Different nutraceuticals are often considered by parents of infants and children with abdominal pain and disorders of the gut-brain interaction. Herb extracts and natural compounds have long been used in traditional medicine, but clinical pediatric trials are very limited. This narrative review based on relevant studies identified through Pubmed-Medline literature search updated to October 2023, focused on the effect of nutraceuticals in infantile colic, functional abdominal pain and irritable bowel syndrome in children and adolescents. Significant reduction of colic episodes and crying time was reported in two studies on fennel (seeds oil or tea), in three studies on different multiple herbal extracts (all including fennel), in one study on Mentha piperita, and in at least two double-blind randomized controlled studies on Lactobacillus reuteri DSM 17938 and Bifidobacterium lactis BB-12 (108 CFU/day for at least 21 days) in breast-fed infants. Compared to placebo, in children with functional abdominal pain or irritable bowel syndrome a significant reduction of pain was reported in two studies supplementing peppermint oil capsules or psyllium fibers, in one study on corn fiber cookies or partial hydrolysed guar gum or a specific multiple herbal extract (STW-5) or vitamin D supplementation. To date, there is a moderate certainty of evidence with a weak grade of recommendation for Lactobacillus reuteri DSM 17938 (108 CFU/day) for reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 x109 CFU twice daily) for reducing pain frequency and intensity in children with IBS. Further large and well-designed pediatric studies are needed to prove efficacy and safety of different herbal extracts and prolonged use of studied products in infants and children with pain disorders of the gut-brain interaction.

The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.

The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut-brain axis, which significantly regulates the body's physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasizes the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-Amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s Disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut-brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut-brain axis and venture to clarify microbiota-based therapeutic strategies for AD.

Polyphenols are the most prevalent naturally occurring phytochemicals in the human diet and range in complexity from simple molecules to high-molecular-weight polymers. They have a broad range of chemical structures and are generally categorized as "neuroprotective," "anti-inflammatory," and "antioxidant" given their main function of halting disease onset and promoting health. Research has shown that some polyphenols and their metabolites can penetrate the blood-brain barrier and hence increase neuroprotective signaling and neurohormonal effects to provide anti-inflammatory and antioxidant effects. Therefore, multi-targeted modulation of polyphenols may prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for difficult-to-treat neuropsychiatric disorders. Therefore, multi-target modulation of polyphenols has the potential to prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for such nervous system diseases. Herein, we review the therapeutic benefits of polyphenols on autism-spectrum disorders, anxiety disorders, depression, and sleep disorders, along with in vitro and ex vivo experimental and clinical trials. Although their methods of action are still under investigation, polyphenols are still seldom employed directly as therapeutic agents for nervous system disorders. Comprehensive mechanistic investigations and large-scale multicenter randomized controlled trials are required to properly evaluate the safety, effectiveness, and side effects of polyphenols.

The aim of this study is to assess of rare earth elements (REE) content in hair samples in children, living in Lovozero village, near REE mining site, and possible effects of REEs on the prevalence of nervous system diseases in the Lovozersky district (Murmansk region, Kola Peninsula). School-age children (53 persons) were recruited for analysis of REE content in their hair samples. REEs (Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) content was estimated by inductively coupled plasma mass spectrometry (ICP-MS). Analysis of REE content in the hair of children living in the Russia, Kazakhstan and China indicates REEs intake from environment. A possible contribution of REEs to the nervous system disorders is supported by the link between REE content in the hair samples of children, living near REE mining (China) and by manifesting cognitive disorders in these children. It also turn out that highest prevalence of the nervous system diseases in children 15-17 years old manifested in the Lovozersky district then in other area in the Murmansk region. The paper discusses the possible contribution of REEs to the prevalence of episodic paroxysmal disorders (G40-G47), cerebral palsy (G80-G83), epilepsy and status epilepticus (G40-G41).

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<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<0.05, low vs. high sleep quality), and eating disorders (OR: 1.047, 95% CI: 1.004, 1.092, p<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.

IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.

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.

A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.

Human gut microbiome is associated with various diseases, including autism spectrum disorders (ASD). Variations of the taxonomical composition in the gut microbiome of children with ASD have been observed repeatedly. However, features and parameters of the CRISPR-Cas systems in the gut microbiome of children with ASD have not been investigated yet. Here we demonstrate such an analysis in comparison with the healthy microbiome. For the identification of CRISPR-Cas systems, we used a combination of the publicly available tools suited for completed genomes with subsequent filtrations. In all considered datasets, the microbiomes of children with ASD contained fewer arrays per Gb of assembly, than the control group, but the arrays included more spacers on average. These patterns were observed systematically in our datasets, although their statistical significance hardly matched the thresholds. CRISPR arrays from the microbiomes of children with ASD differed from the control group neither in the fractions of spacers with protospacers from known genomes, nor in the sets of known bacteriophages providing protospacers. The majority of bacterial protospacers of the gut microbiome systems for both children with ASD and the healthy ones was located in the prophage islands.

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.

The Work Ability Index (WAI) is the most widely used questionnaire for the self-assessment of working ability. Because of its different applications, shorter versions, and widespread use in healthcare activities, it is worthwhile assessing its characteristics. The WAI was distributed online among the workers of a healthcare company; the results were compared with data contained in the workers' personal health records and with absence registers. 340 out of 575 workers (59.1%) participated; 6.5% of them reported poor work ability. Exploratory factor analysis indicated that the one-factor version best described the characteristics of the WAI. The scores of the complete WAI, the shorter form without the list of diseases, and the minimal one-item version (WAS) had equal distribution and were significantly correlated. The WAI score was inversely related to age and significantly lower in women than in men, but it was higher in night workers than in colleagues due to the probable effect of selective factors. The WAI score was also correlated with absenteeism, but no differences were found between males and females in the average number of absences, suggesting that cultural or emotional factors influence the self-rating of the WAI. Workers tended to overreport illnesses in the online survey compared to data collected during occupational health checks. Musculoskeletal disorders were the most frequently reported illnesses (53%). Psychiatric illnesses affected 21% of workers and had the greatest impact on work ability. Multilevel ergonomic and human factor intervention seems to be needed to recover the working capacity of healthcare workers.

Glycogen storage disorders (GSDs) are a group of inherited metabolic disorders characterized by defects in enzymes involved in glycogen metabolism. Deficiencies in enzymes responsible for glycogen breakdown and synthesis can impair mitochondrial function. For instance, in GSD type II (Pompe disease), acid alpha-glucosidase deficiency leads to lysosomal glycogen accumulation, which secondarily impacts mitochondrial function through dysfunctional mitophagy, which disrupts mitochondrial quality control generating oxidative stress. In GSD type III (Cori disease), the lack of the debranching enzyme causes glycogen accumulation and affects mitochondrial dynamics and biogenesis by disrupting the integrity of muscle fibers. Malfunctional glycogen metabolism can disrupt various cascades thus causing mitochondrial and cell metabolic dysfunction through various mechanisms. These dysfunctions include altered mitochondrial morphology, impaired oxidative phosphorylation, increased production of reactive oxygen species (ROS), and defective mitophagy. The oxidative burden typical of GSDs compromises mitochondrial integrity and exacerbates the metabolic derangements observed in GSDs. The intertwining of mitochondrial dysfunction and GSDs underscores the complexity of these disorders and has significant clinical implications. GSD patients often present with multisystem manifestations, including hepatomegaly, hypoglycemia, and muscle weakness, which can be exacerbated by mitochondrial impairment. Moreover, mitochondrial dysfunction may contribute to the progression of GSD-related complications, such as cardiomyopathy and neurocognitive deficits. Targeting mitochondrial dysfunction thus represents a promising therapeutic avenue in GSDs. Potential strategies include antioxidants to mitigate oxidative stress, compounds that enhance mitochondrial biogenesis, and gene therapy to correct the underlying mitochondrial enzyme deficiencies. Mitochondrial dysfunction plays a critical role in the pathophysiology of GSDs. Recognizing and addressing this aspect can lead to more comprehensive and effective treatments, improving the quality of life of GSD patients. This review aims to elaborate on the intricate relationship between mitochondrial dysfunction and various types of GSDs. The review presents challenges and treatment options for several GSD

Here, we review findings and trends in sleep research in 2020-2021 demonstrating how COVID-19 and sleep disorders can induce the BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the controlling of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of the BBB leakage and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.

Brain disorders pose a significant global healthcare challenge due to their complexity and profound impact on individuals and society. This review explores recent advancements in brain disease research, deepening our understanding and progress towards treatments. Technological innovations, like high-resolution imaging and optogenetics, play a pivotal role in illuminating cellular structures and dissecting neural circuits. Genetic analysis identifies dis-ease-associated genes and mutations, yet translating findings to clinical applications remains challenging. Epigenomics, transcriptomics, and proteomics provide molecular insights, un-covering disrupted pathways in conditions like Alzheimer's disease. Stem cell models elucidate developmental mechanisms, and immunotherapies, including CAR T cells, emerge as prom-ising strategies for brain cancers like glioblastoma. Genome editing tools, exemplified by CRISPR, enable precise modification of disease genes in models, deepening our understanding of pathogenesis. Multifaceted approaches integrating human studies, animal models, and bi-oinformatics propel the field forward. However, complexities persist, as disease specificity for cell types or brain regions remains an enigma, and genetic factors interact with environmental influences, highlighting disease intricacies. Ultimately, interdisciplinary efforts combining bi-ophysical and psychospiritual perspectives are essential to fully understand brain health and unlock transformative treatments for these debilitating disorders. A comprehensive under-standing of brain disorders is vital to improve the quality of life for millions and alleviate the global burden of neurological afflictions. Continued collaborative research will lead to an era of improved brain health worldwide.

Sleep disturbances and chronic pain are prevalent and interrelated conditions that significantly impact individuals' quality of life. Understanding the intricate dynamics between sleep and pain is crucial for developing effective treatments that enhance the well-being of affected individuals and reduce the economic burden of these debilitating conditions. This narrative review examines the complex relationship between sleep disturbances and chronic pain. We describe the prevalence and types of sleep disturbances and sleep disorders in chronic pain patients. Posteriorly we critically review the clinical and experimental evidence investigating the relationship between sleep disturbances and chronic pain aiming to clarify the impact of chronic pain on sleep and, conversely, the impact of sleep disturbances on pain perception. We conclude that a bidirectional relationship between chronic pain and sleep disturbances is almost a consensus in the literature, however, the strength of each direction of the association is less clear. As of now, the literature suggests that sleep impairment is a stronger predictor of pain than pain is a predictor of sleep impairment. Additionally, addressing sleep disturbances in chronic pain patients is crucial, as poor sleep has been linked to higher levels of disability, depression, and pain-related catastrophizing.

