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.

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.

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.

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.

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.

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.

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.

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.

Developmental Coordination Disorder (DCD) is a neurodevelopmental condition characterized by non-progressive central motor impairments. Mild movement disorder features have been observed in DCD. Until now, the etiology of DCD remains unclear. Recent studies suggested a genetic substrate in some patients with DCD, but comprehensive knowledge about associated genes and underlying pathogenetic mechanisms is still lacking. In this study, we first identified genes described in literature in patients with a diagnosis of DCD according to the official diagnostic criteria. Second, we exposed the underlying pathogenetic mechanisms of DCD, by investigating tissue- and temporal gene expression patterns and brain-specific biological mech-anisms. Third, we explored putative shared pathogenetic mechanisms between DCD and frequent movement disorders with a known genetic component, including ataxia, chorea, dystonia, and myoclonus. We identified 12 genes associated with DCD in literature, which are ubiquitously expressed in the central nervous system throughout brain development. These genes are involved in cellular processes, neural signaling and nervous system development. There was a remarkable overlap (62%) in pathogenetic mechanisms between DCD-associated genes and genes linked with movement disorders. Our findings suggest that some patients might have a genetic etiology of DCD, which could be considered part of a pathogenetic movement disorder spectrum.

Studies investigating the acute effect of postprandial exercise (PPE) on glucose responses exhibit significant heterogeneity in terms of participant demographic, exercise protocol, and exercise timing post-meal. As such, this study aimed to further analyze the existing literature on the impact of PPE on glycemic control in individuals with overweight, obesity, and type 2 diabetes (T2D). Literature search was conducted through databases including PubMed, CINAHL, and Google Scholar. Thirty-one original research studies that met the inclusion criteria were selected. The random-effect meta-analysis was performed to compare postprandial glucose area under the curve (AUC) and 24-h mean glucose levels between PPE and the time-matched no-exercise control (CON). Subgroup analysis was conducted to explore whether the glucose-lowering effect of PPE could be influenced by exercise duration, exercise timing post-meal, and disease status of participants. This study revealed significantly reduced glucose AUC (Hedges’ g = -0.317; SE = 0.057; p < 0.05) and 24-hour mean glucose levels (Hedges’ g = -0.328; SE = 0.062; p < 0.05) following PPE than CON. The reduction in glucose AUC was greater (p < 0.05) following PPE lasting >30 min than ≤30 min. The reduction in 24-hour mean glucose levels was also greater (p < 0.05) following PPE initiated ≥60 min than <60 min post-meal and in those with T2D than those without T2D. PPE offers a viable approach for glucose management and can be performed in various forms so long as exercise duration is sufficient. The glucose-lowering effect of PPE may be further enhanced by initiating it after the first hour post-meal. PPE represents a promising strategy, particularly for patients with T2D.

Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia and anemia. Moreover, it is associ-ated with SRSF2 mutations and rarely with CSF3R variants. The presented case is an 84-year-old patient with persistent anemia and monocytosis. Due to the presence of dysmorphic granulocytes, monocyte atypia and myeloid precursors in peripheral blood, the patient was submitted to bone marrow examination. The diagnosis was consistent with CMML type 2. Hemocoagulative test showed an increase of fibrinolysis markers. Next generation targeted sequencing showed TET2 and SRSF2 mutations, along with an unexpected CSF3R germline missense variant, rarely encountered in CMML. The pa-tient started Azacitidine treatment reaching normal hemostatic process values. In con-clusion, we identified a heterozygous germline mutation that, cooperating with TET2 and SRSF2 variants, have been responsible for the hemorrhagic manifestation.

This scoping review aims to identify the available evidence concerning the clinical and psychosocial impacts of the communication of oral potentially malignant disorders (OPMDs), and to map and analyze knowledge gaps regarding truth-telling about risk factors, malignant transformation, treatment, and follow-up approaches. Search strategy was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Each publication involved a different study design, study population, types of OPMDs, and results on the important aspects of the professional-patient communication about the diagnosis of OPMDs. Although specific protocols on OPMDs communication have not yet been reported, there is an elevated interest on this topic since the strategies and skills on professional communication could provide better clinical outcomes to the patients. A list of recommendation strategies on how to communicate an OPMD diagnosis is proposed; however, future studies are still needed to design specific communication protocols for OPMD.

Office workers often experience occupational musculoskeletal disorders. The aim of the current systematic review was to investigate the effectiveness of workplace exercise intervention on the oldest age group of office workers who have been reported in the literature so far, in terms of workability and well-being. Randomized Controlled Trials were used and the methodological guidelines of PRISMA were followed. The keywords used were: office workers, older, exercise intervention, workplace, microbreaks, workability and well-being. The databases searched were: PubMed, PEDro, ResearchGate, CINAHL, PsychINFO and Science Direct. PROSPERO ID: CRD42022329656. Five studies (total number of participants: 1190, mean age: 46,4) met the inclu-sion criteria. Their quality was deemed to be moderate to high, according to PEDro and MPSER scales. Workplace interventions of gradually increased strengthening and moderate stretching exercises, isometric positioning and postural reminders, either with or without supervision, result in decreasing musculoskeletal pain, disability, sick-leave from work and in the improvement of quality of life and physical activity of the middle-aged office workers, without negative impact on their workability. Despite the worldwide aging workforce, there is a knowledge gap due to research absence in the field of microbreak exercise interventions in the group of older office workers.

In the last two decades, our knowledge of synaptic proteomes and their relationship to normal brain function and neuropsychiatric disorders has been expanding rapidly through the use of more powerful neuroproteomic approaches. However, mass spectrometry (MS) based neuroproteomic studies of synapses still need cell-type, spatial, and temporal proteome information. With the advancement of sample preparation and MS techniques, we have just begun to identify and understand proteomes within a given cell type, subcellular compartment, and cell-type-specific synapse. Here, we review the progress and limitations of MS-based neuroproteomics of synapses in the mammalian CNS and highlight the recent applications of these approaches in studying neuropsychiatric disorders such as major depressive disorder and substance use disorders. Combining neuroproteomic findings with other omics studies can generate an in-depth, comprehensive map of synaptic proteomes and possibly identify new therapeutic targets and biomarkers of several central nervous system disorders.

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

Functional somatic disorders (FSD) characterized by persistent and disabling physical symptoms are common in adolescents. Diagnostic uncertainty and insufficient illness explanations are proposed perpetuating factors that may constitute barriers for treatment engagement. This study evaluates the impact of manualized assessment and psychoeducation on diagnostic certainty and various clinical outcomes in adolescents with multi-system FSD. Ninety-one adolescents (15-19 years) included in a randomized trial testing group-based therapy (AHEAD) received systematic assessment (4 hrs.) and a subsequent psychiatric consultation (1.5 hrs.). Clinical outcomes included self-reported physical health, symptom severity, illness perception, illness related behavior, and psychological flexibility assessed before and approximately two months after assessment, prior to specialized treatment. Data were analyzed using t-tests. Immediately following assessment 71 (80.7%) adolescents out of 88 reported a higher diagnostic certainty and 74 (84.1%) reported that attending assessment gave them positive expectations for future treatment. A clinically relevant improvement of physical health was not observed at two months but considerable reductions were seen on symptom severity, illness worry, negative illness perceptions, limiting illness behavior and psychological inflexibility. The results underpin the importance of systematic assessment and psychoeducation which may be effective in their own right in specialized treatment of adolescents with severe FSD.

