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Digestive Diseases and Sciences May 2023Cystic Fibrosis (CF) is associated with gut dysbiosis, local and systemic inflammation, and impaired immune function. Gut microbiota dysbiosis results from changes in...
BACKGROUND AND AIMS
Cystic Fibrosis (CF) is associated with gut dysbiosis, local and systemic inflammation, and impaired immune function. Gut microbiota dysbiosis results from changes in the complex gut milieu in response to CF transmembrane conductance regulator (CFTR) dysfunction, pancreatic malabsorption, diet, medications, and environmental influences. In several diseases, alteration of the gut microbiota influences local and systemic inflammation and disease outcomes. We conducted a systematic review of the gut microbiota in CF and explored factors influencing dysbiosis.
METHODS
An electronic search of three databases was conducted in January 2019, and re-run in June 2021. Human, animal, and in vitro studies were included. The primary outcome was differences in the gut microbiota between people with CF (pwCF) and healthy controls. Secondary outcomes included the relationship between the gut microbiota and other factors, including diet, medication, inflammation, and pulmonary function in pwCF.
RESULTS
Thirty-eight studies were identified. The literature confirmed the presence of CF-related gut dysbiosis, characterized by reduced diversity and several taxonomic changes. There was a relative increase of bacteria associated with a pro-inflammatory response coupled with a reduction of those considered anti-inflammatory. However, studies linking gut dysbiosis to systemic and lung inflammation were limited. Causes of gut dysbiosis were multifactorial, and findings were variable. Data on the impact of CFTR modulators on the gut microbiota were limited.
CONCLUSIONS
CF-related gut dysbiosis is evident in pwCF. Whether this influences local and systemic disease and is amenable to interventions with diet and drugs, such as CFTR modulators, requires further investigation.
Topics: Animals; Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Dysbiosis; Bacteria; Inflammation
PubMed: 36600119
DOI: 10.1007/s10620-022-07812-1 -
Medical Principles and Practice :... 2023The purpose of this review was to ascertain whether patients with Brugada syndrome (BrS) having SCN5A mutations have a more severe clinical phenotype and prognosis than...
OBJECTIVE
The purpose of this review was to ascertain whether patients with Brugada syndrome (BrS) having SCN5A mutations have a more severe clinical phenotype and prognosis than do patients without SCN5A mutations.
METHODS
A comprehensive Scopus database search was conducted; studies were selected by using Brugada syndrome and SCN5A as keywords for the main query.
RESULTS
The available literature consistently shows greater electrophysiological abnormalities in patients with BrS having SCN5A-related etiology. These include conduction disorder evidenced by longer QRS, PQ, and His-ventricular interval duration. Novel lines of evidence suggest that SCN5A mutations are predictors of malignant arrhythmic events. In addition, SCN5A-positive patients and their carrier relatives frequently suffer from various abnormal cardiac phenotypes such as sick sinus syndrome and progressive conduction disorder. Rare variants have also been shown to play a role in cases of epilepsy, hyperthyroidism, irritable bowel syndrome, and malignancy.
CONCLUSION
In this review, we show how the SCN5A mutation status predicts phenotypic characteristics and prognosis in patients with BrS. We conclude that SCN5A mutations weakly predict greater malignant arrhythmic event risk in BrS patients. However, SCN5A mutations do not show robust enough associations with severity indicators to be an independent part of current risk stratification strategies. With advancing knowledge of BrS genetics, the integration of data on rare variants of SCN5A and polygenic risk scores could make an impact on clinical decision-making.
Topics: Humans; Brugada Syndrome; Phenotype; NAV1.5 Voltage-Gated Sodium Channel; Mutation; Electrocardiography
PubMed: 36446338
DOI: 10.1159/000528375 -
Frontiers in Physiology 2022Endocannabinoids (eCBS) are endogenously derived lipid signaling molecules that serve as tissue hormones and interact with multiple targets, mostly within the...