This review article provides a comprehensive overview of the anatomical structure of the human brain, highlighting its key components and their functional significance. The brain is the central organ of the nervous system, responsible for controlling and coordinating various bodily functions. The article begins with an introduction to the brain's gross anatomy, including the cerebrum, cerebellum, brainstem, and diencephalon. It then delves into the detailed microstructure of the brain, discussing neurons, glial cells, and the complex network of neural connections. The review also explores the functional organization of the brain, emphasizing the roles of different regions such as the frontal, parietal, temporal, and occipital lobes. It discusses the importance of the limbic system in emotional processing and the basal ganglia in motor control. Additionally, the article covers the brain's vascular system and the blood-brain barrier, which are crucial for maintaining the brain's homeostasis. Recent advancements in neuroimaging techniques, such as magnetic resonance imaging (MRI) and functional MRI (fMRI), have significantly enhanced our understanding of brain anatomy and function. These techniques have enabled researchers to map brain activity in real-time, providing insights into cognitive processes and neurological disorders. The article concludes by discussing the implications of understanding brain anatomy for clinical practice, including the diagnosis and treatment of neurological conditions. It also highlights areas for future research, emphasizing the need for further exploration of the brain's structural and functional complexity.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

Intracranial compliance (ICC) plays a pivotal role in understanding the underlying mechanisms of various brain disorders and is of great clinical importance. Therefore, addressing the challenges in practical application of ICC is crucial for neurosurgeons. This study explored the significance of ICC assessment considering the time-dependency of specific brain disorders through two distinct approaches: short and large time elapsed (TE) in measuring volume or intracranial pressure (ICP) changes in the ICC equation (∆Volume/∆ICP). Variations in ICC values were observed across various ICC assessment methods and different TE values. Notably, the compensatory response of the brain exhibited non-monotonic and variable changes in a large TE for certain brain disorders, diverging from patterns observed in short TE assessments. Furthermore, the recovery behavior of the brain changed under different brain disorders when exposed to short and long TE conditions. These findings emphasized the dynamic nature of ICC and provided valuable insights into the correct practical assessment of ICC by selecting the appropriate TE, as well as considering the differences in strain rates and loading durations on the brain in different brain disorders. These insights also shed light on the reasons why, despite its clinical significance, ICC monitoring has not yet become a standard component of clinical care, unlike ICP monitoring.

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissoci-ated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9-days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular via-bility over time. Overall, this human-centered model offers a promising resource to study the cel-lular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics.

The aim of the current study has been to assess externalizing problems from a gender perspective in the juvenile population. This objective has been evaluated though the Child and Adolescent Assessment System questionnaire (SENA), to measure the dimension of externalized problems. A total of 128 Spanish students took part in the survey, comprising 58 (45.3%) male and 67 (52.3%) female, aged between 12 and 16 years old (M= 13,7; Sd= 1,14). The sample was taken from three High- Schools (state and private-subsidized) in Madrid, Spain. The research for this study was conducted through a descriptive, inferential, quantitative, ex post facto design. The data analysis was performed using SPSS 27.0. The result revealed an increase in externalized problems: Attention (M= 2.65, Sd=.88), Anger Control (M= 2.27, Sd=.85) and Hyperactivity- Impulsivity (M= 2.26, Sd=.68). In addition, female students score highly in Attention Problems (F= 4.124; Sig.: .004), Hyperactivity-Impulsivity (F: 6.18; Sig.: <.001), and Anger Control (F: 2.3; Sig.: .062). This study highlights the impact and increase on students externalized mental health problems currently. It is essential to have a protective environment and promote the development of emotional intelligence, encouraging the mental health in young people. This article is part of the findings of the research project “Therapeutic Innovation Classroom for the accompaniment of teenager with Serious Mental Disorder” (Reference: 2021V/EU-UNED/02).

Long Covid is a heterogeneous clinical condition in which Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and brain fog stand out among the different clinical symptoms and syndromes. The cerebral metabolic alterations and neuroendocrine disorders seem to constitute an important part of Long Covid. Given the substantial lack of drugs and effective therapeutic strategies, hypothalamic phospholipid liposomes which have been on the market for several years as adjuvant therapy of cerebral metabolic alterations resulting from neuroendocrine disorders, can be taken into consideration in an overall therapeutic strategy that aims to control the Long Covid associated symptoms and syndromes. Their pharmacological mechanisms and clinical effects strongly support their usefulness in Long Covid. Our initial clinical experience corroborates this rationale. Further research is imperative in order to obtain robust clinical evidence.

Smoking a cigarette before bed or first thing in the morning is a common habit. In this review the relationship between smoking and sleep is investigated, based on the existing literature. Tobacco smoking disrupts sleep architecture by reducing slow wave and rapid eye movement (REM) sleep and undermining sleep quality. Furthermore, smoking affects sleep-related co-morbidities, such as obstructive sleep apnoea-hypopnea syndrome (OSAHS), insomnia, parasomnias, arousals, bruxism, restless legs but also non-sleep-related conditions such as cardiovascular, metabolic, respiratory, neurologic, psychiatric, inflammatory, gynecologic and pediatric. This review aims to consolidate all the existing knowledge about the relationship between smoking and sleep.

. Background: Recent studies suggest that acquired brain injury with impaired consciousness in infancy is related to more severe and persistent effects and may have a cumulative effect on ongoing development. In this work, we aim to describe vocational outcome in a group of patients at 15 years from a severe brain lesion they suffered in developmental age. Methods: This study included a total of 147 patients aged 1.5 to 14 years with acquired brain lesion. Clinical, functional details (“Glasgow Outcome Scale – Extended”, “Functional Independent Measure”, Intelligence Quotient) were collected at the time of their first hospitalization and vocational outcome was determined after 15 years. Results: 94 patients (63.9%) presented with traumatic brain injury, while 53 patients (36.1%) presented with a brain lesion of other origin. Traumatic patients had a higher probability to be partly or fully productive than non-traumatic ones: 75.5% of traumatic subjects were working –taking into account limitations due to the traumatic event, versus 62.3% of non-traumatic ones. A relationship between some clinical variables and the vocational outcome was found. Conclusions: Rehabilitation should adequately emphasize “vocational rehabilitation” because a significant proportion of people experiencing a disorder of consciousness in childhood may show good social integration in adult age.

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.

Adverse childhood experiences (ACEs) refer to traumatic life events in childhood that comprise abuse (e.g., psychological, physical, sexual), neglect (psychological and physical), indirect violence or household dysfunctions. Studies have found ACEs to be related to severe short-, medium- and long-term consequences in victims’ health. The current work consists of a real-world, multicentric, prevalence study of health outcomes in children <16 years suspected of ACEs by physicians. It relies on electronic health records and healthcare registries from a Portuguese local healthcare unit between January 2001 and December 2021 (N=40 536). Three health outcome groups were analyzed: (1) traumatic injuries and intoxications (2) mental health disorders, and (3) physical disorders. Keywords and ICD-9, ICD-10, and ICPC-2 codes from were employed. Children suspected of ACEs represent 2% (n=918). Social problems, injuries and intoxications, mental health disorders, and physical disorders arise in higher percentages in suspected victims than in non-suspected individuals. Findings uncover that child victims of ACEs may be underdiagnosed. Given the severe consequences for their current and future health, this should be taken as a critical warning for healthcare professionals. Detection and reports in health units are fundamental for early treatment, aiming to avoid an escalation of damage and prevent re-victimization.

In the field of nasal delivery, one of the most fascinating applications is the delivery of drugs directly to the central nervous system bypassing the blood brain barrier. This approach would provide a series of benefits, such as dose lowering and direct targeting of potent drugs, ultimately reducing their systemic side effects. Recently, clinical trials have explored the nasal administration of insulin for the treatment of Alzheimer’s disease, with promising results. The use of nanomedicines could provide further options for making nose-to-brain delivery reality. In particular, apart from the selection of devices able to deposit the formulation in the upper part of the nose, surface modification of these nanomedicines appears the key strategy to optimize the delivery of drugs from the nasal cavity to the brain. In this review, nanomedicines delivery approaches based on surface electrostatic charges, mucoadhesive polymers, as well as chemical moieties targeting nasal epithelium, will be discussed and critically evaluated for nose-to-brain delivery.

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: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

Postural instability (PI) in Parkinson’s disease (PD) exposes patients to increased risk of falls (RF). Although dopaminergic therapy and deep brain stimulation (DBS) improve motor performance in advanced PD patients, their effects on PI and RF are not clear. PI and RF were assessed by a stabilometric platform in 6 advanced PD patients. Patients were evaluated on and off dopaminergic medication and four DBS conditions: bilateral-DBS, DBS of the more- or less-affected side and DBS-off. Dopaminergic medication alone worsened PI and RF, DBS alone worsened RF, and no medication/DBS combination produced an improvement in postural control with respect to the OFF-medication/DBS-off condition. When ON-medication, PI and RF significantly improved after turning the DBS on, regardless of medication condition. Among DBS conditions, bilateral-DBS provided the maximal improvement of PI and RF when ON medication, and minimal worsening of PI and RF when OFF medication, whereas patients performed worse when in most-affected side DBS condition. These results can help in developing the best therapeutic strategy for postural disorders in patients with advanced PD.

The definition of patients with Special Needs (SN) is used in the literature to refer to individuals with mental and physical disorders for whom the usual perioperative pathways are not applicable due to lack of cooperation, regardless of age. Studies in the literature recognize the appropriateness of general anesthesia for performing day surgery dental care in this type of patient. The present retrospective, single-center, observational study involved 41 uncooperative patients aged between 3 and 17 undergoing dental surgery under general anesthesia. The main objective was to assess the possible incidence of difficult airway management, understood as difficulty ventilating and/or intubating the patient. A secondary objective was to highlight the influence of general anesthesia on patient outcomes by testing the incidence of perioperative complications. Tracheal intubation was successfully completed in all of the patients considered, and in no case did the patient have to be woken up because of difficulty in airway management. No perioperative complications attributable to anesthesia were found in any patients. From the present experience, it can be concluded that general anesthesia is a suitable option for performing dental care in pediatric subjects with special needs, and that although the peculiar peri-operative management of these patients might increase the risk of possible anesthesia-related side effects, no complications have been encountered in any case.

Adiponectin (APN) has been thoroughly investigated for its role in various human disorders. It is fascinating to note that this peptide plays an essential role as a therapeutic agent to cure a plethora of disorders. Our aim is to elucidate the applications and therapeutic potential of this peptide, demonstrating its involvement in age-related macular degeneration (AMD) and other metabolic disorders. APN has been correlated with many ocular disorders and metabolic disorders. The localization and expression of APN in various tissues were the first markers of its local actions. Screening this peptide on a wider platform helps to confirm its application as a novel peptide in various diseases. Altered levels of APN have been well elucidated in the progression of metabolic disorders, and its targeted administration has resulted in combating dysregulation of biochemical and molecular pathways involved in disease pathology. A close association of oxidative stress is also known to contribute to the onset of retinal disorders. Among so many APN has been shown to have a promising response in the context of wet AMD, but further studies are needed to elucidate its full potential in humans.