Atypical Anorexia Nervosa (AAN) had been found to have significant physical and psychological complications at presentation but has not been described in a multi-ethnic Asian population. This retrospective cohort analysis aimed to characterize the baseline presentation of adolescents with Anorexia nervosa (AN) (N=317) and AAN (N=141) in an Asian cohort that presented to a specialist paediatric eating disorder program between January 2010 to October 2020 for assessment. In patients with AAN, there were increased proportions of males (16% vs 7%) and of Malay ethnicity (11% vs 4%) compared to AN. Adolescents with AAN had lower admission rates (61% vs 81%) as well as lower rates of bradycardia (45% vs 75%) and hypotension (7% vs 21%) but higher rate of syncope (13% vs 7%) compared to adolescents with AN. However, adolescents with AAN had higher frequency of psychological complications including self-harm and drug overdose (14% vs 1.5%) requiring admission as well as higher rates of purging (45.1% vs 14.8%) and for Eating Disorder Questionnaire score in the shape domain was more severe. Asian adolescents with AAN manifest with physical complications of malnutrition and had worse eating disorder psychopathology with higher frequency of other psychological co-morbidities underlining the severity of the illness.

Temporomandibular joint disorders (TMD) are characterized by their multifactorial etiology and pathogenesis. A 3-year prospective study was conducted in a Portuguese TMD department to study the prevalence of different TMD signs and symptoms and their association with risk factors and comorbidities. Five hundred ninety-five patients were included using an online database: EUROTMJ. Most patients were female (80.50 %), with a mean age of 38.20±15.73 years. The main complaints were temporomandibular joint (TMJ) clicking (13.26%), pain (12.49%), and masticatory muscle tension (12.15%). The main clinical findings were myalgia (74%), TMJ clicking (60-62%) and arthralgia (31-36%). Risk factors such as clenching (60%) and bruxism (30%) were positively associated with TMJ pain and myalgia. Orthodontic treatment (20%) and wisdom tooth removal (19%) were positively associated with TMJ clicking, while jaw trauma (6%) tracheal intubation (4%) and orthognathic surgery (1%) were positively associated with TMJ crepitus, limited man-dibular range of motion and TMJ pain, respectively. 42.88% of TMD patients had other associated chronic diseases, most of them were mental behavioral or neurodevelopmental disorders (33.76%), namely, anxiety (20%) and depression (13%). The authors also observed a positively association of mental disorders with the degree of TMJ pain and myalgia. Online database seems to be a relevant scientific instrument for healthcare providers who treat TMD. The authors expect that EUROTMJ database can serve as a milestone for other TMD departments.

The article presents the potential of liposomal cannabidiol in the treatment of Panic Disorder, when used in integration with Complex Cognitive Psychotherapy. The advantages of the integrated treatment, developed by the Author, and based on the use of liposomal cannabidiol combined with cognitive psychotherapy, are discussed. A new and original tool is presented and described, developed, and tested for the first time by the Author and called NegEnt Panic Blocker.

SCARED-C instrument (the child version, 41 items) is used for screening anxiety in children between 8 to 18 years old and has been first introduced by Birmaher & collab. in 1995, with good psychometric data - internal consistency from α =.74 to .93 - and good discriminative validity indices in the original versions (1997, 1999). Since then, many countries have adopted the scale, for its utility in identifying five subsets of anxiety disorders (subscales): somatic/panic disorder, generalized anxiety, separation anxiety, social phobia, and school avoidance. The present study contains the first Romanian translated and adapted version of the SCARED-C instrument on a community sample of 477 children (8-18 years old) from Mureș county schools. The instrument showed moderate to good internal consistency (α Cronbach from to .63 to .91 for the total scale) and good test-retest reliability (.70) on a subset of 85 children sample. A confirmatory factorial analysis (CFA) was conducted to test the factor structure of the Romanian version of SCARED-C; results showed that SCARED-C has good psychometric properties to be used for screening anxiety in Romanian children and adolescents. The implications for using SCARED-C in dental practice are discussed. Future studies need to be conducted for exploring convergent and discriminative validity of the instrument and the sensitivity to current DSM-V criteria. Application on a dental pediatric sample is also required.

This study aimed to report the magnitude of modifiable lifestyle factors, their relationships with metabolic disorders in Burkinabè adults by using nationally representative data. This cross-sectional study included 4100 adults selected through multistage cluster sampling performed during the first national survey conducted in 2013 in Burkina Faso. The modifiable factors we considered were tooth cleaning, fruit and/or vegetable (FV) intake, substances’ use, physical activity and overweight/obesity, while metabolic syndrome abnormal components defined metabolic disorders. We performed logistic regressions. 31.1% cleaned the teeth at least twice a day, 14.7% consumed five or more FV, 39.7% used alcohol and/or tobacco, the prevalence of physical inactivity and overweight/obesity was respectively 6.6% and 17.7%. About 41.0% had at least two metabolic disorders and 9.5% had at least three. Lifestyle factors associated with having at least two metabolic disorders were overweight/obesity, more FV intake (when five or more aOR=1.5, p<0.001), physical inactivity (aOR=1.3, p<0.05), tooth cleaning (aOR=0.8, p<0.01). Except for consuming five or more FV (aOR=1.4, p=0.09), the same trend of relationships was observed with having at least three metabolic disorders. Excluding overweight/obesity and physical inactivity, unhealthy modifiable lifestyle factors were common and tooth cleaning was found as a protective practice for metabolic disorders.

This study was conducted to examine whether there are quantitative or qualitative differences in the connectome between psychiatric patients and healthy controls and to delineate the connectome features of major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD) and the severity of these disorders. Toward this end, we have performed effective connectivity analysis of resting state functional MRI data in these three patient groups and healthy controls. We have used spectral Dynamic Causal Modeling (spDCM), and the derived connectome features were further subjected to machine learning. The results outlined a model of 5 connections, which discriminate patients from controls, comprising major nodes of the limbic system (amygdala (AMY), hippocampus (HPC) and anterior cingulate cortex (ACC)), the salience network (anterior insula (AI), fronto-parietal and dorsal attention network (middle frontal gyrus (MFG) corresponding to dorsolateral prefrontal cortex, frontal eye field (FEF)). Notably, the alterations in the self-inhibitory connection of the anterior insula emerged as a feature of both mood disorders and SCZ. Moreover, 4 out of the 5 connectome features that discriminate mental illness from controls are features of mood disorders (both MDD and BD), namely the MFG→FEF, HPC→FEF, AI→AMY, and MFG→AMY connections, whereas one connection is a feature of SCZ, namely the AMY→SPL connectivity. A large part of the variance in the severity of depression (31.6%) and SCZ (40.6%) was explained by connectivity features. In conclusion, dysfunctions in the self-regulation of the salience network may underpin major mental disorders, while other key connectome features shape differences between mood disorders and SCZ, and can be used as potential imaging biomarkers.

