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Nutrients Sep 2023Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from... (Review)
Review
Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, and maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections and developing autoimmunity. This systematic review examines vitamin D's mechanisms and effects on enhancing innate and acquired immunity against microbes and preventing autoimmunity. The study evaluated the quality of evidence regarding biology, physiology, and aspects of human health on vitamin D related to infections and autoimmunity in peer-reviewed journal articles published in English. The search and analyses followed PRISMA guidelines. Data strongly suggested that maintaining serum 25(OH)D concentrations of more than 50 ng/mL is associated with significant risk reduction from viral and bacterial infections, sepsis, and autoimmunity. Most adequately powered, well-designed, randomized controlled trials with sufficient duration supported substantial benefits of vitamin D. Virtually all studies that failed to conclude benefits or were ambiguous had major study design errors. Treatment of vitamin D deficiency costs less than 0.01% of the cost of investigation of worsening comorbidities associated with hypovitaminosis D. Despite cost-benefits, the prevalence of vitamin D deficiency remains high worldwide. This was clear among those who died from COVID-19 in 2020/21-most had severe vitamin D deficiency. Yet, the lack of direction from health agencies and insurance companies on using vitamin D as an adjunct therapy is astonishing. Data confirmed that keeping an individual's serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) (and above 40 ng/mL in the population) reduces risks from community outbreaks, sepsis, and autoimmune disorders. Maintaining such concentrations in 97.5% of people is achievable through daily safe sun exposure (except in countries far from the equator during winter) or taking between 5000 and 8000 IU vitamin D supplements daily (average dose, for non-obese adults, ~70 to 90 IU/kg body weight). Those with gastrointestinal malabsorption, obesity, or on medications that increase the catabolism of vitamin D and a few other specific disorders require much higher intake. This systematic review evaluates non-classical actions of vitamin D, with particular emphasis on infection and autoimmunity related to the immune system.
Topics: Adult; Humans; Vitamin D; Autoimmunity; COVID-19; Immune System; Autoimmune Diseases; Vitamins; Vitamin D Deficiency
PubMed: 37686873
DOI: 10.3390/nu15173842 -
Phytomedicine : International Journal... Jul 2023Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between... (Review)
Review
BACKGROUND
Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between antioxidant defenses and reactive oxygen species, the skin no longer can keep its integrity and homeostasis. Chronic inflammation, premature skin aging, tissue damage, and immunosuppression are possible consequences induced by sustained exposure to environmental and endogenous reactive oxygen species. Skin immune and non-immune cells together with the microbiome are essential to efficiently trigger skin immune responses to stress. For this reason, an ever-increasing demand for novel molecules capable of modulating immune functions in the skin has risen the level of their development, particularly in the field of natural product-derived molecules.
PURPOSE
In this review, we explore different classes of molecules that showed evidence in modulate skin immune responses, as well as their target receptors and signaling pathways. Moreover, we describe the role of polyphenols, polysaccharides, fatty acids, peptides, and probiotics as possible treatments for skin conditions, including wound healing, infection, inflammation, allergies, and premature skin aging.
METHODS
Literature was searched, analyzed, and collected using databases, including PubMed, Science Direct, and Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., and several combinations of these keywords.
RESULTS
Natural products offer different solutions as possible treatments for several skin conditions. Significant antioxidant and anti-inflammatory activities were reported, followed by the ability to modulate immune functions in the skin. Several membrane-bound immune receptors in the skin recognize diverse types of natural-derived molecules, promoting different immune responses that can improve skin conditions.
CONCLUSION
Despite the increasing progress in drug discovery, several limiting factors need future clarification. Understanding the safety, biological activities, and precise mechanisms of action is a priority as well as the characterization of the active compounds responsible for that. This review provides directions for future studies in the development of new molecules with important pharmaceutical and cosmeceutical value.