Lack of sleep is a factor that disrupts the receptors' reception of information from the environ-ment and contributes to the emergence of problems with maintaining balance. The main pur-pose of this study was to find out whether Computer Dynamic Posturography could be a useful tool in distinguishing between people who sleep well from people with insomnia. The study participants were 76 male students who were divided into groups based on the results obtained from the Pittsburgh Sleep Quality Questionnaire. In each group, postural stability had been tested using three main tests: Strategy Organization Test SOT, Motor Control Test MCT and Ad-aptation Test ADT. The results of the analysis show that the obtained results differ in the exam-ined groups under the SOT test. Among people with insomnia, higher values of the tested pa-rameters were noted, than with people who sleep well, which translates into a worse ability to maintain balance. The greatest impact is observed when using eyesight and a vestibular system to maintain a stable posture. It was confirmed that Computer Dynamic Posturography is used to differentiate between people who sleep well from people with insomnia in the group of men. Lack of sleep significantly disturbs postural stability.

The co-occurrence of substance use disorders (SUDs) and psychiatric conditions, often referred to as comorbidity or concurrent disorders, presents intricate challenges in both diagnosis and treatment. This comprehensive narrative review aims to synthesize and critically evaluate the existing evi-dence surrounding the management of individuals with comorbid SUDs and psychiatric disorders. Comorbidity in these domains carries profound implications for clinical practice, research, and policymaking, emphasizing the need for a holistic understanding of the intricate dynamics that arise when these conditions coexist. This review explores recent research findings, evidence-based guidelines, and emerging trends within the field, offering valuable insights for clinicians, re-searchers, and policymakers seeking to navigate the complex terrain of comorbidity in substance use and psychiatric disorders.

Sensory processing challenges are crucial yet often neglected aspects in the care of children with neurodevelopmental disorders and genetic conditions. They represent a key area of interest in neuroscience, as they significantly impact children's daily functioning and quality of life. This observational study examines the characteristics of these challenges in a group of 614 children, aged 3 to 14 years and 11 months, divided into three groups: 183 with neurodevelopmental disorders (Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, developmental delays, learning disorders), 89 with genetic conditions (22q11.2 Deletion Syndrome, Williams Syndrome, Pseudohypoparathyroidism), and 342 controls. Sensory processing was assessed using the Sensory Profile 2 (SP2). Results indicated that children with neurodevelopmental disorders and genetic conditions exhibited significant sensory processing difficulties compared to controls. The SP2 identified sensory challenges across different sensory systems, with varying configurations depending on the diagnosis. Children with neurodevelopmental disorders and genetic conditions show marked sensory processing challenges impacting daily lives and well-being. These findings highlight the importance of early identification and tailored evidence-based interventions to address these specific sensory processing issues. Further research should explore the long-term impact of these interventions in these different populations and their integration into broader therapeutic programs.

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

Background. The role of exercise programs during Substance Use Disorder (SUD) treatment is considered particularly supportive in fostering positive psychological and behavioral changes. The aim of this feasibility study was to explore the acute effects of cycling exercise in an immersive virtual reality (IVR) environment on attentional control and self-efficacy expectations of indi-viduals undergoing SUD treatment. Methods. A total of 20 individuals (mean age of 37.75 years) enrolled in a SUD treatment program participated in the study. They were instructed to complete a single session of cycling with a self-selected duration within the IVR system. Results. Following the cycling session, pre-post measures indicated a statistically significant im-provement in self-efficacy expectations and attentional control measured with the Stroop test. The results revealed that participants expressed high levels of intention for future use, inter-est/enjoyment, and positive attitudes toward the IVR exercise system. Qualitative data indicated that participants found the IVR exercise system enjoyable, expressed a strong intention to use it, and did not encounter technical difficulties or negative emotions. Conclusions: In conclusion, it seems that engaging in a brief period of self-selected exercise within a virtual environment can result in temporary activation of cognitive changes, heightened self-efficacy expectations, and a motivating approach to increasing physical activity participation among individuals with SUD, thus suggesting the feasibility of this approach.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

Artificial Intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use ChatGPT holds a prom-inent position using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for gen-erating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT in-tegration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex data sets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.

Incorrect sitting posture, characterized by asymmetrical or uneven positioning of the body, often leads to spinal misalignment and muscle tone imbalance. Prolonged maintenance of such postures can adversely impact well-being and contribute to the development of spinal deformities and musculoskeletal disorders. In response, smart-sensing chairs equipped with cutting-edge sensor technologies have been introduced as a viable solution for real-time detection, classification, and monitoring of sitting postures, aiming to mitigate the risk of musculoskeletal disorders and promote overall health. This comprehensive literature review evaluates the current body of research on smart-sensing chairs, with a specific focus on the strategies used for posture detection and classification, as well as the effectiveness of different sensor technologies. A meticulous search across MDPI, IEEE, and Google Scholar databases yielded 34 pertinent studies that utilize non-invasive methods for posture monitoring. The analysis reveals that Force Sensing Resistors (FSR) are the predominant sensors utilized for posture detection, whereas Convolutional Neural Networks (CNN) and Artificial Neural Networks (ANN) are the leading machine learning models for posture classification. However, it was observed that CNNs and ANNs do not outperform traditional statistical models in terms of classification accuracy, due to constrained size and lack of diversity within training datasets. These datasets often fail to comprehensively represent the array of human body shapes and musculoskeletal configurations. Moreover, this review identifies a significant gap in the evaluation of user feedback mechanisms, essential for alerting users to their sitting posture and facilitating corrective adjustments.

Introduction Urolithiasis, a prevalent urological condition (8-13% globally) exhibits regional variations, influenced by water quality, climate, health factors and diet. Sri Lanka with its tropical climate and dietary patterns is part of the "Stone Belt" of Asia. This study in Northern Sri Lanka examines urinary stone compositions and assesses the prevalence of metabolic disorders among urolithiasis patients. Methods This prospective cross-sectional study, conducted at tertiary urology centre from July 2022 to June 2023, focused on surgically treated urolithiasis patients. Institutional ethical clearance was obtained. Patient details and investigational findings were collected through questionnaires and data extraction forms. Stone analysis utilized Fourier transform infrared spectroscopy and detailed metabolic evaluation of 24 hour urine collection sample is carried out. Results This study followed 153 surgically treated urolithiasis patients, primarily male (64.3%), mean age 48.64. Ureteric colic (48.4%) was common, with kidney stones (45.8%) prevalent; 57.52% had recurrent stones. Diabetes mellitus (DM=23.5%) was the top comorbidity. Calcium oxalate monohydrate (COM) stones (78.4%) were most frequent, followed by uric acid (12.4%). COM predominated in 40-59 age group. No significant gender-stone type association. 86.9% had metabolic abnormalities, notably hypocitraturia (60.1%). 23% had both hypocitraturia and hypomagnesuria. Some metabolic disorders showed gender differences, with a marginal age-metabolic disorders association (p < 0.061). Urine oxalate levels were normal with higher variability in males. Conclusion Middle-aged males with urolithiasis commonly presented with ureteric colic and predominantly had calcium oxalate monohydrate stones. Recurrent stones were common, often accompanied by metabolic abnormalities such as hypocitraturia and hypomagnesuria, with diabetes mellitus as the primary comorbidity.

Attention to the work-related musculoskeletal disorders (WMSDs) involve also statistical surveys showing an increasing trend in the incidence of WMSDs. Technological development retrieves new tools and methods for the assessment of physical load at work. In addition to the conventional questionnaires and scaling assessment systems, these methods are mostly based on the direct sensing of appropriate parameters, which allows more precise quantification. The aim of this paper is to compare the assessment of ergonomic risk through current legislative regulations. A Captiv wireless sensor system was used at a car headlight quality control assembly workplace for sensing, data acquisition and data processing. During the evaluation of the postures and movements at work, we discovered differences in the applicable standards: Decree 542/2007 Coll. (Slovak legislation), STN EN 1005-4+A1, French standards default in the Captiv system. Standards define the thresholds for hazardous postures with significant differences in several evaluated body segments, which also affects the final evaluation of the measurements. Based on the results of our research, we found that respondents were in an acceptable position for approximately 63% of the total duration of the work activity in terms of the Legislative method, 44% with Captiv and 27% with Standards method.

The study of the human microbiome has been a hot topic during the last decades and more recently the skin microbiome has aroused great interest as well. So that, scientists have turned their attention to the role of the skin microbiome in skin health, and its relationship with different disorders as atopic dermatitis, psoriasis, acne, and rosacea, among others. Numerous studies and investigations have been performed to study the role of pre and probiotics as nutraceuticals in the treatment of skin diseases, with growing evidence along the last ten years. This review gathers information on the use of “nutribiotics” in skin care health, focus on the main dermatological diseases and other skin conditions. Clinical studies show that nutribiotics could be a new tool to improve skin health and pre, pro, syn, post and para-probiotics seem to be beneficial on several skin disorders, as well as repairing the skin barrier, or promoting wound healing. In conclusion, skin microbiome has emerged as a new field with high potential to develop disruptive solutions to manage skin health and disease. Future advances in this field may facilitate the treatment of skin dysbiosis being nutribiotics a suitable method for skin care.

Depression is estimated to be a leading contributor to the global mental health-related burden. The determinants of this huge prevalence lie in the fact that depressive symptoms may be comorbid in a wide variety of disorders, thus complicating and exacerbating their clinical pictures. This makes the treatment of depressive symptoms even more difficult since many pharmacological and pharmacokinetic interactions should be considered by physicians approaching the therapy. Hence, depression still represents a challenge for both psychiatrists and the other clinicians, in terms of its high rates of relapse and resistance despite well-established protocols. It is also complicated by the well-known latency in its complete response to current antidepressant treatments. In this context, the search for new strategies in antidepressant treatment is mandatory; even including revising the use of “old” pharmacotherapies by considering their specific features may help to perfecting the treatment of depression, both in its standalone psychiatric manifestation and in the framework of other clinical conditions. The results of a consensus of experts regarding the possible use of trazodone as a valuable strategy for addressing the “real world” unmet needs of depression treatment is herein reported. This is based on the unique characteristics of this drug possibly delivering a rapid antidepressant action as compared to other selective serotonin reuptake inhibitors (SSRIs) as well as on its pharmacodynamic malleability and pharmacokinetic tolerability when used in the milieu of other drugs in treating comorbid depressive symptoms.

Venous thromboembolism (VTE) is a serious health condition and represents an important cause of morbidity and, in some cases, mortality. According to the latest estimates from the Centers for Disease Control and Prevention, 3 out of 10 people with VTE will have recurrence of clotting event within 10 years. The American Heart Association reports that VTE is more common in people over 40 years of age, and that risk doubles with each decade. The World Health Organization advises that the world’s population of people aged 60 years is going to be doubled by 2050. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are the two main conditions that make up VTE. People with VTE are initially treated with anticoagulants to prevent conditions such as stroke and to reduce the recurrence of VTE. However, thrombolytic therapy is used for people with PE experiencing with low blood pressure or in severe cases of DVT. Despite the approval of direct anticoagulants in 2010, there is clear evidence that the search for new drugs that are more effective or safer than the current antithrombotic treatments continues. Thrombin plays a crucial role in regulating hemostasis and maintaining blood coagulation, and therefore serves as a major target for the treatment of hemostatic disorders such as thromboembolic syndromes, disseminated intravascular coagulation, thrombocytopenia, and acquired hemostatic disorders such as platelet dysfunction and excessive anticoagulation, among other pathologies. This review focuses on the progress in research on new anticoagulants and novel delivery systems for antithrombotic targeting to vascular embolisms.

