Individual Variation In Response Research Articles

L-arginine Supplementation in Endurance Athletes: A Systematic Review of Recovery Mechanisms and Performance Enhancement

L-arginine, a semi-essential amino acid, has garnered significant attention for its potential to enhance athletic performance, particularly within endurance sports. Recognized for its multifaceted roles in cardiovascular, immune, and metabolic functions, L-arginine serves as a precursor to biologically active molecules, including nitric oxide (NO), creatine, and polyamines, which are integral to muscle function and recovery. Through its ability to stimulate NO production, L-arginine promotes vasodilation, enhancing blood flow and oxygen delivery to active muscles, thereby improving exercise efficiency and endurance. Additionally, L-arginine influences muscle protein synthesis (MPS) via activation of the mTOR signaling pathway, aids in ammonia detoxification within the urea cycle, and supports cellular energetics by facilitating ATP production. These mechanisms collectively underscore its potential to support prolonged physical exertion, reduce muscle fatigue, and expedite post-exercise recovery. This systematic review examines current evidence on L-arginine supplementation in endurance athletes, focusing on its physiological impacts, mechanisms of action, and potential to enhance recovery and performance. Despite promising findings, variability in individual responses and mixed results across studies highlight the need for refined dosing strategies and further research into long-term safety and efficacy. This review provides a comprehensive overview of L-arginine's potential as a supplement in sports nutrition, aiming to inform evidence-based recommendations for its application in endurance training and recovery strategies.

Efficacy and Safety of Lithium for Suicide and Suicide-Related Behaviors in Youth: A Review of the Literature

Objectives: This systematic review evaluates the anti-suicidal properties of Lithium in children and adolescents with Bipolar Disorder (BD), addressing gaps in evidence regarding its efficacy and safety in reducing suicidality and self-harming behaviors. Methods: A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus up to February 2024. Eligible studies were those focusing on patients aged 25 years or younger, examining Lithium therapy and its impact on suicidal ideation and behaviors. The review included randomized controlled trials, longitudinal prospective and retrospective studies, and cross-sectional studies, while excluding expert opinions and case reports. Results: Evidence generally supports the efficacy of Lithium in reducing suicidal ideation and self-harming behaviors in youth with BD, though results are mixed. Randomized controlled trials demonstrated its effectiveness in mitigating suicidal thoughts during acute manic episodes, with effects persisting post-treatment. Longitudinal studies suggested that Lithium might offer superior outcomes compared to other mood stabilizers, although its specific impact on suicidality remains inconclusive. Cross-sectional studies and retrospective analyses reveal associations between Lithium use and reduced self-harming behaviors, but causality remains uncertain. While mood-stabilizing effects of Lithium offer potential benefits for reducing suicidality in youth, evidence on its direct impact on emotional dysregulation (ED) and long-term efficacy is limited. Variability in individual responses and adherence issues underscore the need for further research. Future studies should include larger, diverse samples, focus on ED symptoms, and explore Lithium mechanisms in suicidality prevention. Conclusions: Lithium remains a promising treatment for mood stabilization and reduction in suicidality in youth with BD.

Influence of intestinal microbiota on the metabolism of main cardiotropic drugs

The intestinal microbiota is one of the most important pathogenetic links in the development of cardiovascular diseases. Every year the world scientific community finds new interactions at the level of signaling molecules, metabolites and microorganisms, identifying more and more patterns and cause-and-effect relationships which indicate the commonality of the intestinal microbiota (GM) and cardiovascular diseases. The state of the host's intestinal community, its qualitative and quantitative composition, directly and indirectly affects the fundamental pathogenetic mechanisms of the development of cardiovascular diseases. Despite the fact that there are scientifically based methods of treatment, cardiovascular diseases remain the leading cause of death in the world. This phenomenon is partly due to wide variations in individual response to cardiovascular drugs. The pharmacological effects of cardiotropic drugs are quite different even within groups of patients comparable in age and gender. Every year intestinal microbiota is more and more evident to be responsible for this intraspecific variability. Gut microbes influence drug metabolism in several pharmacokinetic ways, and conversely, drugs can have significant effects on the microbiome and therefore pharmacodynamic processes. Drugs can alter the gut microenvironment and microbial metabolism, influence bacterial growth, thereby changing the composition and functions of the microbial community. One of the most important functions of GM, related to “intestinal-cardiovascular system”, is participation in the metabolism of major cardiotropic medications, such as digoxin, statins, ezetimibe, antithrombotic drugs, calcium channel blockers (CCBs), beta blockers (BB), gliflozins and inhibitors of the renin-angiotensin-aldosterone system (RAAS).