Endocannabinoids (eCBS) are endogenously derived lipid signaling molecules that serve as tissue hormones and interact with multiple targets, mostly within the endocannabinoid system (ECS). The ECS is a highly conserved regulatory system involved in homeostatic regulation, organ formation, and immunomodulation of chordates. The term "cannabinoid" evolved from the distinctive class of plant compounds found in , an ancient herb, due to their action on CB1 and CB2 receptors. CB1/2 receptors are the primary targets for eCBs, but their effects are not limited to the ECS. Due to the high interest and extensive research on the ECS, knowledge on its constituents and physiological role is substantial and still growing. Crosstalk and multiple targeting of molecules are common features of endogenous and plant compounds. Cannabimimetic molecules can be divided according to their origin, natural or synthetic, including phytocannabinoids (pCB's) or synthetic cannabinoids (sCB's). The endocannabinoid system (ECS) consists of receptors, transporters, enzymes, and signaling molecules. In this review, we focus on the effects of cannabinoids on Cys-loop receptors. Cys-loop receptors belong to the class of membrane-bound pentameric ligand gated ion channels, each family comprising multiple subunits. Mammalians possess GABA type A receptors (GABAAR), glycine receptors (GlyR), serotonin receptors type 3 (5-HT3R), and nicotinic acetylcholine receptors (nAChR). Several studies have shown different modulatory effects of CBs on multiple members of the Cys-loop receptor family. We highlight the existing knowledge, especially on subunits and protein domains with conserved binding sites for CBs and their possible pharmacological and physiological role in epilepsy and in chronic pain. We further discuss the potential for cannabinoids as first line treatments in epilepsy, chronic pain and other neuropsychiatric conditions, indicated by their polypharmacology and therapeutic profile.
PubMed: 36439263
DOI: 10.3389/fphys.2022.1044575 -
BMC Neurology Nov 2022Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of...
BACKGROUND
Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of clinical and imaging characteristics as well as of antibody dynamics.
CASE PRESENTATION
We report a 32-year-old male patient who presented with psychosis, decreased consciousness and movement disorders and was tested positive for anti-NMDA receptor antibodies. Forty-four months after symptom onset and diagnosis of autoimmune encephalitis, he suffered from relapse. At this time, the patient developed anti-MOG and anti-Caspr2 antibodies. Treatment with plasmapheresis, steroids and rituximab eventually led to substantial clinical and radiological improvement. Anti-Caspr2 antibodies persisted, anti-NMDA receptor antibodies decreased, while anti-MOG antibodies turned negative again.
CONCLUSION
We provide long-term longitudinal follow-up of a patient with anti-NMDA receptor encephalitis who developed triple antibody positivity at the time of relapse. Antibody dynamics were associated with clinical disease course.
Topics: Male; Humans; Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Myelin-Oligodendrocyte Glycoprotein; Follow-Up Studies; Autoantibodies; Neoplasm Recurrence, Local; Receptors, N-Methyl-D-Aspartate; Demyelinating Diseases
PubMed: 36384491
DOI: 10.1186/s12883-022-02974-x -
Neurology India 2022Introduction of international consensus criteria (2015 IPND criteria) for neuromyelitis optica spectrum disorders (NMOSDs) has improved diagnostic accuracy for aquaporin... (Review)
Review
Introduction of international consensus criteria (2015 IPND criteria) for neuromyelitis optica spectrum disorders (NMOSDs) has improved diagnostic accuracy for aquaporin 4 (AQP4)-IgG-associated and seronegative NMOSDs. This study aimed to review relevant publications related to the incidence and prevalence of NMOSDs and provide an updated review of the global epidemiology of NMOSDs in the light of new diagnostic criteria. A comprehensive literature search was performed from January 2015 to June 2021 by using appropriate keywords in PubMed, Scopus, and Web of Science. Relevant papers that fulfilled inclusion criteria were shortlisted and reviewed. Twenty-one papers were selected for this review. Incidence of NMOSDs was 0.04-0.25/100,000 in predominantly white and 0.34-1.31/100,000 in nonwhite populations. Prevalence was 0.70-1.91/100,000 in white and 0.86-4.52/100,000 in nonwhite populations. The 2015 IPND criteria significantly improved the incidence and prevalence rates for NMOSDs when compared to the Wingerchuk 2006 criteria. Incidence of MOG-IgG-associated NMOSDs was 0.12-0.13/100,000, with prevalence in children 0.03-1.4/100,000 and in adults 0.65-2/100,000. In this systematic review, studies that used uniform diagnostic criteria and confirmed cases after testing for AQP4-IgG were included. The prevalence of NMOSDs was estimated to be <5/100,000 globally. A clear bias was seen in favor of nonwhite and indigenous populations. This review highlights the need for prospective population-based epidemiological studies and the importance of surveys in nonwhite populations around the globe.
