HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p < 0.0001; and WMH: 0.0004±0.0007; p < 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p < 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

In patients with schizophrenia, metabolic syndrome is associated with cognitive impairments. We carried out a second analysis of data from a longitudinal trial to examine the relationship between weight gain and cognitive function in patients with first-episode schizophrenia (FES) over the first 6-month antipsychotic treatment. Baseline and 6-month endpoint measurements were taken for both cognitive function and body weight. Linear and logistic regression analyses were applied to investigate the bidirectional relationship between weight gain and cognitive function. Clinically relevant weight gain (CRW) was defined as an increase in body weight ex-ceeding 7%. The final analysis included 337 participants. Lower baseline scores in processing speed (OR=0.837, p=0.007), working memory and attention (OR=0.889, p=0.043), and executive function (OR=0.863, p=0.006) domains were significantly associated with CRW at the 6-month endpoint. After adjusting for confounders, CRW was found to be associated with improvement in the Brief Visuospatial Memory Test (p=0.036). The findings suggest that patients with lower baseline cognitive performance experienced more substantial weight gain. Conversely, weight gain was correlated with cognitive improvements, particularly in the domain of visual learning and memory. This suggested a potential bidirectional relationship between weight gain and cog-nitive function in patients with first-episode schizophrenia.

Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins and decrease levels of toxic proteins. ASOs are being developed for the treatment of several diseases, including motor neuron diseases (MNDs), a group of neurodegenerative disorders characterised by the loss of motor neurons, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MND, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits, often associated with the development of neurodegenerative diseases. The formation of reactive oxygen species (ROS) and oxidative stress have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice, we observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus). This elevation was accompanied by astrogliosis, microgliosis and the accumulation of amyloid precursor protein (APP). Concurrently, r-mTBI mice displayed impaired motor learning and spatial memory deficits. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as gliosis, oxidative stress, axonal damage, and white matter damage. These findings underscore the role of NHE1 upregulation in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 as a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

Introduction: The association between epilepsy and myasthenia gravis has rarely been reported, and only in small case series. Objective: To report the frequency of epilepsy and myasthenia gravis and to describe a case series of patients with myasthenia gravis and epilepsy, focusing on their clinical characteristics and searching for a possible physiopathological mechanism. Methods: A retrospective, observational, adult center study was conducted in 2022. Patients were recruited from the database of the outpatient clinic of the Myasthenia Gravis unit and Epilepsy unit. Results: Five patients were included. Frequency of epilepsy in the myasthenia gravis cohort was 5/469 (1.1%), and of myasthenia gravis in the epilepsy cohort was 5/1432 (0.35%). All patients suffered focal epilepsy, mainly fronto-central, and drug-resistant in half of them. Myasthenia gravis was generalized and with exacerbations in half of them. Three patients were thymectomized. Other autoimmune diseases were found in 2 (40%). Epilepsy onset preceded myasthenia gravis onset in all patients. Both diseases were considered autoimmune-related in 3/5 (60%). Conclusion: Epilepsy and myasthenia gravis are only infrequently associated. In adult patients, epilepsy onset precedes myasthenia onset in most cases. In some cases, epilepsy has an autoimmune aetiology and coexists with other autoimmune conditions.

Introduction Meningioma is the second most common primary intracranial tumor of the central nervous system. in Sudan, meningioma is the most common primary brain tumor, among Sudanese patients, Surgical total excision of meningioma offers a better survival, however, Chemotherapy has largely been unsuccessful for meningioma treatment, and therefore, refractory and recurrence meningioma treated with palliative surgery and radiotherapy. Monosomy of chromosome 22 is the utmost common genetic alteration among meningioma and many genes were investigated and described in the development of this tumor of which , NF2 hSNF5/INI1gene, P53. In addition to this, Molecular signal pathways in meningioma, and that contribute to the survival, proliferation, self-renewal, and differentiation properties of normal stem cells which are abnormally activated and nominated as cancerous stem cell (CSCs). Objectives 1/ To identify the possible pathway of candidate genes in both setting and whole genes hypothesis free approach 2/ To assess the presence of mutations in candidate genes among histological subtypes of meningioma in Sudan. Material and methods This is a prospective cross-sectional study done at the National Center of Neurological Sciences (NCNS) Khartoum, from 2018 to 2021. The study included all cerebral tumors that were radio- logically diagnosed preoperatively as meningioma. Ethical approval was taken from Institute of Endemic disease, Khartoum University, and written consent was obtained Three DNA extracts were randomly selected from 20 meningioma tissue samples and processed for WES. All genes harboring exonic and splice site variations stratified into SNVs and INDELs sets were prepared. The 1000G online database was used to explore novel mutations per 3 samples. SIFT and PolyPhen-2 programs were used to predict possible impact of amino acids substitution. To address meticulous genes interaction and particular centrality, all shared genes within the class INDEL and SNVs were used as input on Network Analysis to predict protein- protein interaction and functional gene ontology. Finally, shared mutations within genes of centrality were detected via Sanger sequencing and mutations were correlated between histological sub-types and recurrenceThree non meningioma brain tumor used as control. Results WES analysis revealed high number for mutational signature within 2 classes (INDEL and SNVs) per 3 samples, the findings of 1000 genome online database showed number of novel mutations; 5618 in fibrous , 6032 in meningothelial while in recurrent fibrous sample 5930. Network analysis of shared genes per each class (INDEL, SNVs), showed UBC is the most protein of remarkable degree centrality over thousand of genes. Whereas, all shared genes per 3 samples within the 2 classes (INDEL and SNVs) revealed Akt1 with the highest degree of centrality and betweenness. Akt1 rs17846829was detected in 20% of the samples, while CD44 stemness gene revealed mutation A>G (rs9666607) in all meningioma samples (100%), this mutation was associated with 60% of the recurrence. Conclusions Nevertheless, the present study, highlight how such complex molecular processes might contribute to tumorogenesis, in attempt to shed light over thousands of genes and multifaceted network analysis rather than a solitary gene which is challenging question.

Background: Older adults with bipolar disorder (OABD) are individuals aged 50 years and older with bipolar disorder (BD). People with BD may have fewer coping strategies or resilience. A long course of the disease, such as in OABD, could impact the development of resilience strategies, but this remains under-researched in OABD. Therefore, this study aims to assess resilience levels within the OABD and explore associated factors, hypothesizing that resilience could improve psychosocial functioning, wellbeing and quality of life of OABD patients. Methods: This study sampled 33 OABD patients from the OABD cohort at the Bipolar and Depressive Disorders Unit of Hospital Clinic of Barcelona. This was an observational, descriptive and cross-sectional study. Demographic and clinical variables as well as psychosocial functioning, resilience and cognitive reserve were analyzed. Resilience was measured using the CD-RISC-10. Non-parametric tests were used for statistical analysis. Results: The average CD-RISC-10 score was 25.67 points (SD 7.87). Resilience negatively correlated with the total number of episodes (p = 0.034), depressive episodes (p = 0.001), and the FAST (p < 0.001). Participants with normal resilience had a lower FAST (p = 0.046), a higher CRASH (p = 0.026), and more EOBD (p = 0.037) compared to those with low resilience. Conclusions: OABD individuals may exhibit lower resilience levels which correlate with more psychiatric episodes, particularly the number of depressions and worse psychosocial functioning and cognitive reserve. Better understanding and characterization of resilience could aid in early identification of patients requiring additional support to foster resilience and enhance OABD management.

Based on non-invasive neuroimaging techniques and graph theory-based network analyses, many researchers have tried to use small-world network model to elucidate sex differences in the brain. This manuscript aims to compile the related research findings from the past few years and summarize the sex differences in human brain networks from the perspective of small-world properties. We reviewed published reports examining altered small-world properties in both the functional and structural brain networks between males and females. Based on four patterns of altered small-world properties proposed--randomization, regularization, stronger small-worldization and weaker small-worldization, we found that current results point to a significant trend toward more regularization in females and more randomization in males in the functional brain networks. As for particular topological properties, the most consistent findings include a significant shift toward higher global efficiency in males and higher local efficiency in females in the functional network studies. On the other hand, there seems to be no consensus to date on the sex differences in small-world properties of the structural brain networks. Nevertheless, we noticed that the sample sizes in many published studies are limited, and future studies with larger samples are warranted to obtain more reliable results. We anticipate that the conclusions in this manuscript will contribute to a deeper understanding of neurobiological mechanisms underlying the sex differences in the brain.

Myeloperoxidase (MPO) is an enzyme that contains a heme group, found mostly in neutrophils and in small amounts in monocytes and plays a major role in their anti-microbial activity. However, excessive levels of MPO have been linked to various disorders and identified as a major cause of tissue destruction. Inhibiting its activity can reduce the severity and extent of tissue damage. Over activity of MPO during chronic inflammation has been shown to be involved in tumorigenesis by inducing a hyper-mutagenic environment through oxidant interaction with DNA, causing DNA modification. Vascular endothelium is one of the most important targets of MPO and high levels have been associated with increased rates of cardiomyopathy, ischemic stroke, heart failure, myocardial infarction, and atrial fibrillation. Therefore, it may be considered a therapeutic target in the treatment of cardiovascular disorders. MPO also participates in the pathogenesis of neurodegenerative diseases. For example, an increase in MPO levels has been observed in the brain tissue of patients with Alzheimer's, Multiple sclerosis (MS), and Parkinson's diseases. In Alzheimer's disease, active MPO is mostly found in the location of beta amyloids and microglia. Therefore, targeting MPO may be a potential treatment and prevention strategy for neurological disorders. This review will discuss MPO's physiological and pathological role in cancer, cardiovascular, and neurological disorders.

