Group Of Disorders Research Articles

Mitochondrial fission and fusion in neurodegenerative diseases:Ca2+ signalling.

Neurodegenerative diseases (NDs) are a group of disorders characterized by the progressive loss of neuronal structure and function. The pathogenesis is intricate and involves a network of interactions among multiple causes and systems. Mitochondria and Ca2+ signaling have long been considered to play important roles in the development of various NDs. Mitochondrial fission and fusion dynamics are important processes of mitochondrial quality control, ensuring the stability of mitochondrial structure and function. Mitochondrial fission and fusion imbalance and Ca2+ signaling disorders can aggravate the disease progression of NDs. In this review, we explore the relationship between mitochondrial dynamics and Ca2+ signaling in AD, PD, ALS, and HD, focusing on the roles of key regulatory proteins (Drp1, Fis1, Mfn1/2, and Opa1) and the association structures between mitochondria and the endoplasmic reticulum (MERCs/MAMs). We provide a detailed analysis of their involvement in the pathogenesis of these four NDs. By integrating these mechanisms, we aim to clarify their contributions to disease progression and offer insights into the development of therapeutic strategies that target mitochondrial dynamics and Ca2+ signaling. We also examine the progress in drug research targeting these pathways, highlighting their potential as therapeutic targets in the treatment of NDs.

Molecular cytogenetic study of the fetal genome in idiopathic recurrent pregnancy loss.

Despite numerous studies on the causes of recurrent pregnancy loss (RPL), nearly half of cases remain unidentified, which determines the research relevance. This study aims to investigate microchromosomal variations in the fetal genome associated with the development of idiopathic RPL. The research was supported by the Centre for Molecular Medicine and the Research Institute of Obstetrics, Gynecology and Perinatology and conducted over a period of 2 years. The study employed the Prepito automatic analyzer from PerkinElmer and the ChemagicPrepito nucleic acid extraction system, to isolate 100 DNA samples from conception products of women with idiopathic RPL, and, subsequently, to analyze for the presence of full-genome chromosomal abnormalities by array comparative genomic hybridisation (aCGH) using CGX-HD microarrays (8x60K), Format 1: CGX (80x60K), a ScanRI microarray scanner (PerkinElmer, Finland), and Genoglyphix, Cytogenomix software. The study determined that 83% of the materials studied had a normal molecular karyotype, while unbalanced chromosomal abnormalities were detected in 17% of cases, of which 35.3% of abortions had aneuploidies and 64.7% had various structural abnormalities. Among the aneuploidies, 66.7% were trisomies and 33.3% were monosomies. In the group of structural disorders, 81.8% were microdeletions, while microduplications accounted for 18.2%. The data obtained on the frequency and structure of chromosomal abnormalities detected in abortions in the sample surveyed showed that idiopathic RPL is not caused by chromosomal abnormalities of embryos and, unlike all other forms of RPL, has a different cause not related to chromosomal abnormalities. This study conducted molecular cytogenetic analysis of the fetal genome related to RPL. Its findings can help optimize the process of counseling patients with idiopathic RPL.

Bronchiolitis in adults: etiology, diagnostic and therapeutic approach.

Bronchiolitis is a heterogeneous group of disorders, each with its own clinical and radiographic presentation, treatment options and prognosis. Until now classifications were based on pathology and radiology. Bronchioles are smaller than 2mm in diameter and do not contain cartilage and mucous glands in their walls. Bronchiolitis is the term used to designate a disorder of the bronchioles and can have multiple etiologies. A specific diagnosis requires an extensive anamnesis, physical examination, pulmonary function testing, radiographic studies and pathological investigation. We made a classification of bronchiolitis based on etiology, in order to give a diagnostic and therapeutic guidance. Further investigation is needed to optimize treatment for specific types of bronchiolitis. In this paper, a classification of bronchiolitis based on etiology is made. The paper provides in the diagnostic and therapeutic approach, although further investigation is needed to optimize treatment for specific types of bronchiolitis.

