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Neuroscience and Biobehavioral Reviews Jul 2024H-Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique that can be used to quantify the concentrations of metabolites in the brain in vivo. MRS findings in... (Meta-Analysis)
Meta-Analysis Review
H-Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique that can be used to quantify the concentrations of metabolites in the brain in vivo. MRS findings in the context of autism are inconsistent and conflicting. We performed a systematic review and meta-analysis of MRS studies measuring glutamate and gamma-aminobutyric acid (GABA), as well as brain metabolites involved in energy metabolism (glutamine, creatine), neural and glial integrity (e.g. n-acetyl aspartate (NAA), choline, myo-inositol) and oxidative stress (glutathione) in autism cohorts. Data were extracted and grouped by metabolite, brain region and several other factors before calculation of standardised effect sizes. Overall, we find significantly lower concentrations of GABA and NAA in autism, indicative of disruptions to the balance between excitation/inhibition within brain circuits, as well as neural integrity. Further analysis found these alterations are most pronounced in autistic children and in limbic brain regions relevant to autism phenotypes. Additionally, we show how study outcome varies due to demographic and methodological factors , emphasising the importance of conforming with standardised consensus study designs and transparent reporting.
Topics: Humans; Autistic Disorder; Magnetic Resonance Spectroscopy; Brain; gamma-Aminobutyric Acid; Glutamic Acid
PubMed: 38796123
DOI: 10.1016/j.neubiorev.2024.105728 -
The Lancet. Infectious Diseases May 2024Targeted next-generation sequencing (NGS) can rapidly and simultaneously detect mutations associated with resistance to tuberculosis drugs across multiple gene targets....
BACKGROUND
Targeted next-generation sequencing (NGS) can rapidly and simultaneously detect mutations associated with resistance to tuberculosis drugs across multiple gene targets. The use of targeted NGS to diagnose drug-resistant tuberculosis, as described in publicly available data, has not been comprehensively reviewed. We aimed to identify targeted NGS assays that diagnose drug-resistant tuberculosis, determine how widely this technology has been used, and assess the diagnostic accuracy of these assays.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Library, Web of Science Core Collection, Global Index Medicus, Google Scholar, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform for published and unpublished reports on targeted NGS for drug-resistant tuberculosis from Jan 1, 2005, to Oct 14, 2022, with updates to our search in Embase and Google Scholar until Feb 13, 2024. Studies eligible for the systematic review described targeted NGS approaches to predict drug resistance in Mycobacterium tuberculosis infections using primary samples, reference strain collections, or cultured isolates from individuals with presumed or confirmed tuberculosis. Our search had no limitations on study type or language, although only reports in English, German, and French were screened for eligibility. For the meta-analysis, we included test accuracy studies that used any reference standard, and we assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcomes for the meta-analysis were sensitivity and specificity of targeted NGS to diagnose drug-resistant tuberculosis compared to phenotypic and genotypic drug susceptibility testing. We used a Bayesian bivariate model to generate summary receiver operating characteristic plots and diagnostic accuracy measures, overall and stratified by drug and sample type. This study is registered with PROSPERO, CRD42022368707.
FINDINGS
We identified and screened 2920 reports, of which 124 were eligible for our systematic review, including 37 review articles and 87 reports of studies collecting samples for targeted NGS. Sequencing was mainly done in the USA (14 [16%] of 87), western Europe (ten [11%]), India (ten [11%]), and China (nine [10%]). We included 24 test accuracy studies in the meta-analysis, in which 23 different tuberculosis drugs or drug groups were assessed, covering first-line drugs, injectable drugs, and fluoroquinolones and predominantly comparing targeted NGS with phenotypic drug susceptibility testing. The combined sensitivity of targeted NGS across all drugs was 94·1% (95% credible interval [CrI] 90·9-96·3) and specificity was 98·1% (97·0-98·9). Sensitivity for individual drugs ranged from 76·5% (52·5-92·3) for capreomycin to 99·1% (98·3-99·7) for rifampicin; specificity ranged from 93·1% (88·0-96·3) for ethambutol to 99·4% (98·3-99·8) for amikacin. Diagnostic accuracy was similar for primary clinical samples and culture isolates overall and for rifampicin, isoniazid, ethambutol, streptomycin, and fluoroquinolones, and similar after excluding studies at high risk of bias (overall sensitivity 95·2% [95% CrI 91·7-97·1] and specificity 98·6% [97·4-99·3]).