The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. It implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumor cells, circulating tumor DNA, transfer RNA and circular DNA or RNA derived from body fluids. Its application includes early disease diagnosis, surveillance of disease activity, and treatment response monitoring, with growing evidence for validating this methodology in cancer, liver disease, and central nervous system (CNS) disorders. This review will provide an overview of mentioned liquid biopsy components, which could serve as valuable biomarkers for the evaluation of complex neurological conditions, including Alzheimer’s disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, traumatic brain injury, CNS tumors, and neuroinfectious diseases. Furthermore, this review highlights the future directions and potential limitations associated with liquid biopsy.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Lyme disease, the leading vector-borne ailment in the U.S., annually affects an estimated 476,000 individuals, predominantly in the Northeast and Upper Midwest. Despite its increasing incidence, the evaluation of risk within U.S. cities, including natural public lands, remains inadequate. This study focuses on blacklegged tick occurrences and Borrelia burgdorferi infection prevalence in 24 Staten Island parks, aiming to assess Lyme disease exposure risk. Monthly acarological risk index (ARI) calculations from 2019 to 2022 revealed elevated values (0.16-0.53) in specific parks, notably Wolfe’s Pond Park, High Rock Park, Clay Pit Pond Park, Clove Lake Park, and Fair View Park. June (0.36) and November (0.21) consistently exhibited heightened ARIs, aligning with peak tick collection months. Despite stable yearly infection rates at 28.97%, tick densities varied significantly between parks and years. Identifying a high transmission risk in specific parks in Staten Island, a highly urbanized part of New York City, emphasizes the continuous necessity for Lyme disease risk management, even within the greenspaces of large cities.

Neural membranes are composed of phospholipids, sphingolipids, cholesterol and proteins. In re-sponse to cell stimulation or injury, metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahex-aenoic acid from the sn-2 position of glycerol moiety by the action of phospholipases A2. Ara-chidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotri-enes, and thromboxane are also involved in cell proliferation, differentiation, and blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called as specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell pro-tective effects. Sphingolipid derived-metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hy-droxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.

Poverty has long been associated intricately with neurological disorders. Majority of the previous studies designed to describe the effects of poverty on neurological ailments have mostly linked the association of hypoxic ischemic encephalopathy and nutritional deficiency disorders with poverty. Authors herein try to delve deeper into this issue. The association of begging with neuropsychiatric disorders is robust. The burden of probable autosomal dominant neurological ailments is very common among beggars; followed by neurological disorders with social stigma like abnormal movements, facial dysmorphism and gait unsteadiness. Dearth of support from family members in autosomal dominant neurological disorders (as family members are likely to be suffering from similar neurodegenerative disorder ) and poor perception about neurological diseases, misconceptions, myths and low educational attainment at large in the society can be implicated as the often overlooked but important factors underneath this association of begging and neurological disorders.

Neurological / neurovascular disorders constitute the leading cause of disability and second leading cause of deaths in the world. Some of the major neurological / neurovascular disorders or diseases include stroke, Alzheimer’s disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, etc. Their pathophysiology is considered as highly complex and has been blamed as the main obstacle in the development of any drugs for these diseases. In this review, we have described the endothelin system, their involvement in neurovascular disorders, importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN - sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders / diseases. We have highlighted the results of our pre-clinical and clinical studies related to these diseases. The phase I, safety and tolerability study of sovateltide has shown it as a highly safe and well tolerable compound at tested dosages, while pre-clinical and clinical phase II studies have demonstrated its efficacy in treating acute ischemic stroke, where it is currently being developed as a “First in Class” drug. Its testing in Alzheimer’s disease (AD), acute spinal cord injury and neonatal hypoxic-ischemic encephalopathy (HIE) is currently being carried out and are at different stages of drug development. Successful completion of these studies will prove the involvement of ETBRs signaling in neurological / neurovascular diseases and help in development of novel neurological drugs in future.

Transactive response DNA-binding protein of 43 kDa (TDP-43) is a major component of pathological inclusions in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The detection of TDP-43 in biofluids is crucial for the development of diagnostic and prognostic indicators of disease and therapeutic development for TDP-43 related proteinopathies. Despite its potential as a biomarker for numerous neurological disorders, the lack of a sensitive and reproducible TDP-43 assay hinders progress in TDP-43-based therapy development, underscoring the need for an effective and standardized method for accurate quantification. In this study, we developed and validated a sensitive immunoassay for the detection of TDP-43 in human biofluids using the Meso Scale Discovery (MSD) platform. We used this immunoassay to quantify TDP-43 levels in the plasma and serum of healthy controls and ALS patients. Our results indicate a reduction of total TDP-43 in the blood of ALS patients compared to healthy controls.

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). Methods: We diagnosed mild NCD (n=42) and major NCD (n=164) through DSM-5 criteria on 206 participants aged>65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. Results: In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (=-1.05-p<.0001) and minor NCD (=-0.06-p<.01). In the fully-adjusted multivariate regression model (sex-age-education-multimorbidity-depressive symptoms-antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (=0.09-p<.001). The effect of loneliness on IADL (=-0.26-p<.0001) and ADL (=-0.24-p<.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL:=0.26-p<.0001-ADL:=0.05-p=0.01). Minor NCD displayed different levels of MMSE (=6.68-p<.001), but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill’s test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. Conclusions: We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD.

Functional neurological disorders (FND) are relatively frequent disabling conditions. Given their complexity, multidisciplinary rehabilitation is envisaged. Whole-body cryostimulation (WBC) represents a promising adjuvant treatment, mainly because of its anti-inflammatory and exercise-mimicking effects. Here, we propose a novel use of WBC in a wheelchair-ridden 61-year-old woman diagnosed with FND and other comorbidities, who, after several therapeutic and rehabilitation failures, underwent a multidisciplinary rehabilitation program including WBC. The 4-week program included physiotherapy, nutritional intervention, psychological support, and WBC. Questionnaires to assess disease impact, pain level, perceived fatigue and sleep quality were administered. At discharge, improvements in body composition, haematological biomarkers, physical performance, and questionnaire scores were observed. The patient was able to walk with a walker for medium distances, even outdoors. We observed unprecedented improvements, particularly in functional parameters and questionnaire scores. Although we cannot ascertain to which extent WBC per se contributed to the improvements measured, subjective reporting and our clinical observation were that WBC, the only intervention not previously experienced by the patient, acted as a booster for the rehabilitation interventions. Further research will be necessary to rule out any possible placebo effect and to assess the effects of WBC on FND.

Imaging-based biomarkers have developed as an effective tool in neurology, providing vital understandings of the structural, functional, and molecular changes associated with neurological disorders. Imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) have been widely employed to record disease-related alterations in the brain. These techniques provide a wide range of biomarkers, such as functional connectivity patterns, volumetric measurements, molecular imaging agents, and perfusion parameters, enabling the correct identification of neurological disorders. These biomarkers have proven useful in early diagnosis, disease progression tracking, therapy response prediction, and surgical planning. This review emphasizes the various obstacles and limitations that are associated with imaging-based biomarkers. Technical constraints, standardization obstacles, ethical concerns, regulatory challenges, and cost-effectiveness concerns all offer substantial barriers to wider use. It is vital to overcome these challenges if imaging biomarkers are to be successfully integrated into routine clinical practice. Imaging technology advancements like high-resolution imaging, multimodal imaging, and artificial intelligence-based analysis hold immense promise for imaging-based biomarkers in the future. While more study and standardization are needed, their ongoing development and integration into clinical practice have the potential to revolutionize the diagnosis, treatment, and management of neurological disorders, resulting in better patient care and outcomes.

Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore the functional association between protein disorder properties and different mental diseases. To address this gap, we collected disrupted gene sets for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control gene set from normal brains using DisGeNET and GeneCards databases. The state-of-the-art predictor IUPred2A was then utilized to calculate the disorder properties , followed by a thorough comparison between the disordered proteins in mental diseases and healthy controls. Functional enrichment analysis and protein-protein interaction networks were conducted to investigate the IDPs’ functional roles in psychiatric diseases. Additionally, we demonstrated the role of IDPs in protein binding formations through a case study of alpha-synuclein using protein docking. Our findings reveal that differentially expressed proteins in mental disorders, especially in ASD and ADHD, exhibit more IDPs than those in healthy controls. IDPs in psychiatric disorders are significantly enriched in neurodevelopmental pathways and play an important role in in gene expression regulation. Our results indicate distinct functional patterns of disorder proteins among mental diseases and healthy controls. When comparing the IDPs between ASD and ADHD, we observed that IDPs in ADHD are more likely linked to the synaptic signaling and regulation, while IDPs in ASD are more tendentiously related to diverse and complex biological processes. Our work offers valuable insights into the important functions of IDPs in psychiatric disorders, enhancing our understanding of the molecular mechanisms involved in psychiatric disorders.

Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival and plasticity. In this review, we focus on the role of BDNF for corticostriatal plasticity in movement disorders, including Parkinson’s Disease (PD) and dystonia. We discuss the mechanisms how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Disruption of these pathways can lead to aberrant plasticity, ultimately affecting motor function. Advancing our understanding of these mechanisms could pave the way towards innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological science studies the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on the functions, and their treatment. Both psychotherapy and neurological science deal with the brain; nevertheless, they continue to stay polarized far. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss and Viktor Frankl, and it has been committed to account for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose of life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological science, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the existential phenomenological psychotherapy potently plays a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

In the contemporary accelerated pace of life, emphasizing the importance of sleep quality is essential for enhancing overall well-being and health. This study investigates the link between poor sleep quality and key factors affecting wellness, such as mental health and eating disorders. Through a cross-sectional analysis involving 407 participants, utilizing established measures including the Depression Anxiety Stress Scale (DASS-21), the Eating Disorder Examination Questionnaire Short (EDE-QS), and the single-item Sleep Quality Scale (SQS), data was collected and analyzed using SPSS v28 and R-Statistics. The findings reveal a significant correlation (p&lt;0.05) between DASS-21, EDE-QS, and SQS, indicating that individuals experiencing poor sleep quality exhibit higher levels of depression, anxiety, and stress. Furthermore, multinomial logistic regression analysis highlights low sleep quality as a risk factor for both mental health (OR: 1.071, 95% CI: 1.042, 1.102, p&lt;0.05, low vs. high sleep quality), and eating disorders (OR: 1.047, 95% CI: 1.004, 1.092, p&lt;0.05, low vs. high sleep quality). Overall, these results underscore the critical role of sleep quality in mental health and suggest insomnia as a predictive factor for both poor mental well-being and disordered eating habits. Further research through randomized controlled trials is warranted to validate the findings of this cross-sectional study.

