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Brain Imaging and Behavior Apr 2024Post-traumatic stress disorder (PTSD) is a debilitating condition which has been related to problems in emotional regulation, memory and cognitive control. Psychotherapy... (Meta-Analysis)
Meta-Analysis Review
Post-traumatic stress disorder (PTSD) is a debilitating condition which has been related to problems in emotional regulation, memory and cognitive control. Psychotherapy has a non-response rate of around 50% and understanding the neurobiological working mechanisms might help improve treatment. To integrate findings from multiple smaller studies, we performed the first meta-analysis of changes in brain activation with a specific focus on emotional processing after psychotherapy in PTSD patients. We performed a meta-analysis of brain activation changes after treatment during emotional processing for PTSD with seed-based d mapping using a pre-registered protocol (PROSPERO CRD42020211039). We analyzed twelve studies with 191 PTSD patients after screening 3700 studies. We performed systematic quality assessment both for the therapeutic interventions and neuroimaging methods. Analyses were done in the full sample and in a subset of studies that reported whole-brain results. We found decreased activation after psychotherapy in the left amygdala, (para)hippocampus, medial temporal lobe, inferior frontal gyrus, ventrolateral prefrontal cortex, right pallidum, anterior cingulate cortex, bilateral putamen, and insula. Decreased activation in the left amygdala and left ventrolateral PFC was also found in eight studies that reported whole-brain findings. Results did not survive correction for multiple comparisons. There is tentative support for decreased activation in the fear and cognitive control networks during emotional processing after psychotherapy for PTSD. Future studies would benefit from adopting a larger sample size, using designs that control for confounding variables, and investigating heterogeneity in symptom profiles and treatment response.
Topics: Humans; Stress Disorders, Post-Traumatic; Brain; Emotions; Psychotherapy; Brain Mapping; Magnetic Resonance Imaging
PubMed: 38049598
DOI: 10.1007/s11682-023-00831-0 -
Cancers Oct 2023The receptor for advanced glycation end-products (RAGE) has been implicated in driving prostate cancer (PCa) growth, aggression, and metastasis through the fueling of... (Review)
Review
The receptor for advanced glycation end-products (RAGE) has been implicated in driving prostate cancer (PCa) growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarizes and analyzes the current clinical and preclinical data to provide insight into the relationships among RAGE levels and PCa, cancer grade, and molecular effects. A multi-database search was used to identify original clinical and preclinical research articles examining RAGE expression in PCa. After screening and review, nine clinical and six preclinical articles were included. The associations of RAGE differentiating benign prostate hyperplasia (BPH) or normal prostate from PCa and between tumor grades were estimated using odds ratios (ORs) and associated 95% confidence intervals (CI). Pooled estimates were calculated using random-effect models due to study heterogeneity. The clinical meta-analysis found that RAGE expression was highly likely to be increased in PCa when compared to BPH or normal prostate (OR: 11.3; 95% CI: 4.4-29.1) and that RAGE was overexpressed in high-grade PCa when compared to low-grade PCa (OR: 2.5; 95% CI: 1.8-3.4). In addition, meta-analysis estimates of preclinical studies performed by albatross plot generation found robustly positive associations among RAGE expression/activation and PCa growth and metastatic potential. This review demonstrates that RAGE expression is strongly tied to PCa progression and can serve as an effective diagnostic target to differentiate between healthy prostate, low-grade PCa, and high-grade PCa, with potential theragnostic applications.
PubMed: 37835583
DOI: 10.3390/cancers15194889 -
Schizophrenia Bulletin Jan 2024Consistent with postmortem findings in patients, most animal models for schizophrenia (SCZ) present abnormal levels of parvalbumin (PV), a marker of fast-spiking... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Consistent with postmortem findings in patients, most animal models for schizophrenia (SCZ) present abnormal levels of parvalbumin (PV), a marker of fast-spiking GABAergic interneurons, in the prefrontal cortex (PFC) and hippocampus (HIP). However, there are discrepancies in the literature. PV reductions lead to a functional loss of PV interneurons, which is proposed to underly SCZ symptoms. Given its complex etiology, different categories of animal models have been developed to study SCZ, which may distinctly impact PV levels in rodent brain areas.
STUDY DESIGN
We performed a quantitative meta-analysis on PV-positive cell number/density and expression levels in the PFC and HIP of animal models for SCZ based on pharmacological, neurodevelopmental, and genetic manipulations.
RESULTS
Our results confirmed that PV levels are significantly reduced in the PFC and HIP regardless of the animal model. By categorizing into subgroups, we found that all pharmacological models based on NMDA receptor antagonism decreased PV-positive cell number/density or PV expression levels in both brain areas examined. In neurodevelopmental models, abnormal PV levels were confirmed in both brain areas in maternal immune activation models and HIP of the methylazoxymethanol acetate model. In genetic models, negative effects were found in neuregulin 1 and ERBB4 mutant mice in both brain regions and the PFC of dysbindin mutant mice. Regarding sex differences, male rodents exhibited PV reductions in both brain regions only in pharmacological models, while few studies have been conducted in females.