Progress in the study of toxic effects of drugs on the male reproductive system

This paper provides a comprehensive summary of the toxic effects of drugs on the male reproductive system, with a special focus on the mechanisms of testicular and sperm damage caused by chemotherapeutic agents, antibiotics, and immunosuppressants. Drug-induced reproductive toxicity usually manifests through multiple pathways including direct injury, interference with hormone regulation, oxidative stress, and DNA damage. These mechanisms can lead to impaired spermatogenesis, decreased testicular function, and long-term infertility, thereby seriously affecting male reproductive health. Specifically, chemotherapeutic drugs, such as cisplatin and cyclophosphamide, have been widely documented to cause direct damage to the testes, leading to significant decreases in sperm quantity and quality. Antibiotics and nonsteroidal anti-inflammatory drugs also negatively affect reproductive function by affecting mitochondrial function and inducing oxidative stress in the testicular cells. Although important advances have been made in recent years in the study of drug-induced reproductive toxicity, further exploration is needed to assess the variability of individual responses to drugs and develop long-term protective measures. Future research should focus on developing accurate toxicity assessment methods, customized therapeutic regimens, and enhanced fertility protection strategies, such as the use of antioxidants and methods for the cryopreservation of testes and sperm. Interdisciplinary collaboration will provide new solutions for balancing disease treatment and fertility preservation, especially in the use of high-risk drugs, such as anticancer therapies, where achieving both efficacy and reproductive health will be an important clinical challenge.

NASA’s Top Human System Research and Technology Needs for Mars

NASA is working with industry and international partners to return humans to the Moon and to eventually enable humans to explore Mars. Within NASA, several organizations work together to identify, prioritize, fund, execute, and operationalize the research and technology development (R&TD) that will be necessary to enable crew health and performance (CHP) during these future missions. These organizations include flight programs, the Health and Medical Technical Authority (HMTA), the Human Research Program, the Space Technology Mission Directorate, System Capability Leadership Teams, and other organizations, many of which existed for several years prior to the creation of the Moon-to-Mars (M2M) Program Office in 2023. A variety of constructs, vocabularies, and processes exist for managing risks and supporting strategic planning across these organizations. For example, M2M objectives, program risks, human system risks, human research gaps, capability gaps, and envisioned futures are all constructs currently used within NASA to identify and prioritize R&TD needs. These strategic planning constructs are evolving to allow M2M objectives and R&TD investments to be aligned and traced at a detailed level. A recognized need exists among stakeholder organizations to identify and communicate the highest CHP R&TD priorities in a unified and digestible way that addresses the perspectives of NASA’s CHP community. To achieve this, the HMTA arranged a series of discussions with representatives of NASA’s CHP community, during which the 8 highest priority CHP capabilities that will enable human missions to Mars, referred to as the “top human system capability needs for Mars”, were identified. The list includes Earth-independent human operations; Mars-duration food system; Mars-duration effects on human physiology; risk mitigations for vehicle atmospheres; computational injury and anthropometric models; exploration exercise countermeasures; individual variability in responses to spaceflight; and sensorimotor countermeasures. Existing tools and processes for strategic planning and risk management were evaluated, as well as the technical practicalities, cost, and schedule feasibility associated with potential R&TD investments in different capability need areas. This capability needs report is not owned by any one NASA organization and does not replace existing strategic or program planning processes; rather it aims to complement and inform them with a unified set of community generated priorities. These top capability needs will be re-evaluated periodically based on R&TD progress and the evolving M2M architecture.

