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.

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<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<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.

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.

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.

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.

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.

Glycosylation, the most significant modification of proteins, plays an essential role in cellular processes. Congenital disorders of glycosylation (CDG) are multisystemic diseases resulting from mutations affecting glycosylation steps. Diagnosis of CDG relies on biochemical assays, such as isoelectric focusing. Despite its significance, CDG cases remain unreported in Cuba due to the lack of implemented diagnostic methods. This study aimed to evaluate transferrin glycoforms for diagnosing congenital N-glycosylation defects. We conducted a cross-sectional descriptive study using serum samples from 17 patients stored at the National Center for Medical Genetics of Cuba for suspected CDG. Results revealed abnormal glycosylation patterns in 7 patients, suggesting congenital N-glycosylation defects. We conclude that the implementation of transferrin glycoform analysis could pioneer a preliminary diagnosis of CDG in Cuba.

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.

Brain imaging studies have recently provided some evidence in favour of covert cognitive processes ongoing in patients with disorders of consciousness (DoC) (e.g., minimally consciousness states, vegetative state/unresponsive wakefulness syndrome) engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer’s motor system maps others’ actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, provided that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. Results indicate that some form of motor resonance is spared in a subset of patients with DoC with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials following the stimulation of the median nerve at the wrist (i.e., the temporal marker signalling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters.

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.

Improper sitting positions are known as the primary reason for back pain and the emergence of musculoskeletal disorders (MSD) among individuals who spend prolonged time working with computer screens, keyboards, and mice. At the same time, it is well understood that automated technological tools can play an important role in the process of unhealthy habit alteration, so plenty of research efforts are focused on research and technology development (RTD) activities that aim to provide support to the prevention of back pain or the development of MSD. Here, we report on creating a new resource in support of RTD activities aiming at the automated detection of improper sitting positions. It consists of multimodal multisensory recordings of 100 persons made with a video recorder, camera, and wrist-attached sensors that capture physiological signals (PPG, EDA, Skin temperature), as well as motion sensors (three-axis accelerometer). Our multimodal multisensory dataset (MMD-MSD) opens new opportunities for modeling the body stance (sitting posture and movements), physiological state (stress level, attention, emotional arousal, valence), and performance (success rate on the Stroop test) of people working with a computer. Finally, we demonstrate two use cases: improper neck posture detection from pictures and cognitive load detection from physiological signals.

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 (< 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.

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.

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.

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.

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.

The term `motor control´ encompasses a wide range of mechanisms thought to be implicated in the organization of movements. Their study, like that of any other scientific field, must use specific notions to get to grips with them. This review is therefore organized along a series of notions that are frequently used in motor control, and we will discuss them with particular emphasis on neurological conditions, which may disrupt normal motor functioning. We will start with a short description of the roles of space and time, in which movements take place. Subsequently we will deal with kinematics and kinetics (dynamics) of movements. Then, we will list the inputs to motoneurons (MNs), which, in different forms, convey signals from the central nervous system (CNS) to skeletal muscles and muscle spindles, including central pattern generators (CPGs), sensory inputs and supraspinal descending fiber systems. Some helpers in movement organization will be introduced, such as internal models and neuronal network models. A relatively brief section on sensory-motor learning will follow because learning abilities are required to endow the sensory-motor system with flexibility and adaptability. The major emphasis is placed on neurological processes, which result from genetic modifications, autoimmune diseases, neurodegenerative diseases, infections in the nervous system as well as vascular and traumatic lesions. These neurological diseases lead to a variety of impairments and symptoms, particularly movement derangements including cerebellar ataxia, spasticity, and (other) movement disorders such as Parkinson’s syndromes. The conclusion is that there is no unique top controller that controls ´motor control`.

Lower limb exoskeletons have the potential to reduce the prevalence of work-related musculoskeletal disorders; however, they often lack user-oriented control strategies. Human-in-the-loop (HITL) controls can adapt an exoskeleton’s assistance in real-time, to optimize the user-exoskeleton interaction. This study presents a HITL control for a knee exoskeleton to minimize the users’ physical effort, a parameter innovatively evaluated by their interaction torque with the exoskeleton (a muscular effort indicator) and metabolic cost. This work innovates by estimating the user’s metabolic cost within the HITL control through a machine-learning model. The regression model was able to estimate the metabolic cost, in real-time, with a root-mean-squared error of 0.66 W/kg and a mean absolute percentage error of 26%, making faster (10s) and less noisy estimations than a respirometer (K5, Cosmed) device. The HITL reduced the user’s metabolic cost and interaction torque by 7.3% and 32.3%, respectively, when compared to a zero-torque control. The developed HITL control surpassed both a non-exoskeleton and a zero-torque condition regarding the user’s physical effort, even for a simple task such as slow walking. Furthermore, the user-specific control enabled a lower metabolic cost than the non-user-specific assistance. This proof-of-concept demonstrated the potential for HITL controls in assisted working.

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.

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.

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.

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.

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.

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.

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.

Introduction: Postpartum hypertension (PPHT) is hypertension that persists or develops directly after pregnancy. PPHT affects 10% of pregnancies and is the most common cause for re-hospitalization after giving birth. In general, PPHT stems from hypertensive disorders of pregnancy (HDP). The aim of the current interim report of the Basel PPHT registry is to describe the cohort, and to determine feasibility and acceptance of a home-based telemonitoring management strategy (HBTMS) in women with PPHT. Methods: Enrollment in the cohort began in June 2020 during the SARS-CoV-2 pandemic at the University Hospital Basel. Women in the maternity ward were screened for preexisting hypertension, HDP, and de novo postpartum hypertension and after consenting, were enrolled. In this pragmatic non-randomized prospective trial, women in the PPHT cohort could choose, between a HBTMS or usual care which consisted of in-hospital appointments at the hypertension clinic. HBTMS was defined as a smartphone application or a programmed spreadsheet to report blood pressure followed by telephone consultations. Standard of care was hospital-based visits as clinically needed after discharge. All participants were assessed three months after delivery with a standardized clinical visit including a 24-hour blood pressure measurement, blood, biomarker, and urine analysis. Results: 311 participants were enrolled from 06/20-08/23. Mean age was 34±5.3 years. Regarding pregnancy-related medical history: 10 % had preexisting hypertension, 27.3 % gestational hypertension, 53% preeclampsia (PE), 0.3% eclampsia, 6% HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) and 18.3% had de novo PPHT. More than one diagnosis was possible. Family history of cardiovascular disease was seen in 49.5%, 7.5% had a family history of PE. 23.3% were determined as high risk for PE during pregnancy. The most common type of delivery was C-Section (68.5%), mean hospital stay was 6.3 days (±3.9) and IUGR (intrauterine growth restriction) was seen in 21% of the newborns. 99% of participants chose a home-based management strategy. Conclusion: This first description of the Basel PPHT Cohort showed that a HBTMS is well accepted. This is particularly relevant in the direct postpartum period and even more pertinent when the exposure of hospital visits should be avoided when possible.

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.