Expert consensus on neuropsychological assessment for mild cognitive impairment (2025 edition)

Mild cognitive impairment (MCI) is a state of objective cognitive decline that falls between normal aging and dementia, with a high prevalence among the elderly in China. Cognitive impairments in MCI patients involve multiple cognitive domains such as memory, language, attention, executive, visuospatial functions, and social cognition, as well as non-cognitive domains such as neuropsychiatric, mood, sleep, daily living activities, and frailty. The assessment and clinical diagnosis of MCI highly rely on neuropsychological testing. In order to standardize the neuropsychological assessment of MCI, the Dementia and Cognitive Disorders Group of the Chinese Society of Neurology formulated this consensus document. It recommends tools for assessing global cognition, various cognitive domains, and non-cognitive functions suitable for both clinical and research settings. The consensus proposes assessment procedures and precautions based on the experiences of domestic researchers. Based on the latest international and domestic research advancements, using the Delphi method and the GRADE evidence system, 24 recommendations were formulated in 5 aspects of MCI: global cognitive function assessment, various cognitive domains assessment, non-cognitive assessment, the use of neuropsychological scales, and precautions in neuropsychological assessment, aiming to improve the diagnosis and management of MCI in China.

Outcomes of Total Joint Arthroplasty in Patients Who Have Ehlers-Danlos Syndrome: A Systematic Review and Meta-Analysis.

Patients who have Ehlers-Danlos Syndrome (EDS), a group of connective tissue disorders characterized by aberrant collagen synthesis and processing, have an increased likelihood of requiring a total joint arthroplasty (TJA), including total hip or knee arthroplasty (THA or TKA). This study aimed to synthesize outcomes following TJA in patients who have EDS. This study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that described outcomes of TJA in EDS patients were searched from PubMed, Medline, The Cochrane Library, and Embase. Case series and cohort studies were included if they identified patients who had EDS who underwent either primary THA or TKA. Rates of reoperation and/or revision, instability or frank dislocation, aseptic loosening, periprosthetic fractures, periprosthetic joint infection (PJI), medical complications, wound complications, and readmissions were collected and compared to patients who do not have EDS undergoing TJA for osteoarthritis when available. Individual pooled comparative meta-analysis was performed for each variable. Patient-reported outcome measures (PROMs) were collected and qualitatively described. The search yielded eight publications with 1,769 EDS patients (1,011 THA and 758 TKA) describing outcomes after TJA, seven of which were included in the meta-analysis. Following THA, EDS patients were at increased risk of all-cause revision (OR [odds ratio] = 2.40, P < 0.001), instability/dislocation (OR = 3.22, P < 0.001), and aseptic loosening (OR = 3.76, P < 0.001). Following TKA, EDS patients were at increased risk of all-cause revision (OR = 1.54, P = 0.006), instability (OR = 2.96, P < 0.001), periprosthetic fracture (OR = 2.91, P = 0.009), and wound complications/hematoma (OR = 2.91, P < 0.001). There were no differences in medical complications, PJI, or readmission. The PROMs were similar between the cohorts and significantly improved compared to the baselines. Patients who have Ehlers-Danlos have an increased risk of implant-related complications following TJA. The EDS patients undergoing arthroplasty may benefit from careful planning with surgical techniques and constrained designs that minimize instability.

High-prediction QSAR Modeling Study Based on the Efficacy of a Novel 6-hydroxybenzothiazole-2-carboxamide Targeted Monoamine Oxidase B in the Treatment of Neurodegenerative Diseases.