Topics: Humans; Skin Aging; Reactive Oxygen Species; Biological Products; Antioxidants; Inflammation; Anti-Inflammatory Agents; Polyphenols; Peptides; Polysaccharides
PubMed: 37119762
DOI: 10.1016/j.phymed.2023.154824 -
British Journal of Sports Medicine Oct 2023Intention is the proximal antecedent of physical activity in many popular psychological models. Despite the utility of these models, the discrepancy between intention... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Intention is the proximal antecedent of physical activity in many popular psychological models. Despite the utility of these models, the discrepancy between intention and actual behaviour, known as the intention-behaviour gap, is a central topic of current basic and applied research. The purpose of this meta-analysis was to quantify intention-behaviour profiles and the intention-behaviour gap.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Literature search was conducted in June 2022 and updated in February 2023 in five databases.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Eligible studies included a measure of physical activity, an assessment of physical activity intention and the employment of the intention-behaviour relationship into profile quadrants. Only papers published in the English language and in peer-reviewed journals were considered. Screening was assisted by the artificial intelligence tool ASReview.
RESULTS
Twenty-five independent samples were selected from 22 articles including a total of N=29 600. Random-effects meta-analysis revealed that 26.0% of all participants were non-intenders not exceeding their intentions, 4.2% were non-intenders who exceeded their intentions, 33.0% were unsuccessful intenders and 38.7% were successful intenders. Based on the proportion of unsuccessful intenders to all intenders, the overall intention-behaviour gap was 47.6%.
CONCLUSION
The findings underscore that intention is a necessary, yet insufficient antecedent of physical activity for many. Successful translation of a positive intention into behaviour is nearly at chance. Incorporating mechanisms to overcome the intention-behaviour gap are recommended for clinical practice.
Topics: Humans; Intention; Artificial Intelligence; Exercise; Health Behavior
PubMed: 37460164
DOI: 10.1136/bjsports-2022-106640 -
Life Sciences Aug 2023Cortical spreading depolarization (CSD) is a wave of pathologic neuronal dysfunction that spreads through cerebral gray matter, causing neurologic disturbance in... (Review)
Review
AIMS
Cortical spreading depolarization (CSD) is a wave of pathologic neuronal dysfunction that spreads through cerebral gray matter, causing neurologic disturbance in migraine and promoting lesion development in acute brain injury. Pharmacologic interventions have been found to be effective in migraine with aura, but their efficacy in acutely injured brains may be limited. This necessitates the assessment of possible adjunctive treatments, such as nonpharmacologic methods. This review aims to summarize currently available nonpharmacological techniques for modulating CSDs, present their mechanisms of action, and provide insight and future directions for CSD treatment.
MAIN METHODS
A systematic literature review was performed, generating 22 articles across 3 decades. Relevant data is broken down according to method of treatment.
KEY FINDINGS
Both pharmacologic and nonpharmacologic interventions can mitigate the pathological impact of CSDs via shared molecular mechanisms, including modulating K/Ca/Na/Cl ion channels and NMDA, GABA, serotonin, and CGRP ligand-based receptors and decreasing microglial activation. Preclinical evidence suggests that nonpharmacologic interventions, including neuromodulation, physical exercise, therapeutic hypothermia, and lifestyle changes can also target unique mechanisms, such as increasing adrenergic tone and myelination and modulating membrane fluidity, which may lend broader modulatory effects. Collectively, these mechanisms increase the electrical initiation threshold, increase CSD latency, slow CSD velocity, and decrease CSD amplitude and duration.
SIGNIFICANCE
Given the harmful consequences of CSDs, limitations of current pharmacological interventions to inhibit CSDs in acutely injured brains, and translational potentials of nonpharmacologic interventions to modulate CSDs, further assessment of nonpharmacologic modalities and their mechanisms to mitigate CSD-related neurologic dysfunction is warranted.
Topics: Humans; Cortical Spreading Depression; Migraine Disorders; Serotonin; Neurons; Brain Injuries
PubMed: 37302793
DOI: 10.1016/j.lfs.2023.121833 -
Circulation. Cardiovascular... Sep 2023Short-term (≤6 months) dual antiplatelet therapy (DAPT) and DAPT de-escalation become attractive for patients with acute coronary syndrome. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Short-term (≤6 months) dual antiplatelet therapy (DAPT) and DAPT de-escalation become attractive for patients with acute coronary syndrome.
METHODS
A systemic search identified randomized controlled trials that included patients with acute coronary syndrome treated using (1) standard DAPT (12 months) with clopidogrel, prasugrel (standard/low dose), or ticagrelor; (2) extended DAPT (≥18 months); (3) short-term DAPT (≤6 months) followed by P2Y inhibitor or aspirin; (4) 12-month DAPT with unguided de-escalation from potent P2Y inhibitors to low-dose potent P2Y inhibitor or clopidogrel at 1 month; and (5) guided selection DAPT with genotype or platelet function tests. The primary efficacy outcome (major adverse cardiovascular events) was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding.
