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MedRxiv : the Preprint Server For... Dec 2023Traumatic brain injury (TBI) has been discussed as a risk factor for Alzheimer's disease (AD) due to its association with dementia risk and earlier cognitive symptom...
Traumatic brain injury (TBI) has been discussed as a risk factor for Alzheimer's disease (AD) due to its association with dementia risk and earlier cognitive symptom onset. However, the mechanisms behind this relationship are unclear. Some studies have suggested TBI may increase pathological protein deposition in an AD-like pattern; others have failed to find such associations. This review covers literature that uses positron emission tomography (PET) of amyloid-β and/or tau to examine subjects with history of TBI who are at risk for AD due to advanced age. A comprehensive literature search was conducted on January 9, 2023, and 24 resulting citations met inclusion criteria. Common methodological concerns included small samples, limited clinical detail about subjects' TBI, recall bias due to reliance on self-reported TBI, and an inability to establish causation. For both amyloid and tau, results were widespread but inconsistent. The regions which showed the most compelling evidence for increased amyloid deposition were the cingulate gyrus, cuneus/precuneus, and parietal lobe. Evidence for increased tau was strongest in the medial temporal lobe, entorhinal cortex, precuneus, and frontal, temporal, parietal, and occipital lobes. However, conflicting findings across most regions of interest in both amyloid- and tau-PET studies indicate the critical need for future work in expanded samples and with greater clinical detail to offer a clearer picture of the relationship between TBI and protein deposition in older subjects at risk for AD.
PubMed: 38077068
DOI: 10.1101/2023.11.30.23298528 -
Journal of Alzheimer's Disease : JAD 2024A key aspect of synaptic dysfunction in Alzheimer's disease (AD) is loss of synaptic proteins. Previous publications showed that the presynaptic machinery is more... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A key aspect of synaptic dysfunction in Alzheimer's disease (AD) is loss of synaptic proteins. Previous publications showed that the presynaptic machinery is more strongly affected than postsynaptic proteins. However, it has also been reported that presynaptic protein loss is highly variable and shows region- and protein-specificity.
OBJECTIVE
The objective of this meta-analysis was to provide an update on the available literature and to further characterize patterns of presynaptic protein loss in AD.
METHODS
Systematic literature search was conducted for studies published between 2015-2022 which quantified presynaptic proteins in postmortem tissue from AD patients and healthy controls. Three-level random effects meta-analyses of twenty-two identified studies was performed to characterize overall presynaptic protein loss and changes in specific regions, proteins, protein families, and functional categories.
RESULTS
Meta-analysis confirmed overall loss of presynaptic proteins in AD patients. Subgroup analysis revealed region specificity of protein loss, with largest effects in temporal and frontal cortex. Results concerning different groups of proteins were also highly variable. Strongest and most consistently affected was the family of synaptosome associated proteins, especially SNAP25. Among the most severely affected were proteins regulating dense core vesicle exocytosis and the synaptic vesicle cycle.
CONCLUSIONS
Results confirm previous literature related to presynaptic protein loss in AD patients and provide further in-depth characterization of most affected proteins and presynaptic functions.
Topics: Humans; Alzheimer Disease; Proteins; Presynaptic Terminals
PubMed: 38073390
DOI: 10.3233/JAD-231034 -
Psychiatry Research Jan 2024Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a... (Meta-Analysis)
Meta-Analysis
Addiction is a substantial health concern; craving-the core symptom of addiction-is strongly associated with relapse. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that reduces cravings by altering cortical excitability and connectivity in brain regions. This systematic review and meta-analysis was conducted (following the PRISMA guidelines) to evaluate the efficacy of tDCS in reducing cravings for substances. Our analysis included 43 randomized, sham-controlled trials involving 1,095 and 913 participants receiving tDCS and sham stimulation, respectively. We analyzed the changes in craving scores and found that tDCS led to a moderate reduction in cravings compared with the sham effects. This effect was particularly pronounced when bilateral stimulation was used, the anodal electrode was placed on the right dorsolateral prefrontal cortex, current intensities ranged from 1.5 to 2 mA, stimulation sessions lasted 20 minutes, and the electrodes size was ≥35 cm². Notably, tDCS effectively reduced cravings for opioids, methamphetamine, cocaine, and tobacco but not for alcohol or cannabis. Our findings indicate tDCS as a promising, noninvasive, and low-risk intervention for reducing cravings for opioids, methamphetamine, cocaine, and tobacco. Additional studies are warranted to refine stimulation parameters and evaluate the long-term efficacy of tDCS in managing substance cravings.