Topics: Adult; Child; Humans; Neuromyelitis Optica; Incidence; Prevalence; Prospective Studies; Consensus; Aquaporin 4; Immunoglobulin G; Autoantibodies
PubMed: 36352564
DOI: 10.4103/0028-3886.359235 -
International Journal of Molecular... Aug 2022DOG1 is a transmembrane protein originally discovered on gastrointestinal stromal tumors and works as a calcium-activated chloride channel protein. There are a limited... (Meta-Analysis)
Meta-Analysis Review
DOG1 is a transmembrane protein originally discovered on gastrointestinal stromal tumors and works as a calcium-activated chloride channel protein. There are a limited number of articles on the potential utility of this antibody in the diagnosis of salivary gland tumors in routine practice. In this study, we aimed to investigate the role of DOG1 as an immunohistochemical marker in patients with salivary acinic cell carcinoma (ACC) through meta-analysis. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2010 to September 2021. The literature search revealed 148 articles, of which 20 were included in the study. The overall rate of DOG1 expression in salivary acinic cell carcinoma was 55% (95% CI = 0.43-0.58). Although ACC is a challenging diagnosis, paying careful attention to the cytomorphological features in conjunction with DOG1 immunostaining can help to reach an accurate diagnosis.
Topics: Biomarkers, Tumor; Carcinoma, Acinar Cell; Chloride Channels; Humans; Salivary Gland Neoplasms
PubMed: 36077107
DOI: 10.3390/ijms23179711 -
Psychiatria Polska Apr 2022Currently, we observe a huge number of publications describing the role of glycine transporter (GlyT1) inhibitors in schizophrenia treatment. The concept of application... (Review)
Review
Currently, we observe a huge number of publications describing the role of glycine transporter (GlyT1) inhibitors in schizophrenia treatment. The concept of application for these drugs derives from the glutamatergic theory of schizophrenia. This theory explains psychotic disturbances as the consequence of NMDA receptor functioning defect. The role of the mentioned receptor depends mostly on the presence of cofactors. One such cofactor is the simplest aminoacid, glycine. This amino acid affects the glycine-binding site, located on the NR1 subunit of NMDAR and enables activation of the receptor. Substances enhancing the access of glycine to the receptor could hypothetically improve neuroplasticity. Higher efficacy of these neuroplastic processes may protect from cognitive deterioration and negative symptoms in the course of schizophrenia. In this article we present a systematic review of current literature on the topic of GlyT1 inhibitors in schizophrenia treatment (the state of literature as of November 2019). Firstly, we described the preclinical reasons for glycine enhancement use. Next, we used CINAHL, EMBASE, EMCARE, Medline, PsycINFO, PubMed and Google Scholar databases to extract and analyze evidence from clinical trials. GlyT1 inhibitors seem to have a potential in searching for novel substances in the treatment of negative symptoms, but their capacity to reduce cognitive deficits is not evidenced. So far, the clinical efficacy of several substances was proven, including N-methylglycine (sarcosine), bitopertin and derivatives obtained with chemical synthesis. Some of these substances demonstrate a beneficial clinical effect, but the number of published reports in this area is disproportionate to the value of evidence.
Topics: Glycine; Glycine Plasma Membrane Transport Proteins; Humans; Receptors, N-Methyl-D-Aspartate; Sarcosine; Schizophrenia
PubMed: 35988070
DOI: 10.12740/PP/OnlineFirst/126661 -
Drug and Alcohol Dependence Oct 2022Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting... (Review)
Review
BACKGROUND
Nicotine produces its effects by binding to nicotinic acetylcholine receptors (nAChRs). Variants of genes encoding properties of nAChRs are candidates for affecting likelihood of smoking cessation.
METHODS
A systematic review was conducted summarizing evidence of associations between single nucleotide polymorphisms (SNPs) of nAChR genes and smoking cessation. From 24 articles meeting inclusion criteria, summary odds ratios (ORs) for associations between nine SNPs and smoking cessation were calculated from 26 studies (N = 233-29,072) stratified by gene, ancestry, study design, and pharmacotherapy; SNPs in linkage disequilibrium were pooled. Results for a tenth SNP from two GWAS were summarized.