INTERPRETATION
Targeted NGS is highly sensitive and specific for detecting drug resistance across panels of tuberculosis drugs and can be performed directly on clinical samples. There is a paucity of data on performance for some currently recommended drugs. The barriers preventing the use of targeted NGS to diagnose drug-resistant tuberculosis in high-burden countries need to be addressed.
FUNDING
National Institutes of Allergy and Infectious Diseases and Swiss National Science Foundation.
PubMed: 38795712
DOI: 10.1016/S1473-3099(24)00263-9 -
International Journal of Molecular... May 2024Inherited muscular diseases (MDs) are genetic degenerative disorders typically caused by mutations in a single gene that affect striated muscle and result in progressive... (Review)
Review
Inherited muscular diseases (MDs) are genetic degenerative disorders typically caused by mutations in a single gene that affect striated muscle and result in progressive weakness and wasting in affected individuals. Cardiac muscle can also be involved with some variability that depends on the genetic basis of the MD (Muscular Dystrophy) phenotype. Heart involvement can manifest with two main clinical pictures: left ventricular systolic dysfunction with evolution towards dilated cardiomyopathy and refractory heart failure, or the presence of conduction system defects and serious life-threatening ventricular arrhythmias. The two pictures can coexist. In these cases, heart transplantation (HTx) is considered the most appropriate option in patients who are not responders to the optimized standard therapeutic protocols. However, cardiac transplant is still considered a relative contraindication in patients with inherited muscle disorders and end-stage cardiomyopathies. High operative risk related to muscle impairment and potential graft involvement secondary to the underlying myopathy have been the two main reasons implicated in the generalized reluctance to consider cardiac transplant as a viable option. We report an overview of cardiac involvement in MDs and its possible association with the underlying molecular defect, as well as a systematic review of HTx outcomes in patients with MD-related end-stage dilated cardiomyopathy, published so far in the literature.
Topics: Humans; Cardiomyopathy, Dilated; Heart Transplantation; Muscular Dystrophies
PubMed: 38791328
DOI: 10.3390/ijms25105289 -
Children (Basel, Switzerland) Apr 2024CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as... (Review)
Review
CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. The present study highlights the importance of considering the investigation of the CACNA1C gene in children's neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder.
PubMed: 38790536
DOI: 10.3390/children11050541 -
Cells May 2024This systematic review aims to gather evidence on the mechanisms triggered by diverse preconditioning strategies for mesenchymal stem cells (MSCs) and their impact on... (Review)
Review
This systematic review aims to gather evidence on the mechanisms triggered by diverse preconditioning strategies for mesenchymal stem cells (MSCs) and their impact on their potential to treat ischemic and traumatic injuries affecting the nervous system. The 52 studies included in this review report nine different types of preconditioning, namely, manipulation of oxygen pressure, exposure to chemical substances, lesion mediators or inflammatory factors, usage of ultrasound, magnetic fields or biomechanical forces, and culture in scaffolds or 3D cultures. All these preconditioning strategies were reported to interfere with cellular pathways that influence MSCs' survival and migration, alter MSCs' phenotype, and modulate the secretome and proteome of these cells, among others. The effects on MSCs' phenotype and characteristics influenced MSCs' performance in models of injury, namely by increasing the homing and integration of the cells in the lesioned area and inducing the secretion of growth factors and cytokines. The administration of preconditioned MSCs promoted tissue regeneration, reduced neuroinflammation, and increased angiogenesis and myelinization in rodent models of stroke, traumatic brain injury, and spinal cord injury. These effects were also translated into improved cognitive and motor functions, suggesting an increased therapeutic potential of MSCs after preconditioning. Importantly, none of the studies reported adverse effects or less therapeutic potential with these strategies. Overall, we can conclude that all the preconditioning strategies included in this review can stimulate pathways that relate to the therapeutic effects of MSCs. Thus, it would be interesting to explore whether combining different preconditioning strategies can further boost the reparative effects of MSCs, solving some limitations of MSCs' therapy, namely donor-associated variability.
Topics: Humans; Mesenchymal Stem Cells; Animals; Mesenchymal Stem Cell Transplantation; Nervous System Diseases
PubMed: 38786067
DOI: 10.3390/cells13100845 -
JMIR MHealth and UHealth May 2024Unaddressed early-stage mental health issues, including stress, anxiety, and mild depression, can become a burden for individuals in the long term. Digital phenotyping... (Review)
Review
BACKGROUND
Unaddressed early-stage mental health issues, including stress, anxiety, and mild depression, can become a burden for individuals in the long term. Digital phenotyping involves capturing continuous behavioral data via digital smartphone devices to monitor human behavior and can potentially identify milder symptoms before they become serious.