Secondary movement disorders (SMDs) represent a heterogeneous group of neurological conditions characterized by abnormal, involuntary movements resulting from various underlying causes. This comprehensive review aims to thoroughly understand SMDs, including their epidemiology, pathophysiology, clinical manifestations, diagnostic approach, and management strategies. SMDs encompass a spectrum of movement abnormalities, including dystonia, chorea, athetosis, myoclonus, tics, and tremors. They can arise from a multitude of etiologies, such as drug-induced effects, post-infectious processes, metabolic disturbances, and structural brain lesions. The epidemiology of SMDs varies depending on the underlying cause, with some conditions being more prevalent in specific populations or age groups. Understanding the pathophysiology of SMDs is crucial for accurate diagnosis and targeted management. Diagnosing SMDs requires a comprehensive approach, including a detailed history, physical examination, laboratory investigations, neuroimaging studies, and sometimes electrophysiological studies. Management of SMDs is multifaceted and may involve pharmacological, non-pharmacological, and surgical interventions. Individualized treatment plans are essential, considering the underlying cause, severity of symptoms, and patient preferences. Emerging concepts in the field of SMDs include advancements in genetic research, identification of biomarkers, and development of novel therapeutic approaches. There is a growing focus on patient-centered care and improving the quality of life for individuals with SMDs. In conclusion, SMDs pose diagnostic and therapeutic challenges, requiring a multidisciplinary approach for optimal management. Continued research and collaboration are essential for advancing our understanding and treatment of these complex disorders.

Freezing of Gait (FoG) is a disabling motor complication in Parkinson’s disease (PD), affecting approximately 50% of advanced PD patients. It is characterized by sudden and transient inability to initiate or maintain walking, leading to falls and reduced quality of life. This study investigates the relationship between white matter integrity and step initiation impairments in FoG. Forty-three PD patients (26 with FoG) underwent diffusion-weighted imaging to assess white matter DTI metrics and kinematic analysis during step initiation tasks. Multiple regression analyses were conducted to explore the connection between white matter tract integrity and step initiation behavior. The multiple regression analysis shows that (1) Right Inferior Longitudinal Fasciculus RD explained 31% of APA duration’s variance; (2) Corpus Callosum Forceps Major explained 25% of the step length's variance. There was a positive correlation between the Right Inferior Longitudinal Fasciculus RD and APA duration and a negative correlation between Corpus Callosum Forceps Major RD and step length. The findings suggest that compromised white matter integrity in RILF and CC contributes to impaired motor control during step initiation in FoG. These regions are critical for inhibitory control and interhemispheric coordination, crucial for APA execution and step length regulation.

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to explore the mechanisms behind the vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactivated protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.

Although the neurofilament light chain (NfL) is used as a biomarker for neurodegenerative decline, its use in surgery- and anaesthesia-induced acute cognitive dysfunction remains controversial. We aimed to synthesise the evidence to explore the potential of NfL as an established biomarker for perioperative neurocognitive disorders (PND). We systematically searched the PubMed, EMBASE, MEDLINE, Cochrane Library electronic databases, and Cochrane Central Registry of Clinical Trials. Our results show that CSF NfL levels positively correlated with blood NfL levels (r = 0.63; 95% confidence interval [CI], 0.42-0.77). The pooled standardised mean difference (SMD) showed a significantly higher preoperative CSF NfL levels (SMD = 0.27; 95% CI, 0.07-0.47) and both pre- and postoperative blood NfL levels (SMD = 0.53, 95% CI, 0.40-0.66 and SMD = 0.58, 95% CI, 0.43-0.73) in the postoperative delirium (POD) group. Postoperative blood NfL levels were significantly elevated in both POD group (SMD = 0.49; 95% CI, 0.34-0.64) and no-POD group (SMD = 0.67; 95% CI, 0.53-0.81). Our meta-analysis indicates that NfL may serve as a potential biomarker for POD, and elevated preoperative blood NfL levels could be a risk factor for POD. Further studies are needed to confirm the association of CSF/blood NfL levels with other PND types.

There is mounting evidence that patients with severe COVID-19 disease may have symptoms that continue beyond the acute phase, extending into the early chronic phase. Often referred to as 'Long COVID'. Simultaneously, case investigations have shown that COVID-19 individuals might have a variety of neurological problems. The accurate and accessible assessment of cognitive function in patients post COVID-19 infection is thus of increasingly high importance for both public and individual health. Little is known about the influence of COVID-19 on the general cognitive levels but more importantly, at sub functions level. Therefore, we first aim to summarize current level of evidence supporting a negative impact of COVID-19 infection on cognitive functions. 27 studies have been included in the systematic review representing a total of 94,103 participants (90,317 COVID-19 patients and 3,786 healthy controls). We then performed a meta-analysis summarizing the results of 5 studies (959 participants, 513 patients) to quantify the impact of COVID-19 on cognitive functions. The overall effect, expressed in Standardized Mean Differences, is -0.56 [95%CI -0.79 ; -0.34]. To prevent disability, we finally discuss the different approaches available in rehabilitation to help these patients and to avoid long-term complication.

Background: The pandemic caused by the SARS-CoV-2 virus demonstrated the importance of prevention through a healthy diet and lifestyle, the most vulnerable people being those with severe chronic conditions, those who are overweight, and those with an unbalanced immune system. Methods: The evaluation of the eating habits and lifestyle of the Romanian population in the post-pandemic period was carried out based on a cross-sectional observational study with the help of a questionnaire. Results: 4704 valid answers were registered (3136 female and 1568 male respondents). Among the respondents, most of them belong to the young population, 2892 between the ages of 18 and 40, i.e., 61.5%. Most male respondents are overweight (1400) and obese (780). Most respondents indicated a tendency to consume 1-2 meals per day irregularly (p=0.6167). Only 974 respondents adopted a healthy diet, and 578 a healthy lifestyle. Conclusion: The present study reports low adherence to a healthy diet (20.7%) and healthy lifestyle (12.28%), especially among the young population (&lt; 30 years). In the current context, it reports a reduced tendency to consume vegetables and fruits among the population, below the daily average recommended by the nutrition guidelines, a tendency towards sedentary behavior, and even deficient hydration of some of the respondents; these negative aspects can create a long term a series of nutritional and psycho-emotional imbalances. Our results evidence that complex surveys among the population are regularly required to investigate nutritional or lifestyle deficiencies; moreover, it could be helpful in further educational measures in nutrition, food, and environmental safety.

Histamine (HA), a biogenic monoamine, exerts its pleiotropic effects through four H1R–H4R histamine receptors, which are also expressed in brain tissue. Together with the projections of HA-producing neurons located within the tuberomammillary nucleus (TMN), which innervate most areas of the brain, they constitute the histaminergic system. Thus, while remaining a mediator of the inflammatory reaction and immune system function, HA also acts as a neurotransmitter and a modulator of other neurotransmitter systems in the central nervous system (CNS). Although the detailed causes are still not fully understood, neuroinflammation seems to play a crucial role in the etiopathogenesis of both neurodevelopmental and neurodegenerative (neuropsychiatric) diseases, such as autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), Alzheimer's disease (AD) and Parkinson's disease (PD). Given the increasing prevalence/diagnosis of these disorders and their socioeconomic impact, the need to develop effective forms of therapy has focused researchers' attention on the brain's histaminergic activity and other related signaling pathways. This review presents the current state of knowledge concerning the involvement of HA and the histaminergic system within the CNS in the development of neurodevelopmental and neurodegenerative disorders.

Objective: The causes of vertigo and dizziness in children are diverse and require attention from various specialists. Numerous authors have reported that the commonest type of vertigo in children is migraine-associated vertigo (vestibular migraine and benign paroxysmal vertigo of childhood - BPV). We aimed to check whether this could be applied to our group of patients. Materials and methods: A retrospective case series of 257 consecutive pediatric vertigo and diz-ziness patients referred to the tertiary pediatric ENT clinic from 2015 to 2020. Patients received a complete audiovestibular workup and were referred to pediatric neurologists and other special-ists depending on the signs and symptoms. Results: Of 257 children aged 1-17 years, almost one fifth of them, 49/257 (19.1 %) had a central type of vertigo, 20/257 of them (7.8%) had benign paroxysmal vertigo of childhood and 4/257 (1.6%) had a migrainous type of vertigo. Most of the children, 112/257 (43.6%), remained unclas-sified, without a final diagnosis. Conclusion: Due to the numerous possible causes, a child presenting with dizziness and vertigo requires a multidisciplinary approach. In the majority of cases, vertigo spells are self-limiting. They stop spontaneously and sometimes remain clinically undiagnosed. The most prevalent reasons for pediatric vertigo may be temporary hemodynamic (vaso-vagal) and psychological imbalance.

An 8-month-old, 3.4 kg, castrated male Toy Poodle was referred for progressive tetraparesis and respiratory disorder without a history of trauma. Diagnostic imaging, including dynamic CT and MRI, revealed concurrent atlanto-occipital dislocation (AOD) and atlantoaxial instability (AAI) with spinal cord compression. This case was unique due to its congenital nature and the absence of trauma. The surgical intervention involved precise removal of the C1 vertebra's ventral articular facet, which was compressing on the spinal cord, attributed to its fixed and malaligned position within the atlantooccipital joint. Following facetectomy, the stabilization of the occipital bone to the C2 vertebra was achieved by screws, wire, and polymethyl methacrylate. Postoperative recovery was monitored with CT and radiographs, showing successful decompression and gradual improvement in gait, despite mild residual ataxia. The dog experienced postoperative complications with screw loosening at 114 days, which was managed successfully by extracting the problematic screws. Postoperatively, the dog showed a near-normal gait and experienced no pain through 21 months of monitoring. This case represents the first report of concurrent congenital AOD and AAI treated with ventral surgical approach, contributing new insights to the understanding and management of such complex cranio-cervical junction disorders in veterinary neurosurgery.

Many people in the USA have lost their lives or become addicted to opioids via prescription opioids given for chronic pain. The chronic pain epidemic has emerged due to a convergence of factors, including the medicalization of pain as well as injuries happening in the workplace, in the home, or during recreation. Opioid prescriptions rose precipitously from the late 1990’s through to approximately 2020, and despite public awareness, still are increasing. This review examines literature on integrative approaches to chronic pain as delineated by pain type. The review is organized by the most common causes of chronic pain, and randomized controlled trials, meta-analyses and systematic reviews are extracted for each cause of chronic pain. Several promising interventions may alleviate chronic pain of some causes, and some interventions may work across pain causes. Lowering inflammation through dietary or lifestyle regimens may be a general way of reducing pain. Pain can be alleviated through several adjunctive and integrative treatment approaches, which may serve to lower the need for opioid medication.

Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids serum levels in a cohort of Parkinson’s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients, and healthy subjects with (GBA-C) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn &amp; Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-C and HC were also considered. Clinical assessment included the MDS-UPDRS and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-C (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p&lt;0.05, Fisher’s exact test) and higher MDS-UPDRS part-II (p&lt;0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-DHP. Allopregnanolone was the only neurosteroid significantly lower (p&lt;0.01, Dunn’s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.