Neurodegenerative diseases are a group of disorders characterized by progressive neuronal degeneration and death, of which Alzheimer's disease and Parkinson's disease are the most common. These diseases are closely associated with increased expression of monoamine oxidase B (MAO-B), an important enzyme that regulates neurotransmitter concentration, and its overactivity leads to oxidative stress and neurotoxicity, accelerating the progression of neurodegenerative diseases. Therefore, the development of effective MAO-B inhibitors is important for the treatment of neurodegenerative diseases. This study aims to improve the prediction of the efficacy of novel 6-hydroxybenzothiazole- 2-carboxamide compounds in inhibiting MAO-B by improving the quantitative constitutive effect relationship (QSAR) modeling and to provide a theoretical basis for the discovery of novel neuroprotective drugs. The study first optimized the structures of 36 compounds using the heuristic method (HM) in CODESSA software to construct linear QSAR models. Subsequently, key descriptors were screened by using the gene expression programming (GEP) technique to generate nonlinear QSAR models and validate them. The R², F-value, and R²cv of the linear model were 0.5724, 10.3752, and 0.4557, respectively, whereas the nonlinear model constructed by the GEP algorithm showed higher prediction accuracies by achieving R² values of 0.89 and 0.82, and mean squared errors (MSE) of 0.0799 and 0.1215 for the training and test sets, respectively. In addition, molecular docking experiments confirmed that the novel compound 31 was tightly bound to the MAO-B active site with significant inhibitory activity. In this study, we successfully improved the prediction ability of the efficacy of novel 6-hydroxybenzothiazole-2-carboxamide compounds to inhibit MAO-B by improving the QSAR model. This not only provides new drug candidates for the treatment of neurodegenerative diseases, but also provides important theoretical guidance for subsequent drug design and development, which can help accelerate the process of new drug discovery and reduce the disease burden of patients.

DEPDC5 mutations in familial epilepsy syndrome: genetic insights and therapeutic approaches

Background. DEPDC5 (disheveled, Egl-10 and pleckstrin domain-containing protein 5) familial epilepsy syndrome is a group of epilepsy disorders caused by mutations in DEPDC5 gene, which is a part of the gap activity towards rag 1 (GATOR1) complex involved in regulating the mechanism target of rapamycin (mTOR) pathway. These mutations lead to hyperactivation of the mTOR pathway, disrupting the shaping of neurons and resulting in increased excitatory transmission and the development of epilepsy. The incidence and prevalence of DEPDC5 familial epilepsy syndrome are not well established, but studies suggest it may account for up to 10% of familial focal epilepsy cases. Genetic testing, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) are important in diagnosing the disorder, although normal MRI results are common.Objective: to explain the rare sporadic mutation in DEPDC5 gene with p.R389H, a variant of unknown significance.Case report. A 6-year-old South-Asian girl was born at 34-weeks from non-consanguineous marriage without any prenatal events. She had hyperbilirubinemia by week-1, which was successfully treated with phototherapy. Her initial seizure occurred when she was three months old, just 2 days after the fever from the vaccination had subsided. It was considered a simple-febrile seizure and no treatment was given. At 3.5-months, she started having recurrent seizures. Workup including MRI/ infectious/metabolic panel was non-conclusive. EEG during the initial presentation showed epileptiform activity from the left temporal region. Despite being on multiple anti-epileptic drugs, the child was diagnosed with refractory epilepsy. Subsequently, EEG at 2.5-years showed inter-ictal bi-hemispheric epileptiform activity. EEG at 5-years showed inter-ictal spikes and wave discharges from bilateral fronto-temporal region with secondary generalization. By 3-years, MRI showed mildly deformed corpus callosum with inadequate thickening of splenium. DNA analysis confirmed heterozygous missense mutation in exon 16 of DEPDC5 gene, without chromosomal abnormalities. Mother was heterozygous for the same mutation but no mutations in the father was found. The child has grossly delayed milestones. Corrected age is approximately 1-year for fine motor and language, 1.5-years for gross motor, 2.5-years for cognition, social skills. She had developed autistic features as well with significant impaired auditory/visual processing. She had hypotonia (Right&gt;Left), wide-based gait, and extrapyramidal movements.Conclusion. DEPDC5 gene mutation results in amino acid substitution of Histidine for Arginine at codon 389. This mutation has shown to be inherited in familial pattern. This R389H variant is not present in the 1000 genomes database and is predicted to be benign. However, It rather appears to be a sporadic mutation, which is a very rarely observed phenomena. Such patients may respond well to mTOR inhibitors such as rapamycin, making prompt diagnosis and treatment crucial.

Blood biomarker profiles in young-onset neurocognitive disorders: A cohort study.