Objective The study aims to investigate the risk factors of bad psychosomatic health among students in quarantine during the first wave of the COVID-19 pandemic. Method:The survey was conducted on-line, on a sample of 1,978 respondents in Poland. The study was carried out by the end of the summer semester. The questionnaire was designed in a way which allows for the observation of main risk factors which have impact on the students’ mental health. The variance analysis and the hierarchical regression analysis were used to determine the predictors of mental health. Results:The results indicate that average and high levels of psychosomatic disorders were observed among 61% of respondents. The hierarchical regression analysis has revealed that the main factors influencing the level of mental health disorders were educational burnout, satisfaction with life, strategies for coping with stress and gender. As indicated by the respondents, mental health disorders increase in tandem with educational burnout, the application of emotion-focused coping strategies and the lack of satisfaction with one’s life. Moreover, it was observed that female respondents scored higher on the scale of disorders in comparison to males. Conclusions:The results of research indicate that distance education and negative coping strategies are the main risk factors of mental health disorders among students during the pandemic.

1) Background: Fetal Growth Restriction (FGR) has been associated with adverse perinatal outcomes and epigenetic modifications that impact gene expression leading to permanent changes of fetal metabolic pathways and thereby influence development of disease in childhood and adult life. Both clinical and experimental studies showed that maternal nutrition during pregnancy is critical since malnutrition adversely affects fetal growth and physiology. In this study, we investigated the result of maternal food restriction on liver protein expression in Wistar male newborn pups. (2) Materials & methods: Pups born to food restricted mothers were subdivided to FGR and non-FGR groups. Livers of control, FGR and non-FGR groups were analyzed using quantitative proteomics. (3) Results: In total 6665 proteins were profiled. Of these, 451 and 751 were differentially expressed in FGR and non-FGR vs. control respectively, whereas 229 were common between the two groups. Bioinformatics analysis of the differentially expressed proteins (DEPs) in FGR vs. control revealed: induction of the super-pathway of cholesterol biosynthesis and inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway. In the DEPs of non-FGR vs. control groups there was inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway as well. (4) Conclusion: This study demonstrates the impact of prenatal food restriction on the proteomic liver profile of FGR and non-FGR offspring underlying the importance of both prenatal adversities and birth weight on liver dependent postnatal disease.

Psychiatry remains in a permanent state of crisis, which fragmented psychiatry from the field of medicine. The crisis in psychiatry is evidenced by the many different competing approaches to psychiatric illness including psychodynamic, biological, molecular, pan-omics, precision, cognitive and phenomenological psychiatry, folk psychology, mind-brain dualism, descriptive psychopathology, and postpsychiatry. The current “gold standard” DSM/ICD taxonomies of mood disorders and schizophrenia are unreliable and preclude to employ a deductive reasoning approach. Therefore, it is not surprising that mood disorders and schizophrenia research was unable to revise the conventional classifications and did not provide more adequate therapeutic approaches. The aim of this paper is to explain the new nomothetic network psychiatry (NNP) approach, which uses machine learning methods to build data-driven causal models of mental illness by ensembling risk-resilience, adverse outcome pathways (AOP), cognitome, brainome, symptomatome, and phenomenome latent scores in a causal model. The latter may be trained, tested and validated with Partial Least Squares (PLS) analysis. This approach not only allows to compute pathway-phenotypes or biosignatures, but also to construct reliable and replicable nomothetic networks, which are, therefore, generalizable as disease models. After integrating the validated feature vectors into a well-fitting nomothetic network, clustering analysis may be applied on the latent variable scores of the R/R, AOP, cognitome, brainome, and phenome latent vectors. This pattern recognition method may expose new (transdiagnostic) classes of patients which if cross-validated in independent samples may constitute new (transdiagnostic) nosological categories.

It is not established whether SARS-CoV-2 (COVID-19) patients with movement disorders, are at greater risk for more serious outcomes than the larger COVID-19 population beyond the susceptibility associated with greater age. We reviewed electronic health records and conducted telephone interviews to collect the demographics and clinical outcomes of patients seen at our Movement Disorders Center who tested positive for COVID-19 from 8 March 2020 through 6 June 2020. Thirty-six patients were identified, 23 men and 13 women, median age of 74.5 years. They primarily carried diagnoses of idiopathic Parkinson disease (n=22; 61%) and atypical parkinsonism (n=7; 19%) with the balance having other diagnoses. Twenty-seven patients (75%) exhibited alteration in mental status and fifteen (42%) had abnormalities of movement as common manifestations of COVID-19; in 61% and 31%, these were the presenting symptoms of the disease. 67% of patients in our cohort required hospitalization, and the mortality rate was 39%.. These data demonstrate that in patients with movement disorders, the likelihood of hospitalization and death after contracting COVID-19 was substantially greater than in the general population. Patients with movement disorders frequently presented with altered mental status, generalized weakness, or worsening mobility but not anosmia.

Neuromuscular disorders cause progressive muscular weakness, which limits upper extremity mobility and performance during activities of daily life. A dynamic arm support can improve mobility and quality of life. However, their use is often discontinued over time for unclear reasons. This study aimed to evaluate whether users of dynamic arm supports demonstrate and perceive quantifiable mobility benefits over a period of two months. Nine users of dynamic arm supports were included in this observational study. They had different neuromuscular disorders and collectively used four different arm supports. They were observed for three consecutive weeks during which they were equipped with a multi-sensor network of accelerometers to assess the actual use of the arm support and they were asked to provide self-reports on the perceived benefits of the devices. Benefits were experienced mainly during anti-gravity activities and the measured use did not change over time. The self-reports provided contextual information in domains such as participation to social life, in addition to the sensor system. However self-reports overestimated the actual use by up to three-fold compared to the accelerometer measures. A combination of objective and subjective methods is recommended for meaningful and quantifiable mobility benefits during activities of daily life.

Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.

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

Adverse childhood experiences are known to program children for disrupted biological cycles, premature aging, microbiome dysbiosis, immune-inflammatory misregulation, and chronic disease multimorbidity. To date, the microbiome has not been a major focus of deprogramming efforts despite its emerging role in every aspect of ACE-related dysbiosis and dysfunction. This article examines: 1) the utility of incorporating microorganism-based, anti-aging approaches to combat ACE-programmed chronic diseases (also known as noncommunicable diseases and conditions, NCDs) and 2) microbiome regulation of core systems biology cycles that affect NCD comorbid risk. In this review microbiota influence over three key cyclic rhythms (circadian cycles, the sleep cycle, and the lifespan/longevity cycle) as well as tissue inflammation and oxidative stress are discussed as an opportunity to deprogram ACE-driven chronic disorders. Microbiota, particularly those in the gut, have been shown to affect host-microbe interactions regulating the circadian clock, sleep quality, as well as immune function/senescence and regulation of tissue inflammation. The microimmunosome is one of several systems biology targets of gut microbiota regulation. Furthermore, correcting misregulated inflammation and increased oxidative stress is key to protecting telomere length and lifespan/longevity and extending what has become known as the healthspan. This review article concludes that to reverse the tragedy of ACE-programmed NCDs and premature aging, managing the human holobiont microbiome should become a routine part of healthcare and preventative medicine across the life course.

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

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.

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.

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.

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.

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.

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.

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.

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.

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).