A screening questionnaire for autism symptoms is not yet available in Poland, and there are no recommendations regarding screening for developmental disorders in Polish primary health care. The aim of the study was to assess the opinions of parents and physicians on the legitimacy and ne-cessity of screening for autism spectrum disorders, potential barriers to the implementation of the screening program, and the evaluation and presenting the process of the online ASD screen-ing, which was part of the validation program of the Polish version of one of the screening tools. The study involved 418 parents whose children were screened online and 95 primary care physi-cians who expressed their opinions in prepared surveys. The results indicate that both parents and doctors perceive the need to screen children for ASD in general population without a clear preference as to the screening method (online or in-person). Online screening may prove to be at least a partial method of solving numerous indicated systemic difficulties - including: time con-straints, lack of experienced specialists in the field of developmental disorders or related to the organizational difficulties of health care.

Anxiety disorders are among the most common mental disorders worldwide, and often respond incompletely to existing treatments. Selenium, a micronutrient that is a component of several biologically active selenoproteins, is also involved in several aspects of brain functioning, and may exert antidepressant and anxiolytic effects through multiple pathways. The current paper is a scoping review of translational, observational and interventional evidence on the potential role of selenium and its compounds in the management of anxiety and related disorders. Evidence from animal models suggests that this approach may be promising. Though evidence from observational studies in humans is inconsistent and affected by several confounding factors, the available evidence from randomized controlled trials suggests that selenium supplementation may be beneficial in the management of certain anxiety-related conditions, such as anxiety in medically ill patients, prevention of anxiety following exposure to traumatic stress, and obsessive-compulsive disorder. This paper provides a critical evaluation of the existing evidence base, including unanswered questions that could serve as the focus of further research, and outlines the potential benefits and risks associated with the use of selenium in anxiety disorders.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as ASD necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, and communication, restricted, repetitive behavioral patterns with association to several additional impairments such as somatosensory, motor and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD like-behavior from the etiologic, pathogenetic and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), Lipopolysaccharide (LPS) and propionic acid or other well-documented immunogens or pathogens, like mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, Polychlorinated biphenyls (PCBs), organophosphate pesticides - chlorpyrifos (CPF) and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during the early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic like behavior (i.e. fragile X, Rett syndrome, SHANK gene mutation Neuroligin genes and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

Lower urinary tract dysfunction is clinically important because it may cause urinary tract infections, mainly due to accumulation of residual urine, and adversely affect renal function. In addition, it may cause urinary incontinence, strongly affecting the child’s quality of life. The function of the lower urinary tract is closely associated with function of the bowel because constipation is commonly present with bladder dysfunction. The interplay between the lower urinary tract and bowel function, coupled with common conditions such as detrusor overactivity and voiding dysfunction, requires a nuanced diagnostic approach. Detrusor overactivity, a benign but socially harmful condition, is the principal cause of daytime urinary incontinence in childhood. It needs to be differentiated from more serious conditions such as neurogenic bladder dysfunction or urethral obstruction. Voiding dysfunction, a habitual sphincter contraction during voiding, is common in children with detrusor overactivity, may be selflimiting but may also result in residual urine and urinary tract infections. It may resemble, in severe cases, the neurogenic bladder dysfunction, most often caused by spinal dysraphism which very often leads to recurrent urinary tract infections and high intravesical pressures, jeopardizing renal function. Voiding diary is crucial in the initial evaluation of lower urinary tract function in children.

Biological, environmental, behavioral, and social factors can influence sleep and lead to sleep disorders or diseases. Sleep disorders are common, numerous and heterogeneous in terms of their etiology, pathogenesis, and symptomatology. Management of sleep-wake circadian disorders (SWCD) includes education to sleep hygiene, behavioral strategies, psychotherapy (cognitive behavioral therapy (CBT), particularly), instrument-based treatments (i.e. positive airway pressure therapy, hypoglossal nerve stimulation), and pharmacotherapy. Depending on the disease, therapy varies and is executed sequentially, or can be a combination of several forms of therapy. Drugs used for SWCD include traditional sleep or wake-promoting agents, chronotherapeutic agents. Recently, novel medications, which are more precisely acting on specific neurochemical systems (i.e. orexin system) important for sleep and wake, are also increasingly being used. In this review, the pharmacotherapy of common sleep disorders (insomnia, sleep-related breathing disorder, central disorders of hypersomnolence, circadian rhythm sleep wake disorders, parasomnias, and sleep-related movement disorders) embedded in the overall therapeutic concept of each disorder is presented. There is also an outlook on possible future pharmacotherapies.

This study analyzes the eating behavior and factors associated with the presence of disordered eating attitudes in patients undergoing bariatric surgery. It is a cross-sectional, descriptive, and analytical study conducted at a hospital in the Amazon region of Brazil. The Disordered Eating Attitude Scale reduced version (DEAS-s) was used to assess the risk of eating disorders and the Three-Factor Eating Questionnaire (TFEQ-R21) to characterize eating behavior. A total of 205 patients participated, with a mean age of 37.5 ± 8.6 years, the majority being female (93.7%; p&lt;0.001), the mean BMI was 45.3±6.7 kg/m2. It was found that cognitive restraint had the highest mean (52.6±19.9; p&lt;0.001). As for the DEAS-s, the question with the highest mean was "spending one or more days without eating or consuming only liquids to lose weight" (2.80±1.99). Female participants had a higher score in the emotional eating (p=0.016). Disordered eating attitudes showed a correlation with emotional eating and uncontrolled eating. These results suggest that candidates for bariatric surgery may have susceptibility to eating disorders. The importance of a multidisciplinary team in monitoring during the preoperative period is highlighted.

Anxiety disorders significantly reduce patients' quality of life. Current pharmacological treatments, primarily benzodiazepines and antidepressants, are associated with numerous side effects. Consequently, there is a continual search for alternative methods to traditional therapies that are less burdensome for patients and broaden their therapeutic options. In this review, we examined recent evidence on alternative treatments for anxiety disorders, including physical activity, mindfulness, VR technology, biofeedback, herbal remedies, and transcranial magnetic stimulation (TMS), cryotherapy, hyperbaric therapy, vagus nerve stimulation, MDMA, electroconvulsive therapy (ECT), and eye movement desensitization and reprocessing (EMDR) therapy. Our objective was to determine the role of these selected alternative methods in the treatment of anxiety disorders. Alternative treatments significantly expand the options available to patients and clinicians, with many serving as adjuncts to traditional therapies. Among the methods presented, mindfulness has the most significant therapeutic potential.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene-expressed profiling identified significantly different neuregulin-2 (NRG2) gene expressions between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD. The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23±2.80) was significantly lower than that of controls (9.27±4.78, p < 0.001). Next, we resequenced all exons of NRG2 in other 349 ASD subjects, who were compared with super-controls from the Taiwan Biobank using case-control association analysis to determine the existence of mutations or single-nucleotide polymorphisms (SNPs). We identified three SNPs, including two noncoding ones, IVS3 + 13A > G (rs889022) and IVS9 + 32T > A (rs182642591), and one insertion/deletion (indel) SNP, named indel GCCCGGC, rs1323957797, in the NRG2 coding region. The genotype and allele frequency distribution of rs1323957797 significantly differed between ASDs and controls (p < 0.0001). Our findings showed significant differences in genotype and allele frequency distribution of the indel SNP, rs1323957797, located in the EGF-like domain region at the C-terminal of the NRG2 precursor protein. Together with our findings, the indel SNP mutation was significantly more common in ASDs than controls, leading to lower NRG2 expression than controls, influencing NRG2 function. Our study’s findings suggest that NRG2 is a susceptibility gene for ASD.

Background: Monk healers provide an accessible and popular service in Southeast Asia, but little is known on the substance use status of their clients. This investigation intended to assess and compare the rate and correlates of substance use disorders in two different treatment settings (monk healers=MH and primary health care=PHC) in Thailand. Methods: In a cross-sectional study, 1024 patients (591 of MH and 613 of PHC) responded to screening measures of the “World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test Lite”, and two common mental disorders (major depression and generalized anxiety disorder) from November 2018 to February 2019. Logistic regression was used to estimate the determinants of any substance use disorder in the MH and PHC setting. Results: The prevalence of substance use disorder was higher in MH clients than PHC patients: any substance use disorder 11.7% (95% Confidence Interval-CI: 9.3%-14.5%) vs 5.4% (95% CI: 3.9%-7.5%), tobacco use disorder 7.6% (95% CI: 5.7%-9.9%) vs 2.5% (95% CI: 1.5%-4.0%), alcohol use disorder 10.0% (95% CI: 8.4%-13.6%) vs 4.3% (95% CI: 3.0%-6.3%), any drug use disorder 4.2% (95% CI: 2.8%-6.1%) vs 0.3% (95% CI: 0.08%-1.3%), and any past three months drug use 8.2% (95% CI: 6.2%-10.7%) vs 1.5%, 95% CI: 0.8%-2.8%). In adjusted logistic regression analysis, among MH clients, male sex (Adjusted Odds Ratio-AOR: 9.52, 95% Confidence Interval-CI: 5.06-17.92) was positively, and were married (AOR: 0.32, 95% CI: 0.16-0.61) and high social support (AOR: 0.40, 95% CI: 0.16-0.99) were negatively associated with any substance use disorder. Among PHC patients, male sex (AOR: 7.05, 95% CI: 2.99-16.63) was positively and age (AOR: 0.95, 95% CI: 0.92-0.98) was negatively associated with any substance use disorder. Conclusion: The proportion of substance use disorders among MH attendees was more than twice that of PHC attenders in Thailand, calling for collaboration in controlling substance use disorders between the two treatment systems.

While classical NOD-like receptor pyrin domain containing protein 1 (NLRP1) and NLRP3 inflammasomal proteins have been extensively investigated, the contribution of NLRP2 is still ill-defined in the nervous system. Given the putative significance of NLRP2 in orchestrating neuroinflammation, further inquiry is needed to gain a better understanding of its connectome, hence its specific targeting may hold a promising therapeutic implication. Therefore, bioinformatical approach for extracting information, specifically in the context of neuropathologies, is also undoubtedly preferred. To the best of our knowledge, there is no review study selectively targeting only NLRP2. Increasing, but still fragmentary evidence should encourage researchers to thoroughly investigate this inflammasome in various animal- and human models. Taken together, herein we aimed to review the current literature focusing on the role of NLRP2 inflammasome in the nervous system and more importantly, we provide an algorythm-based protein network of human NLRP2 for elucidating potentially valuable molecular partnerships.