Delve into the dynamic realms of neuroscience, neurology, and psychiatry with this groundbreaking editorial, unveiling the intricate mechanisms of brain function and dysfunction. Explore the latest advancements in molecular biology, genetics, epigenetics, pharmacology, and neuroimaging that are revolutionizing our understanding of neurological and psychiatric disorders. Uncover the challenges and gaps in translating cutting-edge research into practical clinical applications, aiming to enhance the lives of patients and their families. Discover the pivotal role of neuroplasticity in reshaping the brain's adaptability throughout life, alongside the promising potential of non-invasive brain stimulation techniques like transcranial magnetic stimulation and transcranial direct current stimulation. Embark on a journey of innovation and collaboration as researchers and clinicians strive to bridge the gap between bench and bedside, offering hope for improved diagnosis, prevention, and treatment of complex neurological and psychiatric conditions. Join us in this exploration of transformative ideas and novel interventions that hold the key to a brighter future for individuals and society.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

Researchers are dedicated to providing effective solutions for serious problems such as mental health. This field of study ranges from understanding the impact of mental health ailments on individuals to identifying trends in mental health diseases based on various data points. Unfortunately, the journey from diagnosis to receiving a proper mental health regimen is costly and inaccessible to many. This necessitates the introduction of an affordable alternative that enables individuals with internet access to connect to a platform to determine whether they require the services of a mental health professional. Additionally, such a platform can assist mental health professionals in quickly identifying patients with mental health conditions. Our proposed solution leverages hidden trends in data obtained from 700 mental health patients at The local mental hospital in Pakistan. We have used this data to train a machine learning classifier capable of distinguishing between Psychotic and Neurotic disorders. Psychotic disorders are a group of mental health conditions characterized by a loss of touch with reality whereas neurotic disorders are a group of mental health conditions characterized by excessive worry, anxiety, or stress that does not involve a loss of touch with reality. Our model achieved an overall accuracy score of 73%, indicating successful prediction of the correct diagnosis in 73 out of 100 pipeline tests. While these results may not seem significant, an increase in data points would surely allow for further improvements in these results and the overall solution we propose.

Background:In view of fact, the drawback of the armed conflict between Sudanese army and rapid support force was shocking, mass migration to neighboring countries, and many civilian were died, behind the war there were another factors for death, among these factors is brain tumors. The objectives of this study: To build up information and correlation between demographic data, brain tumors, surgery type and limitation of surgical resources, and to identify neurosurgical practice during armed conflict and how surgical resources can be utilized. Methods:This was a case report study, done at Almubarik hospital from April 2024 to July 2024.Ethical approval was taken from the National Center for Neurological Sciences.The operating room at Almubarik hospital includes X-ray viewing box, operating table, which is design for obstetrical and gynecology operation. very limited instruments for completing the surgery (forceps, straight dissector and scissors).Moreover, regarding anesthesia in this new situation there is no invasive BP, CVP, core temperature or even capnograph, all this made difficulties in monitoring the patient. In this conflict period, due to the lake of monitoring of the drugs and inappropriate storage, we used to give IV propofol , midasolam , morphine , lidocaine and nondepolrising muscle relaxant. ETT size 7 for all adult patients as it is the only big size available. Halothane MAC was used as volatile agent with propofol. pracetamol , magnisum sulphate ,are given as analgesia.Nevertheless,, for positing we manipulate our operating table by adding special head rest which was manually made from iron par and semi firm bellows are constructed on it tightly, so prone position was made. Conclusion: Despite of the infrastructural limitations, brain tumor surgery has special nature in the context of this conflict. Brain tumor surgery is challenges, and need not only skillful neurosurgeon but advance technology and well trained staff.

Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.

Mobile health technologies enable continuous, quantitative assessment of mobility and gait in real-world environments, facilitating early diagnosis of gait disorders, disease progression monitoring, and prediction of adverse events like falls. Traditionally, mobile gait assessment predominantly relied on body-fixed sensors positioned at the feet or lower trunk. Here, we investigate the potential of an algorithm utilizing an ear-worn motion sensor for spatiotemporal segmentation of gait patterns. We collected 3D acceleration profiles from the ear-worn sensor during varied walking speeds in 53 healthy adults. Temporal convolutional networks were trained to detect stepping sequences and predict spatial relations between steps. The resulting algorithm, mEar, accurately detects initial and final ground contacts (F1 score of 99% and 91%, respectively). It enables determination of temporal and spatial gait cycle characteristics (among others stride time and stride length) with good to excellent validity at a precision sufficient to monitor clinically relevant changes in walking speed, stride-to-stride variability, and side asymmetry. This study highlights the ear as a viable site for monitoring gait and proposes its potential integration with in-ear vital sign monitoring. Such integration offers a practical approach to comprehensive health monitoring and telemedical applications, by integrating multiple sensors in a single anatomical location.

Human Activity Recognition (HAR) technology enables continuous behavior monitoring, particularly valuable in healthcare. This study investigates the viability of using an ear-worn motion sensor for classifying daily activities, including lying, sitting/standing, walking, ascending stairs, descending stairs, and running. Fifty healthy participants (between 20 and 47 years old) engaged in these activities while under monitoring. Various machine learning algorithms, ranging from interpretable shallow models to state-of-the-art deep learning approaches designed for HAR, were employed for classification. Results demonstrate the ear sensor's efficacy, with deep learning models achieving 98% accuracy rate of classification. The obtained classification models are agnostic regarding which ear the sensor is worn and robust against moderate variations in sensor orientation (e.g., due to differences in auricle anatomy), meaning no initial calibration of the sensor orientation is required. The study underscores the ear's efficacy as a suitable site for monitoring human daily activity and suggests its potential for combining HAR with in-ear vital signs monitoring. This approach offers a practical method for comprehensive health monitoring by integrating sensors in a single anatomical location. This integration facilitates individualized health assessments, with potential applications in tele-monitoring, personalized health insights, and optimizing athletic training regimes.

Mental Disorders are an important public health problem. The main of this study was to analyze the prevalence of Mental Disorders and Environmental Quality. Data on the Prevalence of Mental Disorders, Gross Domestic Product, and Median Years of Schooling from 178 countries were used. A positive association was observed and was independent of Gross Domestic Product and Median Years of Schooling.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA). Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration. Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

Background/Objectives: Intracranial Epidermoid Cysts (IECs) are extremely rare intracranial tumors. The primary treatment is surgery; however, cyst adherence results in difficult removal; subtotal resection yields high recurrence rates. The mechanisms of IECs remain unknown, consequently, advances in treatment have fallen short. Tumor genetic profiling has rendered targets for drug development and for which FDA-approved options exist, reshaping cancer treatment. The genetics of IECs has not been explored. We applied Whole Exome Sequencing (WES) in IECs to gain insights into the mechanisms of oncogenesis and identify actionable targets. Methods: We performed WES in tumor tissue and matching blood, when available. Read processing, quality control and somatic variant calling followed GATK best practices. Read alignments were also used for somatic copy-number inference. Data analyses and visualizations were conducted in R. Results: Top altered genes were associated with immune system and microenvironment, suggesting an immune evasion mechanism. Recurrent and deleterious NOTCH2 and USP8 alterations were identified in 50% and 30% of the cohort, respectively. Frequent amplifications in deubiquitinases and beta-defensins, strengthened the involvement of an immune mechanism for oncogenic transformation. Drug-gene interactions highlighted NOTCH2 as clinically relevant for which FDA-approved treatments exists. Conclusions: Top altered genes may have a role in shaping an epidermoid cyst-permissive tumor microenvironment and modulating tumor immune evasion. USP8 and NOTCH2 may be clinically relevant drivers of IECs. NOTCH2 may be an interesting candidate for drug repurposing.

Pharmacogenetics and DNA methylation influence therapeutic outcomes and provide insights into potential therapeutic targets for brain-related disorders. To understand the effect of genetic polymorphisms on drug response and disease risk, we analyzed the relationship between global DNA methylation, drug-metabolizing enzymes, transport genes, and pathogenic gene phenotypes in serum samples from two groups of patients: Group A, which showed increased 5-methylcytosine (5mC) levels during clinical follow-up, and Group B, which exhibited no discernible change in 5mC levels. We identified specific SNPs in several metabolizing genes, including CYP1A2, CYP2C9, CYP4F2, GSTP1, and NAT2 that were associated with differential drug responses. Specific SNPs in CYP had a significant impact on enzyme activity, leading to changes in phenotypic distribution between the two patient groups. Group B, which contained a lower frequency of normal metabolizers and a higher frequency of ultra-rapid metabolizers compared to patients in Group A, did not show an improvement in 5mC levels during follow-up. Furthermore, there were significant differences in phenotype distribution between patient Groups A and B for several SNPs associated with transporter genes (ABCB1, ABCC2, SLC2A9, SLC39A8, and SLCO1B1) and pathogenic genes (APOE, NBEA, and PTGS2). These findings appear to suggest that the interplay between pharmacogenomics and DNA methylation has important implications for improving treatment outcomes in patients with brain-related disorders.

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this disease may have long-term adverse neurological consequences. COVID-19 occurs from the infection by a positive-sense single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The membrane fusion protein of SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme 2 (ACE2), to initiate membrane fusion between the virus and host cell. The spike protein of SARS-CoV-2 contains the furin protease recognition site and its cleavage enhances the infectivity of this virus. The binding of SARS-CoV-2 to the ACE2 receptor has been shown to downregulate ACE2, thereby increasing the levels of pathogenic angiotensin II (Ang II). The furin protease cleaves between the S1 subunit of the spike protein with the binding domain toward ACE2 and the S2 subunit with the transmembrane domain that anchors to the viral membrane, and this activity releases the S1 subunit into the blood circulation. The released S1 subunit of the spike protein also binds to and downregulates ACE2, in turn, increasing the level of Ang II. Considering that a viral particle contains many spike protein molecules, furin-dependent cleavage would release many free S1 protein molecules each of which can downregulate ACE2, while the infection with a viral particle only affects one ACE2 molecule. Therefore, the furin-dependent release of S1 protein would dramatically amplify the ability to downregulate ACE2 and produce Ang II. We hypothesize that this amplification mechanism that the virus possesses, but not the infection per se, is the major driving force behind COVID-19 associated neurological disorders.

