer develops, its cells also need vitamin B6 to replicate. During the ensuing tug of war over a limited supply of vitamin B6, pancreatic cancer almost always emerges as the victor. A researcher at the University of Oklahoma College of Medicine is following a promising trail of clues in an effort to reverse that reality.

Kamiya Mehla, Ph.D., is an associate professor of oncology science in the OU College of Medicine and a researcher with the OU Health Stephenson Cancer Center. Her research seeks ways to invigorate the body’s immune system against invaders like pancreatic cancer, and has attracted the attention of funding agencies. Over the past year, she has earned $2.6 million in grants from the National Institutes of Health and the U.S. Department of Defense.

In a recent publication in the journal Cancer Discovery, Mehla details the role of vitamin B6 in healthy people and when pancreatic cancer is present. Vitamin B6, which can be found in a variety of foods like chicken, fish and bananas, supports immune system cells, including natural killer (NK) cells, which are the first to respond to anything from cancer to a common cold. However, in the presence of pancreatic cancer, NK cells are noticeably absent. That’s because the cancer cells use up all the vitamin B6 that the NK cells need to do their job.

Pancreatic cancer is very difficult to treat, and only 11% of people who are diagnosed survive for five years. It’s important that researchers study pancreatic cancer from many different angles in order to develop new treatments. My laboratory is focused on the role of vitamin B6 because we know it boosts the immune system, but we need to understand more about how it affects cancer cells. We hope that our work opens new avenues for developing novel treatments for pancreatic cancer.”

Kamiya Mehla, Ph.D., associate professor of oncology science, OU College of Medicine

In her lab, Mehla found that giving more vitamin B6 still doesn’t help the NK cells – the pancreatic cancer cells actually grew more when they could devour additional nutrients. She studied the actions that cancer cells take to deplete vitamin B6, then devised ways to impede them. She ultimately discovered a three-part strategy. Step one involves reducing the expression of a particular gene in order to block the pathway through which the cancer takes up vitamin B6. The second step is to supply more vitamin B6, and the third utilizes a therapy to enhance the function of NK cells, like a tune-up for a car engine. When the strategy was tested in mice, it reduced the amount of pancreatic cancer cells.

“That was encouraging to discover,” Mehla said, “and it is important to know because the immune system needs to be strong in order for other treatments, like chemotherapy, to be effective. Therapy will not work if the immune system is not able to do its part.”

Mehla plans to continue her research in this area and to expand to related concerns. Because pancreatic cancer causes problems throughout the body in its attempt to gain more nutrients, she will study how a shortfall of vitamin B6 affects other organs, particularly the liver, when cancer cells are present. She is also studying whether a lack of vitamin B6 contributes to the onset of cachexia, a muscle-wasting condition that affects the majority of people with pancreatic cancer.

The Department of Defense is funding Mehla’s research on cachexia. Because military members may be exposed to hazards like radiation and chemical toxins, they can face an increased risk of developing pancreatic cancer as they age. In addition to the cancer itself, cachexia diminishes the quality of life of many war veterans, Mehla said.

“When patients have such a dramatic loss of muscle, they are less likely to respond to treatment,” she said. “Pancreatic cancer is a systemic disease. It’s not just sitting there. It’s trying to extract nutrients from multiple areas to help it survive. That’s why it’s important to take a broad look at how we can stimulate the immune system against tumors.”

Source:

Journal reference:

He, C., et al. (2024). Vitamin B6 Competition in the Tumor Microenvironment Hampers Antitumor Functions of NK Cells. Cancer Discovery. doi.org/10.1158/2159-8290.cd-23-0334.

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February 24, 2024
Ginseng enhances muscle recovery and reduces fatigue in athletes

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Ginseng is one of the most popular food supplements in the world. It is made out of various plants and herbs and is thought to provide many benefits, with numerous studies pointing at possible anti-inflammatory and antioxidant benefits as well as anti-cancer effects. A group of researchers at the Universitat Oberta de Catalunya (UOC) has now found that it can also be helpful for exercise.

According to the findings of the study, which was carried out as part of a master’s degree final project and was recently published in the open-access journal Nutrients, taking ginseng has a direct effect on reducing fatigue and helps muscles to recover after sport.

