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

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

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

Autism spectrum disorder (ASD) is a common condition with lifelong implications and a strong hereditary component suggesting genetic underpinnings. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes not associated with ASD (P = 0.0002, odds ratio 29), validating that most are indeed disease related. Only 14/34 (41%) of PDV cases had the variant listed on the laboratory report, and reanalysis increased diagnostic yield from 28% to 68%. Variants that we assigned as PDVs yet not on the report were predominately de novo in genes not yet reported as ASD associated. Many subjects both with and without a PDV had inherited Qualifying variants in known ASD-associated genes, suggesting polygenic inheritance. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate high yield of trio-WGS for revealing molecular diagnoses in ASD that is greatly enhanced by re-analyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.

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.

Background: One of the most common occupational health hazard and serious health concern, now a days, recognized is Musculoskeletal disorders (MSDs). The high prevalence among students and teachers is a major cause of decline in their health related quality of life and work performance. This study aimed to identify the prevalence of musculoskeletal disorders among teachers and students during online education. Methods: A cross-sectional survey was conducted among university faculty members and students who were involved in online education during COVID-19. Data collection was carried out electronically through a validated Arabic version of the Nordic Musculoskeletal Questionnaire (NMQ) which is self reported. A total of 175 respondents responded to the questionnaire (response 60%). Results: The prevalence of any part of the body was 90.3%. The commonest site of MSDs for past 12 months was the low back (65.7%), the neck (58.3%), and shoulders (57.7%). Females (80%) suffered more than males (20%). The students reported slightly higher MSDs as compared to teachers (93.1% vs 90.3). Binominal regression analysis showed association of females with low back pain “OR: 2.24 (95% CI): 1.04-4.83; p = 0.03” and neck pain “OR: 2.7 (95% CI): 1.24–5.84; p = 0.012)” while bad posture was associated with pain in upper back “OR: 3.46 (95% CI): 1.73-6.93; p = 0.001”. Conclusion: The faculty members and students are prone to high MSDs during online classes and significant measures should be taken to reduce the prevalence by addressing associated risk factors.

Background: Evidence suggests that there is substantial comorbidity between fibromyalgia and Axis II pathology (i.e., personality disorders - PDs). The aim of the current study was to find out the exact cluster (A, B, C) PDs or traits that are more prominent in FM and may be predictors of FM diagnosis. Methods: Data from 86 subjects (53 with FM and 33 controls without FM) was analyzed in an observational, cross-sectional, comparative study. The assessment of categorical PDs and traits was performed independently with the Structured Clinical Interview for Personality Disorders (SCID-II). Binary logistic regression was used to determine FM predictors among PDs traits. Results. Compared with controls, FM patients had higher rate of PDs diagnoses (56.7 vs 18.2%, P<.001). However, the rate was significantly higher only for borderline PD diagnosis (28.3% vs 6.1% P<.05). The binary logistic regression analysis showed that schizotypal and schizoid (cluster A), borderline (cluster B), and dependent (cluster C) personality traits may be significant predictors of fibromyalgia (Nagelkerke R2 = 0.415). Conclusions: Our results may reflect association of FM with personality traits of all three PD clusters: A (eccentric), B (dramatic), C (anxious). However, the most consistent evidence seems to be for borderline PD.

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.

Social communication skills, especially eye contact and joint attention, are highly impaired in autism spectrum disorder (ASD) and predict functional outcomes. Applied Behavior Analysis is one of the best evidence-based treatments for ASD, but it is not accessible to most families in low- and middle-income countries (LMICs) as it is a costly and intensive and needs to be delivered by highly specialized professionals. Parental training has emerged as an effective alternative. The aim of this study was to test the efficacy of a parental intervention group via video modeling to acquire eye contact and joint attention. Four graded measures of eye contact and joint attention (full physical prompt, partial physical prompt, gestural prompt, and independent) were assessed in 34 children with ASD and intellectual disability (ID). There was a progressive reduction in the level of prompt required over time to acquire eye contact and joint attention, and a positive correlation between the time of exposure to the intervention and acquisition of the abilities. This parent training using video modelling to teach eye contact and joint attention skills to children with ASD and ID is a low-cost intervention that can be applied in low- resource settings.

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.

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induce the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted in the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions which share high identity between SARS-Cov-2 anti-gens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.