Background: Hashimoto’s thyroiditis (HT) is an autoimmune disease that progressively leads to thyroid gland destruction and hypothyroidism. Patients produce antibodies against two thyroid-specific antigens: thyroglobulin and thyroid peroxidase. As a result of the abnormal amount of thyroid hormone produced and its autoimmune etiology, patients with HT display a higher frequency of either autoimmune or non-autoimmune dermatological disorders. On ultrasound examination, HT can be detected by observing an enlarged thyroid gland with hypoechoic parenchymal regions or by observing a small gland indicating atrophy and diffusely heterogeneous parenchyma. Changes in the parenchymal vascularity can be observed as decreased or increased levels of vascularization. Objective: This study aimed to analyze the role of clinical data and ultrasound evaluation of patients with HT in suggesting an association with dermatological disorders. Patients and methods: Complete dermatological and endocrinological assessments as well as ultrasonography of the thyroid and lymphnodes were performed in HT patients. Results: The data obtained showed that a family history of thyroid disease, increased diameter of the inferior thyroid artery, and the presence of cervical lymphadenopathy were more frequent in the group of patients with dermatological diseases. Taken together, our results suggest the usefulness of ultrasound in determining a possible association between HT and dermatological disorders.

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.

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.

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.

The exploration of three-dimensional (3D) DNA structures marks a pivotal shift in genomics, offering unprecedented insights into the intricacies of cellular regulation, disease genesis, and the potential for novel diagnostic and therapeutic strategies. This study delves into the dynamic nature of 3D genome organization, investigating how these structures influence cellular functions in response to environmental changes and over time. Through a combination of real-time imaging and advanced computational models, we aim to unravel the complex interplay between 3D DNA structures, non-coding RNAs, and chromatin organization, and their collective impact on gene expression and cellular differentiation. A significant focus is placed on understanding the role of 3D DNA structures in the development and progression of genetic disorders. By employing comprehensive genomic and epigenomic profiling, this research seeks to identify structural aberrations linked to diseases, paving the way for the development of targeted diagnostics and therapies. Additionally, the study explores the potential of genome editing technologies, such as CRISPR-Cas systems, in correcting these structural abnormalities, while also addressing the ethical, legal, and social implications (ELSI) of such interventions. Integrating data from various genomic analyses, we propose the development of advanced computational models to predict the effects of 3D DNA structures on gene expression and cellular function. This integrative approach not only promises to enhance our understanding of genomic regulation but also sets the stage for groundbreaking advances in genomics-based diagnostics and therapeutics. The findings of this study have the potential to revolutionize our approach to treating genetic disorders, offering a new frontier in personalized medicine.

The COVID-19-medical emergency has ended worldwide, yet there is still a need to evaluate the psychological impact of these years of unprecedented changes on students’ life. Methods: This study aims to assess and compare COVID-19-related stressors (Relationships-and-Academic-Life; Isolation; Fear-of-Contagion) and psychophysical symptoms reported by university students in April-2020, April 2021, and April 2022. The predictive role of COVID-19-related stressors on psychophysical symptoms within each time was also tested. Data were collected among 637 university students in April-2020 (n = 197), April-2021 (n = 200), April-2022 (n = 240). Results: In April-2022, perceived Isolation and Fear-of-Contagion decreased from the peak registered in April-2021, but stress related to Relationships-and-Academic-Life remained noteworthy high. A sharp and ongoing increase in psychophysical symptoms was found, with more than 50% of students reporting clinical levels of Sleep-Disorders, Depression, Psychoticism, and Interpersonal-Sensitivity. In April-2022, students still perceiving stress related to Relationships-and-Academic-Life and Isolation were at risk for Anxiety, Somatization, and Sleep-Disorders, while those still perceiving stress related to Fear-of-Contagion were also at risk for Depression, Obsessive-Compulsive, and Psychoticism. Conclusion: Findings emphasized the long-lasting detrimental effects of the COVID-19-related stress. Interventions must pinpoint the complex post-pandemic adjustment process and their effects on university students' psychophysical health.

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.

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.

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.

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.

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 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.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

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.

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

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

Background: Granular cell tumor is a benign neurogenic tumor of the subcutaneous and submucosal area. The tongue is the most affected site of the oral cavity. The clinical presentation is non-specific and manifests as a submucosal nodule or mass. Because of its non-specific presentation, a definitive diagnosis an only be established after a histopathological examination and an immunohistochemical study to search for a neurogenic origin. Methods: We report the case of a 48-year-old man who was referred for the management of a nodular lesion on the tip of his tongue that had increased in size over the previous three months. Results: A complete surgical excision was performed for the histopathological exam, and an immunohistochemical study confirmed a strong expression of S100 and CD68. A diagnosis of granular cell tumor was confirmed. There was no recurrence et three years follow-up. Conclusion: the GCT is a rare tumor of nervous origin of the oral mucosa, it is non-specific in expression, with a good prognosis after complete excision. the histological and immunohistochemical diagnosis of the lesion is essential for the diagnosis.

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.

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.

The pathophysiology of Nonketotic Hyperglycinemia (NKH), a rare neuro-metabolic disorder associated with severe brain malformations and life-threatening neurological manifestations, remains incompletely understood. Therefore, a valid human neuronal model is essential. We aimed to investigate the impact of GLDC gene variants, which cause NKH, on cellular fitness during the differentiation process of human induced pluripotent stem cells (iPSCs) into iPSC-derived astrocytes and to identify sustainable mechanisms capable of overcoming GLDC deficiency. We developed the GLDC27-FiPS4F-1 line and performed metabolomic, mRNA abundance and protein analyses. The study showed that although GLDC27-FiPS4F-1 maintained the parental genetic profile, it underwent a metabolic switch to an altered serine-glycine-one-carbon metabolism with a coordinated cell growth and cell cycle proliferation response. We then differentiated the iPSCs into neural progenitor cells (NPCs) and astrocyte-lineage cells. Analysis showed that GLDC-deficient NPCs had shifted towards a more heterogeneous astrocyte lineage with increased expression of the radial glial markers GFAP and GLAST and the neuronal markers MAP2 and NeuN. In addition, we detected changes in other genes related to serine and glycine metabolism and transport, all consistent with the need to maintain glycine at physiological levels. These findings improve our understanding of the pathology and offer new perspectives for therapeutic options.

Infertility is affecting around 20 % of couples in the age of procreation but however in some societies as many as one-third of all couples are unable to conceive. Different factors are contributing to male fertility declining such us endocrine disruptors environmental and professional exposures, oxidative stress and life style changes with risks of de novo epigenetics dysregulation. Since the fantastic development of new technologies of Omes and Omics , the contribution of inherited or de novo genomes and epigenome disorders contributions in male infertility are more elucidated and relevant. More than somatic genome investigation of infertile men (from chromosome to single or multiple gene point mutations) many others techniques become available in molecular andrology laboratory to investigate the genome and epigenome integrity, the maturation and the competency of the spermatozoa and its physiological environment. All those new methods of assessment are demonstrating the role of genetics and epigenetics disorders contribution on reproductive pathology and are helping the professional of assisted reproductive technology to propose different management strategy of male infertility to improve the clinical outcomes and minimize the risk of genetics or metabolic disorders at birth.