“We’ve found that ginseng can play a significant role as a nutritional supplement when it comes to recovering after exercise,” said Borja Muñoz, a fitness coach and one of the study’s lead authors, who has conducted this research under the supervision of his tutor Patricia Martínez, a dietician and nutritionist and course instructor at the UOC’s Faculty of Health Sciences, together with the experts Rafael Bailón and Laura Esquius, a researcher at the UOC’s Foodlab group. To carry out the study, they systematically reviewed over 700 articles from the scientific literature and meticulously analyzed their findings to confirm these benefits for healthy adults engaging in physical exercise.

When taken together with a balanced diet, ginseng can provide additional nutrition for athletes or anyone else who does physical exercise on a regular basis. It’s also worth noting that, unless it’s medically contraindicated in any given case, taking ginseng on a regular basis is considered beneficial (or at least not harmful) for healthy people.”

Borja Muñoz, fitness coach and one of the study’s lead authors

Evidence and benefits of ginseng

The review has concluded that taking ginseng can significantly reduce post-exercise muscle damage in healthy adults. Furthermore, it improves muscle regeneration and helps the body recover from both muscle fatigue and damage after physical exercise.

Specifically, the exertion and intensity involved in sport result in damage to muscles. This is mainly inflammatory damage. The active ingredients of the compounds contained in ginseng stimulate the central nervous system, have antioxidant and anti-inflammatory properties and regulate cortisol, the stress hormone, benefiting many of the body’s metabolic functions and helping the immune system perform as it should.

Specifically, taking ginseng systematically for a long time can mitigate the response of the biological markers, mainly creatine kinase (CK) and interleukin 6 (IL-6), responsible for exercise-induced muscle damage and inflammation. Furthermore, it reduces and mitigates the appearance of lactate in the blood. Lactate is a chemical compound produced by the body when muscles have insufficient oxygen due to overexertion that hinders muscles’ ability to contract, the main cause of muscle fatigue.

Potential to reduce the risk of injury

It should also be noted that, by reducing fatigue, taking ginseng on a regular basis may also help reduce the risk of injury, particularly in the case of muscles or ligaments, which can in turn improve athletic performance.

“Although recovery times vary based on the nature of the injury and between individuals, the damaged structures share the same physiological processes. That’s why professionals in this field must obtain the most efficient physiological context, to ensure that each person can recover as well and as quickly as possible. This is where ginseng comes in, as it can play a significant role in recovering from injuries,” said Muñoz about the possible benefits to athletes, based on their own personal characteristics, of taking ginseng according to a schedule.

A common product in traditional Chinese medicine

The study arose from Muñoz’s interest in confirming by means of scientific evidence the empirical experiences observed by him when doing work experience as a fitness coach and injury specialist in a football club in China. Muñoz observed that ginseng, a supplement very commonly used in traditional Chinese medicine, was widely used by football players, who reported beneficial effects from taking it.

“Our aim was to learn more about the effects of ginseng in a specific situation, in this case in connection with exercise, and to provide verifiable evidence of its ability to improve the body’s response to the stimuli of chronic load in sport, helping athletes to recover between training sessions, as the footballers themselves reported that it worked just like an energy drink,” said Muñoz. In fact, there are currently countless products for athletes on the market, such as tablets and specific drinks.

Establishing a scheduled consumption protocol for the future

According to these experts, this may pave the way for studying the benefits of ginseng in greater depth and assessing how using it as a supplement can improve performance in sport. In fact, one of its main possible effects is stimulating and speeding up the body’s regeneration processes following muscle damage.

“Of the possible future research we’re considering, a study to establish a scheduled consumption protocol to find out exactly how and when athletes should take ginseng to optimize its benefits within a given timeframe is particularly appealing, as the studies carried out in relation to these cases suffer from a lack of diversity and scientific evidence,” said Martínez.

The authors stressed in this regard that the methodology to be used in each type of situation must be clarified in order to learn more about how to improve supplementation with ginseng. “There’s still a significant amount of work to do, as ginseng has potential to increase athletes’ physical performance and help prevent certain injuries, particularly muscle injuries,” concluded Muñoz.

Source:

Universitat Oberta de Catalunya

Journal reference:

Muñoz-Castellanos, B., et al. (2023). Effect of Ginseng Intake on Muscle Damage Induced by Exercise in Healthy Adults. Nutrients. doi.org/10.3390/nu16010090.

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February 23, 2024