Young-onset neurocognitive symptoms result from a heterogeneous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the Biomarkers in Younger-Onset Neurocognitive Disorders cohort, a study of individuals <65 years old presenting with neurocognitive symptoms for a diagnosis and who have undergone cognitive and biomarker analyses. Sixty-five participants (median age at assessment of 56 years, 45% female) were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia, and categorized as either early-onset Alzheimer's disease (n = 18), non-Alzheimer's disease neurodegeneration (n = 23) or primary psychiatric disorders (n = 24). Levels of neurofilament light chain, glial fibrillary acidic protein and phosphorylated-tau 181, apolipoprotein E genotype and late-onset Alzheimer's disease polygenic risk scores were determined. Information-theoretic model selection identified discriminatory factors. Neurofilament light chain, glial fibrillary acidic protein and phosphorylated-tau 181 levels were elevated in early-onset Alzheimer's disease compared with other diagnostic categories. A multi-omic model selection identified that a combination of cognitive and blood biomarkers, but not the polygenic risk score, discriminated between early-onset Alzheimer's disease and primary psychiatric disorders (area under the curve ⩾ 0.975, 95% confidence interval: 0.825-1.000). Phosphorylated-tau 181 alone significantly discriminated between early-onset Alzheimer's disease and non-Alzheimer's disease neurodegeneration causes (area under the curve = 0.950, 95% confidence interval: 0.877-1.00). Discriminating between early-onset Alzheimer's disease, non-Alzheimer's disease neurodegeneration and primary psychiatric disorders causes of young-onset neurocognitive symptoms is possible by combining cognitive profiles with blood biomarkers. These results support utilizing blood biomarkers for the work-up of young-onset neurocognitive symptoms and highlight the need for the development of a young-onset Alzheimer's disease-specific polygenic risk score.

Hypomyelinating Leukodystrophy 14 (HLD14)-Related UFC1 p.Arg23Gln Decreases Cell Morphogenesis: A Phenotype Reversable with Hesperetin.

In the central nervous system (CNS), proper interaction between neuronal and glial cells is crucial for the development of mature nervous tissue. Hypomyelinating leukodystrophies (HLDs) are a group of genetic CNS disorders characterized by hypomyelination and/or demyelination. In these conditions, genetic mutations disrupt the biological functions of oligodendroglial cells, which are responsible for wrapping neuronal axons with myelin sheaths. Among these, an amino acid mutation of the ubiquitin-fold modifier conjugating enzyme 1 (UFC1) is associated with HLD14-related disease, characterized by hypomyelination and delayed myelination in the brain. UFC1 is a critical component of the UFMylation system, functioning similarly to E2-conjugating enzymes in the ubiquitin-dependent protein degradation system. We describe how a missense mutation in UFC1 (p.Arg23Gln) leads to the aggregation of UFC1 primarily in lysosomes in FBD-102b cells, which are undergoing oligodendroglial cell differentiation. Cells with mutated UFC1 exhibit reduced Akt kinase phosphorylation and reduced expression of differentiation and myelination marker proteins. Consistently, these cells exhibit impaired morphological differentiation with a reduced ability to extend widespread membranes. Interestingly, hesperetin, a citrus flavonoid with known neuroprotective properties, was found to restore differentiation abilities in cells with the UFC1 mutation. These findings indicate that the HLD14-related mutation in UFC1 causes its lysosomal aggregation, impairing its morphological differentiation. Furthermore, the study highlights potential therapeutic insights into the pathological molecular and cellular mechanisms underlying HLD14 and suggests hesperetin as a promising candidate for treatment.

Congenital muscular dystrophies and myopathies: the leading cause of genetic muscular disorders in eleven Chinese families