RESULTS
People of European ancestry with minor alleles of CHRNA5 rs16969968 and CHRNA3 rs1051730 had longer time to cessation [HR = 0.90, 95 % CI 0.88 - 0.92 (n = 2 studies)] and lower odds of cessation [OR = 0.88, 95 % CI 0.80 - 0.97 (n = 5 cohort studies), OR = 0.64, 95 % CI 0.45 - 0.90 (n = 4 placebo arms)]. Risk of persistent smoking associated with these alleles was attenuated in smokers receiving nicotine replacement therapy (NRT). Recipients of bupropion alone or with NRT with these alleles had higher, though not statistically significant, odds of cessation. Results for CHRNA5 rs588765 and rs680244 were similar to rs16969968/rs1051730 findings. Evidence was limited for other SNPs.
CONCLUSION
Evidence consistently indicates the minor alleles of four SNPs within CHRNA3 or CHRNA5 are risk alleles for cessation failure. Analysis by pharmacotherapy revealed bupropion may be the most efficacious intervention for people with these alleles.
Topics: Bupropion; Genetic Variation; Humans; Nicotine; Polymorphism, Single Nucleotide; Receptors, Nicotinic; Smoking Cessation; Tobacco Products; Tobacco Use Cessation Devices
PubMed: 35981468
DOI: 10.1016/j.drugalcdep.2022.109596 -
Molecular Neurobiology Oct 2022Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between... (Review)
Review
Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.
Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between the inflammatory background and two well-recognized functional and structural findings of schizophrenia pathophysiology: the dopamine-glutamate aberrant interaction and the alteration of dendritic spines architecture, both believed to be the "quantal" elements of cortical-subcortical dysfunctional network. In this systematic review, we tried to capture the major findings linking inflammation, aberrant glutamate-dopamine interaction, and post-synaptic changes under a direct and inverse translational perspective, a paramount picture that at present is lacking. The inflammatory effects on dopaminergic function appear to be bidirectional: the inflammation influences dopamine release, and dopamine acts as a regulator of discrete inflammatory processes involved in schizophrenia such as dysregulated interleukin and kynurenine pathways. Furthermore, the link between inflammation and glutamate is strongly supported by clinical studies aimed at exploring overactive microglia in schizophrenia patients and maternal immune activation models, indicating impaired glutamate regulation and reduced N-methyl-D-aspartate receptor (NMDAR) function. In addition, an inflammatory/immune-induced alteration of post-synaptic density scaffold proteins, crucial for downstream NMDAR signaling and synaptic efficacy, has been demonstrated. According to these findings, a significant increase in plasma inflammatory markers has been found in schizophrenia patients compared to healthy controls, associated with reduced cortical integrity and functional connectivity, relevant to the cognitive deficit of schizophrenia. Finally, the link between altered inflammatory/immune responses raises relevant questions regarding potential new therapeutic strategies specifically for those forms of schizophrenia that are resistant to canonical antipsychotics or unresponsive to clozapine.
Topics: Antipsychotic Agents; Dopamine; Glutamic Acid; Humans; Inflammation; Receptors, N-Methyl-D-Aspartate; Schizophrenia
PubMed: 35963926
DOI: 10.1007/s12035-022-02976-3 -
Structural Heart Alterations in Brugada Syndrome: Is it Really a Channelopathy? A Systematic Review.Journal of Clinical Medicine Jul 2022Brugada syndrome (BrS) is classified as an inherited cardiac channelopathy attributed to dysfunctional ion channels and/or associated proteins in cardiomyocytes rather... (Review)
Review
Brugada syndrome (BrS) is classified as an inherited cardiac channelopathy attributed to dysfunctional ion channels and/or associated proteins in cardiomyocytes rather than to structural heart alterations. However, hearts of some BrS patients exhibit slight histologic abnormalities, suggesting that BrS could be a phenotypic variant of arrhythmogenic cardiomyopathy. We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria. Our comprehensive analysis of structural findings did not reveal enough definitive evidence for reclassification of BrS as a cardiomyopathy. The collection and comprehensive analysis of new cases with a definitive BrS diagnosis are needed to clarify whether some of these structural features may have key roles in the pathophysiological pathways associated with malignant arrhythmogenic episodes.
PubMed: 35956023
DOI: 10.3390/jcm11154406