-
The Ocular Surface Jul 2024Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular... (Review)
Review
Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular or systemic condition that damages the trigeminal nerve can lead to corneal neuropathy. However, the condition currently does not have standardized diagnostic criteria or treatment protocols. The primary aim of this systematic review was to evaluate the efficacy and safety of interventions for treating corneal neuropathy. Randomized controlled trials (RCTs) that investigated corneal neuropathy treatments were eligible if the intervention(s) was compared to a placebo or active comparator. Comprehensive searches were conducted in Ovid MEDLINE, Ovid Embase and clinical trial registries from inception to July 2022. The Cochrane Risk-of-Bias 2 tool was used to assess study methodological quality. Certainty of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 RCTs were included. Evaluated interventions comprised regenerative therapies (n = 6 studies), dietary supplements (n = 4), anti-glycemic agents (n = 3), combination therapy (n = 3), supportive therapies (n = 2) and systemic pain pharmacotherapies (n = 2). Nine RCTs were judged at high risk of bias for most outcomes. Definitions for corneal neuropathy in the populations varied substantially across studies, consistent with lack of consensus on diagnostic criteria. A diverse range of outcomes were quantified, likely reflecting absence of an agreed core outcome set. There was insufficient evidence to draw definitive conclusions on the efficacy or safety of any intervention. There was low or very low certainty evidence for several neuroregenerative agents and dietary supplements for improving corneal nerve fiber length in corneal neuropathy due to dry eye disease and diabetes. Low or very low certainty evidence was found for neuroregenerative therapies and dietary supplements not altering corneal immune cell density. This review identifies a need to standardize the clinical definition of corneal neuropathy and define a minimum set of core outcome measures. Together, this will provide a foundation for improved phenotyping of clinical populations in studies, and improve the capacity to synthesize data to inform evidence-based care. Protocol registration: PROSPERO ID: CRD42022348475.
Topics: Humans; Cornea; Corneal Diseases; Randomized Controlled Trials as Topic; Trigeminal Nerve Diseases; Quality of Life
PubMed: 38688453
DOI: 10.1016/j.jtos.2024.04.004 -
The subcortical default mode network and Alzheimer's disease: a systematic review and meta-analysis.Brain Communications 2024The default mode network is a central cortical brain network suggested to play a major role in several disorders and to be particularly vulnerable to the...
The default mode network is a central cortical brain network suggested to play a major role in several disorders and to be particularly vulnerable to the neuropathological hallmarks of Alzheimer's disease. Subcortical involvement in the default mode network and its alteration in Alzheimer's disease remains largely unknown. We performed a systematic review, meta-analysis and empirical validation of the subcortical default mode network in healthy adults, combined with a systematic review, meta-analysis and network analysis of the involvement of subcortical default mode areas in Alzheimer's disease. Our results show that, besides the well-known cortical default mode network brain regions, the default mode network consistently includes subcortical regions, namely the thalamus, lobule and vermis IX and right Crus I/II of the cerebellum and the amygdala. Network analysis also suggests the involvement of the caudate nucleus. In Alzheimer's disease, we observed a left-lateralized cluster of decrease in functional connectivity which covered the medial temporal lobe and amygdala and showed overlap with the default mode network in a portion covering parts of the left anterior hippocampus and left amygdala. We also found an increase in functional connectivity in the right anterior insula. These results confirm the consistency of subcortical contributions to the default mode network in healthy adults and highlight the relevance of the subcortical default mode network alteration in Alzheimer's disease.