BackgroundCongenital muscular dystrophies (CMDs) and myopathies (CMYOs) are a clinically and genetically heterogeneous group of neuromuscular disorders that share common features, such as muscle weakness, hypotonia, characteristic changes on muscle biopsy and motor retardation. In this study, we recruited eleven families with early-onset neuromuscular disorders in China, aimed to clarify the underlying genetic etiology.MethodsEssential clinical tests, such as biomedical examination, electromyography and muscle biopsy, were applied to evaluate patient phenotypes. Whole exome sequencing was used to screen for prospective variants responsible for muscular diseases, followed by co-segregation analysis in the families and prenatal diagnosis via Sanger sequencing, if appropriate. Nanopore sequencing and optical genome mapping were applied for detecting complicated genome rearrangements.ResultsFourteen variants in nine genes (ATL1, LMNA, KLHL40, FKRP, DMD, ACTA1, MSTO1, RYR1 and LAMA2) associated with congenital muscular conditions were identified in the ten families mentioned above. Among them, five novel variants, c.1153_1155del in LMNA, c.577 A > G in ACTA1, c.694T > G in MSTO1, c.5938del in LAMA2, and a rare genome fusion ogm[GRCh38] fus(X; X)(p22.31;p21.1) involving DMD, have not been recorded in public databases to the best of our knowledge.ConclusionsCMDs and CMYOs were probably responsible for most of the cases (9/11) of genetic muscular defects in this study. Molecular analysis is highly beneficial for the precise diagnosis, genetic counseling and prenatal diagnosis of families suspected of having genetic muscular disorders.Clinical trial numberNot applicable.

Human PBMC-based humanized mice exhibit myositis features and serve as a drug evaluation model

Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune disorders characterized by immune cell infiltration of muscle tissue accompanied by inflammation. Treatment of IIMs is challenging, with few effective therapeutic options due to the lack of appropriate models that successfully recapitulate the features of IIMs observed in humans. In the present study, we demonstrate that immunodeficient mice transplanted with human peripheral blood mononuclear cells (hPBMCs) exhibit the key pathologic features of myositis observed in humans and develop graft-versus-host disease. The hPBMC mice exhibit elevated serum levels of creatine kinase and aspartate transaminase, markers of myositis, and increased expression levels of myositis-related genes, such as vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and serum amyloid A1, in muscle tissues. Histopathologic and flow cytometric analyses reveal the infiltration of CD8+ T cells in the muscle tissue of hPBMC mice, similar to that observed in patients with myositis, particularly in those with polymyositis. Transplantation of CD8+ T cell-depleted hPBMC leads to a significant reduction in polymyositis-like symptoms, in agreement with previous studies demonstrating CD8+ T cells as the main pathologic drivers of polymyositis. Furthermore, the transcriptome analysis of muscle tissue from hPBMC mice reveal extensive upregulation of characteristic genes of polymyositis, providing further support that hPBMC mice accurately reflect the pathophysiology of myositis in humans. Finally, administration of prednisolone or tacrolimus, which are commonly used for IIM treatment, leads to significant alleviation of myositis findings. Therefore, we propose that hPBMC mice should be considered as a model that accurately reflects the pathophysiology of myositis in human patients.

Insights into eye genetics and recent advances in ocular gene therapy.

The rapid advancements in the field of genetics have significantly propelled the development of gene therapies, paving the way for innovative treatments of various hereditary disorders. This review focuses on the genetics of ophthalmologic conditions, highlighting the currently approved ophthalmic gene therapy and exploring emerging therapeutic strategies under development. Inherited retinal dystrophies represent a heterogeneous group of genetic disorders that manifest across a broad spectrum from infancy to late middle age. Key clinical features include nyctalopia (night blindness), constriction of the visual field, impairments in color perception, reduced central visual acuity, and rapid eye movements. Recent technological advancements, such as multimodal imaging, psychophysical assessments, and electrophysiological testing, have greatly enhanced our ability to understand disease progression and establish genotype-phenotype correlations. Additionally, the integration of molecular diagnostics into clinical practice is revolutionizing patient stratification and the design of targeted interventions, underscoring the transformative potential of personalized medicine in ophthalmology. The review also covers the challenges and opportunities in developing gene therapies for other ophthalmic conditions, such as age-related macular degeneration and optic neuropathies. We discuss the viral and non-viral vector systems used in ocular gene therapy, highlighting their advantages and limitations. Additionally, we explore the potential of emerging technologies like CRISPR/Cas9 in treating genetic eye diseases. We briefly address the regulatory landscape, concerns, challenges, and future directions of gene therapy in ophthalmology. We emphasize the need for long-term safety and efficacy data as these innovative treatments move from bench to bedside.

