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Journal of Integrative Neuroscience Feb 2024Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions.
METHODS
We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist.
RESULTS
The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%-1.4%,) and 6.5% (95% CI: 4.7-8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5-54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%.
CONCLUSIONS
Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.
Topics: Humans; Female; Neuromyelitis Optica; Aquaporin 4; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid
PubMed: 38419451
DOI: 10.31083/j.jin2302035 -
Journal of Psychiatric Research Apr 2024This study investigates the influence of N-methyl-D-aspartate receptor (NMDAR) antagonists on the mismatch negativity (MMN) components of event-related potentials (ERPs)... (Meta-Analysis)
Meta-Analysis Review
The effect of N-methyl-D-aspartate receptor antagonists on the mismatch negativity of event-related potentials and its regulatory factors: A systematic review and meta-analysis.
This study investigates the influence of N-methyl-D-aspartate receptor (NMDAR) antagonists on the mismatch negativity (MMN) components of event-related potentials (ERPs) in healthy subjects and explores whether NMDAR antagonists have different effects on MMN components under different types of antagonists, drug dosages, and deviant stimuli. We conducted a comprehensive literature search of PubMed, EMBASE, and the Cochrane Library from inception to August 1, 2023 for studies comparing the MMN components between the NMDAR antagonist intervention group and the control group (or baseline). All statistical analyses were performed using Stata version 12.0 software. Sixteen articles were included in the systematic review: 13 articles were included in the meta-analysis of MMN amplitudes, and seven articles were included in the meta-analysis of MMN latencies. The pooled analysis showed that NMDAR antagonists reduced MMN amplitudes [SMD (95% CI) = 0.32 (0.16, 0.47), P < 0.01, I = 47.3%, p < 0.01] and prolonged MMN latencies [SMD (95% CI) = 0.31 (0.13, 0.49), P = 0.16, I = 28.3%, p < 0.01]. The type of antagonist drug regulates the effect of NMDAR antagonists on MMN amplitudes. Different antagonists, doses of antagonists, and types of deviant stimuli can also have different effects on MMN. These findings indicate a correlation between NMDAR and MMN, which may provide a foundation for the application of ERP-MMN in the early identification of NMDAR encephalitis.
Topics: Humans; Receptors, N-Methyl-D-Aspartate; Evoked Potentials, Auditory; Electroencephalography; Evoked Potentials; Acoustic Stimulation
PubMed: 38402843
DOI: 10.1016/j.jpsychires.2024.02.004 -
Cells Jan 2024Acetylcholine signaling is attenuated in early Alzheimer's disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine... (Review)
Review
Acetylcholine signaling is attenuated in early Alzheimer's disease (AD) and other dementias. A significant reduction in the expression of nicotinic acetylcholine receptors (nAChRs) in the brain of AD patients has also been reported in several molecular biological and in situ labeling studies. The modulation of the functional deficit of the cholinergic system as a pharmacological target could therefore have a clinical benefit, which is not to be neglected. This systematic review was conducted to identify clinical trials, which evaluated the safety and efficacy of nicotinic acetylcholine receptor agonists using Clinicaltrial (CT) and EudraCT databases. Structured searches identified 39 trials, which used 15 different drugs designed to increase the function of the nAChRs. Most of the identified clinical trials were phase II trials, with some of them classified as ongoing for several years. The systematic screening of the literature led to the selection of 14 studies out of the 8261 bibliographic records retrieved. Six trials reported detailed data on adverse events associated with the intervention, while twelve trials reported data on efficacy measures, such as attention, behavior and cognition. Overall, smost of the physical side effects of cholinergic agonists were reported to be well tolerated. Some trials also reported improvements in attention. However, the efficacy of these drugs in other cognitive and behavioral outcomes remains highly controversial.
Topics: Humans; Alzheimer Disease; Receptors, Nicotinic; Brain; Nicotinic Agonists; Cognition
PubMed: 38334629
DOI: 10.3390/cells13030237 -
Age and Ageing Jan 2024Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear.
METHODS
We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model.
RESULTS
We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis.
CONCLUSIONS
In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.
Topics: Humans; Aged; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Glycated Hemoglobin; Diabetic Ketoacidosis; Sodium-Glucose Transporter 2; Frail Elderly; Heart Failure; Death; Glucose; Sodium
PubMed: 38287703
DOI: 10.1093/ageing/afad254 -
Psychopharmacology Feb 2024Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce dopaminergic transmission but have limited activity at postsynaptic receptors and so may have antipsychotic activity with lower risk of tardive dyskinesia.