A large body of evidence, replicated in many mouse models of Alzheimer Disease (AD), demonstrated the therapeutic efficacy of oral rapamycin. Administration of m-TOR inhibitors (mTOR-Is), early after the clinical onset, greatly diminished cognitive impairment, amyloid angiopathy, intracellular beta Amyloid and neurofibrillary tangles load. The daily intake of rapamycin has always been 2.24g/Kg/24h. In humans the maximal tolerated oral dose is a few milligrams/day, and at this dosage patients are severely immunosuppressed. Thanks to rapalogs’ scarce CNS-related side effects, we administered intracerebroventricularly (ICV) high doses of the mTOR-I everolimus in a mouse model of AD (3xTg-AD) without significant systemic effects. The instability of the liquid formulation at body temperature (BT) made the treatment very short. Nevertheless, the efficacy of the treatment was high and much longer lasting than expected. In order to set up a thermostable, translational liquid formulation of mTOR-Is, we loaded everolimus in distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) micelles by the thin layer method. The formulation we obtained maintained over 95% of activity after 14 days at BT. We can envision short, potentially periodic ICV treatments in AD patients which replicate results obtained on animal models. The treatment could benefit also Tuberous Sclerosis and Multiple Sclerosis patients.

Background: Diagnostic accuracy of Parkinson’s disease (PD), a synucleinopathy, based on diagnostic criteria is suboptimal. A biomarker for synucleinopathies is pivotal both from a clinical and from a research aspect. CSF a-synuclein has been extensively studied over the past two decades as a candidate biomarker of synucleinopathies. Herein we present data on studies focusing on total, phosphorylated and oligomeric CSF a-synuclein in PD. Methods: Pubmed, Scopus and Web of Science were searched for studies with &gt;10 PD patients and control subjects, with data (mean, SD) on total, phosphorylated or oligomeric a-synuclein. Cohen’s d, as a measure of effect size, was calculated for all a-synuclein forms. Subgroup analysis and meta-regression were performed in an effort to explain between-study heterogeneity. Results: Thirty studies on total, six studies on oligomeric and one study on phosphorylated a-synuclein were included. Total a-synuclein was decreased and oligomeric a-synuclein increased in PD patients vs. controls. Effect size was medium for total and high for oligomeric a-synuclein. A-syn forms provided suboptimal combined sensitivity/specificity for the differentiation of PD from controls. There was significant between-study heterogeneity. PD cohort characteristics (sex, age, disease duration, UPDRS, H&amp;Y) and study characteristics (study design, healthy vs. neurological controls, control for CSF blood contamination, method of a-syn measurement) could not account for between-study heterogeneity. Publication bias was limited. Conclusions: CSF a-synuclein levels lack sufficient accuracy to be used as biomarkers for PD. Standardization of (pre)analytical variables may improve the discriminatory power of a-synuclein forms in the future.

Limited understanding exists regarding the intricate dynamics between the levels of social inhi-bition exhibited by both wives and husbands concerning their perceived family support and de-pressive symptoms, particularly within couples who are parents of children diagnosed with au-tism spectrum disorder (ASD). This study used the actor-partner, interdependence mediation model to analyze data collected from 397 pairs of Chinese parents with children diagnosed with ASD. The findings of the study revealed significant indirect actor effects, indicating that the levels of social inhibition exhibited by both wives and husbands were associated with their own de-pressive symptoms through their respective perceptions of family support. In general, the study did not find significant partner effects, except for some indirect effect (IE) of wives on their hus-bands' depressive symptoms through the wives' perceived social support. This observation sug-gests that cultural norms and role expectations within the family context may influence these dy-namics. These results underscore the potential importance of interventions aimed at addressing social inhibition and enhancing perceived family support to alleviate depressive symptoms in this population. Additionally, interventions targeting fathers should emphasize the importance of their involvement in parenting and collaboration with their partners in caring for children with ASD. Such collaborative efforts may contribute to improved outcomes for both parents and chil-dren within families affected by ASD.

Revealing the underlying pathomechanisms of neurological and psychiatric disorders, searching for new biomarkers, and developing novel therapeutics all require translational research. In vivo and in vitro disease models have been instrumental in casting light on complex polygenic, multifactorial, and heterogeneous disease mechanisms. In the most recent years, advanced preclinical models have revealed the intriguing interaction of sex/gender and aging with the pathogenesis and clinical manifestations of psychiatric and neurological diseases. However, despite these advancements, there is still a great deal of work to be done to fully comprehend the underlying mechanisms of these diseases and to develop treatments that can significantly improve the lives of those who suffer from them. The current challenge in the field of neurological and psychiatric diseases is to develop disease-modifying, effective treatments for these complex and long-lasting debilitating conditions with a high burden of disease.The first edition of the research topic ‘Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models’ reinforces translational research playing a critical role in bridging the gap between basic research and clinical applications. Also, it provides a platform for researchers to share their findings and advancements in translational research in this field. This new collection gathers 25 papers offering insights into the latest advancements in translational research and potential new avenues for treatments. These papers cover various topics, including the development of new preclinical models, the use of in vitro and in vivo methods, and the application of qualitative and quantitative research methods.

Pericytes are increasingly recognized as being important in the control of blood-brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse-human species differences have contributed to confusion. Herein we summarize our present knowledge on the identification of pericytes and pericyte subsets in humans, primarily focusing on recent findings in humans and nonhuman primates. Precise identification and definition of pericytes and pericyte subsets in humans may help us to better understand pericyte biology and develop new therapeutic approaches specifically targeting disease-associated pericyte subsets.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Objective: Mechanical bowel preparation is essential for the visualisation of the colon during colonoscopy, and previous studies have identified changes in gut microbiota composition after bowel preparation and colonoscopy. Considering the gut microbiota is increasingly implicated in mood, we aimed to explore the potential impact of this intervention on mood and the microbiota-gut-brain axis. Methods: We conducted a pre-post intervention study, with timepoints of one week before and one month after bowel preparation and colonoscopy, in community-dwelling adults referred for colonoscopy. Our primary outcome was change in average Hospital Anxiety and Depression Scale depression sub-scores using generalised estimating equations. We also examined changes in average anxiety, stress, and quality of life scores, and faecal microbiota composition and potential function using 16S rRNA sequencing. We further explored associations between changes in depressive symptoms and the gut microbiota and conducted post-hoc analyses to explore potential effect modifiers. Key Results: 59 participants were included in the analyses. Depressive symptoms decreased one-month post-procedure compared to baseline (adjusted β=−0.64; 95%CI: −1.18, −0.11). Irritable bowel syndrome (IBS) appeared to moderate this relationship (1.78; 0.292, 3.26); depressive symptoms increased in those with, and decreased in those without, IBS. Changes in gut microbiome composition included reduced alpha diversity, modest effects on beta-diversity, and increases in genera associated with potential health benefits, one-month post-procedure compared to baseline. Increases in the CLR-transformed abundance of Ruminococcaceae UCG-009 were associated with improvements in depressive symptoms. Conclusions: There is preliminary evidence of a potential mental health effect of bowel preparation and colonoscopy, which may be associated with changes to the gut microbiota. There may also be a differential mental health impact of this procedure for those with and without IBS. Considering the limitations of our study, further research is required to confirm these findings and their clinical relevance.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodelling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events.From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

The aims of this systematic review and meta-analysis were to evaluate the risk of inmates with mental disorder of being placed into disciplinary confinement (DC) and its effect on mental health. A systematic search of studies was performed in PubMed, PsycINFO, Web of Science, and Google Scholar. The meta-analysis was conducted using random-effects models. Heterogeneity among study point estimates was assessed with Q statistics and quantified with I2 index. Publication bias was assessed with Egger’s test. Quality assessment was based on the GRADE Checklist for observational studies. Guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed throughout. First, a meta-analysis of 5 articles including 27,455 inmates showed than incarcerated individuals with a mental disorder were 1.23 times (OR=1.23, CI=1.10; 1.38) more likely to be placed in DC than incarcerated individuals without a mental disorder. Particularly, having a severe mental disorder (OR=1.31, p&lt;0.001), a personality disorder (OR=1.66, p&lt;0.001) and having previously received mental health services (OR=1.16, p=0.024) increased the risk of being placed in DC. Secondly, a systematic review of 5 articles including 171,300 inmates showed more psychological distress, psychiatric symptoms (self-harm, thought disorders, obsessive-compulsive symptoms), need for mental health services and hospitalizations in DC than the general correctional population. Considering the increased risk of placement in DC for incarcerated persons with a mental disorder and its deleterious effect on mental state, it is essential that correction officials create new safe interventions to manage these inmates and offer them proper mental health care to limit its use.

Immersive virtual reality has the potential to motivate and challenge patients that need and want to relearn movements in the process of (neuro-)rehabilitation. The aims of this study were to evaluate the feasibility and users’ acceptance of an innovative immersive virtual reality system (head-mounted display) used in combination with robot assisted gait training in subjects suffering from neurological diseases. Fifteen participants tested a single session of immersive virtual reality by means of head-mounted display during a Lokomat gait session. Training parameters and safety indicators were collected and the acceptance was investigated among the participants and the therapists. The results suggest that the immersive virtual reality system is feasible with respect to safety and tolerance. Furthermore, the very positive overall acceptance of the system suggests that it has potential to be included in a robot assisted gait training session by means of Lokomat. Taken together, this study demonstrates the feasibility and acceptance of an innovative immersive virtual reality system in combination with a robot assisted gait training in subjects suffering from stroke and spinal cord injury, as well as their therapists.

Monkeypox (mpox) caused by the monkeypox virus (MPXV) is currently the most common orthopoxvirus (OPXV) zoonotic disease. Since 2022, a multi-country outbreak of mpox has been reported with atypically rapid human-to-human transmission. The present work aimed to investigate the frequency of MPXV and OPXV DNA detection in different clinical materials taken at acute and convalescent phases of the infection in Bulgarian patients. A total of 181 clinical samples from 42 Bulgarian patients with possible mpox infections were tested. Screening for MPXV DNA (F3L gene) and OPXV DNA (rpo18 gene) were performed by real-time PCR assays. Of all tested patients six (14%) were confirmed with mpox infection. MPXV DNA was detected in 23/181 (12,71%) and OPXV DNA in 20/181 (11,05%) clinical samples. All confirmed patients were men who have sex with men, aged 23 to 44 (at an average age of 35,17±7,91 years) and two of them were HIV positive. The commonest clinical features of patients were fever (5/6), vesicular-pustular rash: perianal (6/6), penile (4/6), and limbs (4/6). MPXV DNA was found with the greatest frequency in specimens of vesicle contents and nasal/oropharyngeal swabs in 6/6 and 5/6. OPXV DNA mainly was detected in vesicle contents (6/6), nasal/oropharyngeal swabs (4/6), and urine (4/6). In the collected follow-up samples, MPXV DNA was detected in the highest percentage in the specimen's vesicle contents (6/6) and urine (6/6) and not demonstrated in samples of feces and saliva. The laboratory surveillance of MPXV is critical to contain the outbreak and to elucidate the new fast transmission of the virus.