RESULTS
This meta-analysis included 32 randomized controlled trials with 103 497 patients. While there were no differences in efficacy between short, unguided de-escalation and guided selection strategies, unguided de-escalation was associated with reduced risk of major adverse cardiovascular events compared with standard DAPT with clopidogrel or ticagrelor (hazard ratio [95% CI], 0.67 [0.49-0.93] and 0.68 [0.50-0.93]). Both short DAPT followed by P2Y inhibitor and unguided de-escalation were associated with reduced risks in safety compared with other strategies, including guided selection (hazard ratio [95% CI], 0.66 [0.47-0.93] and 0.48 [0.33-0.71]). Short DAPT followed by a P2Y inhibitor was associated with reduced risk of major bleeding and all-cause death compared with standard, extended DAPT (eg, versus DAPT with clopidogrel; hazard ratio [95% CI], 0.64 [0.42-0.97] and 0.60 [0.44-0.82]). By rankogram, unguided de-escalation strategy was the safest and most effective strategy in reducing major adverse cardiovascular events and major or minor bleeding while short DAPT followed by P2Y inhibitor was ranked the best for major bleeding and all-cause death.
CONCLUSIONS
In patients with acute coronary syndrome, unguided de-escalation was associated with the lowest risk of major adverse cardiovascular events and major or minor bleeding outcomes, while short DAPT followed by P2Y inhibitor was associated with the lowest risk of major bleeding and all-cause death.
Topics: Humans; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Network Meta-Analysis; Clopidogrel; Ticagrelor; Treatment Outcome
PubMed: 37609850
DOI: 10.1161/CIRCINTERVENTIONS.123.013242 -
The Lancet. Psychiatry Mar 2024There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network meta-analysis to assess and compare the efficacy and safety of pharmacological treatments for psychotic depression.
METHODS
In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, Embase, PsycINFO, PubMed, Scopus, and Web of Science from inception to Nov 23, 2023 for randomised controlled trials published in any language that assessed pharmacological treatments for individuals of any age with a diagnosis of a major depressive episode with psychotic features, in the context of major depressive disorder or bipolar disorder in any setting. We excluded continuation or maintenance trials. We screened the study titles and abstracts identified, and we extracted data from relevant studies after full-text review. If full data were not available, we requested data from study authors twice. We analysed treatments for individual drugs (or drug combinations) and by grouping them on the basis of mechanisms of action. The primary outcomes were response rate (ie, the proportion of participants who responded to treatment) and acceptability (ie, the proportion who discontinued treatment for any reason). We calculated risk ratios and did separate frequentist network meta-analyses by using random-effects models. The risk of bias of individual studies was assessed with the Cochrane risk-of-bias tool and the confidence in the evidence with the Confidence-In-Network-Meta-Analysis (CINeMA). This study was registered with PROSPERO, CRD42023392926.
FINDINGS
Of 6313 reports identified, 16 randomised controlled trials were included in the systematic review, and 14 were included in the network meta-analyses. The 16 trials included 1161 people with psychotic depression (mean age 50·5 years [SD 11·4]). 516 (44·4%) participants were female and 422 (36·3%) were male; sex data were not available for the other 223 (19·2%). 489 (42·1%) participants were White, 47 (4·0%) were African American, and 12 (1·0%) were Asian; race or ethnicity data were not available for the other 613 (52·8%). Only the combination of fluoxetine plus olanzapine was associated with a higher proportion of participants with a treatment response compared with placebo (risk ratio 1·91 [95% CI 1·27-2·85]), with no differences in terms of safety outcomes compared with placebo. When treatments were grouped by mechanism of action, the combination of a selective serotonin reuptake inhibitor with a second-generation antipsychotic was associated with a higher proportion of treatment responses than was placebo (1·89 [1·17-3·04]), with no differences in terms of safety outcomes. In head-to-head comparisons of active treatments, a significantly higher proportion of participants had a response to amitriptyline plus perphenazine (3·61 [1·23-10·56]) and amoxapine (3·14 [1·01-9·80]) than to perphenazine, and to fluoxetine plus olanzapine compared with olanzapine alone (1·60 [1·09-2·34]). Venlafaxine, venlafaxine plus quetiapine (2·25 [1·09-4·63]), and imipramine (1·95 [1·01-3·79]) were also associated with a higher proportion of treatment responses overall. In head-to-head comparisons grouped by mechanism of action, antipsychotic plus antidepressant combinations consistently outperformed monotherapies from either drug class in terms of the proportion of participants with treatment responses. Heterogeneity was low. No high-risk instances were identified in the bias assessment for our primary outcomes.