Phytocannabinoids, including the non-addictive cannabis component cannabidivarin (CBDV), have been reported to hold therapeutic potential in several neurodevelopmental disorders (NDDs). Nonetheless, the therapeutic value of phytocannabinoids for treating Fragile X syndrome (FXS), a major NDD, remains unexplored. Here, we characterized the neurobehavioral effects of CBDV at doses of 20 or 100 mg/kg in the Fmr1-knockout (Fmr1-KO) mouse model of FXS using two temporally-different intraperitoneal regimens: subchronic 10-day delivery during adulthood (Study 1: rescue treatment) or chronic 5-week delivery at adolescence (Study 2: preventive treat-ment). Behavioral tests assessing FXS-like abnormalities included anxiety, locomotor, cognitive, social and sensory alterations. Expression of inflammatory and plasticity markers was investigated in the hippocampus and prefrontal cortex. When administered during adulthood (Study 1), the effects of CBDV were marginal, rescuing at the lower dose only the acoustic hyper-responsiveness of Fmr1-KO mice and at both doses, their altered hippocampal expression of neurotrophins. When administered during adolescence (Study 2), CBDV at both doses prevented the cognitive, social and acoustic alterations of adult Fmr1-KO mice and modified the expression of several inflammatory brain markers in both wild-type littermates and mutants. These findings warrant the therapeutic potential of CBDV for preventing neurobehavioral alterations associated with FXS, highlighting the relevance of its early administration.

Musculoskeletal disorders are a common occurrence in Europe, affecting millions of people and costing billions of euros in social security services. Traditional treatments using drugs like non-steroidal anti-inflammatory drugs (NSAIDs) can cause gastric damage, making prolonged use difficult. To address this issue, the Author has developed NegEnt Spray - Muscles and Joints, a topical medical device that uses liposomal cannabidiol and chamomile hydrolate to reduce inflammation and pain in musculoskeletal disorders. The liposomal technology used in NegEnt Spray allows for better bioavailability and a more targeted action, while chamomile hydrolate provides a natural anti-inflammatory and soothing effect. The spray is non-greasy, absorbs quickly, and can be used under any circumstances. Its pocket-sized design makes it easy to carry and use throughout the day. With NegEnt Spray, patients can alleviate discomfort and pain associated with musculoskeletal disorders without worrying about the side effects of traditional treatments.

Introduction: The concept of hypersexuality belongs to modern parlance, according to a predominantly clinical meaning, understood as a psychological and behavioural alteration as a result of which sexually motivated stimuli are sought in inappropriate ways, often experienced in a way that is not completely satisfactory. Methods: Literature up to February 2023 was reviewed. Results: Forty-two articles were included in the review. Conclusion: Hypersexuality is a potentially clinically relevant condition, consisting of one or more dysfunctional and pathological behaviours of one's sexual sphere and graded according to the severity of impairment of subjective acting out; for this reason, the Perrotta Hypersexuality Global Scale (PH-GS) is suggested, which distinguishes high-functioning forms (pro-active and dynamic hypersexuality) from those of attenuated and corrupted functioning (dysfunctional and pathological hypersexuality of grade I and II). Future research is hoped to address the practical needs of this condition, such as the exact etiopathology, the role of oxytocin in dopaminergic hypotheses (and its ability to attenuate the symptomatology suffered by the patient in terms of manic drive), the best structural and functional personality framing of the subject, and the appropriate therapy to pursue.

Eating competence can play a role in helping adolescents navigate their food choices and attitudes toward eating in a healthy and balanced way. In the present study, we investigated the psychometric properties of the Dutch translation of the Eating Competence Satter Inventory 2.0TM (ecSI 2.0TM), which was developed to assess eating attitudes and behaviors. A sample of 900 Flemish adolescents completed the ecSI 2.0TM DUTCH and two self-report measures on eating disorder symptoms and identity functioning (i.e., confusion and synthesis). Confirmatory factor analysis confirmed the four-factor structure of the ecSI 2.0TM DUTCH, and the resulting four subscales (Eating Attitudes, Food Acceptance, Internal Regulation, and Contextual Skills) showed acceptable to excellent reliability (α ranging from .69 to .91). The ecSI 2.0TM also showed to be scalar invariant across sex and age (&lt;17 years, ≥ 17 years). Boys reported significantly higher ecSI 2.0TM DUTCH scores than girls on the four subscales and the total scale. The two age groups did not differ significantly on the ecSI 2.0TM DUTCH scales. Finally, scores on the ecSI 2.0TM subscales showed no or small negative correlations with adolescents’ BMI, large negative correlations with eating disorder symptoms and identity confusion, and large positive associations with identity synthesis. The Dutch translation of the ecSI 2.0TM is a valid and reliable instrument to assess eating competence skills in male and female adolescents.

Objectives: This study aimed to investigate whether genetic variations in the OPRD1 gene affect psychopathological symptoms and personality dimensions in eating disorders (ED) patients and/or contribute to ED risk. Methods: The study involved 221 female patients with anorexia nervosa (AN), 88 with bulimia nervosa (BN) and 396 controls. Sixteen tag-SNPs in OPRD1 were identified. Psychometric evalu-ations were conducted using the Symptom Checklist 90 Revised (SCL-90R) and the Eating Dis-orders Inventory Test-2 (EDI-2). P-values obtained by regression models were corrected for mul-tiple testing by the FDR method. Results: In AN patients, genotypes rs204077TT and rs169450TT were linked to lower BMI values (FDR-q=0.035 and 0.017, respectively), as was rs2234918 in a log-additive model (BMI: 18.0±0.28, 17.22±0.18 and 16.59±0.39 for TT, TC and CC carriers, FDR-q=0.012). Additionally, AN patients carrying the rs72665504AA genotype had higher scores in Interpersonal distrust (FDR-q=0.030), whilst BN carriers of rs513269TT and rs2873795TT showed lower scores in Ineffectiveness (FDR-q=0.041 and FDR-q=0.021). In the AN group, BMI correlated with variability in a distal haplotype (rs508448/rs204077/rs223491, FDR-q=0.028), which was also associated with the global PST index of SCL-90R (FDR-q=0.048). Associations were more noticeable in BN patients; again, the distal region of the gene was linked to EDI-2 total scores (FDR-q=0.004-0.048 for the four last haplotypes) and two global SCL-90R indices (GSI: FDR-q=0.011 and PSDI: FDR-q=0.003 for the last s204077/rs2234918/rs169450 combination). No associations with ED risk were observed. Conclusions: Genetic variation in the OPRD1 gene, particularly in its distal region, is associated with BMI and psychopathological comorbidities in ED patients.

The aim of this study was to assess the best timing to perform arthrocentesis in the management of temporomandibular disorders with regards to conservative treatment. A systematic search based on PRISMA guidelines, including a computer search with specific keywords, reference list search, and manual search was done. Relevant articles were selected after 3 search rounds for final review based on 6 predefined inclusion criteria, followed by a round of critical appraisal. Eleven publications, including 5 randomized controlled trials and 6 prospective clinical studies informed this review. The studies were divided into 3 groups based on the timing of arthrocentesis: 1). Arthrocentesis as the initial treatment, 2). Early arthrocentesis, and 3). Late arthrocentesis. Meta-analyses compared the efficacy of improvement in mouth opening and pain reduction in the 3 groups. The results were statistically significant and favoured early arthrocentesis, followed by late arthrocentesis in terms of both improvements in mouth opening and pain reduction. All 3 groups showed improvement in mouth opening and pain reduction. We conclude that early arthrocentesis may be able to produce the best clinical results, while arthrocentesis before attempting conservative treatment may produce less favourable outcomes.

Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of WS1 results in death by the age of 30. Severe brain atrophy leads to central respiratory failure, which is the main cause of death in WS1 patients. Mutations in the WFS1 gene, located on chromosome 4p16, account for approximately 90% of WS1 cases. The gene produces wolframin, a transmembrane glycoprotein widely distributed and highly expressed in retinal, neural, and muscular tissues. Wolframin plays a crucial role in the regulation of apoptosis, insulin signaling, and ER calcium homeostasis, as well as the ER stress response. WS1 has been designated as a neurodegenerative and neurodevelopmental disorder due to the numerous abnormalities in the ER stress-mediated system. WS1 is a devastating neurodegenerative disease that affects patients and their families. Early diagnosis and recognition of the initial clinical signs may slow the disease's progression and improve symptomatology. Moreover, it is critical to provide genetic counseling to the patient's relatives in order to reduce the risk of transmitting WS1. Regrettably, there are currently no specific drugs for the therapy of this fatal disease. A better understanding of the etiology of WS1 will make possible the development of new therapeutic approaches that may enhance the life expectancy of patients. This review will examine the pathogenetic mechanisms, development, and progression of neuropsychiatric diseases commonly associated with WS1. A thorough understanding of WS1's neurophysiopathology is critical for achieving the goal of improving patients' quality of life and life expectancy.

Bovine Dewclaw Dermatitis (BDCD) is a hoof disease characterized by inflammation of the second and fifth accessory digits and the skin in this region. This pathology is poorly described in the literature; however, it has recently been observed in beef cattle in the Amazon Biome, Brazil. The objective of this study was to identify the epidemiological factors associated with BDCD onset in cattle in the analyzed biome. Samples were collected from eight farms with extensive breeding systems located in Xinguara, Rondon do Pará, Curionópolis, and Ipixuna do Pará, in the state of Pará, Brazil. A total of 706 Nellore and Nellore crossbred with taurine bovine of both sexes were evaluated, with males aged between 2–4 years and a mean weight of 650 kg and females aged between 2–11 years and a mean weight of 400 kg. Distal extremities were inspected during cattle management, and in case of dewclaw lesions, a specific examination was carried out after proper restraint. Bovine were diagnosed with BDCD in all farms analyzed. Of the 706 cattle inspected, 49 (6.94%) showed BDCD, of which 19 (38.77%) were Nellore and 30 (61.22%) were crossbred. This was the first study to determine BDCD’s occurrence in extensive farming systems in the Amazon re-gion, also showing that pastures with large amounts of stumps and stones, the physical structure of pens, and trauma and injury incidence during animal management are the most important pre-disposing factors for the onset of BDCD.

(1) Background: The prevalence of comorbid psychiatric disorders among the patients with mental disorders is higher than general population. The aim of this study was to estimate the prevalence of comorbid psychiatric disorders among a Mexican adolescent sample diagnosed with eating disorders; (2) Methods: Only Mexican adolescents diagnosed with eating disorders were included in the study. The diagnoses were using the DSM-5 criteria. Adolescents with ages between 12 to 17 years were included. The psychiatric comorbidities were evaluated using MINI-kid and QEWP-R. In addition, the z-score values calculated from BMI; (3) Results: The mean age was 14.08±1.7 years old. In our Mexican sample the diagnoses more frequently were bulimia nervosa (55.61%). We found that 89% of the Mexican adolescents with eating disorders had another psychiatric comorbidity. Major depressive disorder (52.40%) and suicide risk (40%) were the most prevalent comorbidity; (4) Conclusions: Our results showed that bulimia nervosa is the most frequently diagnoses in Mexican adolescent and the suicide and major depressive disorder are the principal comorbidities. This emphasizes the importance that clinicians take in-to consideration the presence of psychiatric comorbidities to achieve an integrative treatment for patients with ED.

In the text, the synthesis and characteristics of the novel ONS-type vanadium(V) complexes with thioanilide derivatives of amino acids are described. They have shown inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1 and SHP2) in the submicromolar range, as well as inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxovanadium(IV)(BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, also including glucose utilization in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.