PubMed: 38665961
DOI: 10.1093/braincomms/fcae128 -
Schizophrenia Research May 2024Motor and cognitive alterations in schizophrenia-spectrum disorders (SSD) share common neural underpinnings, highlighting the necessity for a thorough exploration of the... (Review)
Review
Motor and cognitive alterations in schizophrenia-spectrum disorders (SSD) share common neural underpinnings, highlighting the necessity for a thorough exploration of the connections between these areas. This relationship is crucial, as it holds potential significance in unraveling the underlying mechanisms of SSD pathophysiology, ultimately leading to advancements in clinical staging and treatment strategies. The purpose of this review was to characterize the relationship between different hyper and hypokinetic domains of motor alterations and cognition in SSD. We systematically searched the literature (PROSPERO protocol CRD42019145964) and selected 66 original scientific contributions for review, published between 1987 and 2022. A narrative synthesis of the results was conducted. Hyper and hypokinetic motor alterations showed weak to moderate negative correlations with cognitive function across different SSD stages, including before antipsychotic treatment. The literature to date shows a diverse set of methodologies and composite cognitive scores hampering a strong conclusion about which specific cognitive domains were more linked to each group of motor alterations. However, executive functions seemed the domain more consistently associated with parkinsonism with the results regarding dyskinesia being less clear. Akathisia and catatonia were scarcely discussed in the reviewed literature. The present review reinforces the intimate relationship between specific motor alterations and cognition. Identified gaps in the literature challenge the formulation of definitive conclusions. Nevertheless, a discussion of putative underlying mechanisms is included, prompting guidance for future research endeavors.
Topics: Humans; Schizophrenia; Cognitive Dysfunction; Executive Function
PubMed: 38640851
DOI: 10.1016/j.schres.2024.04.014 -
Neural Regeneration Research Dec 2024The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and...
The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies. Despite the need for non-invasively accessible biomarkers, the majority of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers, which require invasive collection procedures. Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers. In the present study, after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease, we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients. A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289 articles. After screening and exclusion, 34 relevant articles were derived for systematic review. Alpha-synuclein, the histopathological hallmark of Parkinson's disease, has been the most investigated Parkinson's disease biomarker in saliva, with oligomeric alpha-synuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls, while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein, and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease. Beyond alpha-synuclein, other biomarkers targeting different molecular pathways have been explored in the saliva of Parkinson's disease patients: total tau, phosphorylated tau, amyloid-β1-42 (pathological protein aggregation biomarkers); DJ-1, heme-oxygenase-1, metabolites (altered energy homeostasis biomarkers); MAPLC-3beta (aberrant proteostasis biomarker); cortisol, tumor necrosis factor-alpha (inflammation biomarkers); DNA methylation, miRNA (DNA/RNA defects biomarkers); acetylcholinesterase activity (synaptic and neuronal network dysfunction biomarkers); Raman spectra, proteome, and caffeine. Despite a few studies investigating biomarkers targeting molecular pathways different from alpha-synuclein in Parkinson's disease, these results should be replicated and observed in studies on larger cohorts, considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes. Although the need for standardization in sample collection and processing, salivary-based biomarkers studies have reported encouraging results, calling for large-scale longitudinal studies and multicentric assessments, given the great molecular potentials and the non-invasive accessibility of saliva.
PubMed: 38595280
DOI: 10.4103/NRR.NRR-D-23-01677 -
Diagnostic Microbiology and Infectious... Jul 2024Increasing evidence has indicated dysbiosis of the gut microbiota in patients with pulmonary tuberculosis (PTB). However, the change in the intestinal microbiota varies... (Review)
Review
Increasing evidence has indicated dysbiosis of the gut microbiota in patients with pulmonary tuberculosis (PTB). However, the change in the intestinal microbiota varies between different studies. This systematic review was conducted to investigate the characteristics of the gut microbiota in PTB patients. The MBASE, MEDLINE, Web of Science, and Cochrane Library electronic databases were systematically searched, and the quality of the retrieved studies was evaluated using the Newcastle-Ottawa scale. A total of 12 studies were finally included in the systematic review. Compared with healthy controls, the index reflecting α-diversity including the richness and/or diversity index decreased in 6 studies, while β-diversity presented significant differences in PTB patients in 10 studies. Although the specific gut microbiota alterations were inconsistent, short-chain fatty acid-producing bacteria (including Lachnospiraceae, Ruminococcus, Blautia, Dorea, and Faecalibacterium), bacteria associated with an inflammatory state (e.g., Prevotellaceae and Prevotella), and beneficial bacteria (e.g., Bifidobacteriaceae and Bifidobacterium) were commonly noted. Our systematic review identifies key evidence for gut microbiota alterations in PTB patients, in comparison with healthy controls; however, no consistent conclusion could be drawn, due to the inconsistent results and heterogeneous methodologies of the enrolled studies. Therefore, more well-designed research with standard methodologies and large sample sizes is required.