OBJECTIVE
This systematic literature review aimed to answer the following questions: (1) what is the evidence of the effectiveness of digital phenotyping using smartphones in identifying behavioral patterns related to stress, anxiety, and mild depression? and (2) in particular, which smartphone sensors are found to be effective, and what are the associated challenges?
METHODS
We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) process to identify 36 papers (reporting on 40 studies) to assess the key smartphone sensors related to stress, anxiety, and mild depression. We excluded studies conducted with nonadult participants (eg, teenagers and children) and clinical populations, as well as personality measurement and phobia studies. As we focused on the effectiveness of digital phenotyping using smartphones, results related to wearable devices were excluded.
RESULTS
We categorized the studies into 3 major groups based on the recruited participants: studies with students enrolled in universities, studies with adults who were unaffiliated to any particular organization, and studies with employees employed in an organization. The study length varied from 10 days to 3 years. A range of passive sensors were used in the studies, including GPS, Bluetooth, accelerometer, microphone, illuminance, gyroscope, and Wi-Fi. These were used to assess locations visited; mobility; speech patterns; phone use, such as screen checking; time spent in bed; physical activity; sleep; and aspects of social interactions, such as the number of interactions and response time. Of the 40 included studies, 31 (78%) used machine learning models for prediction; most others (n=8, 20%) used descriptive statistics. Students and adults who experienced stress, anxiety, or depression visited fewer locations, were more sedentary, had irregular sleep, and accrued increased phone use. In contrast to students and adults, less mobility was seen as positive for employees because less mobility in workplaces was associated with higher performance. Overall, travel, physical activity, sleep, social interaction, and phone use were related to stress, anxiety, and mild depression.
CONCLUSIONS
This study focused on understanding whether smartphone sensors can be effectively used to detect behavioral patterns associated with stress, anxiety, and mild depression in nonclinical participants. The reviewed studies provided evidence that smartphone sensors are effective in identifying behavioral patterns associated with stress, anxiety, and mild depression.
Topics: Humans; Depression; Stress, Psychological; Anxiety; Phenotype; Smartphone
PubMed: 38780995
DOI: 10.2196/40689 -
Cureus Apr 2024This systematic review aimed to explore the antimicrobial activity of a silver-containing gelling fiber dressing against multidrug-resistant organisms (MDROs) in wound... (Review)
Review
This systematic review aimed to explore the antimicrobial activity of a silver-containing gelling fiber dressing against multidrug-resistant organisms (MDROs) in wound infections. It particularly focuses on burn wounds and evaluates its potential clinical significance in combating antimicrobial resistance. A comprehensive literature search was conducted across multiple databases over the past ten years. It is used to identify relevant studies addressing MDRO infections in wound care and exploring novel antimicrobial approaches. The included studies underwent rigorous methodological assessment. Additionally, the data were synthesized to evaluate the efficacy of silver-containing dressings in inhibiting MDRO growth and eradicating biofilm-associated bacteria. Moreover, this review revealed that silver-containing dressings have constant in vitro antimicrobial activity against 10 MDROs over seven days in simulated wound fluid. However, inhibitory and bactericidal effects were consistently observed against free-living and biofilm phenotypes. The findings suggest potential clinical significance in managing MDRO infections in wounds. This highlights its role in mitigating treatment failure and antimicrobial resistance. Despite the promising implications for wound management practices, this study acknowledges some limitations. In vitro models and the absence of direct clinical validation have also been included. However, the review explains the importance of new approaches. Nanotechnology has been used to address antimicrobial resistance in wound care. Thus, further research and innovation are needed to improve patient outcomes and combat antimicrobial resistance.
PubMed: 38779271
DOI: 10.7759/cureus.58760 -
BMJ Mental Health May 2024Hypersexuality (HS) accompanying neurological conditions remains poorly characterized despite profound psychosocial impacts. We aimed to systematically review the...