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother’s obesity as potentially environmental factors of ASD. The purpose of the present analysis is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) has the potential to alleviate alcoholic liver injury may play essential roles in treating for alcohol-exposed liver disease, however, the hepatoprotective effects and mechanisms remain unclear. In this study, the hepatoprotective effects of HDPs and its potential mechanisms were investigated in alcohol-exposed mice by liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. By applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria while significant increases in Firmicutes at the phylum level, and increased Lactobacillus abundance while decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid metabolism and glycerophospholipid metabolism and identified two important metabolites C00157 and C04230 involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs has a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

The orexin/hypocretin neuropeptide family has emerged as a focal point of neuroscientific research following the discovery that this family plays a crucial role in a variety of physiological and behavioral processes. These neuropeptides serve as powerful neuromodulators, intricately shaping autonomic, endocrine, and behavioral responses across species. Notably, they serve as master regulators of vigilance and stress responses; however, their role in complex processes such as food intake, metabolism, and thermoregulation warrant further investigation. This narrative review provides a journey through the evolution of our understanding of the orexin system, from its initial discovery to the promising progress made in developing orexin derivatives. It goes beyond conventional boundaries, striving to synthesize the multifaceted activities of orexins. Special emphasis is placed on domains such as stress response, fear, anxiety, and learning, in which the authors contributed to the literature with original publications. This article demonstrates the orchestrating role of the orexins in several intricate and integrative physiological processes. It also overviews the advancement of orexin pharmacology, which has already yielded some promising successes, particularly in the treatment of sleep disorders. This interdisciplinary approach to studying neuropeptides unveils their significance as vital connectors between transient functional changes and lasting structural adaptations. Ultimately, it advances our understanding of the intricate physiological and behavioral contributions of the orexin/hypocretin neuropeptide family.

Background: Dual disorders (DD) involve the coexistence of substance use disorder (SUD) with another mental illness, often from psychotic and affective categories. This study explores the ef-fectiveness of brexpiprazole, a third-generation antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder (DSM-V) and comorbid AUD/SUD (DSM-V). Methods: Eighteen enrolled patients underwent psychometric assessments at baseline and one month into brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (PANSS total score, p=0.004), improved CGI total score (p=0.042), and decreased MOAS total score (p=0.012). Quality of life improved in SF-36 subscales (p<0.05). Substance craving reduction, though observed, did not reach statistical significance. Conclusions: This study provides initial evidence supporting brexpiprazole's efficacy and safety with positive effects on psychopathology and quality of life, emphasizing the need for tailored, comprehensive treatment strategies in this complex patient population.

Neurocutaneous disorders, also known as phakomatoses, are congenital and acquired syndromes resulting in simultaneous neurologic and cutaneous involvement. In several of these conditions, the genetic phenomenon is understood, providing a pivotal role in the development of therapeutic options. This review encompasses the discussion of the genetic and clinical involvement of neurocutaneous disorders and examines clinical management and treatment options. With the current advances in genetics, the role of precision medicine and targeted therapy plays a substantial role in addressing management of these conditions. The interconnectedness between therapeutic options highlights the importance of precision medicine in treating each disorder’s unique molecular pathway. This review provides an extensive synthesis of ongoing and current therapeutics in the management of such clinically unique and challenging conditions.

Opioid use disorder has increased in the world in recent years and Iran ranks first in terms of opium smoking in the world. In fact, opium smoking by traditional methods, in addition to dependence on morphine, is a behavioral addiction in Iran. The body position during opium smoking is usually non-standard and non-ergonomic. Over time, changes in muscle tissue, tendons and ligaments, and the connective tissue go from elasticity to neuromuscular plasticity. This study aims to compare sway back posture and musculoskeletal problems between opium smokers and non-drug users. In this comparative and cross-sectional study, 80 opium smokers were compared with 74 non-drug users in terms of sway angle (sway back posture), and musculoskeletal complaints (NORDIC questionnaire) and the association of possible risk factors was investigated. Data were analyzed by Kolmogorov-Smirnov, Correlation Coefficient and paired-t tests using SPSS version 23. There were significant differences between two groups in terms of sway back posture (P=0.007), and neck (<0.001), upper back (<0.001) and lower back (0.006) musculoskeletal complaints. Homelessness, the lifetime duration of opium smoking (in months), and the duration of daily opium smoking (in minutes) had significant correlation with sway back posture and musculoskeletal complaints. Homelessness was the strongest predictor and had strongest correlation. Overall, an increase in the duration of sitting in non-ergonomic positions could lead to increase in sway angle and sway back posture and increase in musculoskeletal complaints of neck, upper back and lower back due to the non-neutral posture of opium smoking. It seems that plasticity and structural and functional adaptations of the posture occurs due to opium smoking and further studies are recommended.

Emotional experiences are a part of our lives. The maladaptive functioning of an individual's emotional field can lead to emotional disturbances of various kinds, such as anxiety and depression. Currently, there is an increasing prevalence of emotional disorders that cause great human suffering and high socio-economic costs. Emotional processing has a biological basis. The major neuroscientific theories of emotion are based on biological functioning, and all of them take into account the anatomy and function of the tenth cranial nerve: the vagus nerve. The vagus nerve connects the subdiaphragmatic and supradiaphragmatic areas and modulates emotional processing as the basis of interoceptive functioning. Auricular vagus nerve stimulation is a new and innovative neuromodulation technique based on the function of the vagus nerve. Several interventions have shown that this new neurostimulation technique is a very promising resource for treating emotional disorders. In this paper, we summarise three neuroscientific theories of emotion, explain what transauricular vagus nerve stimulation is, and present arguments for its use and continued research.

The intricate functionality of the vertebrate retina relies on the interplay between neurotransmitter activity and calcium dynamics, offering important insights into de-velopmental processes, physiological functioning, and disease progression. Neuro-transmitters orchestrate cellular processes to shape the behavior of the retina under diverse circumstances. Despite research to elucidate the roles of individual neuro-transmitters in the visual system, there remains a gap in our understanding of the holistic integration of their interplay with calcium dynamics in the broader context of neuronal development, health, and disease. To address this gap, the present review explores the mechanisms used by the neurotransmitters glutamate, GABA, glycine, dopamine, and acetylcholine and their interplay with calcium dynamics. This con-ceptual outline is intended to inform and guide future research, underpinning novel therapeutic avenues for retinal-associated disorders.

Prolactin (PRL) is a pleiotropic hormone released from lactotrophic cells of the anterior pituitary gland that also originates from extrapituitary sources and plays an important role in regulating lactation in mammals, as well as other actions. Acting in an endocrine and paracrine/autocrine manner, PRL regulates the hypothalamic-pituitary-ovarian axis, thus influencing the maturation of ovarian follicles and ovulation. This review provides a detailed discussion of the current knowledge on the role of PRL in the context of ovulation and ovulatory disorders, particularly with regard to hyperprolactinemia, which is one of the most common causes of infertility in women. Much attention has been given to the PRL structure and the PRL receptor (PRLR), as well as the diverse functions of PRLR signaling under normal and pathological conditions. The hormonal regulation of the menstrual cycle in connection with folliculogenesis and ovulation, as well as the current classifications of ovulation disorders, are also described. Finally, the state of knowledge regarding the importance of TIDA (tuberoinfundibular dopamine), KNDγ (kisspeptin/neurokinin B/dynorphin) and GnRH (gonadotropin-releasing hormone) neurons in PRL- and kisspeptin (KP)-dependent regulation of the hypothalamic-pituitary-gonadal (HPG) axis in women is reviewed. Based on this review, a rationale for influencing PRL signaling pathways in therapeutic activities accompanying ovulation disorders is presented.