De novo KCNB1 missense variant causing developmental and epileptic encephalopathy: Two case reports.

Developmental and epileptic encephalopathy (DEE) defines a group of severe and heterogeneous neurodevelopmental disorders. The voltage-gated potassium channel subfamily 2 voltage-gated potassium channel α subunit encoded by the KCNB1 gene is essential for neuronal excitability. Previous studies have shown that KCNB1 variants can cause DEE. Herein, we report the cases of 2 children with DEE caused by pathogenic variants in the KCNB1 gene. Trio whole-exome sequencing identified novel KCNB1 genotypes, c. 1160C > A and c.1012C > T, which had not been reported previously, in 2 unrelated patients. Two children were admitted to our hospital for a detailed evaluation of frequent seizures. And both of these children have abnormal electroencephalogram and brain magnetic resonance imaging results, accompanied by developmental delay. A genetic study using trio-whole-exome sequencing confirmed the diagnosis of KCNB1-related developmental and epileptic encephalopathy. Both patients accepted the treatment of antiepileptic drugs. 1 patient had seizure remission with a combination of sodium valproate and lamotrigine, and the other was lost to follow-up. Trio-whole-exome sequencing technology was used to determine the etiology of the 2 children with DEE. This study confirmed that genetic testing provides a basis for the diagnosis of children with abnormal electroencephalogram and brain magnetic resonance imaging findings and developmental delay, and provides data supporting a future phenotype-genotype correlation study.

Antidiabetic phytochemicals: an overview of medicinal plants and their bioactive compounds in diabetes mellitus treatment.

Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia due to insufficient insulin secretion or action. Contributing factors include genetic predisposition, obesity, family history, inactivity, and environmental risks. Type 2 diabetes mellitus (T2DM), the most common form, involves impaired insulin secretion by pancreatic β-cells, leading to insulin resistance. By 2045, it is projected that India and China will have approximately 134.3 and 110.8 million diabetic individuals, respectively. Although synthetic drugs are effective in managing DM, they often come with side effects. Consequently, plant-based phytochemicals with antidiabetic properties are gaining attention. Research indicates that around 115 medicinal plants (MPs) have antidiabetic effects, particularly those from the Fabaceae, Liliaceae, and Lamiaceae families. Bioactive compounds like alkaloids, triterpenoids, flavonoids, and phenolics are known to combat DM. Traditional medicinal systems, particularly in developing countries, offer effective DM management. This review highlights the importance of MPs and their bioactive compounds in treating diabetes and underscores the need for further research to commercialize plant-based antidiabetic drugs.

Investigation of peripheral markers of inflammation in patients with different diagnoses on the psychosis spectrum: an observational cross-sectional study

BackgroundIncreasing evidence suggests that inflammatory dysfunction may be important across the psychotic spectrum. In this study, we investigated whether there is a difference between different diagnostic groups, in which psychosis is the common pathway, and healthy controls in markers of peripheral inflammation, such as platelet-lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR), systemic inflammatory response index (SIRI) and systemic immune-inflammatory index (SII), determined by haemogram. Our hypotheses are as follows: patients with a common history of psychosis but with different diagnoses have higher severity of peripheral inflammation compared to healthy controls, regardless of the specific diagnosis. In addition, the severity of peripheral inflammation is similar across different diagnoses across the psychosis spectrum.ResultsBefore and after correction for age and sex, there was no statistically significant difference in PLR between the groups. However, a substantial statistical difference in NLR and SIRI was observed between the groups. According to the post hoc analysis performed to determine which groups the difference was between, schizophrenia and the healthy control group, schizoaffective disorder and the healthy control group, and autism spectrum disorder and the healthy control group differed in terms of NLR; there was only a significant difference in SIRI between autism spectrum disorder and the healthy control group. In addition, there was a statistically significant difference between groups for SII before and after correction for age and sex; however, when paired groups were evaluated using post hoc analysis, no statistically significant differences were found between any two groups. When comparing disorder groups within the psychotic spectrum, it was observed that PLR, NLR, SIRI, and SII levels were comparable.ConclusionsOur results showed that several disorders including schizophrenia, schizoaffective disorder and autistic spectrum disorder, with different diagnoses but similarities in terms of a history of psychosis, had increased inflammation compared to healthy controls. This study contributes to the psychosis spectrum approach in that there was no statistically significant difference in the severity of inflammation in disorder groups with a history of psychosis but with different diagnostic categories. However, further research is needed to completely understand the psychosis spectrum, as bipolar disorder patients have similar inflammation levels to those without mental disorders.