METHODS
We conducted a systematic database search from inception to September 2022 for articles describing the use of VMAT-2 inhibitors in psychosis. Inclusion criteria were as follows: Population: adults diagnosed with psychosis or schizophrenia; Intervention: treatment with tetrabenazine, deutetrabenazine or valbenazine; Comparison: comparison with placebo or/and antipsychotic drug; Outcomes: with efficacy outcomes (e.g. Brief Psychiatric Rating Scale (BPRS) change or clinician assessment) and adverse effects ratings (e.g. rating scale or clinician assessment or dropouts); and Studies: in randomised controlled trials and non-randomised studies.
RESULTS
We identified 4892 records relating to VMAT-2 inhibitor use of which 5 (173 participants) met our a priori meta-analysis inclusion criteria. VMAT-2 inhibitors were more effective than placebo for the outcome 'slight improvement' (risk ratio (RR) = 1.77 (95% CI 1.03, 3.04)) but not for 'moderate improvement' (RR 2.81 (95% CI 0.27, 29.17). VMAT-2 inhibitors were as effective as active comparators on both measures for-'slight improvement' (RR 1.05 (95% CI 0.6, 1.81)) and 'moderate improvement' (RR 1.11 (95% CI 0.51, 2.42). Antipsychotic efficacy was also suggested by a narrative review of 37 studies excluded from the meta-analysis.
CONCLUSIONS
VMAT-2 inhibitors may have antipsychotic activity and may offer promise for treatment of psychosis with the potential for a reduced risk of TD.
Topics: Adult; Humans; Antipsychotic Agents; Psychotic Disorders; Schizophrenia; Tardive Dyskinesia; Tetrabenazine; Vesicular Monoamine Transport Proteins
PubMed: 38238580
DOI: 10.1007/s00213-023-06488-3 -
International Journal of Molecular... Dec 2023Bacteria have existed on Earth for billions of years, exhibiting ubiquity and involvement in various biological activities. To ensure survival, bacteria usually release... (Review)
Review
Bacteria have existed on Earth for billions of years, exhibiting ubiquity and involvement in various biological activities. To ensure survival, bacteria usually release and secrete effector proteins to acquire nutrients and compete with other microorganisms for living space during long-term evolution. Consequently, bacteria have developed a range of secretion systems, which are complex macromolecular transport machines responsible for transporting proteins across the bacterial cell membranes. Among them, one particular secretion system that stands out from the rest is the type V secretion system (T5SS), known as the "autotransporter". Bacterial activities mediated by T5SS include adherence to host cells or the extracellular matrix, invasion of host cells, immune evasion and serum resistance, contact-dependent growth inhibition, cytotoxicity, intracellular flow, protease activity, autoaggregation, and biofilm formation. In a bacterial body, it is not enough to rely on T5SS alone; in most cases, T5SS cooperates with other secretion systems to carry out bacterial life activities, but regardless of how good the relationship is, there is friction between the secretion systems. T5SS and T1SS/T2SS/T3SS/T6SS all play a synergistic role in the pathogenic processes of bacteria, such as nutrient acquisition, pathogenicity enhancement, and immune modulation, but T5SS indirectly inhibits the function of T4SS. This could be considered a love-hate relationship between secretion systems. This paper uses the systematic literature review methodology to review 117 journal articles published within the period from 1995 to 2024, which are all available from the PubMed, Web of Science, and Scopus databases and aim to elucidate the link between T5SS and other secretion systems, providing clues for future prevention and control of bacterial diseases.
Topics: Type V Secretion Systems; Bacteria; Bodily Secretions; Cell Aggregation; Cell Membrane
PubMed: 38203452
DOI: 10.3390/ijms25010281 -
Jornal Brasileiro de Pneumologia :... 2024To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis.
METHODS
This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths.
CONCLUSIONS
Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.
Topics: Humans; Alleles; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis; Quality of Life; Pyridines; Indoles; Pyrazoles; Aminophenols; Quinolones; Pyrrolidines; Benzodioxoles
PubMed: 38198345
DOI: 10.36416/1806-3756/e20230187 -
Pharmacological Research Jan 2024Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and...