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 74% of the world's population still uses plant-based medicines, indicating the ongoing significance of phytochemicals for human health. The study emphasizes the growing body of research examining the role of polyphenols in uncovering their anti-adipogenic and anti-obesity properties. Functions of polyphenols including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids are distinct due to changes in chemical diversity, and structural characteristics. This review methodically investigates the mechanism of how naturally occurring polyphenols mediate obesity and metabolic function. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role in part in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function. The effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required for prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes the holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.

Introduction: Obstructive sleep apnea (OSA) is not only common in the general population but even more so in patients with tumors of the head and neck region. Untreated, it leads to reduced quality of life, increased daytime sleepiness, and other comorbidities. The aim of this study was to determine the difference in the occurrence of OSA in the patient population with head and neck tumors compared to the general population as represented by the Trend cohort of the Study of Health in Pomerania (SHIP) , and to assess the influence of tumor treatment. Methods: Between July 2018 and December 2021, preoperative polysomnography was conducted in 47 patients with histologically confirmed squamous cell carcinoma in the oropharynx, hypo-pharynx, or larynx. A follow-up polysomnography was performed in 23 patients 2-11 months af-ter completing treatment. The collected data was correlated with tumor treatment and tumor size. Results: Of the included patients, 43 were male and four were female. Age ranged from 54 to 90 years. The pretherapeutic measurement found no significant difference in the prevalence of a pathologically elevated apnea-hypopnea index (AHI) in our patients compared to the SHIP-Trend cohort. In the follow-up measurement after treatment completion, a significant deterioration in AHI was observed. Initially, 70 % of patients had an AHI > 5, after therapy this increased to 87 %. The effect was particularly pronounced in the group of patients with advanced tumor stages who had received primary chemoradiation. Conclusion: OSA is a relevant condition in patients with head and neck cancer. Tumor treatment can lead to an increased occurrence of sleep-related breathing disorders, especially in patients with advanced tumor stages undergoing primary chemoradiation. Additional studies are neces-sary to better understand the exact mechanism involved.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder but kidneys are not the only organs involved in this systemic disorder. Individuals with the condition may display additional manifestations beyond the renal system, involving liver, pancreas and brain in the con-text of cystic manifestations, while vascular system, gastrointestinal tract, bones, and cardiac valves in the context of non-cystic manifestations. Despite kidney involvement remain the main feature of the disease, thanks to new generation therapies, early diagnosis and better management of kidney related problems, a new wave of complications must be faced from clinicians who treated polycystic patients. Involvement of the liver represents the most prevalent extrarenal manifestation and grows importance in symptom burden and quality of life. Vascular abnormalities are a key factor for patients’ life expectancy and there’s still de-bate whether to screen or not to screen all patients. Arterial hypertension is often the earliest onset among polycystic patients leading to frequent cardiovascular complications. Although cardiac valvular abnormali-ties is a frequent complication, it rarely leads to relevant problems in the clinical history of polycystic pa-tients. One of the new relevant aspects concern bone disorders, that can exert a considerable influence on the clinical course of these patients. This review aims to provide the “state of art” among extrarenal mani-festation of ADPKD.

Sleep is of vital necessity for health, it has a restorative and protective function for children and adolescents with chronic conditions and their families. The purpose was to identify the scientific production on sleep patterns in children and adolescents with chronic conditions and their families. This integrative review was developed in March and June 2022, of the MEDLINE, Web of Science, CINAHL and PSYCInfo. The articles included were original papers published be-tween January 2007 and mid-2022. Excluded were review studies that did not evaluate sleep and whose participants did not have chronic conditions or were not children, adolescents and/or their families. The searches returned 814 abstracts. After exclusions, 47 studies were selected to be read in full; of these, 29 were selected and were grouped empirically into four categories: major alterations in sleep patterns of children and adolescents with chronic conditions; the relationship between sleep disorders and symptoms in children and adolescents with chronic conditions; impaired sleep patterns of families of children and adolescents with chronic conditions; sleep alterations and their relationship with other problems in families of children and adolescents with chronic conditions. All studies showed sleep pattern impairment in children and adolescents with chronic conditions and their families.

Background: Opinions on the impact of cancer on patients with haemophilia literature are contradicting. There is a lack of data on the clinical presentation and management of cancer in patients with haemophilia (PWH). Methods: Papers were found following a comprehensive search in PubMed, Google Scholar, and Scopus using the terms “cancer” and “haemophilia” without time limits and using the English language as a filter. The references of all retrieved original articles and reviews were assessed for additional relevant articles. Results: Overall, 116 papers were collected. Managing cancer in patients with congenital bleeding disorders, such as haemophilia A and B, requires careful evaluation of bleeding risk and the effect of antitumor treatments on blood coagulation. Generally, patients with haemophilia do not have an increased risk of developing cancer compared to the general population; increased risk is found in the presence of HIV or hepatitis infection. However, if a patient with haemophilia develops cancer, the treatment must be managed to minimise the risk of bleeding. Bleeding and thrombotic complications are important causes of morbidity and mortality in critically ill patients with cancer; replacement therapy with factor VIII or IX or others should be maintained during antitumor treatment. Conclusion: Overall, managing cancer in patients with haemophilia requires careful evaluation and individualised planning involving a multidisciplinary team of physicians experienced in haematology, oncology, and surgery.

Background: Myocarditis is commonly diagnosed in the intensive care cardiology unit (ICCU). No current recommendation nor guideline aids aetiological assessment. Methods: From September 2021 to October 2023, 84 patients with acute myocarditis underwent thorough and systematic serum and blood cell panel evaluations to determine the most common causes of the myocarditis. Results: Of the 84 patients (median age 34 years, range 22–41 years, 79% male), 16 presented with complicated myocarditis. The systematic aetiological assessment revealed that 36% of patients were positive for lupus anticoagulant, 12% for antinuclear antibodies, 8% for anti-heart antibodies, and 12% for anti-striated muscle antibodies. Viral serology did not yield any significant results. After the aetiological assessment, one patient was diagnosed with an autoimmune inflammatory disorder (Still’s disease). T-cell subset analyses indicated that myocarditis severity tended to increase with the T-cell lymphopenia status. Conclusions: A comprehensive, systematic aetiological assessment was of limited value in terms of predicting the clinical or therapeutic outcomes in myocarditis patients presenting to the ICCU.

Immune disorders, characterized by dysregulation at cellular and inflammatory levels, result from a complex interplay of genetics and environmental factors that lead to an abnormal immune response against autoantigens, triggering tissue damage. Recent research highlights reactive antibodies as key players in autoimmune diseases and graft rejection, but the complexity of their determination limits their use in clinic. Hence, we studied the specific binding profile of serological antibodies against a panel of cellular membranes in order to determine whether this antigenic panel could be used to diagnose specific immune disorders in humans. For this purpose, cell membrane microarrays of spleen, liver, and kidney tissues of monkey, rat, and human were developed, and human sera were analyzed, including healthy controls, patients with autoimmune disorders, and kidney transplant patients. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and Human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in the serum of patients as potential biomarkers of immune disorders.

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.