This review examines the effects of lingonberry (Vaccinium vitis-idaea L.) on general and oral health. The effects of lingonberry are based on the vitamins, minerals, fibers and polyphenolic compounds it contains. Lingonberry's bioactive substances have a diverse range of antimicrobial, anti-inflammatory, antiproteolytic, anticarcinogenic and antioxidant properties. Research results suggest that lingonberries can have a positive effect on human health. Berries, lingonberry juice/lingonberry nectar/fermented lingonberry juice and polyphenol fractions have been used in clinical studies. Lingonberries balance post-meal blood sugar, free fatty acids and insulin levels. Fermented lingonberry juice reduces Streptococcus mutans, Candida and periodontal pathogen counts, but is probiotic because it favors growth of Lactobacilli. In addition, it increases saliva secretion and thus lowers the risk of oral infections. It lowers the clinical parameters of periodontitis and the active matrix metalloprotease-8, reducing the low-grade inflammation associated with periodontal diseases. More studies on humans are needed.

Early childhood may be a stressful period for families with a significant impact on parents’ mental health and the child’s healthy development. The goal of the SKKIPPI cohort study was to assess the occurrence and determinants of psychosocial stress and mental health disorders in parents as well as in their offspring in early childhood in three German regions. Based on random samples from three residents' registration offices, parents with infants up to 12 months of age at the time of sampling, were invited to participate in the study. A screening online questionnaire was newly developed, available in four languages, to assess common psy-chosocial stressors and mental health problems of parents with small children. The study enrolled 4,984 mothers and 962 fathers. The most common potential psychosocial stressors at baseline were professional problems (mothers 22%, fathers 33%), lack of social sup-port (20%, 14%), and severe, negative experiences in childhood (22%, 16%). Obses-sive-compulsive thoughts (21%, 16%), depressive (9%, 9%) and anxiety symptoms (11%, 7%) were the most frequently reported mental health problems by both parents. Regulatory prob-lems of the child were reported by between 1.5% and 5.1% of parents. The SKKIPPI study showed that a substantial proportion of parents are burdened by psychoso-cial problems and suffer from mental health problems in the first years after birth. Early pre-ventive and low-threshold support measures should be available in the health and social care system. The newly developed questionnaire can be used to screen in the relevant populations in order to avoid disturbances in the mother-child attachment.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

Mammarenavirus Wenzhouense (WENV) is broadly distributed in Asia, while the he dynamics process of WENV infection remains unclear. A field derived strain of WENV was used to inoculate Sprague-Dawley (SD) rats by intramuscular injection, the process of virus infection was de-tected by controlling time for 28 days. Viral RNA became detectable in the blood at 3 d pi, and remained detectable for about 12 d. In most organ tissues, viral RNA peaked at 7 d pi, then began to decline by 14 d, however remained detectable in intestine and brain tissues at 21 and 28 d pi. Virus shedding had been detected from fecal samples for 5 days from 6 to 11 d pi using qRT-PCR, and was recovered from feces collected at 8 d pi. Horizontal contact infection occurred among cage-mates at 14 and 21 d pi. Antibodies against the nucleocapsid were detected at 5 dpi, next increased and persisted until the end of experiment. The results enabled to discriminate the kinetic of viremic response, virus shedding in feces and horizontal transmission, as well as the potential sites for WENV replication or maintenance of the virus in nature.

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. Dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

A prospective clinical-epidemiological study was conducted to evaluate the dynamics of biomarkers in hospitalized patients with moderate to severe COVID-19 (according to the National Institute of Health severity scale) treated with Anakinra, compared to those receiving standard treatment. The study included 65 patients with a mean age of 75.51±9.54 years, ranging from 44 to 99 years. Among the study participants, 38 (58.5%) were male and 27 (41.5%) were female. The patients were divided into two groups: control group (standard treatment): 24 patients (36.9%) and target group (Anakinra treatment): 41 patients (63.1%). The results showed a significant relationship between the dynamics of leukocytes, ASAT, LDH, D-dimer, ferritin, and IL-6 and the administration of Anakinra. In the control group, no significant dynamics were observed in leukocyte count, D-dimer, ferritin, or IL-6. A statistically significant decrease in ASAT and LDH values in the control group was noted only on Day 7. In the Anakinra group, significantly (or with borderline statistical significance, p&lt;0.1) lower mean values were observed for leukocytes, NLR, D-dimer, ferritin, and IL-6 on Days 3 and 7 compared to the control group. Additionally, significantly lower CRP values were detected in the Anakinra group on Day 7 compared to the control group.

The reasons for the circular sense of human color perception generated by two sorts of color opponent neurons and three cone types are not well understood. Here we use geometrical analysis to examine the hypothesis that opponency, the recursive nature of color perception, and trichromacy arise as the most efficient ways of distinguishing spectrally different points on a plane using a minimum of color classes and receptor types.

Sleep disorders are a frequent problem in pediatrics. The prevalence is variable (from 15 to 50%) although the majority of papers coincide in that 1 every 3 kids can experiment some kind of sleep disorder. Underlying medical problems usually manifest by difficulty to fall asleep or stay asleep. The diagnosis and resolution of the medical problems with the specific treatment should be the prime concern, before starting with the treatment of the sleep behavioral problem

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

Background/Objectives: Obstructive Sleep Apnoea Syndrome (OSA) in children disrupts standard breathing patterns and sleep architecture, potentially leading to severe consequences. Early identification and intervention for OSA are crucial to prevent these issues. This study explored the relationships between waiting times for polysomnography (PSG), clinical history, age at the time of PSG, and PSG outcomes in children; Methods: Two hundred and fourteen children were prospectively enrolled. Data were extracted from medical records on the age at referral for PSG and at the time of its execution, the waiting time for PSG, diagnosis (primary snoring, mild, moderate, and severe OSA), history of snoring and apnoea, medications taken, surgical interventions, passive smoke exposure, and allergies. The records also included the Pediatric Sleep Questionnaire (PSQ); Results: The mean age at referral for PSG was 5.2 (2.8) years, the waiting time for PSG was 5.2 (5.0) months, and the age at the time of PSG was 5.6 (2.8) years. Children with a shorter history of OSA (≤12 months) underwent PSG at an earlier age (4.9 (2.7) years) compared to those with a more extended history (6.0 (2.7) years; p=0.006). A younger age at referral for PSG was associated with a lower PSQ score (r=0.167; p=0.015), a shorter history of apnoea (r=0.216; p=0.003) and snoring (r=0.187; p=0.023), but also with greater OSA severity, expressed as oxygen desaturation index (r=-0.152; p=0.026). In the correlation analysis, the waiting time for PSG, adjusted for age at referral, was longer in children with a prolonged history of apnoea (r=0.195; p=0.023) and snoring (r=0.259; p=0.002) but with a lower PSQ score (r=-0.172; p=0.045); Conclusions: Some children receive delayed treatment, increasing the risk of long-term complications. In evaluating children with suspected OSA, the duration of symptoms and the PSQ score at referral emerge as crucial factors that should be considered to optimise prioritisation for PSG access.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

The Samenta study was conducted in 2009 in the Greater Paris area to estimate the prevalence of psychiatric disorders among the homeless. A cross-sectional survey was performed with a three-stage random sample of homeless people (n = 859), including users of day services, emergency shelters, hot meal distribution, long-term rehabilitation centres and social hotels. Information was collected by a lay interviewer, using the Mini International Neuropsychiatric Interview, and completed by a psychologist through an open clinical interview. In the end, a psychiatrist assessed the psychiatric diagnosis according to the ICD10. One third of the homeless in the Paris area had at least one severe psychiatric disorder: psychotic disorders (13%), anxiety disorders (12%) or severe mood disorders (7%). One in five was alcohol dependent and 18% were drug users. Homeless women had significantly higher prevalence of anxiety disorders and depression and men were more likely to suffer from psychotic disorders. Homeless people of French origin were at higher risk of SPD, as well as people who experienced various adverse life events before the age of 18 (running away, sexual violence, parental disputes, and/or addictions) and those who experienced homelessness for the first time before the age of 26. The prevalence rates of main psychiatric disorders within the homeless population of our study are consistent with those reported in other Western cities. Our results advocate for an improvement in detection, housing and care of psychiatric homeless.

Background: over the past 20 years, the treatment scenario of multiple sclerosis (MS) has radically changed and an ever-increasing number of disease-modifying treatments has emerged. Among high efficacy treatment agents, monoclonal antibodies (mAbs) have become a mainstay in the MS patient’s treatment due to their targeted mechanism, high efficacy and favorable risk profile. The latter varies from drug to drug and a skin cancer warning has emerged with sphingosine 1-phosphate receptors inhibitors. Several cases of skin malignancy in people with MS (pwMS) undergoing therapy with mAbs have also been described, but dermatological follow-up is not currently indicated. Objectives: the aim of this review is to investigate cases of cutaneous ma-lignancy during mAbs therapy and to explore possible pathophysiological mechanisms to evaluate the potential need for regular dermatological follow-up in pwMS treated with mAbs. Methods: literature search for original articles and review in PubMed. No date restrictions. Results: 1019 results were retrieved. Duplicates were removed using Endnote and manually. Only peer-reviewed studies published in English were considered for inclusion. At the end of these screening procedures, 54 studies published between 2001 and 2023 that met the objectives of this review were selected and reported. Conclusions: the available data do not show a clear link be-tween monoclonal antibody (mAb) treatment in pwMS and the risk of skin cancer. At present, these treatments remain contraindicated for people with cancer. Dermatological screening is ad-visable before starting mAb treatment in pwMS, and subsequent follow-up should be individual-ised according to each patient's risk profile.