INTERPRETATION
According to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic-and particularly of fluoxetine and olanzapine-could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies.
FUNDING
None.
Topics: Male; Female; Humans; Middle Aged; Depressive Disorder, Major; Fluoxetine; Perphenazine; Network Meta-Analysis; Bipolar Disorder; Venlafaxine Hydrochloride; Selective Serotonin Reuptake Inhibitors; Depression; Antipsychotic Agents; Olanzapine
PubMed: 38360024
DOI: 10.1016/S2215-0366(24)00006-3 -
Cells Dec 2023The greatest risk factor for neurodegeneration is the aging of the multiple cell types of human CNS, among which microglia are important because they are the "sentinels"... (Review)
Review
The greatest risk factor for neurodegeneration is the aging of the multiple cell types of human CNS, among which microglia are important because they are the "sentinels" of internal and external perturbations and have long lifespans. We aim to emphasize microglial signatures in physiologic brain aging and Alzheimer's disease (AD). A systematic literature search of all published articles about microglial senescence in human healthy aging and AD was performed, searching for PubMed and Scopus online databases. Among 1947 articles screened, a total of 289 articles were assessed for full-text eligibility. Microglial transcriptomic, phenotypic, and neuropathological profiles were analyzed comprising healthy aging and AD. Our review highlights that studies on animal models only partially clarify what happens in humans. Human and mice microglia are hugely heterogeneous. Like a two-sided coin, microglia can be protective or harmful, depending on the context. Brain health depends upon a balance between the actions and reactions of microglia maintaining brain homeostasis in cooperation with other cell types (especially astrocytes and oligodendrocytes). During aging, accumulating oxidative stress and mitochondrial dysfunction weaken microglia leading to dystrophic/senescent, otherwise over-reactive, phenotype-enhancing neurodegenerative phenomena. Microglia are crucial for managing Aβ, pTAU, and damaged synapses, being pivotal in AD pathogenesis.
Topics: Humans; Mice; Animals; Alzheimer Disease; Microglia; Healthy Aging; Aging; Brain
PubMed: 38132144
DOI: 10.3390/cells12242824 -
JAMA Network Open Dec 2023Prosocial interventions encourage voluntary actions that benefit others. Community solidarity in response to the COVID-19 pandemic, expanding mutual aid programs, and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Prosocial interventions encourage voluntary actions that benefit others. Community solidarity in response to the COVID-19 pandemic, expanding mutual aid programs, and health workforce issues have accelerated prosocial health interventions.
OBJECTIVE
To investigate the association of prosocial interventions with health outcomes in clinical trials and observational studies.
DATA SOURCES
In this systematic review and meta-analysis informed by the Cochrane Handbook for Systematic Reviews of Interventions, 5 databases (MEDLINE [via PubMed], Embase, CINAHL, PsycInfo, and Scopus) were searched from database inception through February 23, 2023. The search included terms for altruism and prosocial behaviors, health outcomes, and study type.
STUDY SELECTION
Included studies, determined by multiple reviewers, compared health outcomes in a prosocial intervention group with a nonintervention group.
DATA EXTRACTION AND SYNTHESIS
Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline, data extraction and synthesis captured quantitative and qualitative data. To pool data from quantitative studies, random-effects meta-analyses were used to estimate the impact of prosocial interventions. To combine data from quantitative and qualitive studies, data were transformed into qualitative narratives using meta-aggregation.
MAIN OUTCOMES AND MEASURES
The main outcome was whether prosocial interventions were associated with improved health outcomes. Barriers to and facilitators of implementation of these interventions were assessed.