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

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

The hybrid method proposed in the study, ANFIS-GWO, combines the Adaptive Neuro-Fuzzy Inference System (ANFIS) with Grey Wolf Optimization (GWO) for the diagnosis of liver disorders. ANFIS is a powerful tool that combines the advantages of neural networks and fuzzy logic to create a hybrid model capable of handling complex and uncertain data. GWO is a metaheuristic optimization algorithm inspired by the social behaviour of grey wolves. In the ANFIS-GWO method, the hyperparameters of ANFIS are optimized using GWO. This optimization process aims to fine-tune the ANFIS model based on the available dataset, which consists of 7 characteristic attributes and 354 samples related to liver diseases. By adopting the hyper-parameters, the ANFIS-GWO method enhances the overall performance and accuracy of the diagnostic system. To evaluate the effectiveness of the ANFIS-GWO intelligent medical system, the study employs classification accuracy, sensitivity, and specificity analysis. Classification accuracy measures the overall correctness of the system in predicting liver disease cases. Sensitivity refers to the system’s ability to correctly identify individuals with liver disorders, while specificity measures its ability to correctly identify those without liver disorders. Experimental results demonstrate that the performance of the ANFIS-GWO method surpasses that of traditional Fuzzy Inference Systems (FIS) and ANFIS models that do not undergo an optimization phase. This suggests that the integration of GWO optimization significantly improves the diagnostic accuracy of the ANFIS model for liver disease diagnosis.

Polycystic ovary syndrome (PCOS) is a prevalent condition characterized by manifestations that can influence self-image and potentially result in psychological distress; however, data from literature on sexual function (SF) in PCOS women are contradictory. We aimed to evaluate sexual dysfunction (SD) in PCOS women by carrying out a systematic review and meta-analysis, using the gold-standard assessment tool SD-diagnosis (Female Sexual Function Index:FSFI). Seven databases were analyzed until August-2023; study quality was assessed by risk of bias and Newcastle Ottawa Scale. Our analysis encompassed 25 case-control studies (9933 women). PCOS group presented significantly lower scores in arousal (MD= -0.36 CI95%-0.60;-0.11), lubrication (MD= -0.52 CI95%-0.75;-0.28), orgasm (MD= -0.39 CI95%-0.57;-0.20), satisfaction (MD= -0.32 CI95%-0.50;-0.14) and pain subdomains (MD= -0.46 CI95%-0.75;-0.16), as in overall FSFI score (MD= -2.27 CI95%-3.23;-1.31). Overweight/obese (OW/O) patients exhibited significantly higher overall FSFI than OW/O controls (MD=1.98 CI95%0.68;3.27), particularly in lubrication (MD= -0.34), orgasm (MD= -0.26) and satisfaction (MD= -0.25) subdomains. These findings offer insights regarding SD in PCOS women and emphasize the need to incorporate SF assessment into multidisciplinary care. By this way, PCOS can be also considered a gateway diagnosis to other long-term consequences. Further research should focus on controlling variables, as ethnicity, culture, religion and economic disparities.

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.

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to those NRs modulation, OA exhibited prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

Zn is an essential element for children related to optimal growth, development and nutritional metabolism. We measured Zn bioaccesibility (Zn-BA) levels of foods by Inductively coupled plasma mass spectrometry (ICP-MS) after in vitro digestion-fermentation method from children with gluten related disorders (GRD-CH), obesity (OB-CH) and allergy/intolerance to cow’s milk proteins (AICM-CH). Zn-BA levels in sick children (34.7 ± 28.8, 29.6 ± 30.1 and 26.7 ± 30.4%, respectively) were significantly lower (p &lt; 0.05) than in healthy norm-weight children (HE-CH). For AICM-CH, Zn-BA in animal foods was significantly lower than in plant foods, and in both plant and animal foods from sick and healthy children (p &lt; 0.05). In foods of animal origin in sick and healthy children, Zn-BA in foods heated in liquid media (frying and boiling) was significantly higher than in foods heated by hot air (roasting and grilling). In conclusion, in children the studied diseases diminished the Zn-BA, probably by the alteration of the gut microbiota which could negatively affect their appropriate long-term development. In AICM-CH, the allergy to cow's milk proteins could induce intestinal dysbiosis and inflammatory processes, leading to allergies to other animal food proteins, and to a more pronounced decrease of Zn-BA.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is one of the most controversial diseases in pediatric rheumatology. Despite its first description being published more than 25 years ago as the sudden and rapid onset of obsessive-compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine re-lease in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.