The risk of a fatal outcome was 41% in unvaccinated patients (p = 0.713), which increased by 2.66% with co-infection with two pathogens (p = 0.342) and by 26% with three pathogens (p = 0.005). Additionally, 50% of ICU patients had a triple infection, compared with only 1.3% in the inpatient unit (p = 0.0029). The risk of death and/or ICU admission was 12 times higher (p = 0.042) with an additional pathogen and increased by 95% (p = 0.003) with a third concomitant pathogen. Regular multiplex testing is important for prompt treatment and targeted antibiotic use.

Background: The increasing prevalence of severe obesity among children and adolescents poses a significant challenge for pediatricians and general practitioners. This study aimed to investigate the relationships between biochemical results, anthropometry, blood pressure measurements and bioimpedance analysis (BIA)-derived parameters, to identify potential cardiometabolic complications associated with severe obesity. Methods: The study included 347 children (162 boys, 185 girls) aged 0-19 years, meeting criteria for severe obesity based on BMI thresholds for different age groups. Patients were recruited in four pediatric endocrinology centers in Poland (Zabrze, Cracow, Rzeszow, Szczecin). Each participant underwent anthropometric measurements, pubertal stage assessment, blood pressure measurement, biochemical and hormonal tests and BIA. Results: BMI showed significant associations with fat mass percentage (FM%) and waist-to-height ratio (WHtR), but not waist-to-hip ratio (WHR). The relationship between BMI and FM% was stronger in girls and prepubertal children. Metabolic syndrome (MetS) Z-score showed a strong positive correlation with BMI in pubertal children. Negative correlation between HDL and triglycerides was observed only in boys. Prepubertal children exhibited more significant correlations despite a smaller sample size and shorter duration of obesity. Conclusions: Considering multiple parameters beyond BMI alone provides a better understanding of cardiometabolic risks associated with severe obesity in children. MetS Z-score was not a reliable indicator of increased cardiometabolic risk in younger children. Early-onset severe obesity was associated with a higher risk of metabolic complications. Early intervention is crucial to mitigate metabolic complications in this population.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Background/ObjectivesMental health and substance use disorders (MHD, SUD) affect cardiac allograft and VAD recipients and impact their quality of life and compliance. Limited research on MHDs and SUDs in transplant and MCS candidates and recipients. This study compares the incidence of MHDs and SUDs in transplant list, VAD, and post-transplant patients with that in heart failure patients. MethodsStudy cohorts were derived from the TriNetX using ICD-10 codes. Differences in incidence were examined using the log-rank test. Adults with mental health disorders before the window of time were excluded. Propensity score matching was performed using TriNetX to balance demographic and medical comorbidities. Statistical significance was set at p<0.05. All comparisons were made between propensity-matched cohorts. ResultsTransplant waitlist patients showed a statistically significant increase in the incidence of anxiety, panic disorder, adjustment disorder, depression, mood disorder, alcohol use disorder, and eating disorder. Post-transplant patients showed a statistically significant increase in the incidence of depression and opioid use compared to the heart failure population. VAD patients showed a statistically significant increase in the incidence of depression and a statistically significant decrease in panic disorder and anxiety. ConclusionsThe results pave the pathway for further investigations on prevention and coping strategies because deterioration of mental health will significantly impact compliance with medications as well as patient survival and quality of life. The use of opioids for pain management in the early postoperative period should be further investigated to assess its impact on long-term substance use and addiction. .

In schizophrenia, cognition is closely linked to social competence and influences long-term prognosis. Thus, treatment should target cognitive improvement to enhance the patients’ societal adaptation. This study evaluated the effects of computer-assisted cognitive remediation therapy (CR) using RehaCom® on cognition in patients with schizophrenia. Thirty patients were randomized, with 15 assigned to the CR group and treatment usual care (TAU) and 15 to the TAU alone groups. Over 12 weeks, patients received CR twice weekly, including two computer sessions and one verbal session. Outcomes measured were cognition using the Brief Assessment of Cognition in Schizophrenia and Schizophrenia Cognition Rating Scale, intrinsic motivation using the Quality of Life Scale and Intrinsic Motivation Inventory, psychiatric symptoms using the Positive and Negative Syndrome Scale, negative symptoms using Scale for the Assessment of Negative Symptoms, and functional level using modified Global Assessment of Functioning scale for Functioning. The CR + TAU group demonstrated considerable improvements in cognition, intrinsic motivation, negative symptoms, and functional level compared to the TAU-alone group. These findings indicate that the CR using RehaCom® enhances cognition and other outcomes in schizophrenia.

Background: We evaluate the genetic and phenotypic features of a cohort of 12 Italian patients affected by Retinitis Pigmentosa (RP) associated with RP1 sequence variants.; Methods: Retrospective, single center study (Careggi Hospital, Florence), including a cohort of twelve Italian patients (Five male and seven female) affected by RP carrying pathogenic variants of the RP1 gene. A complete ophthalmic assessment and pedigree analysis was conducted with focus on the onset of disease symptoms, the patient’s age at the first diagnosis, the follow up duration and the possible presence of comorbidities; Results: The mean age at onset of symptoms was 31,0 ± 24,1 years old, with a mean follow-up period of 9,1± 2,4 years. The main symptoms at presentation were hemeralopia and visual field constriction. Fundus evaluation revealed a classic type of RP. Fundus autofluorescence (FAF), Optical Coherence Tomography (OCT), Electroretinogram (ERG), and visual field confirmed in most of the cases the typical features of classic retinitis pigmentosa.; (4) Conclusions: This single-center cohort of Italian patients provided information on the clinical and genetic features of RP1-associated RP. By comprehensively clarifying the genetic variations and their associated clinical manifestations, we can better tailor therapeutic interventions aimed at targeting specific genetic abnormalities. This ultimately promises to improve the prognosis and quality of life for individuals with RP-associated RP1.

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (Pi*M, Pi*S, Pi*Z) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.

Background: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. Methods: We performed a prospective study in 5 referral centers for HIV care in Italy. PLHIV who consented to participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI that started chemoprophylaxis were followed until the ending of therapy. Results: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, 6 were lost to follow-up before discriminating between latent and active TB. Among PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. Defining RWD based on its original intent, which is the collection of data at the point of care for clinical purposes, can distinguish it from conventional clinical trial data. RWD can be generated using experimental designs that resemble those used in conventional clinical trials, but with several advantages, such as improved efficiency and a better balance between internal and external validity. RWD can support pharmacovigilance, insights into disease progression, and the development of external control groups. Prospective RWD collection enables evidence generation based on pragmatic clinical trials (PCTs) that support randomized study designs and expand clinical research to the point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly, patients with poor performance status (PS), hepatitis, or human immunodeficiency virus-infected patients, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.

During the COVID-19 pandemic, individuals with symptoms other than cough or fever have refrained from seeking medical advice. However, a delay in treatment might lead to serious consequences. At the same time, digital health initiatives have emerged to overcome this bottleneck of healthcare. Herein, we report the results of a multi-center initiative using a combination of patient history and artificial intelligence (AI) to identify individuals with rare neuromuscular diseases. First, a questionnaire with 46 items was developed by interviewing patients with muscular dystrophies, amyotrophic lateral sclerosis, Morbus Pompe, neuropathies, and myasthenia gravis. Second, patients with proven neurological diseases answered the questionnaire. Third, a combination of classifiers (artificial neural network, support vector, and random forest) was trained and, finally, the system was challenged with new questionnaires. Users with an abnormal questionnaire pattern received a unique code for data privacy and contact details for a neurologist for further advice. The neurologists confirmed or refuted the AI-based diagnosis. The questionnaire was accessed 3122 times, leading to 853 unique codes. Only for a few patients the computer-based diagnoses and the confirmed final diagnoses were reported to us. However, for these few patients, the genetic testing and high CK levels finally ended their long-lasting diagnostic odyssey.

Aims and Background: People living with mental disorders experience a disproportionately higher burden of tobacco-related disease than the general population. Long-term substitution with less harmful nicotine products could reduce the tobacco-related harm among this population. This study investigated the views and preferences of people with mental health disorders about different nicotine products and their use as long-term substitutes for cigarettes. Methods: Semi-structured focus group discussion followed by a brief questionnaire. The discussion transcripts were analysed for content and themes and quantitative data summarised with descriptive statistics. Results: Twenty-nine participants took part in four focus groups. Vaping devices were the most acceptable nicotine products discussed, however preferences for nicotine products were idiosyncratic and varied along aesthetic, pragmatic, sensory and symbolic dimensions. The concept of tobacco harm reduction was unfamiliar to participants, however they generally agreed with the logic of replacing cigarettes with less harmful nicotine products. Barriers to activating tobacco harm reduction included the symbolism of smoking and quitting; the importance placed on health; the consumer appeal of alternatives; and cost implications. Discussion and Conclusion: Engaging this population in tobacco harm reduction options will require communication that challenges black and white thinking (a conceptual framework in which smoking cigarettes or quitting all nicotine are the only legitimate options) as in practice this serves to support the continuance of smoking. Consumers should be encouraged to trial a range of nicotine products to find the most acceptable alternative to smoking that reduces health harms. Providing incentives to switch to nicotine products could help overcome barriers to using less harmful nicotine products among mental health consumers.

This study delves into the dynamic field of medical education research, emphasizing the integration of research training within medical curricula. It seeks to understand the impact of such integration on the competencies of future medical professionals. The primary aim is to systematically categorize and analyze the current trends and future directions in medical education research. This involves assessing the influence of research training on medical students' skills and the methodologies used in such research. Methods: The research employs an extensive bibliographic literature review across multiple databases. It classifies studies into categories like experiential or case studies, editorials, and original research articles. This classification is based on criteria such as geographical location, research objectives, theoretical frameworks, and methodologies. Results: Findings reveal a diverse landscape in medical education research, with a significant emphasis on research training. The research showcases varying methodologies and approaches used globally, highlighting the thematic focus and geographical distribution of these studies. Conclusion: Medical education research is a globally expansive and evolving field. It underscores the importance of continuous investigation, particularly focusing on integrating research elements at curricular levels and exploring innovative educational strategies. The study also points out potential gaps in research, especially in underrepresented regions, indicating directions for future research efforts.