Topics: Humans; Gastrointestinal Microbiome; Tuberculosis, Pulmonary; Dysbiosis; Bacteria
PubMed: 38581928
DOI: 10.1016/j.diagmicrobio.2024.116291 -
Neuropsychobiology 2024Neurobiological dysfunction is associated with depression in children and adolescents. While research in adult depression suggests that inflammation may underlie the... (Review)
Review
INTRODUCTION
Neurobiological dysfunction is associated with depression in children and adolescents. While research in adult depression suggests that inflammation may underlie the association between depression and brain alterations, it is unclear if altered levels of inflammatory markers provoke neurobiological dysfunction in early-onset depression. The aim of this scoping review was to provide an overview of existing literature investigating the potential interaction between neurobiological function and inflammation in depressed children and adolescents.
METHODS
Systematic searches were conducted in six databases. Primary research studies that included measures of both neurobiological functioning and inflammation among children (≤18 years) with a diagnosis of depression were included.
RESULTS
Four studies (240 participants; mean age 16.0 ± 0.6 years, 62% female) meeting inclusion criteria were identified. Studies primarily examined the inflammatory markers interleukin 6, tumor necrosis factor alpha, C-reactive protein, and interleukin 1 beta. Exploratory whole brain imaging and analysis as well as region of interest approaches focused on the anterior cingulate cortex, basal ganglia, and white matter tracts were conducted. Most studies found correlations between neurobiological function and inflammatory markers; however, depressive symptoms were not observed to moderate these effects.
CONCLUSIONS
A small number of highly heterogeneous studies indicate that depression may not modulate the association between altered inflammation and neurobiological dysfunction in children and adolescents. Replication in larger samples using consistent methodological approaches (focus on specific inflammatory markers, examine certain brain areas) is needed to advance the knowledge of potential neuro-immune interactions early in the course of depression.
Topics: Humans; Adolescent; Child; Inflammation; Brain; Depression; Female; Male; Neuroinflammatory Diseases; Depressive Disorder
PubMed: 38574476
DOI: 10.1159/000538060 -
Therapeutic Advances in Gastroenterology 2024Despite numerous metabolomic studies on ulcerative colitis (UC), the results have been highly variable, making it challenging to identify key metabolic abnormalities in... (Review)
Review
BACKGROUND
Despite numerous metabolomic studies on ulcerative colitis (UC), the results have been highly variable, making it challenging to identify key metabolic abnormalities in UC.
OBJECTIVES
This study aims to uncover key metabolites and metabolic pathways in UC by analyzing existing metabolomics data.
DESIGN
A systematic review.
DATA SOURCES AND METHODS
We conducted a comprehensive search in databases (PubMed, Cochrane Library, Embase, and Web of Science) and relevant study references for metabolomic research on UC up to 28 December 2022. Significant metabolite differences between UC patients and controls were identified, followed by an analysis of relevant metabolic pathways.
RESULTS
This review incorporated 78 studies, identifying 2868 differentially expressed metabolites between UC patients and controls. The metabolites were predominantly from 'lipids and lipid-like molecules' and 'organic acids and derivatives' superclasses. We found 101 metabolites consistently altered in multiple datasets within the same sample type and 78 metabolites common across different sample types. Of these, 62 metabolites exhibited consistent regulatory trends across various datasets or sample types. Pathway analysis revealed 22 significantly altered metabolic pathways, with 6 pathways being recurrently enriched across different sample types.
CONCLUSION
This study elucidates key metabolic characteristics in UC, offering insights into molecular mechanisms and biomarker discovery for the disease. Future research could focus on validating these findings and exploring their clinical applications.
PubMed: 38560428
DOI: 10.1177/17562848241239580 -
Dentistry Journal Mar 2024The objective was to systematically review studies that evaluated the effect of charcoal-based dentifrices (CbDs) and conventional whitening toothpastes (CWTs) on the... (Review)
Review
The Effect of Charcoal-Based Dentifrice and Conventional Whitening Toothpaste on the Color Stability and Surface Roughness of Composite Resin: A Systematic Review of In Vitro Studies.