Background: Identity diffusion plays a central role in the onset of borderline personality and disorders. The Dialectical Behavioral Therapy for Adolescents (DBT-A) is a treatment program for adolescents with emotional instability and dysregulation. The interest of this study is to examine the influence of a standardized and certified DBT-A therapy program on identity development of adolescents with emotion dysregulation in an inpatient setting. Methods: 138 adolescents aged 13 to 18 years with symptoms of emotional instability were assessed before and after a curricular 12-weeks in-patient DBT-A program with standardized instruments for the assessment of identity (AIDA), emotion regulation (FEEL-KJ, SEE) and general psychopathology (SCL-90-R, DIKJ). Results: The results indicate a significant change in identity development, emotion regulation and general symptoms of psychopathology after treatment with DBT-A. A connection between identity scales and psychopathological symptoms of adolescents with diagnosed borderline disorders and impaired emotion regulation could be established. Conclusion: In this large sample of adolescents, DBT-A significantly improved identity and reduced identity diffusion. As identiy disturbance is a core symptom of borderline personality disorder, our results may become clinically relevant for the prevention of personality disorders in emotionally unstable adolescents

Peripheral arterial diseases (PAD) are complex cardiovascular conditions influenced by environmental factors and somatic mutations in multiple genes involved in hematopoiesis and inflammation. While traditional risk factors such as smoking, hypercholesterolemia, and hypertension have been extensively studied, the role of somatic mutations in PAD progression remains underexplored. This article aims to provide a comprehensive review of the molecular mechanisms, genetic landscape, prognostic significance, and clinical implications of somatic mutations in PAD. The expansion of clonal hematopoiesis of indeterminate potential (CHIP) clones in the circulating blood, named clonal hematopoiesis (CH), leads to the infiltration of these clones into atherosclerotic plaques and the production of inflammatory cytokines, increasing the risk of cardiovascular diseases including PAD. Furthermore, recent experimental evidence has demonstrated the involvement of somatically mutated TP53 genes with a high variant allele frequency (VAF) in PAD development and prognosis. The review delves into the relationship between CH and PAD, elucidating the prevalence, impact, and underlying mechanisms of this association. This understanding paves the way for novel therapeutic approaches targeting CHIP to promote tissue regeneration and improve outcomes in PAD patients. It emphasizes the need for further re-search to fully unravel the genetic footprint of the disease and highlights potential clinical implications. The findings presented in this article lay the foundation for personalized medicine approaches and open avenues for the development of targeted therapies based on somatic mutation profiling.

The purpose of this systematic review is to examine the various articles published in the field of neuropsychology of anxiety research in terms of publication type and volume, methodology, and subject matter. The significance of this topic derives from the clinical and functional consequences of cognitive symptoms. Generalized anxiety disorder refers to the cluster of clinical symptoms characterized by predominant anxious anticipation and difficulty controlling worry. In order for the review to be systematic and reproducible, a search of the PsycINFO, Scopus, PubMed, Elsevier databases and an analysis using the PRISMA method are suggested. After analyzing the research data, empirical studies evaluating the clinical neuropsychology of generalized anxiety disorder are discussed.

Eating disorders are a global burden and present personal, family, and societal costs. Most evidence in the literature is based on the relationship between a poor family environment and eating disorders, and the evidence of gender interaction in eating disorders is inconsistent. This study aimed to investigate the relationship between family functioning and disordered eating patterns, the mediating role of negative automatic thoughts, and the moderating role of gender. A sample of 440 (70.9% females, aged 18–21) participated in this study. They completed the Eating Attitudes Test (EAT-26), the Automatic Thoughts Questionnaire (ATQ negative), and the Brief Family Relationship Scale (BFRS). PROCESS MACRO was used to study these relationships. The main findings revealed that family functioning was negatively associated with eating disorders, and that this relationship was negatively mediated by automatic thoughts. Moreover, gender moderated those relationships, and more intensely in females. The results of this study postulate that the prevention of eating disorders should be directed at training individuals to challenge negative thoughts and encourage healthy individuals to be gender mindful.

Hyperacusis, i.e., an increased sensitivity to sounds, is described in several neurodevelopmental disorders (NDDs), including Fragile X Syndrome (FXS). The mechanisms underlying hyperacusis in FXS are still largely unknown and effective therapies are lacking. Big conductance calci-um-activated potassium (BKCa) channels have been proposed as a therapeutic target to treat several behavioral disturbances in FXS preclinical models, but their role in mediating their au-ditory alterations has not been specifically addressed. Furthermore, studies on the acoustic phe-notypes of FXS animal models have mostly focused on central rather than peripheral auditory pathways. Here we provided an extensive characterization of the peripheral auditory phenotype of the Fmr1-knockout (KO) mouse model of FXS at adulthood. We also assessed whether the acute administration of Chlorzoxazone, a BKCa agonist, could rescue the auditory abnormalities of mutant mice. Fmr1-KO mice both at 3 and 6 months showed a hyperacusis-like startle pheno-type with paradoxically reduced auditory brainstem responses associated with a loss of ribbon synapses in the inner hair cells (IHCs). BKCa expression was markedly reduced in the IHCs of KO mice, but only at 6 months, when Chlorzoxazone rescued mutant auditory dysfunction. Our findings highlight the age-dependent and progressive contribution of peripheral mechanisms and BKCa channels to hyperacusis in FXS, suggesting a novel therapeutic target to treat auditory dysfunction in NDDs.

KV channel-interacting proteins (KChIPs) belong to a family of Ca2+-binding EF-hand proteins that are able to bind to the N-terminus of the KV4 channel α-subunits. As the auxiliary subunit, KChIPs are critically involved in regulating the amplitude and gating properties of KV4 channels by modulating their cell surface trafficking, voltage-dependent activation, inactivation kinetics, and recovery rate from inactivation. IKs, ICa,L, and INa can also be regulated by KChIPs. KChIPs are predominantly expressed in the brain and heart, where they contribute to the maintenance of the excitability of neurons and cardiomyocytes by modulating the KV4 currents. Interestingly, all KChIPs can act as transcription factors to control the expression of genes involved in pain, memory, and circadian regulation. Altered expression of KChIPs has been implicated in the pathogenesis of many diseases, such as arrhythmia, heart failure, Alzheimer's disease, etc. In this review, we summarize the research progress of KChIPs in their structural properties, physiological functions, and pathological roles in disease progression, and provide an overview of the therapeutic potential of KChIPs as pharmacological targets for associated disorders.

Maternal infections during pregnancy may increase the risk of psychiatric disorders in offspring. We recently demonstrated that activation of peroxisome proliferator-activate receptor‐α (PPARα), with the clinically available agonist fenofibrate, attenuates the neurodevelopmental disturbances induced by maternal immune activation (MIA) in rat offspring. We hypothesized that fenofibrate might reduce MIA-induced cytokine imbalance using a MIA model based on the viral mimetic polyriboinosinic-polyribocytidilic acid [poly (I:C)]. By using the Bio-Plex Multiplex-Immunoassay-System, we measured cytokine/chemokine levels in maternal serum and in the fetal brain of rats treated with fenofibrate, at 6 and 24 hours after poly (I:C). We found that MIA induced time-dependent changes in the levels of several cytokines/chemokines/colony-stimulating factors (CSFs). Specifically, the maternal serum of the poly (I:C)/CTRL group showed increased levels of (i) proinflammatory chemokine macrophage inflammatory protein 1-alpha (MIP-1α), (ii) tumor necrosis factor-alpha (TNF-), the monocyte chemoattractant protein-1 (MCP-1), the macrophage (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Conversely, in the fetal brain of the poly (I:C)/CTRL group, interleukin 12p70 and MIP-1 levels were lower than in veh/CTRL group. Notably, MIP-1, TNF-, GRO/KC, GM-CSF, and M-CSF levels were lower in the poly (I:C)/FEN than in poly (I:C)/CTRL rats, indicating the protective role of the PPARα agonist. PPARα might represent a therapeutic target to attenuate the consequences of MIA.

Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to severe distress or impairment. Patients suffering with major depressive disorder (MDD) display higher rates of comorbidity with personality disorders, often complicating the treatment, and worsening the outcome. Borderline personality disorder (BPD) is the most common of PD and is frequently associated with MDD, with which shares several features. The most part of research agrees on the fact that comorbid BPD in MDD patients quite double the poor response to treatments. Moreover, no treatment strategy stands out currently to emerge as more effective in these cases, thus urging the call for the need of a new approach. Herein, we revise the current literature on BPD, its neurobiology and comorbidity with MDD, as well as the more recent treatment strategies used. Then, based on its pharmacology, we propose a possible role of trazodone as a valuable tool to approach underlying BPD in MDD

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

Much evidence suggests a correlation between degeneration and mitochondrial impairment. Typical cases of degeneration can also be observed in physiological phenomena (aging) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have as a common denominator the dyshomeostasis of mitochondrial bioenergy. Even neurodegenerative diseases show a bioenergetics imbalance in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is a genetic, and progressive disease with early manifestation and severe penetrance, Parkinson's disease is a pathology with a multifactorial aspect. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early onset diseases linked to gene mutation, others can appear in young adults and senescent only post-injury, and a final group is idiopathic. Huntington's was defined as a hyperkinetic disorder, while Parkinson's is a hypokinetic disorder; but in the middle, there are a lot of similarities as well as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In the review, we would embrace the theories that both diseases start and develop in light of mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

The polygenic and multifactorial nature of many psychiatric disorders has hampered the personalized medicine approach implementation in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into induced pluripotent stem cells (iPSCs) to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that recapitulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depression disorder, bipolar disorder, and autism spectrum disorder. The future perspective will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways to build a disease model that considers individual variability and tailors personalized treatments.

Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress, and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30-150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognized by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, TFAM and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies (MVBs), are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EVs release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.

Objective: to analyze the relationships between sociodemographic variables, intolerance to uncertainty (INT), social support and psychological distress (i.e., indicators of Common Mental Disorders [CMDs] and perceived stress [PS]) in Brazilian men during the COVID-19 pandemic. Methods: a cross-sectional study with national coverage, of the web survey type, and conducted with 1,006 Brazilian men during the period of social circulation restriction imposed by the health authorities in Brazil, for suppression of the coronavirus and control of the pandemic. Structural equation modeling analysis was performed. Results: Statistically significant direct effects of race/skin color (λ=0.268; p-value<0.001), socioeconomic status (SES) (λ=0.306; p-value<0.001), household composition (λ=0.281; p-value<0.001), PS (λ=0.513; p-value<0.001) and INT (λ=0.421; p-value<0.001) were evidenced in the occurrence of CMDs. Black-skinned men, with higher SES, living alone and with higher PS and INT levels presented higher prevalence values of CMDs. Conclusions: high levels of PS and INT were the factors that presented the strongest associations with the occurrence of CMDs among the men. It is necessary to implement actions to reduce the stress-generating sources, as well as to promote an increase in resilience and the development of intrinsic reinforcements to deal with uncertain threats.

Depression is considered by WHO as the main contributor to global disability and it poses dangerous threats to approximately all aspects of human life, in particular public and private health. This mental disorder is usually characterized by considerable changes in feelings, routines, or thoughts. With respect to the fact that early diagnosis of this illness would be of critical importance ineffective treatment, some development has occurred in the purpose of depression detection. EEG signals reflect the working status of the human brain by which are considered the most proper tools for a depression diagnosis. Deep learning algorithms have the capacity of pattern discovery and extracting features from the raw data which is fed into them. Owing to this significant characteristic of deep learning, recently, these methods have intensely utilized in the diverse field of researches, specifically medicine and healthcare. Thereby, in this article, we aimed to review all papers concentrated on using deep learning to detect or predict depressive subjects with the help of EEG signals as input data. Regarding the adopted search method, we finally evaluated 22 articles between 2016 and 2021. This article which is organized according to the systematic literature review (SLR) method, provides complete summaries of all exploited studies and compares the noticeable aspects of them. Moreover, some statistical analysis performs to gain a depth perception of the general ideas of the latest researches in this area. A pattern of a five-step procedure was also established by which almost all reviewed articles fulfilled the goal of depression detection. Finally, open issues and challenges in this way of depression diagnosis or prediction and suggested works as the future directions discussed.

Mast cells (MCs) are best known as key effector cells of immediate type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at host-environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first line defense against pathogens. Their main characteristic, the huge amount of preformed pro-inflammatory mediators embedded in secretory granules, allow for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases, but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs all the way from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

The study assessed the changes in the quality and physical and chemical parameters of apples of four cultivars (‘Gala’, ‘Idared’, ‘Topaz’, ‘Red Prince’) subjected to mechanical vibrations during transport under model conditions and after storage (shelf-life). Quality changes in apples were evaluated based on skin and flesh colour, total soluble solids, dry matter, firmness, titratable acidity, pH value, total polyphenol content and antioxidant capacity. The applied vibrations at a frequency of 28 Hz caused changes in the above parameters, which were visible also after storage and depended on cultivar, but did not show any clear trend or direction. Skin colour varied whereas flesh colour remained stable. Vibrations resulted in a decrease in firmness. The greatest stability of quality parameters, the highest content of bioactive compounds and the highest antioxidant capacity were observed for ‘Red Prince’ and ‘Topaz’ apples – this refers to the control and treated samples before and after storage. However, total polyphenol content and antioxidant capacity increased in all studied cultivars as a result of vibrations and storage, which suggests that 28 Hz mechanical vibrations and short-term cold storage did not reduce the health promoting potential of the apples.

The aim of this article is to analyze the evidence against the effectiveness of intervention programs based on the participation of parents of children with autism. To obtain the data, a systematic search was carried out in four databases (ProQuest-PsychArticles, ProQuest-ERIC, ProQuest-PubMed, and Scopus). These documents were refined under the inclusion/exclusion criteria and a total of 51 empirical studies were selected. They were classified, first, according to the function of the intervention objective and, later, by the methodology applied (19 studies based on comprehensive interventions, 11 focused on the nuclear symptoms of ASD, 12 focused on the promotion of positive parenting and 9 interactions focused on children play). Once all the documents have been analyzed, the evidence indicates scientific efficacy in most studies, mainly in those based on child development and the application of behavioral analysis principles. Also, the positive influence of parent participation in such programs was demonstrated.