Genomic study in opioid-treated cancer patients identifies variants associated with nausea-vomiting

ContextOpioids are the mainstay therapy for patients affected by cancer pain. However, about 10-20% of patients do not benefit from the received analgesic treatment or experience side effects. Genetic variability might account for the variation in individual responses to opioids, both in terms of efficacy and toxicity. ObjectivesThe aim of this genome-wide association study (GWAS) was to identify genetic markers of opioid toxicity, in terms of nausea-vomiting. MethodsCancer patients receiving morphine, oxycodone, buprenorphine, and fentanyl were recruited from different European countries. Data about toxicity (nausea-vomiting score, NVS) and other relevant clinical information were collected, as well as genotyping data. Regression analysis between genotypes of 2,052 patients and NVS was performed, using appropriate covariates, with REGENIE software. ResultsWe found 65 variants associated with NVS (P-value < 1.0×10−5). Of note, 14 intronic variants on chromosome 2 were in NPAS2 gene, encoding a circadian transcription factor reported to play a role in another opioid side effect, the alteration of sleep. Some of these variants were previously identified as splicing quantitative trait loci of the NPAS2 gene. ConclusionsThis is the first GWAS, performed in more than two thousand individually genotyped patients treated with opioids for cancer pain, that investigated the genetic bases of opioid-induced nausea-vomiting. Although further studies are needed to confirm our findings and to characterize the functional role of the identified variants, our results emphasize the importance of performing large pharmacogenomic studies to identify germline variants associated with opioid response, with the ultimate goal of tailoring cancer pain therapies.

Are there compensatory behaviors in response to a sit-stand desk intervention?

Office workers represent one of the most sedentary groups. Alarmingly, more than a third of their sitting time during workdays occurs in prolonged bouts. Sit-stand desk (SSD) interventions have been found to be effective in reducing sitting time, but heterogeneity exists amongst studies, which may be due to compensations outside the workplace. This study aimed to assess the impact of a 6-month SSD intervention on office workers' sitting and standing times during the work shift and outside work (leisure time). A two-arm (1:1) clustered randomized controlled trial was conducted with 38 participants randomly assigned to either the intervention or control group. The intervention included a psychoeducational session, motivational prompts, and environmental modification (SSD implemented in the workplace). The waiting-list control group maintained the usual work conditions and only received the initial session. We employed repeated measures ANCOVA to compare changes between groups while adjusting for relevant covariates, with significance set at 5%. In the intervention group, there was a significant reduction in sitting time at work by 32.97 min, along with a notable increase in standing time by 27.88 min (p<0.05). Although not significant (p>0.05), there was an increase in sitting time in the leisure context of about 23.07 min. This study underscores the effectiveness of SSD as a key strategy to mitigate sitting time among office workers. However, future interventions should consider integrating comprehensive behavioral strategies beyond the workplace to sustain potential increases in sitting time during the leisure time and avoid compensatory behaviors. What is already known on this topic: Sedentary behavior, particularly in the workplace, is associated with increased risks of non-communicable diseases and premature mortality. Previous studies have shown that sit-stand desk (SSD) interventions can significantly reduce sitting time at work. However, uncertainties remain about whether these effects persist outside of the workplace and if compensatory behaviors occur during leisure time. This study demonstrated that a 6-month SSD intervention resulted in a significant reduction of 32.97 minutes in sitting time during work hours and a corresponding increase in standing time. However, a non-significant increase of 23.07 minutes in sitting time during leisure was observed, suggesting potential compensatory behaviors outside of work. Additionally, the response to the intervention varied among participants, highlighting the influence of individual factors. How this study might affect research, practice, or policy: The findings emphasize the importance of extending behavioral interventions beyond the workplace to maintain sustainable reductions in sedentary behavior. To maximize health benefits, future interventions should consider personalized strategies that address sedentary behavior in the workplace and during leisure time. Moreover, the variability in individual responses suggests that more tailored interventions may be necessary to ensure widespread effectiveness.

Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder: A meta-analysis.

Major depressive disorder (MDD) is a substantial global health concern, and its treatment is complicated by the variability in individual response to antidepressants. To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search across PubMed, EMBASE, Web of Science, and the Cochrane Library was conducted without date restrictions, utilizing key terms related to MDD, serotonin 1A receptor polymorphism (5-HTR1A), C-1019G polymorphism, and antidepressant response. Studies meeting inclusion criteria were thoroughly screened, and quality assessed using the Newcastle-Ottawa Scale. Statistical analyses, including χ 2 and I² values, were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly. The initial search yielded 1216 articles, with 11 studies meeting criteria for inclusion. Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy. The heterogeneity was low to moderate, and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests. This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD. The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.

Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications.

Recently, chronic intermittent inhalation of low-dose carbon monoxide (CO) has been postulated as a practice to increase total hemoglobin mass with potential beneficial effects on endurance performance. In this perspective article, we discuss the potential performance enhancing capabilities as well as the safety concerns, which include individual variability in CO response, and acute and chronic health effects. It is also important to note that according to the World-Anti-Doping-Agency (WADA), CO inhalation could fall under "M1. Manipulation of Blood and Blood Components" and therefore could be considered a prohibited method if used as a non-diagnostic tool.

Evaluating Heat Stress Effects on Growth in Tunisian Local Kids: Enhancing Breeding Strategies for Arid Environments.

This study evaluates the impact of thermal load on the weights of Tunisian local kids using 24 models with cubic and quadratic Legendre polynomials, based on daily temperatures (Tmin, Tmax, and Tavg) on the day of weight recording and averaged over 7, 14, and 21 days before weighing. The deviance information criterion (DIC) consistently shows that cubic polynomial models offer a better fit than quadratic models, highlighting their superior accuracy in studying the effects of thermal load on kid weights. The models with the best fit utilized average or maximum temperatures over 14 or 21 days. The patterns of response were similar across the temperature variables and periods, showing a stable weight response at lower temperatures (thermoneutral region) followed by a decline as the temperatures increased. The weight loss was -125 g/°C beyond the moderate heat stress threshold (Tavg21 = 17.7 °C) and -450 g/°C beyond the severe heat stress threshold (Tavg21 = 25.3 °C) for Tavg21. The heat stress thresholds for moderate heat stress (HS1) were 8.6 °C for Tmin14, 27.4 °C for Tmax14, and 18.6 °C for Tavg14; moreover, for acute heat stress (HS2), they were 17.2 °C for Tmin14, 32.4 °C for Tmax14, and 25.5 °C for Tavg14. High variability in individual responses was observed, with differences in the slope of response ranging from 2.0 kg/°C for moderate heat stress to around 3.0 kg/°C for severe heat stress for Tavg. The correlations between the weights under different temperatures were low, indicating that rankings based on weight could change with varying heat conditions. The animals with larger weight levels generally demonstrated better heat tolerance, and those with good heat tolerance under moderate conditions were also likely to have good tolerance under severe conditions.

Longitudinal monitoring of hypertonia through a multimodal sensing glove

As clinical evaluations of neuromuscular disorders such as hypertonia mostly rely on perception-based scales, the imprecise subjective ratings make it difficult to accurately monitor treatment progress. To promote objective evaluation, this work used a multi-modal sensing glove in a double-blind study to enable sensitive monitoring of medication effects across 19 participants. The biomechanical measurements from the sensing glove effectively distinguished patient cohorts receiving a baclofen treatment or a placebo with 95% confidence. Consistent monitoring over a two-month period was demonstrated, closely tracking variations in individual responses to treatment. The biomechanical changes were correlated to neural activities as recorded by electromyography, verifying the medication effects. The sensing glove is shown to be a reliable tool for point-of-care settings to facilitate precise evaluation of hypertonia, essential for tailoring individual treatment choices and timely management of chronic symptoms.

Hierarchical Genomic Analysis of Susceptibility to Schizophrenia in Sudanese multi-case families