CONCLUSION
Overall, our findings support deficits in prefrontal and hippocampal PV interneurons in animal models for SCZ.
Topics: Humans; Mice; Male; Female; Animals; Schizophrenia; Parvalbumins; Disease Models, Animal; Interneurons; Prefrontal Cortex; Hippocampus
PubMed: 37584417
DOI: 10.1093/schbul/sbad123 -
Autism Research : Official Journal of... Dec 2023Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication and interaction, as well as rigid and unchanging interests... (Meta-Analysis)
Meta-Analysis Review
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication and interaction, as well as rigid and unchanging interests and behaviors. Several studies have reported that activated immune-inflammatory and nitro-oxidative pathways are accompanied by depletion of plasma tryptophan (TRP), increased competing amino acid (CAAs) levels, and activation of the TRP catabolite (TRYCAT) pathway. This study aims to systematically review and meta-analyze data on peripheral TRP, CAAs, TRYCAT pathway activity, and individual TRYCATs, including kynurenine (KYN) and kynurenic acid (KA) levels, in the blood and urine of ASD patients. After extensively searching PubMed, Google Scholar, and SciFinder, a total of 25 full-text papers were included in the analysis, with a total of 6653 participants (3557 people with ASD and 3096 healthy controls). Our results indicate that blood TRP and the TRP/CAAs ratio were not significantly different between ASD patients and controls (standardized mean difference, SMD = -0.227, 95% confidence interval, CI: -0.540; 0.085, and SMD = 0.158, 95% CI: -0.042; 0.359), respectively. The KYN/TRP ratio showed no significant difference between ASD and controls (SMD = 0.001, 95% CI: -0.169; 0.171). Blood KYN and KA levels were not significantly changed in ASD. Moreover, there were no significant differences in urine TRP, KYN, and KA levels between ASD and controls. We could not establish increases in neurotoxic TRYCATs in ASD. In conclusion, this study demonstrates no abnormalities in peripheral blood TRP metabolism, indoleamine 2,3-dioxygenase enzyme (IDO) activity, or TRYCAT production in ASD. Reduced TRP availability and elevated neurotoxic TRYCAT levels are not substantial contributors to ASD's pathophysiology.
Topics: Humans; Tryptophan; Kynurenine; Autism Spectrum Disorder; Kynurenic Acid
PubMed: 37909397
DOI: 10.1002/aur.3044 -
Infectious Diseases of Poverty Dec 2023Non-National Immunization Program (NIP) vaccines have played an important role in controlling vaccine-preventable diseases (VPDs) in China. However, these vaccines are... (Review)
Review
BACKGROUND
Non-National Immunization Program (NIP) vaccines have played an important role in controlling vaccine-preventable diseases (VPDs) in China. However, these vaccines are paid out of pocket and there is room to increase their coverage. We focused on four selected non-NIP vaccines in this study, namely Haemophilus influenzae type b (Hib) vaccine, human papillomavirus (HPV) vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine. We aimed to conduct a scoping review of their vaccination rates and the major barriers faced by health systems, providers, and caregivers to increase coverage.
METHODS
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). We searched five English databases (PubMed, Web of Science, EMBASE, Scopus, and WHO IRIS) and four Chinese databases using the search strategy developed by the study team. Two independent reviewers screened, selected studies, and examined their quality. We summarized the non-NIP vaccine coverage data by vaccine and applied the 5A framework (Access, Affordability, Acceptance, Awareness, Activation) to chart and analyze barriers to increasing coverage.
RESULTS
A total of 28 articles were included in the analysis (nine pertaining to vaccine coverage, and another 19 reporting challenges of increasing uptake). Among the four selected vaccines, coverage for the Hib vaccine was the highest (54.9-55.9% for 1 dose or more from two meta-analyses) in 2016, while the coverage of the other three vaccines was lower than 30%. Eight of the nine included articles mentioned the regional disparity of coverage, which was lower in under-developing regions. For example, the three-dose Hib vaccination rate in eastern provinces was 38.1%, whereas the rate in central and western provinces was 34.3% and 26.2%, respectively in 2017. Within the 5A framework, acceptance, awareness, and affordability stood out as the most prominent themes. Among the 12 identified sub-themes, high prices, low vaccine awareness, concerns about vaccine safety and efficacy were the most cited barriers to increasing the uptake.