Neurodevelopmental disorders arise from genetic and/or from environmental factors and are characterized by different degrees of intellectual disability. The mechanisms that govern important processes sustaining learning and memory, which are severely affected in intellectual disability, have classically been thought to be exclusively under neuronal control. However, this vision has recently evolved into a more integrative conception, in which astroglia, rather than just acting as metabolic supply and structural anchoring for neurons, interact at distinct levels modulating neuronal communication and possibly also cognitive processes. Recently, genetic tools have made it possible to specifically manipulate astrocyte activity unraveling novel functions that involve astrocytes in memory function in the healthy brain. However, astrocyte manipulation has also underscored potential mechanisms by which dysfunctional astrocytes could contribute to memory deficits in several neurodevelopmental disorders revealing new pathogenic mechanisms in intellectual disability. Here, we review the current knowledge about astrocyte dysfunction that might contribute to learning and memory impairment in neurodevelopmental disorders, with special focus on Fragile X syndrome and Down syndrome.

Purpose: At a time of a pandemic SARS-CoV2 infection, and in the context of the multiorgan crosstalk widely accepted as a mechanism participating in the pathophysiology of all organs and systems, a correlation between adipose tissue, muscle and the immune system has been investigated. Physical Activity (PA) represents the first line of defence against metabolic diseases and infections, like SARS-CoV2, modulating several crucial functions such as inflammation and immune response. Conversely, obesity, type 2 diabetes and cardiovascular disorders – all correlated with PA - negatively impact on general health status, including susceptibility to infections. Here we review the complex interplay between type 2 diabetes, obesity, immune response, inflammation and viral infections, such as the current SARS-CoV2, focusing on the molecular mechanisms modulated by exercise. Methods: A comprehensive literature search was completed to identify joint biomarkers previously used to investigate acute and chronic exercise training. Results: we show that PA may counteract/mitigate viral adverse effects. We also describe data suggesting that vitamin D supplementation, frequently observed in practitioners of sport and regular exercise, could represent an additional positive factor in supporting COVID-19 with fighting against the virus. Conclusion: Altogether this evidence confirms that an active lifestyle and PA not only counteract dysmetabolic diseases but could also be effective for counteracting SARS-CoV2 infection. It is therefore essential to persuade people to keep active.

Inherited platelet disorders (IPDs) are rare diseases featured by low platelet count and/or defective platelet function. Patients have variable bleeding diathesis and sometimes additional features that can be congenital or acquired. Identification of an IPD is desirable to avoid misdiagnosis of immune thrombocytopenia and use of improper treatments. Diagnostic tools include platelet function studies and genetic testing. The latter can be challenging as the correlation of its outcomes with phenotype is not easy. The immune-morphological evaluation of blood smear (by light- and immunofluorescence microscopy) represents a reliable method to phenotype subjects with suspected IPD. It is relatively cheap, not excessively time-consuming, and applicable to shipped samples. In some forms, it can provide diagnosis by itself, as for MYH9-RD, or in addition to other first-line tests as aggregometry or flow cytometry. In regard to genetic testing, it can guide specific sequencing. Since only minimal amounts of blood are needed for preparation of blood smears, it can be used to further characterize thrombocytopenia in pediatric patients and even newborns. In principle it is based on visualizing alterations in the distribution of proteins, which result from specific genetic mutations, by using monoclonal antibodies. It can be applied to identify deficiencies in membrane proteins, disturbed distribution of cytoskeletal proteins, and alpha as well as delta granules. On the other hand mutations associated with impaired signal transduction are difficult to identify by immunofluorescence of blood smears. This review summarizes technical aspects and the main diagnostic patterns achievable by this method.

The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. SES can influence global health trajectory for an individual or a community, depending if SES is low or high. Sleep is sensitive to environmental stimuli, as well as living conditions. Plenty of studies linked sleep complaints with mood disorders, allostatic load or circadian disruption; but very few or none investigated deeply what happened earlier to sleep depending of SES. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. Even if recent evidence suggested that few of SES indicators like occupational status are linked with sleep disturbances, the relation between SES and health in general with sleep as an outcome or a mediator is not well documented. This scoping review synthetized studies which investigated physiological and psychological mechanisms resulting from a low SES and linked them with sleep disturbances as consequences or as mediators. This review also explore a possible role played by sleep in the relation between socioeconomic status and health inequalities.

Lower back musculoskeletal disorders (MSD) are an important public health problem and the leading cause of disability worldwide, but with prevalence yet unknown among shellfish gatherers. To investigate the prevalence and work-related factors associated with lower back MSD in a population of female shellfish gatherers, an epidemiological cross-sectional study was carried out in Saubara, Bahia – Brazil, in 2013. The Brazilian version of the Job Content Questionnaire (JCQ) and the Nordic Musculoskeletal Questionnaire (NMQ), in addition to a questionnaire containing the physical demands adapted to the artisanal work, were applied to a random sample of 209 female shellfish gatherers. The prevalence of lower back MSD was 72.7%. Using multivariate logistic regression, the shellfish gatherers who had worked for more than 26 years in the activity showed a prevalence of 1.22 (95% CI: 1.04-1.44) times higher compared to those unexposed. Lower back MSD was 1.24 (95%CI: 1.08-1.42) times higher among those more exposed to work sitting with trunk flexion. Those performed manual handling and muscle force with the arms had a prevalence ratio of 1.18 (95%CI: 1.01-1.39). These results show the need for greater awareness of health and social welfare factors impacting workers in small-scale fisheries and will promote the elaboration of health care policies for this occupational class.

Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

Psychiatric disorders share the same pattern of longitudinal evolution and have courses that tend to be chronic and recurrent. These aspects of chronicity and longitudinal evolution of psychiatric disorders are currently studied under the neuroprogression framework. Interestingly, considering the plasticity of the brain, it is necessary to emphasize the bidirectional nature of neuroprogression. We review evidence highlighting alterations of the brain associated with the longitudinal evolution of psychiatric disorders from the framework of neuroplastic adaptation to pathology. This new framework highlights that substantial plasticity and remodelling may occur beyond the classic neuroprogressive framework, which is characterized only by loss of grey matter volume, decreased brain connectivity, and chronic inflammation. We also integrate the brain economy concept in the neuroplastic adaptation to pathology framework, emphasizing that to preserve its economy, i.e., function, the brain learns how to cope with the disease by adapting its architecture. This approach can disentangle both the specific pathophysiology of psychiatric symptoms and the adaptation to pathology, thus offering a new framework for both diagnosis and treatment.

Apart from their established role in embryonic development Nerve Growth Factors (NGFs) have diverse functions in the nervous system. Their role in integration of physiological functioning of the nervous system is now attracting attention. In the present analysis, we propose a novel paradigm about a novel role of NGFs: NGFs play imperative role in maintaining psychological integrity of an individual as a biological system. This function may be mediated through HPA-axis- operated homeostatic mechanisms; stress induced disruption of which may lead to psychiatric disorders. Current literature suggests existence of constitutive homeostatic regulatory mechanisms for NGFs disruption which may lead to pertinent and imperative behavioural effects. NGFs are known to play crucial role in endocrine regulation. This is especially true with the prototype ‘NGF’ and Brain Derived Neurotrophic Factor (BDNF). These moieties have been observed to play important function in maintaining neuro-endocrine homeostasis thereby having a profound impact on the psychological health of an individual. Role of NGFs and HPA-axis activation (in separate studies) in developing psychiatric disorders - especially those born of stress - have been reported. Literature suggests their unique interplay for producing a common effect which might be implicated in stress induced genesis of psychiatric disorders. This aspect, therefore, needs to be elucidated further as a disease etiogenesis model. This model may yield important insights into the biology of psychiatric disorders and may open ways for new therapeutic approaches.