Background Schizophrenia, with its diverse and complex presentation, is a prime candidate for genetic investigation. Its heritability in both familial and sporadic cases, clinical overlap with other psychiatric conditions, and individual variations in response to treatment contribute to its complexity. Numerous genes and associated biochemical pathways show significant differences at the population, familial, and individual levels. Additionally, schizophrenia may represent an evolutionary trade-off for human brain development, creativity, and intellectual performance. Material and Methods This case pseudo-control study analyzed the whole genomes/exomes of seven Sudanese families with multiple siblings affected by schizophrenia. We examined shared variants among family members, including both cases and controls, and unique variants shared between patients but not controls. These variants were filtered based on their impact on protein function, expression levels, allele frequencies, ACMG classification for rare variants, and disease associations. Networks were created to identify central genes and common biological pathways. Results and Discussion The examination of this complex disorder in Sudanese families revealed numerous variants, both common and rare, showing differences between families and between our population and those reported in the literature. This highlights the challenge of accounting for the known heritability of the disease. Our hierarchical approach demonstrates that schizophrenia’s etiology involves the cumulative effect of various interacting variants in an ascending order of influence. Common variants are shared among all samples, while rare variants are shared among two or three families, most of which are associated with schizophrenia. In conclusion The significance lies not merely in the number of detected variants but in understanding their interactive roles, step by step, to reveal the complete picture of the disease’s phenotype.

Drivers of Wolf Activity in a Human-Dominated Landscape and Its Individual Variability Toward Anthropogenic Disturbance.

Wolves (Canis lupus) exhibit contrasted activity patterns along their distribution range. The shift from diurnal to nocturnal habits within and among populations appears to be primarily driven by localized levels of human activity, with ambivalent responses toward such disturbance reported among populations. Yet, the drivers and the underlying individual variability of temporal avoidance patterns toward human remains unexplored. We equipped 26 wolves with GPS-GSM collars, obtaining 54,721 locations. We used step lengths, turning angles, and accelerometer data from recorded locations to infer activity through hidden Markov models (Conners, M. G., T. Michelot, E. I. Heywood, et al. 2021. "Hidden Markov Models Identify Major Movement Modes in Accelerometer and Magnetometer Data From Four Albatross Species." Movement Ecology 9, no. 1: 1-16.). We further explored the probability of activity as a function of a set of proxies of anthropogenic disturbance at different spatial scales and its interaction with different periods of the day by fitting population-level and individual-based hidden Markov models. Wolves were predominantly active during dusk and night, yet variations in activity emerged among individuals across day periods. We did not find clear population-level effects of anthropogenic disturbance predictors, as these were masked by a wide range of individual-specific responses, which varied from positive to negative, with inter-individual variability in responses changing according to different predictors and periods of the day. Our results suggest a non-uniform strategy of wolves in adapting their behavior to human-dominated environments, further underscoring the role of vegetation patches acting as functional refuge cover for buffering the effects of anthropogenic disturbance and boosting the persistence of the species in human-dominated landscapes. This study, for the first time, reveals the individual variability in wolf responses to human disturbance. By fitting hidden Markov models to data from GPS-GSM collars deployed on 26 wolves, we found significant variation between individuals in their responses to different levels of anthropogenic pressure and across different times of day, highlighting a non-uniform strategy for coping with perturbations in human-dominated landscapes. Our findings underscore the diverse behavioral adjustments employed by wolves to persist in these environments and highlight the critical importance of vegetation patches serving as refuge cover.

Antibody response to SARS-CoV-2 mRNA vaccination in Danish adults exposed to perfluoroalkyl substances (PFASs): The ENFORCE study

IntroductionPer- and polyfluoroalkyl substances (PFASs) have immunotoxic effects in children while studies in adults, including recent studies on the SARS-CoV-2 vaccine response have been less consistent. In a cohort of 50–69-year-olds repeatedly vaccinated against COVID-19 in Denmark from early 2021, we aimed to assess the association between serum-PFAS concentrations and SARS-CoV-2 antibody responses. MethodsWe assessed serum-PFAS concentrations among 371 middle-aged adults from the National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE) who had received their first vaccination against COVID-19. Following the second dose and the booster (third) Pfizer-BioNTech mRNA vaccination, we measured the specific spike IgG antibody response. Associations between serum-PFAS concentrations at inclusion and spike IgG antibody concentrations after vaccination were assessed using median regression, and analyses were adjusted for age, sex, presence of diabetes, number of vaccines received, and time since vaccination. We further examined the associations between serum-PFAS concentrations at inclusion and changes in spike IgG antibody concentration between the second dose and booster (third) vaccination. ResultsSerum-PFAS concentrations were not associated with spike IgG antibody concentrations after the SARS-CoV-2 vaccinations, but the increase in response after the booster (third) vaccination compared to after the second vaccination was consistently lower at higher serum-PFAS concentrations. Each doubling in the concentration of seven serum-PFASs was associated with a 802 BAU/mL lower median increase in spike IgG antibody response after the booster (third) vaccination (95% CI: −1812; 208) adjusted for confounders. DiscussionAs many adults were probably not immunological naïve prior to vaccination, our results were likely affected by individual variability in immune response to the vaccination. Despite this uncertainty, the diminished increase in SARS-CoV-2 spike antibody response after the booster (third) vaccination at higher PFAS exposure may potentially reflect an immunotoxic impact of the PFASs.