CONCLUSIONS
There is an urgent need to increase coverage of non-NIP vaccines and reduce disparities in access to these vaccines across regions. Concerted efforts from the government, the public, and society are required to tackle the barriers and challenges identified in this study, both on the demand and supply side, to ensure everybody has equal access to life-saving vaccines in China. Particularly, the government should take a prudent approach to gradually incorporate non-NIP vaccines into the NIP step by step, and make a prioritizing strategy based on key factors such as disease burden, financial resources, and market readiness, with special attention to high-risk populations and underdeveloped regions.
Topics: Humans; Vaccines; Vaccination; Immunization Programs; China; Cost of Illness
PubMed: 38062480
DOI: 10.1186/s40249-023-01150-8 -
ESC Heart Failure Oct 2023Baroreflex activation therapy (BAT) is a possible adjuvant treatment for patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic... (Review)
Review
Baroreflex activation therapy (BAT) is a possible adjuvant treatment for patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy and may be an alternative therapy in patients with contraindications or drug intolerance. Our aim was to evaluate the efficacy and safety of BAT in patients with HFrEF. The protocol for this study was registered with PROSPERO (CRD42022349175). Searches were conducted using MEDLINE, preMedLine (via PubMed), EMBASE, Cochrane Library, Web of Science, Trip Medical Database, WHO International Clinical Trials Registry, and ClinicalTrials.gov. We included randomized controlled trials that compared the effects of BAT with pharmacological treatment. We assessed the risk of bias of each study using the Cochrane RoB2 tool and the certainty of the results using the GRADE approach. We performed a meta-analysis of treatment effects using a fixed-effects or random-effects model, depending on the heterogeneity observed. Two studies were included in the meta-analysis (HOPE4HF and BeAT-HF). The results showed that BAT led to statistically significant improvements in New York Heart Association functional class (relative risk 2.13; 95% confidence interval [CI, 1.65 to 2.76]), quality of life (difference in means -16.97; 95% CI [-21.87 to -12.07]), 6 min walk test (difference in means 56.54; 95% CI [55.67 to 57.41]) and N-terminal probrain natriuretic peptide (difference in means -120.02; 95% CI [-193.58 to -46.45]). The system- and procedure-related complication event-free rate varied from 85.9% to 97%. The results show that BAT is safe and improves functional class, quality of life and congestion in selected patients with HFrEF. Further studies and long-term follow-up are needed to assess efficacy in reducing cardiovascular events and mortality.
PubMed: 37522644
DOI: 10.1002/ehf2.14473 -
Archives of Rehabilitation Research and... Sep 2023To investigate the differences between erector spinae muscle activation in healthy individuals and patients with Chronic Lower Back Pain (CLBP) by conducting (a)... (Review)
Review
OBJECTIVE
To investigate the differences between erector spinae muscle activation in healthy individuals and patients with Chronic Lower Back Pain (CLBP) by conducting (a) systematic review and (b) meta-analysis.
DATA SOURCES
PubMed, ScienceDirect, SPORTDiscus, and Google Scholar were used to conduct the searches, which included studies up to the 31st of March 2023 with no start date specified.
STUDY SELECTION
Any study otherwise meeting eligibility criteria was included if it reported either (1) a standard mean difference effect size; or (2) the means, SDs, and sample sizes for both the patient group and the comparator group.
DATA EXTRACTION
A total of 7 case control trials were used for the systematic review and meta-analysis.
DATA SYNTHESIS
The systematic review and meta-analysis revealed that total standardized mean difference in erector spinae muscle activation between healthy individuals vs patients with CLBP expressed in % maximum voluntary isometric contraction was 0.48 (95% confidence interval=0.21-0.74; <.001) with the heterogeneity being I=0% (=.890). The electromyography (EMG) outputs showed significant differences in activation levels between the healthy and CLBP cohorts (<.001).
CONCLUSIONS
A small effect size was found in the meta-analysis. The muscle activation levels of the erector spinae during forward propulsion were higher in CLBP individuals compared with healthy cohorts. The findings provide more clarity about the muscles that were the focus of previous research, what procedures were used to evaluate muscular contributions and what speeds the participants were moving at during the test sessions. Given the limited methodological quality of the included studies, the findings should be interpreted with caution. Future research should evaluate the effect of other factors such as walking distance and any changes in walking surfaces and gradients (ie, non-flat surfaces).
PubMed: 37744192
DOI: 10.1016/j.arrct.2023.100280 -
Journal of Sports Science & Medicine Mar 2024The primary objective of this systematic review with meta-analysis is to methodically discern and compare the impact of diverse warm-up strategies, including both static... (Meta-Analysis)
Meta-Analysis Review
Examining the Influence of Warm-Up Static and Dynamic Stretching, as well as Post-Activation Potentiation Effects, on the Acute Enhancement of Gymnastic Performance: A Systematic Review with Meta-Analysis.