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

Background: This study aimed to investigate the association between the internal derangement of the temporomandibular joint (TMJ), in particular the severity of disc displacement (DD), and the presence of generalized joint hypermobility (GJH) in growing patients evaluated on magnetic resonance images (MRI). The study also investigated the relationship between the stages of DD severity and age. Methods: This cross-sectional study has been conducted on a pre-orthodontic population (8-16 years). The GJH was assessed with the Beighton test (cutoff ≥ 4) and the final sample of 56 patients was divided into two groups: a Study Group, 30 subjects with GJH, and a Control Group, 26 subjects without GJH. The disc position was evaluated on MRI and the severity of DD was classified in four stages. Pearson's χ2 Test was performed for the analysis of the statistical correlation. Results: A statistically significant relationship between GJH and disc position was found, in particular a disc displacement with reduction (DDwR) and DD severity. It also emerged a positive association between the severity of DD and age, that increased with increasing age. Conclusions: Growing patients with GJH have a higher risk of developing DD and with more severe stages. The risk of developing DD and the severity increases with increasing age.

Ovulatory infertility is a serious clinical problem whose direct causes are still largely unknown. In addition to pathologies that make it impossible for a couple to establish a pregnancy, there are a number of other factors that have a bearing on fertility, including lifestyle factors, particularly diet. Although numerous studies have been performed linking such factors with ovulatory infertility, most of them lack the necessary clinical significance, focusing instead on observational data and establishing associative relationships. This paper includes a literature review focusing on connections between lifestyle factors such as diet, physical exercise, oxidative stress, sleep, and supplementation, and ovulatory infertility. Special emphasis was given to issues such as obesity and insulin resistance and their mutual relationship with other factors linked to ovulatory infertility. In addition, making use of the conclusions of literature review, the authors propose a classification of relationships between ovulation disorders and lifestyle factors in ovulatory infertility based on the WHO classification of ovulation disorders, and indicate areas that merit further research. The data presented in the paper shows that the issues of proper diet and physical exercise are those that would merit from robust clinical studies focused specifically on ovulation infertility, while studies concerning the relationship between oxidative stress, sleep, and supplementation and ovulatory infertility do not seem to be promising directions as far as clinical significance is concerned.

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

The COVID-19 Pandemic generated, in addition to severe symptoms, hospitalizations, and deaths worldwide, stress from the fear of the disease and social uncertainties, from restriction measures and social isolation. Stress from social isolation impacts mental health, aggravating conditions, and triggering neuropsychiatric symptoms in individuals with biopsychosocial vulnerability. During and immediately after the period of social restriction imposed by the Pandemic, the scientific community carried out several research protocols. It revealed results that relevantly demonstrate the harmful effect of the stress induced by the Pandemic situation. This review reports and discusses research results demonstrating impairments in neuropsychiatric disorders such as autism spectrum disorder, dementia, eating disorders, schizophrenia, anxiety, and depression. In addition to studies showing the effect of social isolation on disorders, research results are reported and discussed that evaluated protocols with some possible therapeutic intervention strategies during times of social restriction.

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

There is immense variability in the postharvest quality of Hass avocados. However, there is a lack of knowledge to guaranteeing the robustness of fruit with consistent quality. The aims of this work were to develop a multivariate methodology for evaluating the postharvest quality of avocado and to determine predictive quality markers to manage fruit quality. Fruit samples produced under different nutrient management, elevation, date-to-harvest, and growing-cycle conditions were analyzed. The results highlighted soil and weather differences among orchards. Nutrient management practices based on index balancing in some samples increased both productivity and the fruit size. High variability was observed in the dry matter related to the age of the fruit at harvest. Ripening heterogeneity was very large in low-elevation orchards where the fruit was picked relatively early. High flesh mineral contents delayed fruit ripening. At low growing temperatures, more oleic and linoleic acids were present in fruits. The sensory texture and taste descriptors were affected by the fruit age and related to the flesh composition. Logistic, PLS-DA, and biplot models effectively represented the variabilities in the ripening pattern, composition, and sensory profile of avocado fruits and allowed the samples to be grouped according to the internal fruit quality.

Aim. In the current study, we aimed at identifying resting-state brain networks, which are different in patients with depression compared to healthy individuals. Moreover, we analyzed the potential for clinical use of different network measures that could discriminate the two groups and thus help the diagnostic process. Method and subjects. We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed to investigate functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were made at the functional networks level, using false discovery rate method. Independent samples t-test was performed on the network measures mean values to reveal differences between HC and MDE groups. Permutation-based statistical testing was used to test the significance of the difference between the distributions of the network measures by nodes for HC and MDE groups. Linear discriminant analysis was used to differentiate between the groups. Results and discussion. Significant differences in FC between depressed patients and healthy controls were found with the most prominent changes encompassing within-region as well as between-region connectivity of occipital lobe areas such as precuneus (PreCu), cuneus (Cu), superior occipital gyrus (SOG), lingual gyrus (LG), fusiform gyrus (FG), cerebellum, along with limbic structures including the hippocampus (Hipp) and cingulate gyrus. Linear discriminant analysis demonstrated that the full connectivity matrices, as well as those with only the significant connections identified in advance, were the most precise in differentiating between depression and health. These measures reached precision levels of 97% and 94%, respectively. Conclusion. Our study delivered further evidence about impairment of functional connectivity networks in MDE that may contribute to differentiate patients with depression from healthy subjects.

The modification of proteins by small ubiquitin-related modifier (SUMO) molecules, SUMOylation, is a key post-translational modification involved in a variety of biological processes such as chromosomes organization, DNA replication and repair, transcription, nuclear transport, and cell signaling transduction. In recent years, emerging evidence has shown that SUMOylation regulates the development and homeostasis of the skeletal system, with its dysregulation causing skeletal diseases, suggesting that SUMOylation pathways may serve as a promising therapeutic target. In this review, we summarize the current understanding of the molecular mechanisms by which SUMOylation pathways regulate skeletal cells in the physiological and disease contexts.

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. Method: To determine the effect of a nursing educational intervention on improving healthy sleep, a parallel, open-label clinical trial in subjects with Impaired Fasting Glucose (IFG) or Type 2 Diabetes Mellitus (T2DM) and 18 and older was performed. Study variables were sex, age, fasting glucose, glycated hemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, BMI, antidiabetic treatment and diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. It was intended to develop skills to improve sleep through 9 simple tips. An analysis of covariance was performed on all the mean centered outcome variables controlling for the respective baseline scores. Results: After the intervention, in the experimental group, PSQI dropped, the duration and quality of sleep increased. Further, a decrease in fasting glucose and in HbA1c levels was observed. Conclusion: The proposed intervention has proven to be effective to improve sleep quality, time, and efficiency and in only 3 months, to achieve a decrease in fasting glucose and HbA1c levels. These findings support the importance of sleep and circadian rhythms education focused on improving in T2DM or IFG.