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.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe adverse event that was first observed during the global vaccination campaign against SARS-CoV-2 infection, specifically in those receiving adenoviral vector-based vaccines for Coronavirus disease 2019 (COVID-19). VITT develops 4 to 42 days post-vaccination and is characterized by the development of platelet-activating anti-platelet factor 4 (PF4) antibodies, leading to thrombocytopenia and thrombosis at unusual sites. The rise in awareness and subsequent prompt recognition of VITT was paramount in reducing mortality. Moreover, as vaccination campaigns around the world continue, a better understanding of VITT not only has important clinical implications but is also crucial for future vaccine development. In this review, we summarize the clinical features, pathophysiology, and incidence rates of VITT as well as highlight other anti-PF4 antibody-mediated disorders of growing clinical significance.

Recently, Mulroney,et.al., demonstrated that Pfizer’s ModRNA Covid vaccine, but not AstraZeneca Covid vaccine, produce aberrant foreign proteins in vivo due to reading frame shift in ribosomes. This phenomenon could elucidate the notable surge in autoimmune diseases following the administration of ModRNA vaccines compared to Influenza vaccines between 2020 and 2023, as found in the VAERS database. These findings bear significant implications for the future application of mRNA technology, emphasizing the necessity of modifying the design of the mRNA sequence to mitigate these defects. Remarkably, Mulroney and collaborators achieved a reduction in frame shift proteins by introducing additional edits to the mRNA sequences. This adjustment is pivotal for rectifying the flawed design of the ModRNA employed by Pfizer. In light of these findings, many advocate for the immediate recall and further investigation of these products. The notion of a "future mRNA-based therapy" should be postponed indefinitely.

This study investigated the prevalence of embryonic and connective tissue elements in the filum terminale (FT) of patients with tethered cord syndrome (TCS), examining both typical and pathological histology. FT specimens from 288 patients who underwent spinal cord detethering from 2013-2021 were analyzed. Histopathological examination involved routine hematoxylin and eosin staining and specific immunohistochemistry when needed. Patient details were extracted from electronic medical records. The study found that 97.6% of FT specimens had peripheral nerves, and 70.8% had regular ependymal cell linings. Other findings included ependymal cysts and canals, ganglion cells, neuropil, and prominent vascular features. Notably, 41% showed fatty infiltration, and 7.6% had dystrophic calcification. Inflammatory infiltrates, an underreported finding, were observed in 3.8% of the specimens. The research highlights peripheral nerves and ganglion cells as natural components of the FT, with ependymal cell overgrowth and other tissues potentially linked to TCS. Enlarged vessels may suggest venous congestion due to altered FT mechanics. The presence of lymphocytic infiltrations and calcifications provides new insights into structural changes and mechanical stress in the FT, contributing to our understanding of TCS pathology.

Background: Caring for individuals with mental disorders poses significant challenges for caregivers, often leading to compromised quality of life and mental health issues such as stress, anxiety, and depression. This study aims to assess the extent of these challenges among caregivers in Greece, identifying which demographic factors influence their well-being. Method: A total of 157 caregivers were surveyed using the SF-12 Health Survey for quality of life assessment and the DASS-21 questionnaire for evaluating stress, anxiety, and depression symptoms. T-tests, Kruskal-Wallis tests, Pearson correlation coefficients, and regression analyses were applied to understand the associations between demographics, quality of life, and mental health outcomes. Results: The study found that caregivers, especially women and younger individuals, faced high levels of mental health challenges. Marital status, educational level, and employment status also significantly influenced caregivers' well-being. Depression was the most significant factor negatively correlating with the mental component of quality of life. The magnitude of burden experienced by caregivers highlighted the urgency for targeted social and financial support, as well as strategic treatment programs that consider caregiver well-being. Conclusions: Caregivers of individuals with mental disorders endure significant stress, anxiety, and depression, influencing their quality of life. Demographic factors such as age, gender, marital status, education, and employment status have notable impacts. Findings emphasize the need for society-wide recognition of caregivers' roles and the creation of comprehensive support and intervention programs to alleviate their burden, particularly in the context of the COVID-19 pandemic.

We explore three cases of pediatric neurological diseases, viz. Arthrogryposis, congenital bilateral cataract and Autism by analyzing clinical exomes. As genetic variation attributing to pathogenesis is a significant bottleneck, we attempted to understand and validate them using Sanger validation. We further employ our CONVEX pipeline to infer pathogenic variants and discern the candidate genes for phenotype correlation.

Sleep disorder is a disease that can be categorized as both an emotional and physical problem. It imposes several difficulties and problems, such as distress during the day, sleep-wake disorders, anxiety, and several other problems. Hence, the main objective of this research is to utilize the strong capabilities of machine learning in the prediction of sleep disorders. In specific, this research aims to meet three main objectives. These objectives are to identify the best regression model, the best classification model, and the best learning strategy that highly suits sleep disorder datasets. Considering two related datasets and several evaluation metrics that are related to the tasks of regression and classification, the results revealed the superiority of the MultilayerPerceptron, SMOreg, and KStar regression models compared with the other twenty-three regression models. Also, IBK, RandomForest, and RandomizableFilteredClassifier showed superior performance compared with other classification models that belong to several learning strategies. Finally, the Function learning strategy showed the best predictive performance among the six considered strategies in both datasets and with respect to the most evaluation metrics.

Among hearing aid (HA) users, there is a considerable variability in word-recognition scores (WRS). This variability is most pronounced among individuals with moderately severe to severe hearing loss. The variability cannot be adequately explained by factors such as the pure-tone audiogram, audiogram type, or age. This prospective study was designed to investigate the relationship between tone decay (TD) and WRS in a group of HA users with corresponding pure-tone hearing loss. The study population included 22 patients with hearing loss between 50 and 80 dB HL. Aided WRS, unaided WRS and TD were assessed for both ears. TD was found to be frequency-dependent. TD and WRS were correlated, with up to R=–0.66. The TD test was revealed as a feasible method for explaining the variability in WRS among HA users with hearing loss below 80 dB. This may contribute to improved differential diagnostics. The TD test may thus offer a better understanding of the limitations of HA use in the context of cochlear implant candidacy assessment for HA users.

Tritordeum is an amphiploides species resulting from the hybridization between durum wheat (T. durum) and wild barley (H. chilense). This new cereal is considered a natural crop as it is obtained by traditional breeding techniques. Given its appreciable organoleptic characteristics, agronomic features, presence of interesting components, and good technological properties, tritordeum is of promising interest for the development of health-oriented foods. In this study, we evaluated two registered tritordeum cultivars, Bulel and Aucan. T. durum (Provenzal) was employed as the positive control. The extracted proteins were digested by gastric /pancreatic proteases and their biological effects on Caco-2 differentiated on transwell inserts were determined. Changes in cell viability, monolayer permeability, organization of F-actin microfilaments, and ER stress, triggered by protein-digested samples (DPs) were inspected. Our results showed that exposure to Provenzal-DPs promptly disrupted the tight junction barrier. Conversely, Aucan-DPs did not enhance monolayer permeability; whereas, Bulel-DPs exerted only slight effects. Provental-DPs-induced toxicity was also confirmed by changes in cell viability and by the deep reorganization of the enterocyte cytoskeleton. In contrast, Aucan-DPs and Bulel-DPs did not affect monolayer viability and cytoskeleton structure. Overall, our findings suggest that both tritordeum cultivars could be potential candidates for mitigating the toxicity of wheat flour.