Elevated Kappa Index in the Absence of Cerebrospinal Fluid IgG Oligoclonal Bands: Contribution of Intrathecal IgM and IgA Synthesis.

The kappa index is a well-established marker of intrathecal synthesis (IS) of immunoglobulin (Ig). Routinely used for diagnostic aims, IgG IS, which can be assessed quantitatively (ad hoc formulas) or qualitatively (oligoclonal bands, OCBs), may fail in detecting a humoral immune response within the central nervous system (CNS). The main aim of this study was to evaluate the kappa index for its ability to detect the presence of CNS humoral immunity and to associate it with a distinct group of disorders, in the absence of IgG IS/OCBs. Within the kappa index-positive, IgG OCB-negative (Kappa+OCB-) patient group, we also examined whether IgM/IgA IS, determined with the IgM/IgA index and CSF IgM OCBs, could contribute to disease group stratification. Diagnoses were classified as multiple sclerosis (MS), or other inflammatory (INFL), infectious (INFECT), or non-inflammatory (Other) central/peripheral nervous system disorders. Sixty-nine Kappa+OCB- patients and 50 controls (24 Kappa-OCB- and 26 Kappa+OCB+ patients) were included in this study. The most frequent diagnosis in the Kappa+OCB- group was MS (27/69), followed by INFECT (16/69). Additional evidence of IS was demonstrated through an elevated IgG/IgM/IgA index or by the presence of IgM OCBs in 59%, and through only IgM/IgA IS in 52% of cases. In INFECT patients, the median IgM/IgA indexes were higher (p < 0.001) than in other groups, with 18 patients (95%) presenting an elevated IgM index, 11 patients (58%) presenting CSF IgM OCBs, and 10 patients (53%) presenting an elevated IgA index. The vast majority of all INFECT (16/19) belonged to the Kappa+OCB- group. Our data confirm that the kappa index performs at the highest level in assessing intrathecal humoral immunity and supporting the diagnosis of both MS and CNS infectious disorders, which are also characterized by the intrathecal production of IgM and IgA.

Oral Health Is Associated with Disorders of Gut-Brain Interaction in Adult Women.

The disorders of gut-brain interaction (DGBI) form a heterogeneous group of gastrointestinal disorders that, to date, have no organic basis. The role of oral health in the development of these disorders has not been explored. The objective of this study was to examine the relationship between oral health and the DGBI. Data obtained from 166 women with (n = 113) and without fibromyalgia (n = 55) during a prospective observational study conducted in New Zealand during 2022 was evaluated for correlations between oral health measures (WHO oral health questionnaire), and the DGBI (Rome IV survey). Of the 166 women enrolled in the study, 122 (73.5%) met criteria for at least one DGBI. Women who met criteria for any of the esophageal, gastroduodenal, bowel, and anorectal disorders had significantly lower oral health scores (p < 0.001). For 12 specific DGBI, oral health scores were significantly lower (p < 0.05). Oral health scores were inversely associated with the number of DGBI detected in each participant (ρ = -0.590, p < 0.001, 95% CI [-0.69, -0.48]). The results of this study suggest there is an association between the oral health and the presence, type, and number of DGBIs in women. Further research to examine the nature of this relationship is required.

Circulating microRNAs as Biomarkers of Various Forms of Epilepsy.