Background: Perinatal anxiety and related disorders are common (20%), distressing and impairing. Fear of childbirth (FoB) is a common type of perinatal anxiety associated with negative mental health, obstetrical, childbirth and child outcomes. Screening can facilitate treatment access for those most in need. Objectives: The purpose of this research was to evaluate the accuracy of the Childbirth Fear Questionnaire (CFQ) and the Wijma Delivery Expectations Questionnaire (W-DEQ) of FoB as screening tools for specific phobia, FoB. Methods: A total of 659 English-speaking pregnant women living in Canada and over the age of 18 were recruited to the study. Participants completed an online survey of demographic, current pregnancy, and reproductive history information, as well as the CFQ and the W-DEQ, and a telephone interview to assess specific phobia FoB. Results: Symptoms meeting full and subclinical diagnostic criteria for specific phobia, FoB were reported by 3.3% and 7.1% of participants, respectively. The W-DEQ met or exceeded the criteria for a “good enough” screening tool across several analyses, whereas the CFQ only met these criteria in one analysis, and came close in three others. Conclusions: The W-DEQ demonstrated high performance as a screening tool for specific phobia, FoB, with accuracy superior to that of the CFQ. Additional research, to ensure the stability of these findings, is needed.

Background. Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms.Aim. To examine the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), and CFS-like (Fibro-fatigue Scale) symptoms and immune-inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylceramide in RA. Methods. The serum biomarkers were assayed in fifty-nine RA and fifty-nine patients without increased psychopathology (PP) and fifty healthy controls.Results. There were highly significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tenders and swollen joints, and patient and evaluator global assessment scores. A common latent vector (reflective model) could be extracted from the PP and RA-severity scales, which showed excellent psychometric properties. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning PP and RA symptoms could be explained by the regression on immune-inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. Conclusions. Depression, anxiety, and CFS-like symptoms due to RA are reflective manifestations of the phenome of RA and are mediated via the effects of the same immune-inflammatory, autoimmune, and EOS pathways and lactosylceramide that underpin the pathophysiology of RA. These PP symptoms are clinical manifestations of the pathophysiology of RA.

Children with Fetal Alcohol Spectrum Disorders (FASD) and Autism Spectrum Disorders (ASD) experience significantly higher rates of sleep disturbances than their typically developing peers. Pre-sleep anxiety and waking emotional content is known to affect the content and frequency of nightmares, which can be distressing to children and caregivers. This is the first study to analyse nightmare frequency and content in FASD, and to assess its association with psychometric outcomes. We assessed reports from 277 caregivers of children with ASD (n=61), FASD (n=112), and TD children (n=104) using the Children’s Sleep Habits Questionnaire (CSHQ), the Child Behavior Checklist (CBCL), the Spence Children’s Anxiety Scale (SCAS) and the Behavior Rating Inventory for Executive Functioning (BRIEF). Within the ASD group, 40.3% of caregivers reported their children had nightmares. Within the FASD group, 73.62% of caregivers reported their children had nightmares and within the TD group, 21.36% of caregivers reported their children had nightmares. Correlation analysis revealed significant associations between anxiety and nightmares, maladaptive behaviour and nightmares, and executive functioning and nightmares in the TD and FASD groups, but not ASD group. This paper adds to the emerging body of work supporting the need for sleep interventions as part of clinical practice with regard to children with ASD and FASD. As a relatively niche but important area of study this warrants much needed further research.

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

Apathy is a fundamental neuropsychiatric symptom of Korsakoff’s syndrome (KS) and has also been reported in patients with alcohol use disorder with no (AUD) or less severe cognitive disorders (ALC). However, research on the nature of apathy is limited in these groups. Aim of this study was to examine the multidimensional nature of apathy in patients with KS, ALC and AUD. Moreover, we examined differences between apathy ratings by patients and their professional caregivers, and related apathy to everyday functioning and overall cognition. Twenty-four patients with KS, 24 patients with ALC and 21 patients with AUD participated in this study. Apathy was measured using the Apathy Motivation Index (AMI), which distinguishes behavioral, emotional and social apathy. Both patients and professional caregivers reported social apathy as most prominent symptom, compared to behavioral and emotional apathy. Apathy ratings did not differ across the three patient groups. Discrepancies between patient and caregiver ratings were observed in patients with KS and ALC, with more severe apathy reported by caregivers. Caregiver-reported behavioral and social, but not emotional, apathy was related to everyday functioning. These results show that apathy is present in a substantial proportion of patients with alcohol addiction with or without cognitive impairments.

Genetic disorders are preeminent determinants of infant mortality. The inherited pediatric-onset genetic disorders have consequential stress on child growth and development: several congenital, complex and rare disorders with indistinguishable clinical symptoms where diagnosis always remains a challenging task. Traditional diagnosis methods include biochemical tests followed by chromosomal microarray and sequencing of a single gene or panel of genes. These methods had several limitations, but with the advent of whole-exome sequencing (WES), genetic testing has become cost-effective and transformative. Exome sequencing has been known for its effectiveness, which appropriately elucidates and distinguishes the heterogeneous disorders to avoid misdiagnosis and decode the underlying genetic alterations. WES has led to discovering genes and genomic variants in a broad spectrum of diseases, including autism, epilepsy, congenital heart diseases, neurodevelopmental diseases, cancer, nephrotic disorders, neural tube defects and fetal structural anomalies. WES is significant in producing immense genomic biomarkers that can be made as appropriate pharmacogenomic targets for drug therapy. In this article, we analyze the recent exploration of WES technology to revolutionize not only the process of genetic variation and disease detection but also the convention of preventative and targeted drug discovery.

The objective of this review is to do an overview about the current knowledge of Anti Iglon5 Syndrome, a disease that was first described in 2014. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 are crucial for diagnosis of Anti IgLON5 Syndrome. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. The early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The mortality of anti IgLON5 syndrome is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends of some clinical and analytical characteristic. In addition, future studies are needed to thoroughly study the aspects of pathogenesis and treatment of this important pathological syndrome.

Different factors seemingly account for the emergence of present-day languages in our species. Human self-domestication has been recently invoked as one important force favouring language complexity mostly via a cultural mechanism. As a consequence, evolutionary changes impacting on aggression levels are expected to have fostered this process. Here we hypothesise about a positive effect of dog-human interactions on aggression management and more generally, on our self-domestication, ultimately, contributing to aspects of language evolution. We review evidence of diverse sort (ethological mostly, but also archaeological, genetic, and physiological) supporting a positive feedback loop between dog domestication and human-self domestication that might have favoured the mechanisms promoting structural complexity in human languages.

Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI<0.2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 ± 0.78 µg, 9.15 ± 1.23 µg and 1.42 ± 0.21 µg respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. This theoretical review explores some theories linking environment of people with occurrence of SD, with different patterns associated to SES. A model of interaction is proposed to summarize and conceptualizes these interactions and to promote more research on the topic.

Hospitalized patients frequently have disordered and poor-quality sleep due to a variety of both intrinsic and extrinsic factors. These include frequent nighttime intrusions, insomnia related to pain and unfamiliar environments, dark conditions during the day with loss of natural light, and disruption of natural sleep cycle due to illness. Sleep wake disturbances can result in deleterious consequence on physical, emotional and cognitive status, which may impact patient satisfaction, clinical recovery, and hospital length of stay. Despite this, clinicians frequently fail to document sleep disturbances and are generally unaware of best practices to improve sleep quality in the hospital. The purpose of this review is to discuss sleep disturbances in hospitalized patients with a focus on causes of sleep disturbance, effect of poor quality sleep, high risk populations, considerations for surveillance and prevention, as well as pharmacologic and non-pharmacologic options for treatment.

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