Heritability of movie-evoked brain activity and connectivity.

The neural bases of sensory processing are conserved across people, but no two individuals experience the same stimulus in exactly the same way. Recent work has established that the idiosyncratic nature of subjective experience is underpinned by individual variability in brain responses to sensory information. However, the fundamental origins of this individual variability have yet to be systematically investigated. Here, we establish a genetic basis for individual differences in sensory processing by quantifying (1) the heritability of high-dimensional brain responses to movies and (2) the extent to which this heritability is grounded in lower-level aspects of brain function. Specifically, we leverage 7T fMRI data collected from a twin sample to first show that movie-evoked brain activity and connectivity patterns are heritable across the cortex. Next, we use hyperalignment to decompose this heritability into genetic similarity in where vs. how sensory information is processed. Finally, we show that the heritability of brain activity patterns can be partially explained by the heritability of the neural timescale, a one-dimensional measure of local circuit functioning. These results demonstrate that brain responses to complex stimuli are heritable, and that this heritability is due, in part, to genetic control over stable aspects of brain function.

Gene-based drug therapy for children and youth treated with psychoactive medications.

Psychoactive medications are increasingly used to treat children and youth with mental health conditions, but individual variations in response highlight the need for precision medicine. Pharmacogenetic (PGx) testing is a key component of precision medicine. The number of commercial pharmacogenetic testing companies promoting PGx, with the promise of achieving individualized and effective treatment of mental health conditions, has grown exponentially in recent years. Scientific evidence supporting the use of PGx to manage mental health conditions is limited, especially for paediatric populations. This practice point outlines steps guiding the use and interpretation of PGx testing for psychoactive medications in clinical settings, along with key supportive resources. Practice guidelines have been developed for variants in pharmacogenes encoding cytochrome P450 drug-metabolizing enzymes (e.g., CYP2C19, CYP2D6, CYP2C9) as one determinant of drug concentrations in blood, which can support both drug choice and dosing strategy for certain anti-psychotics, anti-depressants, and anti-epileptics. Adverse drug reactions to some anti-epileptic drugs (e.g., carbamazepine and phenytoin) have been associated with certain human leukocyte antigen types and variants in DNA polymerase gamma (POLG; valproic acid). Evidence remains limited for genetic variants of drug target proteins, making it challenging to identify patients with altered treatment responses at a therapeutic blood concentration.

Role of Probiotics and Prebiotics in Human Health: A Review

Probiotics and prebiotics are essential components in maintaining and enhancing human health, primarily through their beneficial effects on gut microbiota. Probiotics, which are live microorganisms, and prebiotics, which are non-digestible food components, work synergistically to improve digestive health, enhance immune function, and support metabolic health. The historical evolution of probiotics and prebiotics has demonstrated their wide-ranging health benefits, from preventing gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) to managing metabolic disorders like obesity and type 2 diabetes. Clinical applications highlight their role in reducing antibiotic-associated diarrhea, enhancing insulin sensitivity, and mitigating symptoms of allergies and autoimmune diseases. However, the field faces significant challenges, including the need for standardization and quality control, addressing individual variability in response, and ensuring safety and efficacy. The lack of uniform regulatory oversight further complicates the assurance of product reliability and effectiveness. Despite these challenges, emerging trends and innovations, such as next-generation probiotics and prebiotics, personalized nutrition based on microbiome profiles, and advances in biotechnology and bioinformatics, offer promising solutions. These advancements are poised to enhance the specificity and effectiveness of probiotic and prebiotic interventions. For example, genetically engineered probiotics and novel prebiotics derived from non-traditional sources are being explored for their unique health benefits. Personalized approaches can optimize dietary recommendations and supplement formulations based on individual gut microbiome compositions. Future research directions should focus on mechanistic studies to elucidate the specific pathways through which probiotics and prebiotics exert their effects, conducting robust and diverse clinical trials, and developing new strains and compounds from diverse sources. Regulatory frameworks need to be established to ensure the safety, efficacy, and quality of these products. By addressing these challenges and leveraging innovative approaches, probiotics and prebiotics can be optimized to provide personalized and effective health solutions, significantly impacting public health. Integrating these functional foods into daily dietary practices holds the potential for a new era of preventive and therapeutic nutrition, enhancing overall health and well-being.