Background: Epilepsy is a group of disorders characterized by a cluster of clinical and EEG signs leading to the formation of abnormal synchronous excitation of neurons in the brain. It is one of the most common neurological disorders worldwide; and is characterized by aberrant expression patterns; both at the level of matrix transcripts and at the level of regulatory RNA sequences. Aberrant expression of a number of microRNAs can mark a particular epileptic syndrome; which will improve the quality of differential diagnosis. Materials and Methods: In this work; the expression profile of six microRNAs was analyzed: hsa-miR-106b-5p; hsa-miR-134-5p; hsa-miR-122-5p; hsa-miR-132-3p; hsa-miR-155-5p; and hsa-miR-206-5p in the blood plasma of patients suffering from temporal lobe epilepsy (n = 52) and juvenile myoclonic epilepsy (n = 42); n-amount of participants; in comparison with healthy volunteers. The expression analysis was carried out using RT-PCR. Mathematical processing of the data was carried out according to the Livak method. Results: A statistically significant change in the expression of hsa-miR-106b-5p; hsa-miR-134-5p; hsa-miR-122-5p; and hsa-miR-132-3p was found. An increase in the expression of hsa-miR-134-5p and hsa-miR-122-5p was registered in the group of patients with temporal lobe epilepsy compared to the control; as well as an increase in the expression of hsa-miR-132-3p and hsa-miR-106b-5p in the juvenile myoclonic epilepsy group compared to the control. hsa-miR-122-5p; 106b-5p; 132-3p are also able to discriminate groups with different syndromes. Additionally; a number of microRNAs are able to discriminate patients with drug-resistant and drug-sensitive forms of epilepsy from the control; as well as patients with hippocampal sclerosis and patients without hippocampal sclerosis from the control. Conclusion. Our data allow us to propose these microRNAs as plasma biomarkers of various epileptic syndromes.

Insights into laryngeal Castleman disease: A comprehensive scoping review with a case study focus.

Castleman disease (CD) refers to a heterogeneous group of lymphoproliferative disorders, which rarely involves the larynx. Our goal in this study is to elucidate the clinical presentation, diagnostic techniques, and treatment methods of laryngeal CD through a scoping review and the addition of a new case. Due to limited existing literature, we employed a mixed methodology for review. First, we searched Google Scholar using terms related to laryngeal CD. Subsequently, we screened abstracts using Covidence, drawing from databases such as PubMed, Science Direct, ProQuest, and EMBASE. We shortlisted studies for data extraction, focusing on clinical presentations, diagnostics, and treatment methodologies. Finally, we described our additional case. Scoping review revealed five qualifying laryngeal CD articles. Presenting symptoms included dysphagia, hoarseness, and dyspnea. Diagnosis was always established through histopathologic analysis. Management included local excision or radiotherapy. In our additional case, a 71-year-old male with known CD presented with neck swelling, dysphagia, and dysphonia. Exam revealed lymphoid laryngeal and supraglottic hyperplasia and edema. Laryngeal symptoms improved with medical management of CD. Given the rarity of laryngeal CD, its identification and management can be a challenge. Practitioners should be aware of characteristic points in a CD patient's history, physical exam, imaging, and biopsies. Local excision of obstructive lymphoid tissue and radiation are the best-supported therapies. This study aims to build toward improvements in accurate diagnosis and appropriate treatment for laryngeal CD.

Olfactory dysfunction as potential biomarker in neurodegenerative diseases: a narrative review.

Neurodegenerative diseases represent a group of disorders characterized by progressive degeneration of neurons in the central nervous system, leading to a range of cognitive, motor, and sensory impairments. In recent years, there has been growing interest in the association between neurodegenerative diseases and olfactory dysfunction (OD). Characterized by a decline in the ability to detect or identify odors, OD has been observed in various conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). This phenomenon often precedes the onset of other clinical symptoms, suggesting its potential utility as an early marker or prodromal symptom of neurodegenerative diseases. This review provides a vast literature overview on the current knowledge of OD in PD, AD, ALS, and HD in order to evaluate its potential as a biomarker, particularly in the early and prodromal stages of these diseases. We summarize the most common methods used to measure olfactory function and delve into neuropathological correlations and the alterations in neurotransmitter systems associated with OD in those neurodegenerative diseases, including differences in genetic variants if applicable, and cater to current pitfalls and shortcomings in the research.