The objective was to systematically review studies that evaluated the effect of charcoal-based dentifrices (CbDs) and conventional whitening toothpastes (CWTs) on the color stability (CS) and/or surface roughness (SR) of composite resin (CR). The question we focused on was "Do CbD and CWT affect the CS and/or SR of CR?" Indexed databases were searched without language and time restrictions up to and including May 2023 using different keywords. Original experimental studies were included. The risk of bias (RoB) was assessed using the Quality Assessment Tool for In Vitro Studies. Ten in vitro studies performed on CR were included. The number of CR samples assessed ranged between 18 and 200. In one study, CbDs altered the CS and SR of CR, whereas another study showed no difference in changes in the SR and CS of CR when CbDs were compared with CWTs. One study showed that compared with CWTs, CbDs caused changes in the CS of CR but changes in SR were similar between the two dentifrices. One study showed that CbDs and CWTs improved the overall color and enhanced the SR of CR. Three studies had a high RoB, five had a medium RoB, and two had a low RoB. Compared to CWTs, CbDs appeared to affect the CS of CR, but the SR of CR induced by both dentifrices remained consistent. Further well-designed and power-adjusted studies are needed.
PubMed: 38534282
DOI: 10.3390/dj12030058 -
Frontiers in Endocrinology 2024Iron accumulation in the brain has been linked to diabetes, but its role in subcortical structures involved in motor and cognitive functions remains unclear.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Iron accumulation in the brain has been linked to diabetes, but its role in subcortical structures involved in motor and cognitive functions remains unclear. Quantitative susceptibility mapping (QSM) allows the non-invasive quantification of iron deposition in the brain. This systematic review and meta-analysis examined magnetic susceptibility measured by QSM in the subcortical nuclei of patients with type 2 diabetes mellitus (T2DM) compared with controls.
METHODS
PubMed, Scopus, and Web of Science databases were systematically searched [following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines] for studies reporting QSM values in the deep gray matter (DGM) regions of patients with T2DM and controls. Pooled standardized mean differences (SMDs) for susceptibility were calculated using fixed-effects meta-analysis models, and heterogeneity was assessed using I. Sensitivity analyses were conducted, and publication bias was evaluated using Begg's and Egger's tests.
RESULTS
Six studies including 192 patients with T2DM and 245 controls were included. This study found a significant increase in iron deposition in the subcortical nuclei of patients with T2DM compared to the control group. The study found moderate increases in the putamen (SMD = 0.53, 95% CI 0.33 to 0.72, p = 0.00) and dentate nucleus (SMD = 0.56, 95% CI 0.27 to 0.85, p = 0.00) but weak associations between increased iron levels in the caudate nucleus (SMD = 0.32, 95% CI 0.13 to 0.52, p = 0.00) and red nucleus (SMD = 0.22, 95% CI 0.00 0.44, p = 0.05). No statistical significance was found for iron deposition alterations in the globus pallidus (SMD = 0.19; 95% CI -0.01 to 0.38; p = 0.06) and substantia nigra (SMD = 0.12, 95% CI -0.10, 0.34, p = 0.29). Sensitivity analysis showed that the findings remained unaffected by individual studies, and consistent increases were observed in multiple subcortical areas.
DISCUSSION
QSM revealed an increase in iron in the DGM/subcortical nuclei in T2DM patients versus controls, particularly in the motor and cognitive nuclei, including the putamen, dentate nucleus, caudate nucleus, and red nucleus. Thus, QSM may serve as a potential biomarker for iron accumulation in T2DM patients. However, further research is needed to validate these findings.
Topics: Humans; Diabetes Mellitus, Type 2; Iron; Magnetic Resonance Imaging; Brain; Brain Mapping
PubMed: 38510699
DOI: 10.3389/fendo.2024.1331831 -
Environment International Mar 2024The World Health Organization is coordinating an international project aimed at systematically reviewing the evidence regarding the association between radiofrequency... (Meta-Analysis)
Meta-Analysis
Effects of radiofrequency electromagnetic field (RF-EMF) exposure on male fertility: A systematic review of experimental studies on non-human mammals and human sperm in vitro.
BACKGROUND
The World Health Organization is coordinating an international project aimed at systematically reviewing the evidence regarding the association between radiofrequency electromagnetic field (RF-EMF) exposure and adverse health effects. Reproductive health outcomes have been identified among the priority topics to be addressed.