Background/Objectives: The aim of the project is a longitudinal assessment of body image and mental health in scoliosis females pre-, postoperatively and in a follow-up, and implementation (one group-CBT scoliosis sample, CBTSS) or not (second group-control scoliosis sample, CSS) of CBT interventions. A healthy female sample (HFS) was also selected for comparative purposes. Methods. 36 in total AIS patients participated in the 1st and 2nd study phases, whereas 23 were eligible in the follow-up. Regarding HFS, 18 participants were included in the study. The CBT intervention took place pre- and postoperatively, during the patients' stay in hospital. Participants completed the Spinal Appearance Questionnaire (SAQ), Body Esteem Scale (BES) and Strengths and Difficulties Questionnaire-25 (SDQ-25). Body image was also assessed using a virtual reality-based application “Avatar Scoliosis 3D”. Results: The difference between the desired and objective, actual body shape is significant preoperatively both in the CBTSS and CSS at p

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3,136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2,867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p=0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p<0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis were diagnosed with osteoporosis (p=0.002). In Cox-regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusion: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is are needed to understand the underlying pathophysiological mechanisms.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.

It is challenging to differentiate central nervous system (CNS) virus infections and neurological autoimmune diseases in the emergency department. Considering their different pathogenesis, we assume they differ in neuropsychiatric symptoms and laboratory results. 80 patients were included, 50 with CNS virus infections and 30 with CNS autoimmune diseases, confirmed by polymerase chain reaction (PCR) of cerebrospinal fluid (CSF). A binary logistic regression model and receiver operating characteristic (ROC) curve were conducted to examine the discrimination between the two diseases based on neuropsychiatric symptoms and laboratory results. Compared to patients with neurological autoimmune diseases, patients with CNS virus infections had higher incidence of abnormal behavior (p=0.026) and abnormal sensation/thought (p=0.029), higher total (p = 0.005), direct (p = 0.004), and indirect bilirubin (p = 0.004), increased CSF cell (p = 0.01) and CSF white cell counts (p = 0.01). ROC analysis showed that patients with disturbance of consciousness and abnormal sensation/thought were 7.79-fold and 5.07-fold more likely to be diagnosed with CNS virus infections (OR = 7.79, p = 0.008; OR = 5.07, p = 0.032). Each unit increase in blood indirect bilirubin concentration and CSF white cell counts increased risk of developing CNS virus infections by 1.25-fold and 1.01-fold (OR = 1.25, p = 0.016; OR = 1.01, p = 0.011). Our study found that patients with CNS viral infections tend to have higher blood indirect bilirubin concentration, CSF leukocyte count, frequency of disorders of consciousness, and abnormal sensation and thought, which may help differentiate them from neurological autoimmune diseases.

Hemophagocytic lymphohistiocytosis (HLH) is a serious haematologic condition that can be re-lated to various diseases, including tuberculosis (TB). The patient is a previously healthy 26-years-old man, originally from Western Africa, admitted to hospital for fever and weight loss. Given the results of computed tomography (CT) scan, ocular examination and microbiologic tests, a miliary TB with pulmonary, lymph nodal and ocular involvement was diagnosed. Following introduction of antitubercular treatment (ATT) an increase in inflammation indexes and severe pancytopenia were observed; at this point the patient presented six of eight diagnostic criteria for HLH and the diagnosis of HLH secondary to TB was raised. Therefore, HLH treatment with high dose of dexamethasone was started with a good clinical response. We performed a literature re-view of TB-related HLH, which shows a high mortality rate; ATT is necessary to ensure patient survival to remove the antigenic driver. Our patients developed HLH after initiation of ATT as a paradoxical reaction, that may be linked to the release of antigens due to the bactericidal effect of ATT.

Avatar therapy (AT) is a novel virtual reality-based psychotherapy that has been developed to treat auditory verbal hallucinations (AVH) in treatment-resistant schizophrenia patients. Various psychotherapeutic components, such as emotions and sense of presence, could contribute to clinical outcomes. However, the interplay between sense of presence, emotions and clinical response has seldom been investigated. This study aimed to explore the relations between sense of presence, emotions, and clinical outcomes in AT. To conduct this investigation, data from previous and ongoing AT trials were used. Sense of presence and emotions were assessed using standardized questionnaires. AVH were evaluated using the Psychotic Symptom Rating Scales. While sense of presence was positively associated with positive emotions such as control and serenity, no significant associations were found for negative emotions. Moreover, a higher level of sense of presence was associated with a bigger decrease in AVH. Overall, positive emotions seem to be associated with sense of presence in AT. Sense of presence also seems to be involved in the therapeutic outcome, thereby suggesting that this could be an important component related to clinical response. More studies are needed to confirm these trends, which could be generalized to other virtual reality-based psychotherapies.

(1) Background: Youths with multiple risks and severe disadvantages experience poorer health and educational outcomes than less disadvantaged peers. To address problems with coping and self-regulation in this group, mental skills training (MST) approaches more commonly used in sport are an emerging intervention approach. (2) Methods and Results: This narrative review synthesizes literature to explain the need for MST, how it works, and evidence to support it works by focusing on two well evaluated programmes: LifeMatters and My Strengths Training for Life™. (3) Conclusions: To support positive youth development, MST is a strengths-based, flexible and adaptable approach to help fill the shortage of available evidence-based programs for those youths facing multiple disadvantages. The findings of this review may facilitate policy makers, commissioners, program planners, and researchers in the uptake of MST or similar psychoeducational approaches in future.

The clinical practice implies a research translation that helps the use of scientific data and thera-peutic evidence for patient benefits. This review critically summarizes the potential impact of cannabinoids in concomitance with other drugs in the following chronic diseases as Epilepsy, Au-tism Spectrum Disorders (ASD), Oncology, Multiple Sclerosis, and Chronic Pain. The potential in-teractions can change the predicted clinical outcomes of therapeutic protocols and need to be evaluated. Some of the effects would be additive, synergistic or antagonistic, but can also enroll changes in absorption, distribution, metabolism, particularly via cytochrome P450 (CYP) isoen-zymes (e.g CYP2C9 and CYP3A4) and excretion. For instance, the combination of canna-bis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases plasma concentration of Δ-9-tetrahydrocannabinol (THC) and CBD (CBD). Opposable, rifampic-in, a CYP3A4 inducer, stands out for the approximately 20-40% reduction in plasma THC levels and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Indeed, pharmacokinetic interactions have been also reported with antiseizure drugs. Moreover, pharmacodynamic interactions between cannabinoids and drugs with sympathomimetic effects (eg tachycardia, hypertension), central nervous system depressants (eg drowsiness, ataxia), and anticholinergics (eg tachycardia and drowsiness) are also expected. Even though pending further studies, there is currently clinical evidence supporting drug interaction with cannabinoids, demanding doctors evaluate the risk of drug combinations with cannabinoids. The tables herein provided were designed to facilitate the identification of bi-orelevant interactions that may compromise therapeutic efficacy and toxicity.

(1) Background The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated applying data from older cognitively healthy adults living in the US, Ireland and Australia (the norming sample) The study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI) and dementia (1), and to cross-validate the new norms for detecting MCI and dementia (2) in a community sample of older adults with clinical diagnoses; (2)Methods: The validation sample included 142 older adults (mean age=87.7, SD=3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia through a consensus diagnosis as well as by the SKT; (3)Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 60.1% for all three diagnostic groups. The correlation between the SKT and the Addenbrooke’s Cognitive Examination III (ACE-III), a well validated measure of cognitive ability in older adults, was r = 0.3;. (4) Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).

In China, preschool teachers have a significant influence on the development of young children aged 3-6. It is imperative to understand their mental health and the factors associated with it to inform policies, optimize their mental well-being, and support their job performance. This study aimed to investigate the factors contributing to anxiety symptoms among preschool teachers. A sample of 393 Chinese preschool teachers (279 females, 114 males) aged 21-56 completed online questionnaires collecting their socio-demographic and work-related information and assessing anxiety symptoms, interpersonal difficulties, personality traits, perceived stress, resilience, and inner strength. Pearson correlation and multiple linear regression analyses identified significant predictors of anxiety symptoms. The prevalence of anxiety symptoms among the studied cohort was found to be 12.2%. Statistically significant factors positively correlated with anxiety symptoms included objective work-related stress (B=0.149, p<.001), interpersonal difficulties (B=0.921, p<.001), perceived stress (B=0.108, p=.001), and neuroticism (B=0.071, p=.002). The findings highlight the urgent need for measures to reduce work-related stress and anxiety. However, when negative mental health predictors were included, the effect of positive psychological factors became nullified. Positive mental health might have a moderating role in such a negative mental health outcome as anxiety. Therefore, further research is required to understand the impact of positive mental health factors more clearly.

Mouthparts are the main feeding organs of insects, which play vital roles in the feeding process. The morphology of insect mouthparts has greatly evolved according to different foods and feeding habits. Therefore, studying the structure of the mouthparts is the key to understanding their feeding mechanisms. Vibidia duodecimguttata is an important biological control agent for powdery fungus. In this study, the fine morphology of the mouthpart of V. duodecimguttata was studied by scanning electron microscopy. The basic components of mouthpart of V. duodecimguttata are similar to those of other ladybeetles, while the specific morphology of each part is different. In total, six kinds of sensilla were identified on mouthpart, and twelve types of sensilla were divided according to their morphology, length and distribution. In addition, two kinds of glandular structures were also found, perforated plates and cuticular pores. Finally, the morphological differences between mycetophagous and other feeding habits ladybeetles were compared, and the function of each kind of sensilla were discussed, which may lay a solid foundation for further understanding of the feeding mechanism of ladybirds.

Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress play also role in frailty (frail) and metabolic syndrome (MetS). Methods: 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed: waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n=19), NonMetS-frail (n=20), MetS-Nonfrail (n=17), and MetS-frail (n=10). Results: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggests that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors. Conclusions: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome.

Interferon-gamma (IFN-γ) is an important cytokine in host defense against tuberculosis infection. In some cases, administration of IFN-γ during tuberculosis infection can promote faster cure. In the present work, we have shown that in a mouse model, human interferon-gamma, exhibits some anti-tuberculosis activity, especially in combination with isoniazid.