The modeling of psychiatric disorders poses significant challenges due to the complex nature of these conditions, which encompass a range of neuropsychiatric diseases such as autism spectrum disorder (ASD), schizophrenia (SCZ), bipolar disorder (BD), post-traumatic stress disorder (PTSD), anxiety and depression. The rising global prevalence of mental disorders and the urgency for more effective treatments have propelled the development of innovative in vitro models. This review presents a thorough examination of two-dimensional (2D) versus three-dimensional (3D) induced pluripotent stem cell (iPSC) models of neuropsychiatric diseases, offering insights into their respective capacities to mimic neurodevelopment and cellular phenotypes observed in these conditions. Our comparative analysis reveals that while traditional 2D cultures have been instrumental in elucidating disease pathways and high-throughput drug screening, they fall short in replicating the intricate cellular architecture and environment of the human brain. On the other hand, 3D organoid models, including brain organoids, better recapitulate the spatial organization, cell-type diversity, and functional connectivity of brain tissue, offering a more physiologically relevant context for studying disease mechanisms and testing therapeutic interventions. We assess the progress in modeling ASD, Schizophrenia, Bipolar Disorder, PTSD, and depression, highlighting the advanced understanding of disease etiology and potential treatment avenues offered by 3D iPSC technologies. Challenges remain, including the scalability, reproducibility, and maturation of organoids, but the potential for personalized medicine and the elucidation of disease ontogeny is unparalleled. The review concludes with a perspective on the future directions of psychiatric disease modeling, emphasizing the integration of 3D iPSC models with high-throughput technologies and computational approaches to enhance our understanding and treatment of these debilitating conditions.

A single-center, randomized, double-blind, placebo-controlled clinical trial with two arms was conducted in 71 healthy subjects suffering from sleep disturbances, which were treated with a dietary supplement based on an extract of Aloysia citrodora (or Lippia citriodora, lemon verbena) (n = 33) for 90 days. Subjects in the placebo group (n = 38) received capsules of microcrystalline and maltodextrin with the same organoleptic properties. Between-group significant differences in favor of the experimental group were found in the visual analogue scale (VAS) score rating sleep quality; overall score, sleep latency and sleep efficiency of the Pittsburg Sleep Quality Index (PSQI); and sleep latency, sleep efficiency, wakefulness after sleep onset and duration of awakening assessed by actigraphy. Plasma nocturnal melatonin levels also increased significantly in the experimental group. Changes in anthropometric parameters and physical activity levels were not found. This study shows that the administration of a dietary supplement comprised lemon verbena administered for 3 months was associated with a significant improvement of sleep quality as compared with placebo in a population of healthy subjects with sleep problems. Improvements were also apparent at the mid-study visit after 45 days of supplementation.

Background/Objectives: The latest WHO classification underscores the importance of the complete blood count (CBC) and cell morphology assessment in diagnosing lymphoid neoplasms. This study evaluated the diagnostic role of Research Use Only (RUO) parameters from the BC-6800 Plus Mindray analyzer in differentiating cell chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and other lymphoproliferative disorders. Methods: CBCs were performed on 90 patients (66% male, median age 67 years) with pathological blood counts (ALL, n=14; CLL, n=47; other lymphoproliferative disorders, n=29) at Novara’s University Hospital. Univariable and multivariable logistic regression assessed the association of basic (WBC, Hb, RDW, NE#, LY#, MO#, PLT) and research cell parameters (NLR, NMR, LMR, NeuX, NeuY, NeuZ, LymX, LymY, LymZ, MonX, MonY, MonZ). Results: In multivariable analysis, Hb (p=0.02), NeuY (p=0.04), and MonY (p=0.01) independently predicted CLL versus ALL, correctly classifying 93.4% of cases (AUC 0.91, 95% CI 0.81-1.0). MO# (p=0.003), LymY (p&lt;0.0001), and MonY (p=0.004) were independent predictors of CLL versus other lymphoproliferative disorders, classifying 77.6% of cases (AUC 0.86, 95% CI 0.78-0.95). NeuZ (p=0.01) and NeuY (p=0.04) independently predicted ALL versus other lymphoproliferative disorders, classifying 93% of cases (AUC 0.98, 95% CI 0.95-1.0). Conclusions: The use of RUO parameters offers valuable, cost-effective support in the early diagnosis of ALL, CLL, and other lymphoproliferative disorders.

Background: Immersive and non-immersive VR technology has been increasingly employed in training. This has encouraged physicians working in skill development to try using it to improve the learning, emotional recognition, and social skills of various disorders. This study aimed to explore the controlled trials employing VR in autism, ADHD, and dyslexia. Methodology:A literature review has been conducted, on PubMed, Scopus, and Web of Science. Any controlled trial in the pediatric age group, involving the comparison of VR training with other types of therapies in autism, ADHD, and dyslexia was included. Results:Only four controlled trials were identified, comprising a total of 208 patients, with ages ranging from 6-16 years. Out of these studies, two involved patients with autism, one with ADHD, and one with dyslexia. VR was successful in improving emotional recognition but not social interaction in autism. All trials did not mention thoroughly possible complications of prolonged use of VR. Conclusion: Despite being a promising technology, there is still a long road to prove the validity of using VR in skills development. Few controlled trials have been tailored to explore VR advantages over conventional training and therapies, most of them have a limited sample size, a short training course, and no mention of possible setbacks, such as ocular effects and social isolation.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA. However, several are under development, and the FDA anticipates their fast entry, as evidenced by the FDA's actions of issuing GE-specific guidelines. The potential of GE in treating diseases far supersedes any other modality due to the recognized role of genes in most human diseases. While GT products add missing genes, GE tools can overcome many aberrations. However, GE presents many safety challenges, including off-target impact, delivery consistency, and long-term effects of gene-fixing. However, most of these concerns will be resolved once the FDA begins approving them, leading to hundreds of products capable of treating untreatable diseases.

Keywords: Parkinson’s disease; sleep disorders; GBA; Parkin

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.

As artificial intelligence takes an increasingly prominent role in healthcare, a growing body of research is being dedicated to its application in the investigation of communication sciences and disorders (CSD). This study conducts a bibliometric analysis of AI-based research in the field of CSD published up to December 2023. Utilizing the Web of Science and Scopus databases, we identified 15,035 publications, with 4,375 meeting our inclusion criteria. From 1985 onwards, there has been a consistent annual increase in publications, averaging at 16.51%, notably surging from 2012 to 2023. The primary communication disorders studied include autism, dysarthria, dementia, Parkinson’s, and aphasia. Noteworthy AI techniques employed in CSD research encompass machine learning, automatic speech recognition, support vector machine, and deep learning. Our analysis provides a comprehensive overview, serving as a valuable resource for researchers, developers, and professionals seeking to comprehend the evolving landscape of AI in CSD research. Moving forward, collaborative efforts need to prioritize addressing ethical concerns, ensuring data privacy, enhancing methodological enhancements, and considering ecological validity in the application of AI in studies related to communication disorders.

Abstract Introduction: In the last thirty years, brain neuromodulation techniques have been used as an alternative to pharmacological treatment of neurological disorders. Parkinson's disease (PD) is a neurodegenerative disorder leading to bradykinesia, rest tremor, postural changes, and non-motor symptoms such as depression, anxiety, sleep disorders, pain, and cognitive decline that compromises executive functions (EFs), responsible for the orderly execution of behaviors and tasks of daily life and intentional and directed actions. To this date, a few studies with transcranial direct current stimulation (tDCS) have shown beneficial effects in PD patients concerning specific motor and non-motor symptoms, targeting the motor cortex and/or prefrontal regions. Objective: The main objective of this study was to evaluate the effects of left prefrontal tDCS across a broad spectrum of motor and non-motor symptoms of PD using established validated scales. Method: Single-blind randomized clinical trial with 18 volunteers with PD, aged between 45 and 80 years (66.1 ± 9.65), who met inclusion and exclusion criteria. Participants were submitted to assessments of motor and non-motor functions employing psychometric scales and tests to evaluate EFs and were randomly divided into two groups: control (sham stimulation) and experimental (active stimulation). All participants were involved in three separate tDCS sessions. The anode was positioned over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital region, with a direct current intensity of 2mA, lasting 20 minutes. At the end of the three sessions, all participants were reassessed. Results: Significant effects of tDCS on non-motor functions were observed for cognition (verbal fluency of actions, clock copy test, appointment by visual confrontation, and verbal memory with immediate free recall) and subjective assessment of sleep quality (overall restlessness and discomfort in the arms and legs at night, leg and arm cramps at night and distressing dreams). There was also an improvement in the rate of errors and successes for congruent and incongruent stimuli of the Stroop Test. The beneficial effects on motor function were decreased rigidity, improved gait, and greater agility in the finger-tapping test. Conclusion: Three tDCS sessions showed positive results for participants with PD, producing significant improvements in various motor and non-motor functions, including sleep quality, cognition, and EFs. Additionally, the present results indicate that tDCS neuromodulation of the left dorsolateral prefrontal cortex region is feasible, safe, and provides significant objective benefits for PD patients.

Fragile X Syndrome (FXS) is a pervasive developmental disorder and the most common monogenic cause of autism spectrum disorder (ASD). Female heterozygous (HET) carriers play a major role in the transmission of the pathology and present several FXS- and ASD-like behavioral alterations. Despite their clear genetic origins, FXS symptoms are known to be modulated by environmental factors, e.g., the exposure to chronic stress, especially during critical life periods, such as pregnancy. Pregnancy, together with pups’ care, constitutes maternal experience, i.e., another powerful environmental factor affecting several neurobehavioral functions in females. Here we investigated the impact of maternal experience on the long-term effects of stress in Fmr1-HET female mice. Our findings demonstrated that the behavioral abnormalities of HET females, i.e., hyperactivity and memory deficits, were unaffected by stress or maternal experience. In contrast, stress, independently of maternal experience, induced the appearance of cognitive deficits in WT mice. Maternal experience increased anxiety levels in all mice and enhanced their corticosterone levels, concomitantly promoting the effects of stress on social communication and adrenal glands. Our results advance our understanding of the environmental modulation of the behavioral alterations observed in FXS mice and highlight the long-term impact of maternal experience and its interactions with chronic stress.

Papain-like lysosomal cysteine proteases include 11 human cysteine cathepsins which act as endopeptidases and/or exopeptidases. They are involved in numerous physiological and pathological processes. Among them, only cathepsins B, H, C, and X/Z exhibit exopeptidase activity. Their activities are tightly regulated in various ways to prevent potentially hazardous effects on the cell. In this review, we focus on the structural and functional aspects of these four cysteine cathepsins and their role in neurodegeneration and cancer. Neurodegenerative disorders of aging share an endolysosomal dysfunction and accumulation and spread of oligomeric forms of neurotoxic proteins. The accumulation of various protein aggregates activates the microglia, thus inducing the activation and release of cysteine cathepsins and proinflammatory cytokines, leading to neurodegeneration. In cancer, cysteine cathepsins participate in tumor progression and metastasis. Tumor–stromal crosstalk leads to activation of the stroma and overexpression and secretion of proteolytic enzymes, triggering extracellular matrix degradation and the release of soluble factors. Activated stromal cells (i.e., macrophages, fibroblasts, mast cells) secrete additional growth factors, cytokines, and chemokines that are responsible for the regulation of processes leading to tumor progression and metastasis. Therefore, a better understanding of the role of cysteine cathepsins in neurodegeneration and cancer could lead to novel targeted therapeutic approaches.