OBJECTIVES
To evaluate the effect of RF-EMF exposure on male fertility of experimental mammals and on human sperm exposed in vitro.
METHODS
Three electronic databases (PubMed, Scopus and EMF Portal) were last searched on September 17, 2022. Two independent reviewers screened the studies, which were considered eligible if met the following criteria: 1) Peer-reviewed publications of sham controlled experimental studies, 2) Non-human male mammals exposed at any stage of development or human sperm exposed in vitro, 3) RF-EMF exposure within the frequency range of 100 kHz-300 GHz, including electromagnetic pulses (EMP), 4) one of the following indicators of reproductive system impairment:Two reviewers extracted study characteristics and outcome data. We assessed risk of bias (RoB) using the Office of Health Assessment and Translation (OHAT) guidelines. We categorized studies into 3 levels of overall RoB: low, some or high concern. We pooled study results in a random effects meta-analysis comparing average exposure to no-exposure and in a dose-response meta-analysis using all exposure doses. For experimental animal studies, we conducted subgroup analyses for species, Specific Absorption Rate (SAR) and temperature increase. We grouped studies on human sperm exposed in vitro by the fertility status of sample donors and SAR. We assessed the certainty of the evidence using the GRADE approach after excluding studies that were rated as "high concern" for RoB.
RESULTS
One-hundred and seventeen papers on animal studies and 10 papers on human sperm exposed in vitro were included in this review. Only few studies were rated as "low concern" because most studies were at RoB for exposure and/or outcome assessment. Subgrouping the experimental animal studies by species, SAR, and temperature increase partly accounted for the heterogeneity of individual studies in about one third of the meta-analyses. In no case was it possible to conduct a subgroup analysis of the few human sperm in vitro studies because there were always 1 or more groups including less than 3 studies. Among all the considered endpoints, the meta-analyses of animal studies provided evidence of adverse effects of RF-EMF exposure in all cases but the rate of infertile males and the size of the sired litters. The assessment of certainty according to the GRADE methodology assigned a moderate certainty to the reduction of pregnancy rate and to the evidence of no-effect on litter size, a low certainty to the reduction of sperm count, and a very low certainty to all the other meta-analysis results. Studies on human sperm exposed in vitro indicated a small detrimental effect of RF-EMF exposure on vitality and no-effect on DNA/chromatin alterations. According to GRADE, a very low certainty was attributed to these results. The few studies that used EMP exposure did not show effects on the outcomes. A low to very low certainty was attributed to these results.
DISCUSSION
Many of the studies examined suffered of severe limitations that led to the attribution of uncertainty to the results of the meta-analyses and did not allow to draw firm conclusions on most of the endpoints. Nevertheless, the associations between RF-EMF exposure and decrease of pregnancy rate and sperm count, to which moderate and low certainty were attributed, are not negligible, also in view of the indications that in Western countries human male fertility potential seems to be progressively declining. It was beyond the scope of our systematic review to determine the shape of the dose-response relationship or to identify a minimum effective exposure level. The subgroup and the dose-response fitting analyses did not show a consistent relationship between the exposure levels and the observed effects. Notably, most studies evaluated RF-EMF exposure levels that were higher than the levels to which human populations are typically exposed, and the limits set in international guidelines. For these reasons we cannot provide suggestions to confirm or reconsider current human exposure limits. Considering the outcomes of this systematic review and taking into account the limitations found in several of the studies, we suggest that further investigations with better characterization of exposure and dosimetry including several exposure levels and blinded outcome assessment were conducted.
PROTOCOL REGISTRATION
Protocols for the systematic reviews of animal studies and of human sperm in vitro studies were published in Pacchierotti et al., 2021. The former was also registered in PROSPERO (CRD42021227729 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID = 227729) and the latter in Open Science Framework (OSF Registration DOI https://doi.org/10.17605/OSF.IO/7MUS3).
Topics: Animals; Humans; Male; Electromagnetic Fields; Mammals; Radio Waves; Reproduction; Semen; Infertility, Male
PubMed: 38492496
DOI: 10.1016/j.envint.2024.108509