Topics: Humans; Transcranial Direct Current Stimulation; Craving; Prefrontal Cortex; Substance-Related Disorders; Methamphetamine; Cocaine; Double-Blind Method
PubMed: 38043411
DOI: 10.1016/j.psychres.2023.115621 -
Neuroscience and Biobehavioral Reviews Jan 2024Mothers exposed to infections during pregnancy disproportionally birth children who develop autism and schizophrenia, disorders associated with altered GABAergic... (Review)
Review
Mothers exposed to infections during pregnancy disproportionally birth children who develop autism and schizophrenia, disorders associated with altered GABAergic function. The maternal immune activation (MIA) model recapitulates this risk factor, with many studies also reporting disruptions to GABAergic interneuron expression, protein, cellular density and function. However, it is unclear if there are species, sex, age, region, or GABAergic subtype specific vulnerabilities to MIA. Furthermore, to fully comprehend the impact of MIA on the GABAergic system a synthesised account of molecular, cellular, electrophysiological and behavioural findings was required. To this end we conducted a systematic review of GABAergic interneuron changes in the MIA model, focusing on the prefrontal cortex and hippocampus. We reviewed 102 articles that revealed robust changes in a number of GABAergic markers that present as gestationally-specific, region-specific and sometimes sex-specific. Disruptions to GABAergic markers coincided with distinct behavioural phenotypes, including memory, sensorimotor gating, anxiety, and sociability. Findings suggest the MIA model is a valid tool for testing novel therapeutics designed to recover GABAergic function and associated behaviour.
Topics: Male; Pregnancy; Female; Animals; Child; Humans; Rodentia; Interneurons; Prefrontal Cortex; Mothers; Behavior, Animal; Disease Models, Animal; Prenatal Exposure Delayed Effects
PubMed: 38042358
DOI: 10.1016/j.neubiorev.2023.105488 -
Frontiers in Psychology 2023Conventional Buddhist texts illustrate meditation as a condition of relaxed alertness that must fend against extreme hypoarousal (sleep, drowsiness) and extreme...
Conventional Buddhist texts illustrate meditation as a condition of relaxed alertness that must fend against extreme hypoarousal (sleep, drowsiness) and extreme hyperarousal (restlessness). Theoretical, neurophysiological, and neuroimaging investigations of meditation have highlighted the relaxing effects and hypoarousing without emphasizing the alertness-promoting effects. Here we performed a systematic review supported by an activation-likelihood estimate (ALE) meta-analysis in an effort to counterbalance the surfeit of scholarship emphasizing the hypoarousing and relaxing effects of different forms of Buddhist meditation. Specifically, the current systematic review-cum-meta-analytical review seeks to highlight more support for meditation's wake-promoting effects by drawing from neuroimaging research during wakefulness and meditation. In this systematic review and meta-analysis of 22 fMRI studies, we aim to highlight support for Buddhist meditation's wake-promoting or arousing effects by identifying brain regions associated with alertness during meditation. The most significant peaks were localized medial frontal gyrus (MFG) and precuneus. We failed to determine areas ostensibly common to alertness-related meditation such as the medial prefrontal cortex (mPFC), superior parietal lobule, basal ganglia, thalamus, most likely due to the relatively fewer fMRI investigations that used wakefulness-promoting meditation techniques. Also, we argue that forthcoming research on meditation, related to alertness or wakefulness, continues to adopt a multi-modal method to investigate the correlation between actual behaviors and neural networks connected to Buddhist meditation. Moreover, we recommend the implementation of fMRI paradigms on Buddhist meditation with clinically diagnosed participants to complement recent trends in psychotherapy such as mindfulness-based cognitive therapy (MBCT).
PubMed: 38022985
DOI: 10.3389/fpsyg.2023.1136983 -
PloS One 2023Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential... (Meta-Analysis)
Meta-Analysis
Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential therapies for outpatients with coronavirus disease 2019 (COVID-19). However, inhaled corticosteroids have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of inhaled corticosteroids in patients with COVID-19. Randomized controlled trials comparing the efficacy of inhaled corticosteroid treatment in patients with COVID-19 were identified through literature electronic database searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach. Overall, seven trials (eight articles) were included in this systematic review. Compared with usual care, inhaled corticosteroids was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, inhaled corticosteroids use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty. Although based on limited evidence, our results suggest that inhaled corticosteroids treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. More trials and meta-analyses are needed to assess the efficacy of inhaled corticosteroids for COVID-19 treatment.