Abstract: Background: The main aim of the study was to assess the intensity and frequency of cervical spine pain in young people with temporomandibular disorders (TMD). Methods: The pilot study was conducted from June to July 2023. Inclusion criteria were: age (18-30 years), cervical spine pain (for at least 1 month) and consent to participate in the study. The study was conducted based on a physiotherapeutic examination and an original questionnaire. The pain level was assessed using the Visual Analogue Scale (VAS). Among 95 people with cervical spine pain, 51 people (53.7%) constituted the control group (without a history of temporomandibular disorders), while 44 (46.3%) people constituted the study group. Results: The mean age of people participating in the study was 22.2±2.2 years in the study group and 22.5±3.1 years in the control group. The largest group were people aged 21-25 (n=51 people, 53.7%). Patients from the study group more often experienced pain in the stomatognathic system during palpation (both in the muscle, joint and musculoskeletal groups) and had reduced mobility of the temporomandibular joints in every movement (p<0.001). People from the study group were characterized by also less mobility of the cervical spine (p<0.05), apart from extension movement (p>0.05). There was a significant relationship between temporomandibular disorders and cervical spine pain (p<0.05, chi2=10.118, df=1, rc=0.31). The level of back pain was significantly higher in people from the study group (p<0.001, chi2=45.765, df=4, rc=0.57). Conclusions: Our research has shown that the causes of cervical spine pain at a young age may be temporomandibular disorders, which are generally not recognized and properly treated.

The correlation between pain and emotional status in subjects with temporomandibular disorders (TMD) is known. Regardless of that up to date these findings were seldomly confronted with the objective assessment of pain using a digital algometer on the mastication muscles. The aim of the study was to investigate the relationship between the emotional status, chronic pain pain pressure threshold (PPT). 38 subjects were screened for the existence of temporomandibular disorders with the 3Q/TMD questionnaire, for chronic pain (GCPS) and emotional status (PHQ-9 and GAD-7). The results were confronted with the PPT measured with the digital algometer on the masseter muscles. Each subject was examined three times (after 1 month and after 7 months from the initial exami-nation session. Chronic pain scores (GCPS) were found to be higher in the TMD group in all three examination sessions (p<0,05). The pain, depression and anxiety levels were higher in females de-spite the existence of TMD, but only some were significant.A correlation between chronic orofacial pain scores and PPT was found in 2 out of 3 examination sessions. The PPT scores on the masseter muscles did not correlate with the emotional state in the study population.

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassemia and 14,3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization, were included in the study. The patients were divided into three groups according to haemodynamics and overall diagnostic approach: 42,9% had precapillary PH (Pulmonary Arterial Hypertension -PAH group), 25% post-capillary PH and 32.1% Chronic Thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics was recorded. PAH-specific drug therapy received 82.1% of patients and Balloon Pulmonary Angioplasty (BPA) was performed in 6 patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for PAH-group. Patients who underwent BPA improved Pulmonary Haemodynamics. Median survival time was 162 months and the survival rate was 1yr-100%, 2,3,4,5,6 years 96%, 9yrs 90% and 13yrs 78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlights the importance of a correct diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies, however the management should be offered in expert PH centers under patients’ individualized approach.

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

To evaluate whether the extent of cardiac damage in severe aortic stenosis (AS) might be associated with the occurrence of conduction system disorders after TAVI. A total of 153 symptomatic patients with severe AS who had a TAVI were categorized before the procedure according to the extent of cardiac damage: stage 1 (13.5%): no or LV damage; stage 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); stage 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVD whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with resolutive paroxysmal AF with a higher rate for each group increment (group 1: n=0, 0%; group 2: n=11,15.7%; group 3: n=10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n=1, 6.3%; group 2: n=7,10%; group 3: n=9, 27.3%) (p=0.012). No patient in group 1 died during the hospital stay. In conclusion, cardiac damage staging of AS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors like folate, B12, osteocalcin, and more. Not only do these biomarkers serve as indicators of senescence, but they actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual's life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

Mindful Eating (ME) is an increasingly popular dietary practice that may mediate the sympto-matology of Eating Disorders (EDs). Orthorexia Nervosa (ON) is a recently proposed eating dis-order characterized by excessive concern for healthy eating and calorie control. The purpose of this study is to investigate the relationship between ME and Psychological Distress (PD) with EDs and ON. In a cross-sectional study involving 407 adults, this research explored the interplay between ME, PD, and EDs, notably ON. Utilizing validated scales for ME (MES-16), EDs (EDE-QS), ON (ORTO-R), and PD, subcategorized in depression, anxiety, and stress (DASS-21), alongside inquiries into Instagram usage, significant correlations emerged. ME demonstrated a robust negative asso-ciation with both EDE-QS (r=-0.501, p<0.001) and ORTO-R (r=-0.519, p<0.001), while EDE-Q and ORTO-R showed significant correlations with depression, anxiety, and stress (p<0.001). Variations in ORTO-R mean scores were notably distinct across different ME categories (p<0.001), emphasizing the relationship between ME and ON. Additionally, participants with extensive daily Instagram use displayed significantly higher ON scores compared to minimal users (p<0.05). These findings sug-gest a negative link between ME with EDs and ON, highlighting ME's potential role in reducing ON tendencies. Furthermore, Instagram use seems associated with PD and elevated ON levels.

This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants, and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models. Additionally, we conduct a comparative analysis of the molecular targets and effects of synephrine with those of its metabolite, selective glucocorticoid receptor agonist (SEGRA) Compound A (CpdA), which shares a similar chemical structure with synephrine. SEGRA, including CpdA, have been extensively studied as glucocorticoid receptor activators that have a better benefit/risk profile than glucocorticoids due to the reduced adverse effects. We discuss the potential of synephrine usage as a template for the synthesis of new generation of non-steroidal SEGRA. The review also provides insights into the safe pharmacological profile of synephrine.

Since alternative methods (AAs), such as in vitro cultures, organs in silico, or mathematical methods, are not fully able to reproduce the complexity of the human organism, particularly neu-ral processes, and brain structures, animal experimentation remains the only way in which re-search can obtain the necessary knowledge to suggest drug therapies or targeted therapeutic in-terventions. Particularly in neuroscience, transgenic animals allow us to model neurological dis-eases, study the relationship between the brain and behavior, and decipher the function of genes involved in pathological conditions. However, it should never be forgotten that animals are "sen-tient beings" capable of feeling pleasure and pain (Art. 13 of the 2007 Lisbon Treaty). For this rea-son, it is crucial to prioritize the welfare of animals involved in testing by considering their phys-ical, psychological, adaptive, and relational well-being. This is where the concept of a Culture of Care comes in, where the responsibility of care extends beyond the veterinary aspects to include everything that can safeguard the welfare of animals before, during, and after experimentation. This chapter explains the advantages of using the animal model while practicing the culture of care in neuroscience, as both animals and research outcomes benefit from this approach.

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.