RESULTS
The search identified 5229 citations; 30 studies were included in the synthesis. Studies indicated that prosocial interventions were associated with positive health outcomes for givers (17 studies [56.7]) and recipients (8 [26.7%]). Prosocial interventions included acts of kindness (12 studies [40.0%]), cash gifts (7 [23.3%]), pay-it-forward approaches (6 [20.0%]), and expressions of kindness (5 [16.7%]). Improvements were reported in depression, testing for sexually transmitted diseases, vaccine uptake, physical activity, and individual biomarkers. Data from 6 studies (20.0%) demonstrated that pay-it-forward approaches were associated with increased uptake of diagnostic tests or vaccines among vulnerable groups (moderate certainty of evidence). Data from 14 studies (46.7%) suggested that community connectedness facilitated prosocial interventions. Shared vulnerabilities among groups (eg, sexual minority individuals, older adults) may provide a context for collective mobilization to improve health in local communities.
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis found that prosocial interventions were associated with improved health outcomes among vulnerable groups and have been useful for addressing health disparities. Further research is needed to develop and evaluate prosocial interventions.
Topics: Humans; Aged; Pandemics; COVID-19
PubMed: 38064214
DOI: 10.1001/jamanetworkopen.2023.46789 -
Brain and Behavior Aug 2023Numerous studies have described the positive effects of action observation therapy (AOT) on motor recovery among patients with stroke. However, there is no standardized... (Review)
Review
BACKGROUND
Numerous studies have described the positive effects of action observation therapy (AOT) on motor recovery among patients with stroke. However, there is no standardized procedure for when and how to intervene with AOT.
OBJECTIVES
Thus, we reviewed and analyzed previous studies to provide a guideline for the application of AOT in stroke rehabilitation.
METHOD
We searched PubMed, Cochrane Library, and EMBASE from inception to October 31 2022, using title and abstract search terms of "action observation" and "stroke" or "hemiplegia." Of 4108 potential articles, 29 articles (sample size = 429 in AOT groups; sample size = 423 in control groups) that met inclusion criteria were included in final analyses.
RESULTS
The results suggested starting adjuvant AOT > 23 days after stroke onset and conducting 30-40 min/session, 3-5 times/week for at least 4 weeks.
CONCLUSION
Based on our results, many factors will impact the effect of AOT on stroke rehabilitation, when to apply (timing) and how to apply (frequency, single, and total duration) should be fully considered when applying AOT as adjuvant therapy in stroke rehabilitation.
Topics: Humans; Stroke Rehabilitation; Activities of Daily Living; Behavior Observation Techniques; Photic Stimulation; Movement; Gait
PubMed: 37480161
DOI: 10.1002/brb3.3157 -
Frontiers in Microbiology 2023Human cytomegalovirus (HCMV) is one of the main causes of serious complications in immunocompromised patients and after congenital infection. There are currently drugs... (Review)
Review
Human cytomegalovirus (HCMV) is one of the main causes of serious complications in immunocompromised patients and after congenital infection. There are currently drugs available to treat HCMV infection, targeting viral polymerase, whose use is complicated by toxicity and the emergence of resistance. Maribavir and letermovir are the latest antivirals to have been developed with other targets. The approval of letermovir represents an important innovation for CMV prevention in hematopoietic stem cell transplant recipients, whereas maribavir allowed improving the management of refractory or resistant infections in transplant recipients. However, in case of multidrug resistance or for the prevention and treatment of congenital CMV infection, finding new antivirals or molecules able to inhibit CMV replication with the lowest toxicity remains a critical need. This review presents a range of molecules known to be effective against HCMV. Molecules with a direct action against HCMV include brincidofovir, cyclopropavir and anti-terminase benzimidazole analogs. Artemisinin derivatives, quercetin and baicalein, and anti-cyclooxygenase-2 are derived from natural molecules and are generally used for different indications. Although they have demonstrated indirect anti-CMV activity, few clinical studies were performed with these compounds. Immunomodulating molecules such as leflunomide and everolimus have also demonstrated indirect antiviral activity against HCMV and could be an interesting complement to antiviral therapy. The efficacy of anti-CMV immunoglobulins are discussed in CMV congenital infection and in association with direct antiviral therapy in heart transplanted patients. All molecules are described, with their mode of action against HCMV, preclinical tests, clinical studies and possible resistance. All these molecules have shown anti-HCMV potential as monotherapy or in combination with others. These new approaches could be interesting to validate in clinical trials.
PubMed: 38053548
DOI: 10.3389/fmicb.2023.1321116