This study aims to examine the safety profile of antiepileptic drugs (AEDs) using real-world data, with a focus on neurological, skin, and sexual/reproductive disorders. Data were collected from AED-caused reports in the Korea Adverse Event Reporting System Database (KAERS-DB) from 2012 to 2022. Totally, 46,963 adverse drug reaction (ADR)-drug pairs were analyzed. At the system organ class level, the most frequently reported classes for sodium channel blockers (SCBs) were skin (37.9%), neurological (16.7%), and psychiatric disorders (9.7%). However, for non-SCBs, these were neurological (31.2%), gastrointestinal (22.0%), and psychiatric disorders (18.2%). The most common ADRs induced by SCBs were rash (17.8%), pruritus (8.2%), and dizziness (6.7%). In contrast, non-SCBs induced dizziness (23.7%), somnolence (13.0%), and nausea (6.3%). Among the most commonly reported ADRs, rash, pruritus, and urticaria occurred on average two days later with SCBs compared to non-SCBs. Sexual/reproductive disorders were reported at a frequency of 0.23%. SCBs were reported as the cause more frequently than non-SCBs (59.8% vs. 40.2%, Fisher’s exact test, p&lt;0.0001). Based on real-world data, we identified the safety profiles of AEDs. AED-induced ADRs exhibited different patterns depending on the mechanism. Therefore, it is important to establish different pharmacovigilance strategies to ensure proper monitoring.

This study is aimed to assess the prevalence of Coxiella burnetii infection among veterinary medicine students from two Bulgarian Universities, located in Sofia and Stara Zagora. A total of 185 veterinary students blood samples were collected and tested for the detection of C. burnetii phase II antibodies and presence of DNA using an enzyme-linked immunosorbent assay (ELISA) and end-point PCR test, respectively. Out of all samples, 29.7% were positive for at least one C. burnetii phase II antibody marker or by PCR test. Veterinary students from Stara Zagora showed significantly seropositive status of Q fever (33.6%), then those who studied in Sofia (23%). The evidence for recent exposition with detection of anti-C. burnetii IgM (+) antibodies had 14.6%. Seroprevalence among students in Stara Zagora was higher (15.3%). Anti-C. burnetii phase II IgG antibodies were detected in 21.6% examined samples. Our study revealed a higher seropositivity among male students (32.8%) as compared to the female ones (16.0%). End-point PCR assay detected as positive 5.9% blood samples. The relative risk (RR) of Q fever exposure for male students was 40.7%, whereas for female (24.6%). Findings from this study indicated that the C. burnetii infection is widely distributed amongst veterinary students from Bulgaria. The study emphasizes the need for improved safety protocols and infection control measures in veterinary training programs.

The Rose grain aphid, a notable agricultural pest, releases saliva while feeding. Yet, there is a need for a comprehensive understanding of the specific identity and role of secretory proteins released during probing and feeding. Therefore, a combined transcriptomic and proteomic approach was employed to identify putative secretory proteins. The transcriptomic sequencing result led to the assembly of 18030 unigenes out of 31344 transcripts. Among these, 705 potential secretory proteins were predicted and functionally annotated against publicly accessible protein databases. Notably, a substantial proportion of secretory genes (71.5%, 69.08%, and 60.85%) were predicted to encode known proteins in Nr, Pfam, and Swiss-Prot databases, respectively. Conversely, 27.37% and 0.99% of gene transcripts were predicted to encode known proteins with unspecified functions in the Nr and Swiss-Prot databases, respectively. Meanwhile, the proteomic analysis result discovered, 30 salivary proteins. Interestingly, most salivary proteins (53.3% proteins) showed close similarity to A. craccivora, while 36.67% to A. pisum and A. glycines. However, to verify the expression of these secretory genes and characterize the biological function of salivary proteins further intervention should be geared towards gene expression and functional analysis.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

This pilot randomized controlled trial (RCT) aimed to explore whether depression and anxiety could be reduced by psychiatric home healthcare supporters offering brief cognitive behavioral therapy for psychosis (CBTp) at home using a workbook for patients with schizophrenia. Eighteen patients with schizophrenia treated in a psychiatric home nursing service were randomly assigned to two groups: one group received CBTp in addition to usual care (CBTp + TAU group; n=8) and the other received only usual care (TAU group; n=8); 2 patients were excluded due to hospitalization or withdrawal of consent. Eight weekly CBTp sessions were conducted; anxiety/depression, quality of life, self-esteem, and overall functioning were assessed at baseline, week 9, and week 13. There was no significant difference in the primary evaluation; however, a significant improvement (p=0.014) was observed in the secondary evaluation of quality of life. The effect size was 0.95 for primary evaluation and 1.33 for the secondary evaluation, indicating a large effect. This study showed that nurses and occupational therapists can provide CBTp in psychiatric home care for patients with schizophrenia to potentially alleviate anxiety and depression compared to standard psychiatric home care alone. Therefore, larger RCTs with larger sample sizes are recommended.

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), facilitation of short-chain fatty acids (SCFAs) production, activation of the glucagon-like peptide 1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we have discussed research in other disease models that use probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

Extracellular vesicles (EVs) hold enormous potential in the diagnosis and treatment of diseases, benefit from their roles in intercellular signaling, as well as their plentiful presence and stability in body fluids. However, conventional EV isolation methods are labor-intensive, and harvest EVs with low purity and compromised recovery. In addition, the drawbacks, such as limited sensitivity and specificity of traditional EV analysis methods hinder the application of EVs in clinical use. Therefore, it is urgent to develop effective and standardized methods for isolating and detecting EVs. Microfluidics technology is a powerful and rapidly developing technology that has been introduced as a potential solution for the above bottlenecks. It holds the advantages of high integration, short analysis time, low consumption of samples and reagents. In this review, we summarize the traditional techniques alongside microfluidic-based methodologies for the isolation and detection of EVs. We emphasize the separation advantages of microfluidic technology in enhancing EV capture efficiency and precise targeting, while summarizing its analytical role in targeted detection and discussing the significance of EV detection in the tumor microenvironment, providing a direction for achieving automated and high-throughput EV detection in clinical samples.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in people with HIV (PWH). Since lamivudine remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure. ART guidelines do not recommend the use of drugs impacted by resistance-associated mutations as they have been confirmed to comprise a risk factor for virological failure. However, previous authors suggest that 3TC/FTC can remain active even in the presence of M184V. Obtaining the viral resistance profile for each individual both treated or ART-naïve is a key challenge for lifelong treatment management.Given the potential benefits of lamivudine in the ART combinations, the investigation of M184V remains of high interest for clinicians and researchers. This is a review of literature for the challenges in treating both naïve and experienced individuals carrying the M184V resistance mutation, including virological failure, virological suppression, and resistance to ART.

Functional neurological disorder, or FND, is widely misunderstood, particularly when considering recent research that suggests that the illness has a biological rather than a psychiatric basis. Nonetheless, the long-held view that FND is a purely psychiatric disorder without biological basis, or even a contrived (malingered) illness, remains pervasive both in modern medical care and general society. This is because FND involves an intermittent course of involuntary disability that rapidly alternates with improved neurological control. This has in turn caused shaming, low self-efficacy, and social isolation of the patients. Little research has examined the numerous biomarkers that are shared between FND and canonical neurological disorders and the encouraging outcomes that can follow conventional neurological rehabilitation, modified for this disorder. This review summarizes current research on FND biomarkers and physical rehabilitation results. General healthcare providers would benefit their care for their patients through their improved understanding the illness and recourses for support and treatment that are provided in this review.

This study proposed to use wearable EEG to study the impact of vipassana mindfulness practice on beginner's physiological and neurological responses. Mindfulness meditation has been shown to have numerous benefits, including stress reduction, improved attention and cognitive function, and enhanced emotional regulation. The roots of mindfulness meditation in Buddhism emphasize cultivating present-moment awareness and insight. However, the neural mechanisms together with physiological mechanism and their interaction underlying these benefits remain poorly understood. Method: One middle age man (50 years old) participated in this longitudinal study using wearable EEG to investigate the neurophysiological change during a one-month consecutive vipassana mindfulness practice. Both EEG and heart rate responses were recorded each time, before (5 minutes), during (20 minutes), and after (5 minutes) meditation sessions. The EEG and HR data were analyzed by Matlab and EEGlab to examine changes in brainwave activity and heart rate. Results: alpha peak frequency (APF) is significantly lower after mindfulness meditation, as shown by comparison of APF before mindfulness (pre-5) and during mindfulness practice (med-20), and comparison between APF of pre-5 and after mindfulness practice (post-5). The same is with the beta peak power. While for theta peak frequency, it is significant lower during mindfulness meditation (med-20), when comparing to either pre-5 or post-5. See figure 1a. However, peak power index is not so sensitive, and it is more obvious in theta wave band. That is, the theta power peak is significantly lower after meditation, as can be observed in comparison between pre-5 and med-20, also between pre-5 and med-20. See figure 1b. STATE Heart-mean (bpm) Heart-std(bmp) pre-5 69.88 3.88 med-20 68.36 2.81 post-5 69.55 4.13 t-value test (pre-med) 0.0694 0.0003 t-value test (pre-post) 0.7934 0.3656 t-value test (post-med) 0.3193 0.0001 Table 1. The difference of Heart rate (mean and SD) in before (pre-5), during (med-20) and after (post-5)mindfulness meditation. We find significant change in standard deviation (SD) of heart rate between meditation and non-meditation mental states, as shown in table 1. The study provides insights into the underlying neurophysiological mechanisms of mindfulness meditation using wearable EEG devices. It demonstrates that in term of EEG measurement, spectrum frequency can be more sensitive than spectrum power; also heart rate variability as measured by SD is more sensitive to mean of HR. The proposed study contributes to the literature by using wearable EEG devices to collect data in a more accessible and convenient manner.

Background: Pediatric neurological disorders include neurodegenerative disease causing cognitive impairment, vision loss to mention a few. They are one of the important causes of morbidity and mortality in children with diverse etiology. Diagnosis is difficult in spite of genetic work and in only 60% of cases final diagnosis can be achieved. Case presentation: We explore three cases of pediatric neurological diseases, viz. Arthrogryposis, congenital bilateral cataract and Autism by analyzing clinical exomes. In this work, we attempted to understand rare neurological disorders in an Indian pediatric cohort using exome studies. Conclusions: We used our benchmarked CONVEX pipeline for screening consensus variants, wherein EIF2B2 was found to be inherently pathogenic. We map the association of variants and genes, disease correlation to neuroleptic malignant syndrome which is a matching phenotype to the cases.

Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.