Background: The gold standard for the diagnosis of sleep bruxism (SB) and obstructive sleep apnea (OSA) is Polysmnography (PSG). At the end of the apnea episodes there is frequently a final hy-permotor muscle activity that could act as a confusion factor in the diagnosis of SB with the elec-tromyography portable devices. The aim of this study was to compare the concordance on the number of episodes of SB in a population with OSA, between the diagnosis obtained by PSG, an-alyzed manually by a neurophysiologist and that obtained manually and automatically by a portable electromyography (EMG) and electrocardiography (EKG) device. Methods: Twenty-three subjects underwent one night of polysomnographic study with simulta-neous recording with the EMG-EKG device. The variables referring to the number of episodes and the SB index measured with both tools and analyzed in the manual and automatic modes were compared. Masticatory muscle activity was scored according to published criteria. The sample was segmented by severity of OSA according to AASM criteria. ANOVA, correlations, and the Bland–Altman plot were used to quantify the agreement between both methods. The concordance was calculated through the ICC. Results: The total events of SB per night in the PSG study were on average (8.17), lower than the one obtained with EMG-EKG manual analysis (14.13) and automatic (29.26). Both the SB PSG and Manual EMG-EKG episodes decrease from non-OSA (PSG = 16 ± 13,55, EMG-EKG = 16,83 ±11,58) to severe OSA (PSG = 3,14 ± 4,26, EMG-EKG = 9,86 ± 8,09). However, in the case of automatic EMG-EKG mode: the number of SB episodes in severe OSA doubled (41,23 ± 12,50) with respect to non OSA (24,50 ± 12,19). On average: the EMG-EKG device Automatic analysis measures 21.08 units more than PSG. The results with the manual EMG-EKG analysis improved. Conclusion: There is no concordance between the results obtained in the PSG neurophysiologic analysis and those obtained by means of the EMG-EKG device automatic and manual analysis for the diagnosis of SB in a population mostly with OSA. The OSA could act as a confusion factor in the diagnosis of SB with the electromyography portable devices, but further study is needed.

(1) Background: Attention Deficit Hyperactivity Disorder (ADHD) and Developmental Language Disorder (DLD) are neurodevelopmental disorders that affect various areas of chil-dren’s development, such as language. There is an emerging idea that ADHD is characterised by the presence of language difficulties, which could be explained by the high comorbidity between ADHD and DLD. The purpose of this study is to analyse the empirical evidence of language com-petence in children aged 6–17 years old, diagnosed with ADHD and/or DLD. (2) Method: Fifteen studies with experimental designs were identified from Scopus, PsycINFO and WoS databases, reporting on language skills in children diagnosed with ADHD and/or DLD. Studies relating ex-ecutive functioning to language skills in this target population were also included. (3) Results: The literature is heterogeneous and different components of language are also examined. Even though the results are contradictory they convincingly demonstrate that there are overlapping symptoms between ADHD and DLD, such as language skills and executive functions. (4) Conclusions: the differences in the samples limit the generalisability of the results. Therefore, this review highlights the importance of considering language skills when designing individualised interventions for the population with ADHD and DLD, both in comorbidity and in isolation.

The phenomenon of decreased serum uric acid (UA) levels in patients with Parkinson’s disease (PD) and its relationship with purine metabolic pathways remain unclear. We compared inosine, hy-poxanthine, xanthine, and UA levels in serum and cerebrospinal fluid (CSF) of PD patients with those of controls, and investigated the effect of changes in the purine metabolic system on UA levels in PD. Overall, 134 samples (serum, 45 PD patients and 30 controls; CSF, 39 PD patients and 20 controls), were analyzed using liquid chromatography-tandem mass spectrometry. A general linear model (GLM) was used to investigate relationships among purine metabolites. Compared to controls, PD patients had significantly lower UA levels in the serum and CSF, and serum and CSF UA levels were significantly correlated. Additionally, in PD, decreased serum hypoxanthine levels were observed with decreased CSF inosine and hypoxanthine levels, suggesting the involvement of the purine recycling system. GLM analysis indicated that the reduced UA levels in PD were mainly due to sources other than the purine metabolic system, such as exercise, nutritional indices, muscle volume, or adipose tissue. Our results highlight the impairment of purine recycling pathways in PD, as evidenced by the decreased serum hypoxanthine and CSF inosine.

Leukodystrophies, also known as demyelinating diseases, mainly affect the CNS. Clinical presentation of different types of leukodystrophies can be nonspecific and thus, imaging techniques like MRI can be used for a more definitive diagnosis. These diseases are characterized as cerebral lesions with characteristic demyelinating patterns, which can be used as differentiating tools. In this review, we talk about these MRI imaging findings for each leukodystrophy, associated genetics, blood work that can help differentiate, emerging diagnostics, and follow up imaging strategy. The leukodystrophies discussed in this paper include X-linked adrenoleukodystrophy, Metachromatic leukodystrophy, Krabbe’s disease, Pelizaeus-Merzbacher disease, Alexander’s disease, Canavan disease, and Aicardi-Goutières Syndrome.

Background. ADHD is a neurodevelopmental disorder that is accompanied by executive deficits. Objectives. To obtain evidence of the usefulness of the BRIEF-P and to analyse the possible ceiling and floor effect of its scores in the assessment of executive function in preschoolers with signs compatible with a possible diagnosis of ADHD. Methods. Seven articles were selected from 2538 potentially eligible articles from different databases. We included studies assessing samples of individuals with symptoms compatible with ADHD, with age range 2-6 years, published in English or Spanish, during the period 2012-2022. References published in: Science Direct, NCBI (PubMed), ProQuest Education Journals in the last decade. Risk of bias was assessed using the QUADAS-2 questionnaire. The main variables were: age and executive functioning. Conclusions. Executive deficits in early-life individuals with ADHD-compatible symptoms are more extensive than deficits in working memory. BRIEF-P is an instrument that facilitates obtaining a sensitive and discriminative executive profile. It should be used in combination with other neuropsychological performance tests, finding a floor effect in tests associated with warm executive functions and a ceiling effect in cold executive functions. This requires using a variety of tests to assess executive performance in preschoolers with symptoms compatible with ADHD and designing intervention proposals in line with them...

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.

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.

Background. In a changing European agricultural context, diversification of dairy farms is gaining attention. This study seeks to (1) assess musculoskeletal pain prevalence associated with tasks such as butter, yogurt, and cheese production; and (2) analyze associated risks. Methods. Observing 31 mostly female workers, it utilized the ERGOROM questionnaire, a methodology adapted from the Institut National de Recherche et de Sécurité, and Key Indicator Method forms. Results. Findings revealed that tasks like load carrying (42% of workers), manual work (17%), and awkward postures (14%) resulted in musculoskeletal pain, predominantly in the lower back (65%), neck (39%), and dominant upper limb areas (shoulder: 61%, elbow: 26%, and wrist: 65%). While psychosocial risks remained low, concerns arose from workload, hygiene standards, and resource unpredictability. Conclusions. As dairy farming evolves from artisanal to semi-industrial, the study emphasizes the importance of ergonomic adaptations to protect farmer health and prevent musculoskeletal disorders during diversification.

Eating disorders (EDs) refer to a group of diseases characterized by a strong tendency toward chronicity, often involving distortions in body image distortion and other related symptoms The prevalence of EDs has increased in recent years, specifically in athletic populations. Therefore, the purpose of this study was to analyse risky eating attitudes in a sample of 1102 subjects from Se-ville (Spain): 142 women and 960 men aged between 15-25 years old. An online survey, designed using Google Forms, consisted of three questionnaires (EAT-26, SCOFF, and BITE), were com-pleted individually and anonymously. With regards to the cut-off points, the percentage of posi-tive cases with significant scores was 11.43% for EAT-26, 31.22% for SCOFF and 4.36% for BITE. The study found that the probability of testing positive for EDs is significantly higher in women than in men (p < 0.001). Specifically, the risk attitude for EDs in female athletes measured by the EAT-26 test is three times higher than in male athletes, while the risk attitude measured by the SCOFF test is twice as high in females. Risk attitude for EDs in athletes measured by the BITE test is 8 times higher in females than in males. This study’s findings confirm several important as-sumptions made at the outset of the research. There is indeed a higher risk of EDs in athlete populations. Moreover, all three tests therefore show a higher frequency of possible events of EDs in women, with very similar percentages of difference between sexes. The tests also confirm the role played by the coaches in the prevention of EDs in sports and their capacity to reduce ab-normal food-related behaviours. Thus, the future inclusion of these tests in the screening of athletes is highly recommended.

