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Current Issues in Molecular Biology Apr 2024Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in... (Review)
Review
Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in delaying the onset and progression of Parkinson's disease by rebalancing the gut microbiome in the context of the gut-brain axis. Our study aims to organize recent findings regarding these interventions in Parkinson's disease animal models to identify how they affect neuroinflammation and motor outcomes. A systematic literature search was applied in PubMed, Web of Science, Embase, and SCOPUS for gut microbiome-targeted non-dietary interventions. Studies that investigated gut-targeted interventions by using in vivo murine PD models to follow dopaminergic cell loss, motor tests, and neuroinflammatory markers as outcomes were considered to be eligible. A total of 1335 studies were identified in the databases, out of which 29 were found to be eligible. A narrative systematization of the resulting data was performed, and the effect direction for the outcomes was represented. Quality assessment using the SYRCLE risk of bias tool was also performed. Out of the 29 eligible studies, we found that a significant majority report that the intervention reduced the dopaminergic cell loss (82.76%, 95% CI [64.23%, 94.15%]) produced by the induction of the disease model. Also, most studies reported a reduction in microglial (87.5%, 95% CI [61.65%, 98.45%]) and astrocytic activation (84,62%, 95% CI [54.55%, 98.08%]) caused by the induction of the disease model. These results were also mirrored in the majority (96.4% 95% CI [81.65%, 99.91%]) of the studies reporting an increase in performance in behavioral motor tests. A significant limitation of the study was that insufficient information was found in the studies to assess specific causes of the risk of bias. These results show that non-dietary gut microbiome-targeted interventions can improve neuroinflammatory and motor outcomes in acute Parkinson's disease animal models. Further studies are needed to clarify if these benefits transfer to the long-term pathogenesis of the disease, which is not yet fully understood. The study had no funding source, and the protocol was registered in the PROSPERO database with the ID number CRD42023461495.
PubMed: 38785512
DOI: 10.3390/cimb46050244 -
Frontiers in Psychiatry 2024There is a lack of robust research investigating the association between neurocognitive impairments and chronic tobacco smoking in adolescents/young adults. Therefore, a...
There is a lack of robust research investigating the association between neurocognitive impairments and chronic tobacco smoking in adolescents/young adults. Therefore, a systematic review and meta-analysis were conducted to examine this association by pooling cross-sectional studies published from 1980 to 2023. The systematic review assessed the neurocognitive performances between chronic tobacco smokers and non-smokers in each study. The meta-analysis included six studies that compared chronic tobacco smokers against non-smokers using neuropsychological tests covering three neurocognitive domains. The results showed a cross-sectional association between impairpments in across two aspects: and , with the effect size being (SDM = 0.615, p = 0.000) and (SDM = 0.593, p = 0.000) respectively. However, no significant associations were found for (SDM = 0.221, p = 0.425) or (SDM = 0.150, p = 0.581). This study highlights the need for further research to explore a greater number of neurocognitive domains in the context of chronic smoking in adolescents/young adults, particularly motor impulsivity, intelligence and working memory, as well as the socioeconomic factors involved. There is also a need to further study the effects of emerging alternative nicotine administration methods in this age group.
PubMed: 38716120
DOI: 10.3389/fpsyt.2024.1384408 -
Neurobiology of Disease Jul 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial... (Meta-Analysis)
Meta-Analysis
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.
Topics: Humans; Autism Spectrum Disorder; Biomarkers; DNA, Mitochondrial; Mitochondria; Mitochondrial Diseases
PubMed: 38703861
DOI: 10.1016/j.nbd.2024.106520 -
Revista Paulista de Pediatria : Orgao... 2024To describe the long-term health outcomes of neonates affected by necrotizing enterocolitis (NEC) and its implications for quality of life. (Review)
Review
OBJECTIVE
To describe the long-term health outcomes of neonates affected by necrotizing enterocolitis (NEC) and its implications for quality of life.
DATA SOURCE
This is an integrative review, conducted by searching the literature in the following databases: Virtual Health Library (BVS), Latin American and Caribbean Health Sciences Literature (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), and PubMed, using Health Sciences Descriptors (DeCS): "necrotizing enterocolitis," "quality of life," and "prognosis" combined with the Boolean operators AND and OR: "quality of life" OR "prognosis." Inclusion criteria were: publication period between 2012 and 2022.
DATA SYNTHESIS
A total of 1,010 studies were located, of which ten were selected to comprise the bibliographic sample of this review. Children with NEC are prone to exhibit cognitive neurological impairment, especially those who undergo surgical procedures due to more severe conditions. Motor development was considered below average when compared to healthy children, with more noticeable delays in fine and gross motor function development. The search for the relationship between NEC and quality of life revealed that this condition has a negative impact on the well-being of affected individuals.
CONCLUSIONS
NEC has proven to be a serious condition contributing to high rates of morbidity and mortality in newborns, potentially leading to a reduction in the quality of life of affected patients.
Topics: Humans; Infant, Newborn; Enterocolitis, Necrotizing; Prognosis; Quality of Life
PubMed: 38695420
DOI: 10.1590/1984-0462/2024/42/2023188 -
Journal of Neuromuscular Diseases 2024The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD).
METHODS
This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included "Duchenne muscular dystrophy" as a Medical Subject Heading or free text term, in combination with variations of the term "predictor". Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model.
RESULTS
The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40-0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3-7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49-50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias.
CONCLUSION
Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.