Zinc is a crucial trace element in the human body, playing a role in various physiological processes such as oxidative stress, neurotransmission, protein synthesis, and DNA repair. The zinc transporters (ZnTs) family members are responsible for exporting intracellular zinc, while Zrt- and Irt-like proteins (ZIPs) are involved in importing extracellular zinc. These processes are essential for maintaining cellular zinc homeostasis. Imbalances in zinc metabolism have been linked to the development of neurodegenerative diseases. Disruptions in zinc levels can impact the survival and activity of neurons, thereby contributing to the progression of neurodegenerative diseases through mechanisms like cell apoptosis regulation, protein phase separation, ferroptosis, oxidative stress, and neuroinflammation. Therefore, conducting a systematic review of the regulatory network of zinc and investigating the relationship between zinc dysmetabolism and neurodegenerative diseases can enhance our understanding of the pathogenesis of these diseases. Additionally, it may offer new insights and approaches for the treatment of neurodegenerative diseases.
Topics: Humans; Cation Transport Proteins; Disease Progression; Homeostasis; Neurodegenerative Diseases; Zinc
PubMed: 38123108
DOI: 10.1016/j.phrs.2023.107039 -
Molecular Medicine Reports Feb 2024Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in , or , which respectively encode the α, β and γ subunits of...
Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in , or , which respectively encode the α, β and γ subunits of the epithelial sodium channel. In the present study, DNA was extracted from leukocytes in peripheral blood obtained from all members of a family with Liddle syndrome. Whole‑exome sequencing and Sanger sequencing were performed to assess the candidate variant and a co‑segregation analysis was conducted. A frameshift mutation in (NM_ 000336: c.1806dupG, p.Pro603Alafs*5) in the family was identified, characterized by early‑onset hypertension and hypokalemia. The mutation led to the truncation of the β subunit of the epithelial sodium channel and a lack of the conservative PY motif. Furthermore, a systematic review of follow‑up data from patients with Liddle syndrome with mutations was performed. The follow‑up data of 108 patients with pathogenic mutations from 47 families were summarized. Phenotypic heterogeneity was evident in patients with Liddle syndrome and early‑onset hypertension was the most frequent symptom. Patients responded well to targeted amiloride therapy with significant improvements in blood pressure and serum potassium concentration. The present study demonstrates that confirmatory genetic testing and targeted therapy can prevent premature onset of clinical endpoint events in patients with Liddle syndrome.
Topics: Humans; Liddle Syndrome; Epithelial Sodium Channels; Frameshift Mutation; Mutation; Hypertension; Potassium
PubMed: 38099339
DOI: 10.3892/mmr.2023.13142 -
Scientific Reports Nov 2023Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in augmentation with selective serotonin reuptake inhibitors (SSRIs) in the treatment of moderate to severe obsessive-compulsive disorder: a systematic review and meta-analysis of randomized clinical trials.
Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its pharmacological treatment. About 40-60% of the cases are treatment-refractory, and this makes searching for second-line treatment necessary. 5-Hydroxytryptamine-3 (5-HT3) antagonists are among the many medications that have been used in augmentation with SSRIs. In this systematic review and meta-analysis, we assessed the efficacy and safety of 5-HT3 receptor antagonists in augmentation with SSRIs in treating moderate to severe OCD. We searched PubMed, Web of Science, Scopus, Cochrane library, and Google Scholar for relevant trials published up to December 2022. The effect size was the mean difference in Yale-Brown obsessive compulsive scale (Y-BOCS) scores before and after receiving 5-HT3 receptor antagonist drugs in augmentation with SSRIs in moderate to severe OCD patients. We included 6 randomized-controlled trails (RCTs) with 334 patients assessing the effect of the augmentation of SSRIs with ondansetron, granisetron, and tropisetron on treating moderate to severe OCD. Our results were in favor of the experimental group in total (Z = 8.37, P < 0.00001), in the compulsion subgroup (Z = 5.22, P < 0.00001), and in the obsession subgroup (Z = 8.33, P < 0.00001). They are well-tolerated, and have mild side effects and do not result in withdrawal. Augmentation of 5-HT3 antagonists with SSRIs can be beneficial in treating moderate to severe OCD. Further multi-center trials under adequate conditions in longer periods are needed to help come up with a comprehensive action plan.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Serotonin; Receptors, Serotonin, 5-HT3; Treatment Outcome; Randomized Controlled Trials as Topic; Obsessive-Compulsive Disorder; Drug Therapy, Combination
PubMed: 38012263
DOI: 10.1038/s41598-023-47931-x