Topics: Humans; COVID-19; COVID-19 Drug Treatment; Adrenal Cortex Hormones; Budesonide; Treatment Outcome
PubMed: 38015868
DOI: 10.1371/journal.pone.0294872 -
Respiratory Medicine Jan 2024Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to...
Systematic literature review of traits and outcomes reported in randomised controlled trials of asthma with regular dosing of inhaled corticosteroids with short-acting β-agonist reliever, as-needed ICS/formoterol, or ICS/formoterol maintenance and reliever therapy.
INTRODUCTION
Asthma treatments based solely on diagnostic label do not benefit patients equally. To identify patient traits that may be associated with improved treatment response to regular inhaled corticosteroid (ICSs) dosing with short-acting β-agonist reliever or ICS/formoterol-containing therapy, a systematic literature review (SLR) was conducted.
METHODS
Searches of databases including MEDLINE and Embase identified randomised controlled trials (RCTs) of patients with asthma, aged ≥12 years, published 1998-2022, containing ≥1 regular ICS dosing or ICS/formoterol-containing treatment arm, and reporting patient traits and outcomes of interest. Relevant data was extracted and underwent a feasibility assessment to determine suitability for meta-analysis.
RESULTS
The SLR identified 39 RCTs of 72,740 patients and 90 treatment arms, reporting 11 traits and 11 outcomes. Five patient traits (age, body mass index, FEV, smoking history, asthma control) and five outcomes (exacerbation rate, lung function, asthma control, adherence, time to first exacerbation) were deemed feasible for inclusion in meta-analyses due to sufficient comparable reporting. Subgroups of clinical outcomes stratified by levels of patient traits were reported in 16 RCTs.
CONCLUSION
A systematic review of studies of regular ICS dosing with SABA or ICS/formoterol-containing treatment strategies in asthma identified consistent reporting of five traits and outcomes, allowing exploration of associations with treatment response. Conversely, many other traits and outcomes, although being potentially relevant, were inconsistently reported and limited subgroup reporting meant analyses of treatment response for subgroups of traits was not possible. We recommend more consistent measurement and reporting of clinically relevant patient traits and outcomes in respiratory RCTs.
Topics: Humans; Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Formoterol Fumarate; Randomized Controlled Trials as Topic; Meta-Analysis as Topic
PubMed: 38008385
DOI: 10.1016/j.rmed.2023.107478 -
Developmental Cognitive Neuroscience Dec 2023Resting-state functional connectivity (rsFC) has the potential to shed light on how childhood abuse and neglect relates to negative psychiatric outcomes. However, a... (Review)
Review
Resting-state functional connectivity (rsFC) has the potential to shed light on how childhood abuse and neglect relates to negative psychiatric outcomes. However, a comprehensive review of the impact of childhood maltreatment on the brain's resting state functional organization has not yet been undertaken. We systematically searched rsFC studies in children and youth exposed to maltreatment. Nineteen studies (total n = 3079) met our inclusion criteria. Two consistent findings were observed. Childhood maltreatment was linked to reduced connectivity between the anterior insula and dorsal anterior cingulate cortex, and with widespread heightened amygdala connectivity with key structures in the salience, default mode, and prefrontal regulatory networks. Other brain regions showing altered connectivity included the ventral anterior cingulate cortex, dorsolateral prefrontal cortex, and hippocampus. These patterns of altered functional connectivity associated with maltreatment exposure were independent of symptoms, yet comparable to those seen in individuals with overt clinical disorder. Summative findings indicate that rsFC alterations associated with maltreatment experience are related to poor cognitive and social functioning and are prognostic of future symptoms. In conclusion, maltreatment is associated with altered rsFC in emotional reactivity, regulation, learning, and salience detection brain circuits. This indicates patterns of recalibration of putative mechanisms implicated in maladaptive developmental outcomes.