Topics: Muscular Dystrophy, Duchenne; Humans; Glucocorticoids; Walking; Pregnenediones; Latent TGF-beta Binding Proteins
PubMed: 38669554
DOI: 10.3233/JND-230220 -
International Journal of Public Health 2024This systematic review aims to assess the relationship between prenatal and childhood exposure to phthalates and neurodevelopmental outcomes, identifying periods of... (Meta-Analysis)
Meta-Analysis Review
This systematic review aims to assess the relationship between prenatal and childhood exposure to phthalates and neurodevelopmental outcomes, identifying periods of heightened susceptibility. Data sources considered studies examining repeated phthalate exposure during pregnancy and childhood on neurodevelopment. Evaluation included bias risk and study quality criteria. Evidence was synthesized by groups of low and high phthalate molecular weight and exposure measured prenatally and postnatally and outcome measured in childhood. Beta coefficients and their standard errors were extracted, leading to meta-analyses of various neurodevelopmental outcomes: cognition, motor skills, language, behavior, and temperament. Eleven pregnancy and birth cohort studies were identified as relevant. For each phthalate group and outcome combination, there was low or very low evidence of an association, except for prenatal and postnatal phthalate exposure and behavioral development and postnatal exposure and cognition. The estimated effects sizes were relatively small and strong evidence for periods of heightened susceptibility could not be elucidated. No distinction between phthalates of low molecular weight and those of high molecular weight with regards to the outcomes was found.
Topics: Child; Female; Pregnancy; Humans; Phthalic Acids; Cohort Studies; Cognition; Prenatal Exposure Delayed Effects; Environmental Exposure
PubMed: 38590582
DOI: 10.3389/ijph.2024.1606802 -
Journal of Gerontological Nursing Apr 2024To systematically review the prevalence of motoric cognitive risk syndrome (MCR) among community-dwelling older adults and provide evidence-based support for... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To systematically review the prevalence of motoric cognitive risk syndrome (MCR) among community-dwelling older adults and provide evidence-based support for policymakers planning health and social care policies.
METHOD
Web of Science, PubMed, and Cochrane Library databases were searched for cross-sectional, prospective cohort, or population-based longitudinal studies of community-dwelling older adults aged ≥60 years with MCR from inception of the database through December 18, 2021.
RESULTS
Seventeen studies were included. Pooled prevalence of MCR was found to be 10% (95% confidence interval [8%, 12%], I = 98.4%). Results of a subgroup analysis revealed a combined prevalence of MCR of 8.2% in males and 9.2% in females. Pooled prevalence of MCR was 9.7% in Asia and 10.2% in other regions.
CONCLUSION
Prevalence of MCR in community-dwelling older adults is high. Our research may improve the epidemiological understanding of MCR, draw attention to older adults with MCR, and thus promote research of MCR and the formulation of relevant public health policies. With early identification and intervention of MCR, cognitive function can be improved, and the onset of dementia can be delayed or prevented. [(4), 16-24.].
Topics: Male; Female; Humans; Aged; Cognition Disorders; Independent Living; Prospective Studies; Prevalence; Cross-Sectional Studies; Cognition; Risk Factors; Cognitive Dysfunction
PubMed: 38569106
DOI: 10.3928/00989134-20240312-01 -
Biomolecules Feb 2024Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published.
METHODS
We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology.
RESULTS
A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs' involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date.
CONCLUSIONS
It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.
Topics: Child; Adult; Humans; Epilepsy; Mutation; Cerebellum; Phenotype; Brain Injuries; Vesicular Transport Proteins
PubMed: 38540691
DOI: 10.3390/biom14030270 -
Antioxidants (Basel, Switzerland) Mar 2024Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities.... (Review)
Review
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities. Although pharmacological interventions have revealed promising prospects in the management of SCA3, adverse effects may become unbearable. The use of herbal remedies in traditional Chinese medicine (TCM) may serve as potential alternative medicines to delay the progression of the disease. This systematic review is intended to identify, appraise, and summarize the findings of studies pertaining to the therapeutic roles of herbal remedies in TCM targeting oxidative stress in the management of SCA3. A literature search for relevant articles published from 1 January 2013 to 30 June 2023 in three databases, namely PubMed, Web of Science, and Scopus, was carried out according to the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of ten preclinical studies met the inclusion criteria of the systematic review. We recognized the therapeutic potential of , , sp., , , , , , sp., , , , , and . We identified the types of preclinical models expressing polyglutamine (polyQ) expanded mutant protein (mATXN3), inducers of oxidative stress that mimic the SCA3 pathogenesis, and effective doses of the herbal remedies. The modes of action contributing to the attenuation of oxidative stress are activation of antioxidant pathways, ubiquitin-proteasome system and autophagy, regulation of apoptosis, proinflammatory signaling pathway and chaperones, regulation of mitochondrial function and biogenesis, and restoration of neurotransmission and synaptic plasticity. In conclusion, herbal remedies in TCM may possibly delay the progression of SCA3, therefore providing justification for clinical trials.
PubMed: 38539908
DOI: 10.3390/antiox13030375 -
Archivos Argentinos de Pediatria Apr 2024Cerebral palsy is associated with complications such as low bone mineral density, which is more severe in patients with greater motor involvement. Assisted standing...
Cerebral palsy is associated with complications such as low bone mineral density, which is more severe in patients with greater motor involvement. Assisted standing helps to prevent or delay this complication; however, its effect is controversial because the type of stander, the type of standing (dynamic or static), and its dosage are not clear. The objective of this study was to determine the effectiveness of assisted standing on bone mineral density in children with cerebral palsy. A systematic review was carried out in compliance with the PRISMA guidelines, using 5 databases. The results were presented using tables, a risk of bias analysis, and a narrative synthesis. Four studies met the inclusion criteria. Assisted standing generates positive changes in bone mineral density, but further research is required, with studies that have greater methodological rigor, longer follow-up periods, and a larger number of patients.
PubMed: 38527242
DOI: 10.5546/aap.2023-10251.eng