BACKGROUND
Hypersexuality (HS) accompanying neurological conditions remains poorly characterized despite profound psychosocial impacts. We aimed to systematically review the literature on HS in patients with neurological disorders. We conducted a systematic review to identify studies that reported HS in neurological disorders. HS was defined as a condition characterized by excessive and persistent preoccupation with sexual thoughts, urges, and behaviors that cause significant distress or impairment in personal, social, or occupational functioning. Data on demographics, assessment techniques, associated elements, phenotypic manifestations, and management strategies were also extracted. The final analysis included 79 studies on HS, encompassing 32 662 patients across 81 cohorts with neurological disorders. Parkinson's disease was the most frequently studied condition (55.6%), followed by various types of dementia (12.7%). Questionnaires were the most common assessment approach for evaluating HS, although the techniques varied substantially. Alterations in the dopaminergic pathways have emerged as contributing mechanisms based on the effects of medication cessation. However, standardized treatment protocols still need to be improved, with significant heterogeneity in documented approaches. Critical deficiencies include risks of selection bias in participant sampling, uncontrolled residual confounding factors, and lack of blinded evaluations of reported outcomes. Despite growth in the last decade, research on HS remains limited across neurological conditions, with lingering quality and methodological standardization deficits. Key priorities include advancing assessment tools, elucidating the underlying neurobiology, and formulating management guidelines.
PROSPERO REGISTRATION NUMBER
CRD42017036478.
Topics: Humans; Nervous System Diseases; Sexual Dysfunctions, Psychological; Male; Female; Parkinson Disease; Sexual Behavior
PubMed: 38777563
DOI: 10.1136/bmjment-2024-300998 -
Clinical Neurophysiology : Official... Jul 2024Fibromyalgia Syndrome (FMS), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are similar multisymptom clinical syndromes but with... (Review)
Review
Fibromyalgia Syndrome (FMS), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are similar multisymptom clinical syndromes but with difference in dominant symptoms in each individual. There is existing and emerging literature on possible functional alterations of the central nervous system in these conditions. This review aims to synthesise and appraise the literature on resting-state quantitative EEG (qEEG) in FMS, ME/CFS and LC, drawing on previous research on FMS and ME/CFS to help understand neuropathophysiology of the new condition LC. A systematic search of MEDLINE, Embase, CINHAL, PsycINFO and Web of Science databases for articles published between December 1994 and September 2023 was performed. Out of the initial 2510 studies identified, 17 articles were retrieved that met all the predetermined selection criteria, particularly of assessing qEEG changes in one of the three conditions compared to healthy controls. All studies scored moderate to high quality on the Newcastle-Ottawa scale. There was a general trend for decreased low-frequency EEG band activity (delta, theta, and alpha) and increased high-frequency EEG beta activity in FMS, differing to that found in ME/CFS. The limited LC studies included in this review focused mainly on cognitive impairments and showed mixed findings not consistent with patterns observed in FMS and ME/CFS. Our findings suggest different patterns of qEEG brainwave activity in FMS and ME/CFS. Further research is required to explore whether there are phenotypes within LC that have EEG signatures similar to FMS or ME/CFS. This could inform identification of reliable diagnostic markers and possible targets for neuromodulation therapies tailored to each clinical syndrome.
Topics: Humans; Fatigue Syndrome, Chronic; Fibromyalgia; COVID-19; Electroencephalography; Brain
PubMed: 38772083
DOI: 10.1016/j.clinph.2024.04.019 -
PloS One 2024Stem cell research, particularly in the domain of induced pluripotent stem cell (iPSC) technology, has shown significant progress. The integration of artificial...
BACKGROUND
Stem cell research, particularly in the domain of induced pluripotent stem cell (iPSC) technology, has shown significant progress. The integration of artificial intelligence (AI), especially machine learning (ML) and deep learning (DL), has played a pivotal role in refining iPSC classification, monitoring cell functionality, and conducting genetic analysis. These enhancements are broadening the applications of iPSC technology in disease modelling, drug screening, and regenerative medicine. This review aims to explore the role of AI in the advancement of iPSC research.
METHODS
In December 2023, data were collected from three electronic databases (PubMed, Web of Science, and Science Direct) to investigate the application of AI technology in iPSC processing.
RESULTS
This systematic scoping review encompassed 79 studies that met the inclusion criteria. The number of research studies in this area has increased over time, with the United States emerging as a leading contributor in this field. AI technologies have been diversely applied in iPSC technology, encompassing the classification of cell types, assessment of disease-specific phenotypes in iPSC-derived cells, and the facilitation of drug screening using iPSC. The precision of AI methodologies has improved significantly in recent years, creating a foundation for future advancements in iPSC-based technologies.
CONCLUSIONS
Our review offers insights into the role of AI in regenerative and personalized medicine, highlighting both challenges and opportunities. Although still in its early stages, AI technologies show significant promise in advancing our understanding of disease progression and development, paving the way for future clinical applications.
Topics: Induced Pluripotent Stem Cells; Humans; Artificial Intelligence; Regenerative Medicine; Machine Learning
PubMed: 38771829
DOI: 10.1371/journal.pone.0302537