Structural variations (SVs) play a key role in the pathogenicity of hematological malignancies. Optical genome mapping (OGM) is an emerging technology that enables genome-wide detection of all classes of SVs at a high resolution and sensitivity. Identification of cryptic SVs leading to gene disruption or predicted novel gene fusions could be important drivers for cancer development and/or portend a prognostic relevance, which could be used to modify the treatment plan. A cohort of 106 consented cases that had a successful OGM analysis performed were included in the study. Demographic, clinical, laboratory and treatment data were collected. Routine diagnostic and prognostic testing were done on the peripheral blood and bone marrow aspirate as indicated. Additional samples of peripheral blood and/or bone marrow were sent for OGM testing. OGM led to a change in risk stratification in 17/66 (25.75%) of patients with hematological malignancies, the majority of these patients (15/66, 22.72%), having their risk stratification upgraded with a resulting change in treatment of 14 patients. This study highlights the ability of OGM to detect rare, cryptic and clinically relevant variants that potentially impact disease diagnosis, risk stratification and actionable treatment targets.

The determinants of metacognition are still poorly understood in bipolar disorders (BD). We aimed to examine the clinical determinants of metacognition, defined as the agreement between objective and subjective cognition in individuals with BD. The participants consisted of 281 patients with BD who underwent an extensive neuropsychological battery and clinical evaluation. To assess subjective cognition, participants provided a general rating of their estimated cognitive difficulties. Clinical characteristics of BD were also recorded, along with medication. We studied the potential moderation of the association between cognitive complaints and global objective cognitive performance by several clinical variables with ordinal logistic regressions. Depression and impulsivity were associated with greater cognitive complaints. The only variable that moderated the relationship between objective and subjective cognition in the global model was the prescription of antipsychotics. Patients taking antipsychotics had a poorer association between cognitive complaints and objective neuropsychological performance. This result suggests a role for dopamine in the modulation of metacognitive performance, and calls for the systematic control of antipsychotic medication in future studies documenting metacognitive deficits in severe and persistent mental disorders. Depression and impulsivity should be investigated as potential therapeutic targets for individuals with BD and cognitive complaints, before proposing an extensive neuropsychological evaluation.

Temporomandibular disorders (TMD) is a group of orofacial pain conditions which is the most common non-dental pain complaint in the maxillofacial region. Due to the complexity of the etiology and often cyclical nature of the disease, the diagnosis and management of TMD remain a challenge where consensus is still lacking in many aspects. While clinical examination is considered the most important process in the diagnosis of TMD, imaging may serve as a valuable adjunct in selected cases. Depending on the type of TMD, many treatment modalities have been proposed, ranging from conservative options to open surgical procedures. In this review, the authors discuss the present thinking in the etiology and classification of TMD, followed by the diagnostic approach and the current trend and controversies in management.

Insulin resistance is a prominent pathophysiologic syndrome in a plethora of metabolic disorders including obesity, prediabetes, type 2 Diabetes Mellitus (Ten et al., 2007), impaired glucose tolerance, dyslipidemia, polycystic ovary syndrome and hypercoagulability (Smith & LeRoith, 2004). It is strongly associated with obstructive sleep apnea, hypoventilation syndrome, pancreatitis, nonalcoholic fatty liver disease, steatohepatitis, cirrhosis, gall bladder disease, multiple cancers (breasts, uterus, cervix prostate, kidney, colon, esophagus, pancreas and liver), stroke, cataracts, coronary heart disease, and hypertension. It is also associated with causation of abnormal menses, infertility, polycystic ovary syndrome, osteoarthritis, phlebitis and other venous diseases. Insulin resistance is thought to be caused by intrinsic and extrinsic factors that contribute to its development. Once present, insulin resistance affects the metabolism, behavior, physical appearance and has lasting effects. This paper will review the latest evidence in development of insulin resistance, its pathogenesis and manifestation and its relation to other conditions. The final aim is to raise awareness of its role on diet, metabolic, genetics and microbiome.

Modern research achievements support health-promoting effects of natural products and diets rich in polyphenols. Pomegranate (PG) (Punica granatum L.) contain a considerable number of bioactive compounds that exert a broad spectrum of beneficial biological activities, including antimicrobial, antidiabetic, antiobesity, and atheroprotective properties. In this view, the reviewed literature shows that PG intake might reduce insulin resistance, cytokine levels, redox gene expression, blood pressure elevation, vascular injuries and lipoprotein oxidative modifications. Lipid parameters corrective capabilities of PG-ellagitannins are also sufficiently reported to be significantly effective in reducing hyperlipidemia (TC, LDL-C, VLDL-C, and TAGs), plasma HDL-C concentrations, TC/HDL-C and LDL-C/HDL-C ratio. The health benevolent effects of pomegranate consumption appear to be produced through the amelioration of adipose tissue endocrine function, fatty acid utilization, GLUT receptor expression, paraoxonase activity enhancement, PPAR and NFκB modulation. Although the results from animal experiments are encouraging, human findings published in this field are inconsistent and still limited in many points of view. The present review discusses and provides a critical analysis of PG's bioeffects on metabolic syndrome components, type-2 diabetes, obesity, and dyslipidemia, as well as on some cardiovascular-related diseases. A brief overview of the pharmacokinetic properties, safety, and bioavailability of PG-ellagitannins is also included.

Background: The aim of the study is to present the process of monitoring the changes in the effi-ciency of equilibrium reactions in the children with postural disorders, in the course of the thera-peutic process. Methods: The shape of spine and the efficiency of equilibrium reactions in standing posture and during gait were assessed in all the subjects. The subjects were put in 2 groups: with the shape of spine disorder and without one. The recommended set of therapeutic activities in home conditions lasted about 20 minutes and was performed by the child with parent’s supervision. The therapeutic program was based on elements of the PNF and Vojta methods. The following parameters were measured: maximum movement of the center of presure (CoP) in the frontal plane during gate, maximum movement of the CoP in the sagittal plane, movement of the CoP in the frontal plane in static conditions, movement of the CoP in the sagittal plane in static conditions. Results: Six statistically significant differences were recorded, all of them were related to measurement I. The Friedman test result was statistically significant for all the indexes. Post-hoc analyzes were performed using the Dunn-Bonferroni test. Conclusions: 1. The children with shape of spine disorders are featured by lower efficiency of equivalent reactions in relation to the children without disorders. 2. The therapy with the application of neurophysiological methods in the treatment of shape of spine disorders improves equilibrium reactions in these patients. 3. Long-lasting and thorough observations of the therapeutic process in the children with shape of spine disorders should include the monitoring of the efficiency of equilibrium reactions

Adaptive hyperactivity, characterized by increased activity levels and novelty-seeking traits without mood disorders, is prevalent among older adults in Sardinia's "blue zone," an area with high longevity. This study aims to evaluate the adaptive nature of hyperac-tivity concerning quality of life, social rhythms, and mood symptoms in individuals from this region, particularly among older adults over 80. Methods: This observational cross-sectional study included adults and older adults over 80 years from Sardinia's blue zone, recruited from the dermatology clinic at the University Hospital of Cagliari. Partici-pants underwent psychiatric interviews and completed the Mood Disorder Questionnaire (MDQ), Patient Health Questionnaire (PHQ-9), SF-12, and Brief Social Rhythm Scale (BSRS). Data were compared with national and regional normative data. Results: Older adults in the blue zone demonstrated higher MDQ positivity (22.58%) compared to na-tional averages (0.87%), without corresponding increases in dysregulated rhythms, de-pressive symptoms, or reduced quality of life. Younger elders (65-79 years) showed in-creased rhythm dysregulation (BSRS score: 20.64±7.02) compared to adults (17.40±6.09, p=0.040), but this trend was not observed in older elders (80+ years). No significant differ-ences were found in CH3SH and (CH3)2S levels between groups. Conclusions: Hyperactiv-ity observed in older adults from Sardinia's blue zone appears adaptive, not linked to so-cial rhythm dysregulation, depressive symptoms, or diminished quality of life, suggesting resilience factors that may contribute to longevity. These findings support the potential classification of such hyperactivity as beneficial rather than pathological, warranting fur-ther research into biomarkers and psychoeducational interventions to prevent the onset of bipolar disorders in predisposed individuals.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

Movement disorders encompass a diverse group of neurological conditions characterized by abnormal voluntary or involuntary movements. These disorders can be classified broadly into hyperkinetic and hypokinetic disorders. Excessive, involuntary movements, including tremors, dystonia, chorea, and myoclonus characterize hyperkinetic disorders. Tremors are rhythmic, involuntary movements occurring at rest or during movement. Dystonia involves sustained muscle contractions, leading to twisting and repetitive movements or abnormal postures. Chorea manifests as brief, irregular, involuntary movements that flow from one body part to another. Myoclonus consists of sudden, brief muscle contractions, either spontaneous or in response to a stimulus. Hypokinetic disorders are characterized by a lack of movement or difficulty initiating movement, as seen in Parkinson's disease and Parkinsonism. Parkinson's disease is a progressive neurological disorder that primarily affects movement, causing tremors, stiffness, and difficulty with balance and coordination. Parkinsonism refers to a group of disorders with similar symptoms to Parkinson's disease but with different underlying causes. Diagnosing movement disorders involves a thorough clinical evaluation, including a detailed medical history and physical examination. Neuroimaging studies such as MRI, CT scans, and functional imaging techniques may be used to assess brain structure and function. Additionally, laboratory tests, including genetic testing and biochemical markers, can help diagnose certain movement disorders.

Accumulating psychedelic research has demonstrated potential for improving mental health and wellbeing, yet studies in the context of eating disorders (EDs) are limited. This study explores the subjective effects of psychedelic experiences to gain insight into the benefits and risks for people with EDs. Semi-structured interviews were conducted with 11 eligible adults. A purposive sample of eight adults aged 25-54 (M =  36.9) with chronic EDs, diagnosed (N = 7) and undiagnosed (N = 1) were thematically analysed. Reports of cessation or reduction of ED symptoms were unanimous, with two participants reporting recovery, attributed to psychedelic use. Thematic analysis resulted in two superordinate themes, each comprising three subordinate themes. The first superordinate theme, ‘Exploring’ via the ‘gateway to healing’, illustrates mental, emotional, and transcendental elements of psychedelic experiences. The second superordinate theme, ‘Transformation’ and being ‘able to do the work’, illustrates cognitive and behavioural outcomes, with retrospective safety perceptions. This research presents an account representative of the ED population for the therapeutic potential for psychedelic experiences to reduce symptoms and improve wellbeing. Findings provide evidence of therapeutic feasibility to support larger scale research, emphasising the therapeutic use of psychedelics as a potentially promising avenue for chronic and treatment resistant EDs.

Autism spectrum disorder (ASD) is a common condition with lifelong implications. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes (P=0.0002), validating that most are indeed disease related. Sequence reanalysis increased diagnostic yield from 28% to 68%, mostly by inclusion of de novo PDVs in genes not yet reported as ASD associated. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate high yield of trio-WGS for revealing molecular diagnoses in ASD that is greatly enhanced by re-analyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.