The primary objective of this systematic review with meta-analysis is to methodically discern and compare the impact of diverse warm-up strategies, including both static and dynamic stretching, as well as post-activation potentiation techniques, on the immediate performance of gymnasts. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this paper evaluated studies that examined the gymnasts' performance after different warm-up strategies namely stretching (static [SS] or dynamic), vibration platforms (VP) or post-activation, in comparison to control conditions (e.g., mixed warm-up routines; no warm-up). The principal outcomes were centered on technical performance metrics (e.g., split, gymnastic jumps) and physical performance metrics (e.g., squat jump, countermovement jump, drop jump, balance, range of motion). Methodological assessments of the included studies were conducted using the Downs and Black Checklist. From the initial search across PubMed, Scopus, and the Web of Science databases, a total of 591 titles were retrieved, and 19 articles were ultimately incorporated in the analysis. The results revealed a non-significant differences (p > 0.05) between the SS condition and control conditions in squat jump performance, countermovement jump and gymnastic technical performance (e.g., split; split jump). Despite the difference in warm-up strategies and outcomes analyzed, the results suggest that there is no significant impairment of lower-limb power after SS. Additionally, technical elements dependent on flexibility appear to be enhanced by SS. Conversely, dynamic stretching and VP seem to be more effective for augmenting power-related and dynamic performance in gymnasts.
Topics: Humans; Gymnastics; Muscle Stretching Exercises; Warm-Up Exercise; Lower Extremity; Range of Motion, Articular
PubMed: 38455430
DOI: 10.52082/jssm.2024.156 -
Cerebellum (London, England) Oct 2023The cerebellum's role in affective processing is increasingly recognized in the literature, but remains poorly understood, despite abundant clinical evidence for... (Meta-Analysis)
Meta-Analysis
The cerebellum's role in affective processing is increasingly recognized in the literature, but remains poorly understood, despite abundant clinical evidence for affective disruptions following cerebellar damage. To improve the characterization of emotion processing and investigate how attention allocation impacts this processing, we conducted a meta-analysis on task activation foci using GingerALE software. Eighty human neuroimaging studies of emotion including 2761 participants identified through Web of Science and ProQuest databases were analyzed collectively and then divided into two categories based on the focus of attention during the task: explicit or implicit emotion processing. The results examining the explicit emotion tasks identified clusters within the posterior cerebellar hemispheres (bilateral lobule VI/Crus I/II), the vermis, and left lobule V/VI that were likely to be activated across studies, while implicit tasks activated clusters including bilateral lobules VI/Crus I/II, right Crus II/lobule VIII, anterior lobule VI, and lobules I-IV/V. A direct comparison between these categories revealed five overlapping clusters in right lobules VI/Crus I/Crus II and left lobules V/VI/Crus I of the cerebellum common to both the explicit and implicit task contrasts. There were also three clusters activated significantly more for explicit emotion tasks compared to implicit tasks (right lobule VI, left lobule VI/vermis), and one cluster activated more for implicit than explicit tasks (left lobule VI). These findings support previous studies indicating affective processing activates both the lateral hemispheric lobules and the vermis of the cerebellum. The common and distinct activation of posterior cerebellar regions by tasks with explicit and implicit attention demonstrates the supportive role of this structure in recognizing, appraising, and reacting to emotional stimuli.
Topics: Humans; Cerebellum; Emotions; Cerebellar Vermis; Magnetic Resonance Imaging; Neuroimaging; Brain Mapping
PubMed: 35999332
DOI: 10.1007/s12311-022-01459-4 -
Cureus Sep 2023Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute... (Review)
Review
Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. The complement cascade plays an integral role in aHUS. Mutations in the complement cascade, especially in the alternative pathway (AP) lead to an unregulated and continuous activation of the cascade. Eculizumab and ravulizumab are humanized monoclonal antibodies that inhibit the complement cascade. This systematic analysis reviews the evidence for both antibodies to compare them in terms of safety and efficacy. This review will also assess the evidence for biomarker associations with interventions, the role of genetic mutations in the prognosis of disease, and the financial burden of both treatment options. An in-depth search was conducted across PubMed, Science Direct, and Cochrane Library following the PRISMA 2020 guidelines. Both eculizumab and ravulizumab were comparable in safety and efficacy but ravulizumab was preferred by patients and their caregivers as it posed a lower financial burden and had less frequent dosing. Soluble complement 5b-9 (sC5b), especially in urine, has the potential to be used as a biomarker to assess response to treatment. Genetic mutations, especially mutations in complement factor I (CFI), membrane cofactor protein (MCP), and complement factor H (CFH), were associated with a higher risk of recurrence, and therefore care should be taken when attempting to discontinue treatment in this subset of patients. Treatment with a monoclonal antibody should be initiated as soon as a genetic mutation is identified. Blinded, double-arm, clinical trials preferably with larger sample sizes are needed to effectively compare both the monoclonal antibodies.
PubMed: 37905269
DOI: 10.7759/cureus.46185