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nevertheless, the responder rates of recently approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and receptor inhibitors remain around 50 percent. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge on PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.

Sleep-related eating disorder (SRED) is a non-REM parasomnia with potentially significant negative effects on general health (dangerous activities during night eating episodes, obesity, or metabolic syndrome, for example). Although the history of SRED encompasses more than six decades, public awareness and even the awareness of the mental health specialists of this disorder is very limited, a phenomenon that hinders the development of research in this field. Therefore, an updated review, based on a narrative methodology, explored the available evidence for SRED found in four electronic databases (PubMed, Cochrane Collaboration, Google Scholar, and Clarivate/Web of Science). A number of 94 primary and secondary reports were retrieved, investigating aspects regarding the risk factors, epidemiology, clinical data and differential diagnosis, epidemiology, structured evaluation, and treatment of SRED. Based on the results of these reports, Z-drugs, but also certain benzodiazepines, antidepressants, antipsychotics, and psychostimulants may trigger the onset of SRED. Psychiatric and neurologic disorders have also been associated with SRED, either as risk factors or comorbid conditions. Cerebral glucose metabolism dysfunctions, neurotransmitter dysfunctions, and genetic factors have been invoked as pathogenetic contributors. Structured assessment of SRED is possible, but there is a dearth of instruments dedicated to this purpose. Data on the prevalence and treatment of SRED exist, but good-quality epidemiological studies and clinical trials are still missing. In conclusion, future research is expected to address the shortcomings of SRED exploration by creating the conditions for better quality and larger group clinical research. The need for such investigation is granted by the importance of this pathology and its negative functional consequences.

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

Acute respiratory viruses (ARVs) are leading cause of diseases in human worldwide. High risk individuals including children and elderly could potentially develop severe illness that could result in hospitalization or death in the worst case. Most common ARVs are Human respiratory syncytial virus, Human Metapneumovirus, Human Parainfluenza Virus, rhinovirus, coronaviruses (including SARS and MERS CoV), adenoviruses, Human Bocavirus, enterovirus (-D68 and 71), and influenza viruses. The olfactory deficits due to ARVs infection is a common symptom among patients. This mini review provides an overview of the role of SARS-CoV-2 and other common ARVs in the development of human olfactory pathophysiology. We highlight the critical need for understanding the signaling underlying the olfactory dysfunction and the development of therapeutics for this wide-ranging category of AVRs to restore the altered or loss of smell in affected patients.

The impact of the COVID-19 pandemic and the quarantine measures on children and adolescents’ hospitalization psychiatric has been poorly studied, especially in Italy, the first European country to adopt social restrictions. To fill this gap, this retrospective study examined changes in admissions to our child and adolescent psychiatry ward from the emergency department during the two COVID-19 quarantine periods in Italy (March to June 2020; October 2020 to January 2021) compared with two reference periods (defined as 12 months prior to the respective quarantine periods). Specifically, we examined data on the number of inpatients and the distribution of psychopathological disorders (i.e., psychosis, mood disorder) and self-injurious behaviors. The results revealed significantly fewer admissions during the first quarantine period relative to the first reference period and, conversely, significantly more admissions during the second quarantine period relative to the second reference period. Of note, the results showed an increased frequency of mood disorders, non-suicidal self-injurious behaviors and suicidal ideation during the quarantine periods, compared to the reference periods. The findings underline the need to focus on the psychopathological profile of children and adolescents with patient-tailored therapeutic interventions and suggest the importance of developing psychological healthcare services for future emergency periods..

Despite Vitamin B12's recognized importance for the nervous system, there's still a lack of research on the association between Vitamin B12 and sleep, especially in primary care settings. We assessed Vitamin B12 levels in adult primary health care users and investigated correlations with sleep quality, insomnia and sleepiness. In this cross-sectional study, 512 consecutive participants were included. Information regarding anthropometrics, socio-demographics, and medical history was obtained. The Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), and Pittsburg Sleep Quality Index (PSQI) were used to quantify excessive daytime sleepiness (EDS), insomnia symptoms, and sleep quality, respectively. Median Vitamin B12 was 342 (266, 446) pg/mL. After adjustments, Vitamin B12 levels&lt;342 pg/mL showed significant associations with insomnia symptoms [OR (95% CI) 2.434 (1.331–4.452), p=0.004], especially in elderly, non-obese and female participants, with EDS only in obese participants [OR (95% CI) 3.996, (1.006-15.876), p=0.039]. Nonetheless, there was no significant association between B12 levels and poor sleep quality (OR 1.416, 95% CI 0.678-2.958, p=0.354). In conclusion, our results show that lower Vitamin B12 was associated with insomnia symptoms and sleepiness in specific groups of participants. However, further research with objective measurements of sleep is crucial to assess the relationship between sleep and Vitamin B12.

Taste disorders are common among cancer patients undergoing chemotherapy, with a prevalence ranging from 20% to 86%, persisting throughout treatment. This condition leads to reduced food consumption, increasing the risk of malnutrition. Malnutrition is associated not only with worse treatment efficacy and poor disease prognosis but also with reduced functional status and quality of life. The fruit of Synsepalum dulcificum (Daniell), commonly known as miracle berry or miracle fruit, contains miraculin, a taste-modifying protein with profound effects on taste perception. The CLINMIR Protocol is a triple-blind, randomized, placebo-controlled clinical trial designed to evaluate the regular consumption of a food supplement containing a miraculin-based novel food, dried miracle berry (DMB), on the taste perception (measured through electrogustometry) and nutritional status (evaluated through the GLIM Criteria) of malnourished cancer patients under active antineoplastic treatment. To this end, a pilot study was designed with 30 randomized patients divided into three study arms (150 mg DMB + 150 mg freeze-dried strawberries, 300 mg DMB or placebo) for three months. Throughout the five main visits, an exhaustive assessment of different affected parameters susceptible to improvement through regular consumption of the miraculin-based food supplement will be conducted, including electrical and chemical taste perception, smell perception, nutritional and morphofunctional assessment, diet, quality of life, fatty acid profile of erythrocytes, levels of inflammatory and cancer-associated cytokines, oxidative stress, antioxidant defense system, plasma metabolomics, and saliva and stool microbiota. The primary anticipated result is that malnourished cancer patients with taste distortion who consume the miraculin-based food supplement will report an improvement in food taste perception. This improvement translates into increased food intake, thereby ameliorating their nutritional status and mitigating associated risks. Additionally, the study aims to pinpoint the optimal dosage that provides maximal benefits. The protocol adheres to the SPIRIT 2013 Statement, which provides evidence-based recommendations and is widely endorsed as an international standard for trial protocols (https://www.spirit-statement.org/spirit-statement/). The clinical trial protocol has been registered at http://clinicaltrials.gov (NCT05486260).