Existence of multiple transitions of the critical state due to anesthetics

Scale-free statistics of coordinated neuronal activity, suggesting a universal operating mechanism across spatio-temporal scales, have been proposed as a necessary condition of healthy resting-state brain activity. Recent studies have focused on anesthetic agents to induce distinct neural states in which consciousness is altered to understand the importance of critical dynamics. However, variation in experimental techniques, species, and anesthetics, have made comparisons across studies difficult. Here we conduct a survey of several common anesthetics (isoflurane, pentobarbital, ketamine) at multiple dosages, using calcium wide-field optical imaging of the mouse cortex. We show that while low-dose anesthesia largely preserves scale-free statistics, surgical plane anesthesia induces multiple dynamical modes, most of which do not maintain critical avalanche dynamics. Our findings indicate multiple pathways away from default critical dynamics associated with quiet wakefulness, not only reflecting differences between these common anesthetics but also showing significant variations in individual responses. This is suggestive of a non-trivial relationship between criticality and the underlying state of the subject.

Impact of transcranial electrical stimulation on simultaneous stereoelectroencephalography recordings: A randomized sham-controlled study

ObjectiveClinical exploitation of transcranial electrical stimulation for focal epilepsy treatment lacks quantification of the underlying neurophysiological changes. This study explores the immediate effects of transcranial alternating (tACS) and direct (tDCS) current stimulation on local and network brain activity using simultaneous stereoelectroencephalography (SEEG) recordings. MethodsPatients were randomized for personalized tACS (n = 5) or tDCS (n = 6). Active stimulation (20 min) was preceded by sham stimulation (20 min). Changes in interictal epileptiform discharges (IED), functional connectivity (FC) and power spectral density (PSD) were quantified against baseline. ResultsResults demonstrated variable responses. Spike rate decreased in 2/6 subjects following sham and tDCS, while 2/6 showed an increase. Alpha power and aperiodic PSD components generally increased during and after tDCS but decreased following tACS. FC changes varied among subjects and were detectable even during sham sessions. ConclusionsStrong variability suggests that tES does not have a univocal effect on immediate changes in IED or FC, possibly due to the single session format and challenges in affecting subcortical areas. SignificanceThis is the first study to examine intracranial FC changes during tACS and tDCS, highlighting the importance of sham comparisons and individual variability in tES response, offering valuable insights into its application for epilepsy treatment.

Omega-3 Polyunsaturated Fatty Acids in Depression.

Omega-3 polyunsaturated fatty acids have received considerable attention in the field of mental health, in particular regarding the treatment of depression. This review presents an overview of current research on the role of omega-3 fatty acids in the prevention and treatment of depressive disorders. The existing body of evidence demonstrates that omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antidepressant effects that can be attributed to their modulation of neuroinflammation, neurotransmitter function, and neuroplasticity. Nevertheless, clinical trials of omega-3 supplementation have yielded inconsistent results. Some studies have demonstrated significant reductions in depressive symptoms following omega-3 treatment, whereas others have shown minimal to no beneficial impact. A range of factors, encompassing dosage, the ratio of EPA to DHA, and baseline nutritional status, have been identified as having a potential impact on the noted results. Furthermore, it has been suggested that omega-3 fatty acids may act as an adjunctive treatment for those undergoing antidepressant treatment. Notwithstanding these encouraging findings, discrepancies in study designs and variability in individual responses underscore the necessity of further research in order to establish uniform, standardized guidelines for the use of omega-3 fatty acids in the management of depressive disorders.