Topics: Adolescent; Humans; Child; Brain; Amygdala; Brain Mapping; Gyrus Cinguli; Child Abuse; Magnetic Resonance Imaging
PubMed: 37952287
DOI: 10.1016/j.dcn.2023.101322 -
Journal of Crohn's & Colitis May 2024Patients with inflammatory bowel disease [IBD] have a more than two fold higher risk of venous thromboembolic events [VTE] than the general population. The aetiology is... (Meta-Analysis)
Meta-Analysis
Anti-tumor Necrosis Factor Alpha Versus Corticosteroids: A 3-fold Difference in the Occurrence of Venous Thromboembolism in Inflammatory Bowel Disease-A Systematic Review and Meta-analysis.
BACKGROUND AND AIMS
Patients with inflammatory bowel disease [IBD] have a more than two fold higher risk of venous thromboembolic events [VTE] than the general population. The aetiology is complex, and the role of medication is not precisely defined. We aimed to assess the effects of anti-tumor necrosis factor alpha [anti-TNFα] drugs and conventional anti-inflammatory therapy, namely corticosteroids [CS], immunomodulators [IM], and 5-aminosalicylates [5-ASA] on VTE in IBD.
METHODS
A systematic search was performed in five databases on November 22, 2022. We included studies reporting VTE in the distinct categories of medications, determined the proportions, and calculated the odds ratios [OR] with 95% confidence intervals [CI], using the random-effects model. The risk of bias was evaluated with the Joanna Briggs Institute Critical Appraisal Checklist and the Risk of Bias in Non-randomized Studies of Interventions tool.
RESULTS
The quantitative analysis included 16 observational studies, with data from 91 322 IBD patients. Patients receiving anti-TNFα medication had significantly less VTE [proportion: 0.05, CI: 0.02-0.10], than patients treated with CS [proportion: 0.16, CI: 0.07-0.32], with OR = 0.42 [CI: 0.25-0.71]. IMs resulted in similar proportions of VTE compared with biologics [0.05, CI: 0.03-0.10], with OR = 0.94 [CI: 0.67-1.33]. The proportion of patients receiving 5-ASA having VTE was 0.09 [CI: 0.04-0.20], with OR = 1.00 [CI: 0.61-1.62].
CONCLUSIONS
Biologics should be preferred over corticosteroids in cases of severe flare-ups and multiple VTE risk factors, as they are associated with reduced odds of these complications. Further studies are needed to validate our data.
Topics: Humans; Venous Thromboembolism; Inflammatory Bowel Diseases; Adrenal Cortex Hormones; Tumor Necrosis Factor-alpha; Mesalamine
PubMed: 37952112
DOI: 10.1093/ecco-jcc/jjad193 -
Reumatologia Clinica Nov 2023Olecranon bursitis (OB), characterized by inflammation and fluid collection in the olecranon bursa is a commonly encountered out-patient condition. The data is...
OBJECTIVE
Olecranon bursitis (OB), characterized by inflammation and fluid collection in the olecranon bursa is a commonly encountered out-patient condition. The data is heterogeneous regarding a stepwise and standardized approach to aseptic OB treatment and the efficacy of intra-bursal corticosteroid injections (CSI). The objective of this review is to systematically evaluate the non-surgical treatment options for aseptic OB.
METHODS
This systematic review was conducted in accordance with PRISMA recommendations. The English and non-English literature search was performed in 5 medical databases to identify studies evaluating the treatment of OB. All included studies were evaluated for risk of bias (RoB) using the revised Cochrane RoB tool for randomized control trials (RCTs) and the Newcastle-Ottawa Scale (NOS) for case-control and cohort studies.
RESULTS
For the final analyses, 2 RCTs and 2 observational studies were included. The RoB for the RCTs was high and both failed to demonstrate a significant difference in terms of the resolution of OB and bursal tenderness among various invasive and non-invasive treatment options. Corticosteroid injection (CSI) was associated with a significant decline in the duration of symptoms. However, it was associated with a higher number of complications including bursal infection and skin atrophy.
CONCLUSION
Based on the available data, it appears that the clinical resolution of aseptic OB can occur with conservative methods if implemented earlier in the disease course. Although CSI is more effective than other treatments, it should be reserved for refractory cases because of a higher complication rate.
Topics: Humans; Olecranon Process; Elbow Joint; Bursitis; Adrenal Cortex Hormones
PubMed: 37945181
DOI: 10.1016/j.reumae.2023.05.004