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

Non-pharmacologic options like the ketogenic diet (KD) and intermittent fasting (IF) are practical nutritional interventions with minor reported side effects like gastrointestinal symptoms, dyslipidemia, and hypomagnesemia for various medical ailments. In conjunction with IF, KD shows promise in weight loss, diabetes management, cardiovascular disorders, polycystic ovarian syndrome, cancer, and chronic neurological disorders. Based on prior research, we have examined the mechanism of action of KD and IF and their effect on neurological diseases, cancer, and obesity. We have also suggested evidence-based recommendations for the safer practice of KD and IF. Despite potential benefits, long-term adherence to KD poses challenges. Periodic KD implementation may thus benefit newly diagnosed overweight or obese patients with type 2 diabetes mellitus, aiding blood glucose and lipid management while promoting weight loss. KD is a high-fat and low-carbohydrate diet with a ratio of fat to carbohydrates and protein being 4:1 or 3:1, and thus, for peripheral tissues and the brain, fatty acids become the mandatory source of cellular energy. Ketone bodies have been used as the primary energy source during fasting. KD has been utilized as an effective treatment for refractory epilepsy since the 1920s. Evidence of the neuroprotective role of KD in diseases like epilepsy, stroke, traumatic brain injury, Alzheimer’s disease, and other neurological diseases has been noted. Since the 1960s, KD has become a popular method for obesity treatment. In addition, KD has been suggested as a potent anticancer therapy when used alone or as an adjuvant. KD may increase tumor cell sensitivity when combined with classic chemotherapy and radiotherapy. Thus, the probability that modifying the diet can help manage obesity, cancer, and chronic neurological disease without depending on pharmacological treatment and their serious side effects for a lifetime is promising and requires further investigation. KD holds promise as a potential adjunctive therapy in various neurological disorders, offering new avenues for treatment and neuroprotection. IF has shown potential in slowing the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's by promoting antioxidant defense and suppressing inflammation. KD and IF show promise in cancer therapy by targeting altered cancer cell metabolism. Additionally, KD may enhance the effects of standard treatments like chemotherapy and radiotherapy. Some of the most robust reports of keto's possible benefits have come from glioblastoma, a very aggressive brain cancer. KD has also shown strong evidence for its effectiveness in weight loss, mainly attributed to its appetite-suppressing action in ketosis. However, long-term adherence to KD can be challenging, and periodic KDs may help manage blood glucose and lipid levels in overweight or obese patients with type 2 diabetes mellitus. Likewise, IF may be more effective than regular calorie restriction for achieving weight loss goals when combined with exercise programs. More prospective human studies are warranted to evaluate both KD and IF's potential therapeutic effectiveness and safety.

Abstract Psychiatric care in Spain has experienced relevant changes both in the legislative and conceptual frameworks. This new approach advocates for the combination of carrying out mental health promotion, prevention of alterations and early diagnosis and treatment, enhancing actions against stigma and emphasising the attention on the most vulnerable groups, like childhood and youth. For that, it has seen fit to perform a nursing intervention on Education and Promotion of mental health for teachers and counsellors of a secondary school located in Valencia, with the general objective of assessing their impact on stigma. Non-randomised clinical trial in which a nursing intervention on Education and Promotion of mental health was performed. Pre-intervention tools: multiple choice test validated by a group of experts; pre and post-intervention: AQ-27 (stigma attribution); in order to check its acceptance, satisfaction surveys were used. The inferential analysis included the Wilcoxon Test (pre and post AQ-27) and the Pearson Correlation Test for the quantitative variables of interest. Sample (n=22): women aged 47.96 ± 10.12 years with 18.64 ± 10.34 years of work experience. The predominant stigmatising attitude before and after intervention was “Coercion”. The ones with lower score were “Segregation” and “Anger”. The p-values obtained in the Wilcoxon Test were statistically significant (p-value <0.05) except for “pre and post Responsibility” and “pre and post Pity”. The following constructs of interest were faced: “Age” vs “Fear” (r= -0.48, moderate), “Professional experience” and “Fear” (r= -0.46, moderate) and “Help” and “Psychosis test” (r= 0.51, severe). The overall satisfaction score was 9/10. Despite the scores obtained in “Coercion” and “Psychosis”, the intervention was useful for reducing stigma in the sample.

Background and aims: Only one cohort study exists on the incidence of the risk of malnutrition (RM) in older adults, though numerous cross-sectional –and that cohort research– have reported several risk factors associated with the prevalence and incidence of this condition. However, alterations of body composition and impaired physical performance as exposition variables of RM have not been explored. This study assessed the incidence of RM and determined its association with excess fat mass, low total lean tissue, gait speed, and handgrip strength as exposition variables for RM in community-dwelling older adults. Methods: This is a secondary analysis in older adults (≥60 years old) derived from the study “Frailty, dynapenia, and sarcopenia in Mexican adults (FraDySMex)” a prospective cohort project conducted from 2014 to 2019 in Mexico City. At baseline, volunteers underwent body composition analysis and physical performance tests. Several covariates were identified through comprehensive geriatric assessment. At baseline and follow-up, RM was assessed using the long form of the mini nutritional assessment (MNA-LF) scale. Associations between the exposition variables and RM were assessed by multiple logistic regression. Results: The cohort included 241 subjects. Average age was 75.6±7.8 years; 83.4% were women. The mean follow-up period was 4.1 years, during which 28.6% of subjects developed RM. This condition was less likely to occur in subjects with excess fat mass index, even after adjusting for several covariates. RM was also more likely to occur in subjects with low total lean tissue index, according to both an unadjusted model and after adjusting for the corresponding variables. Regarding the association between RM and gait speed, RM was also more likely to occur in subjects with low gait speed according to both the unadjusted and adjusted models. Similar results were found for RM in relation to low handgrip strength; however, after adjusting for the associated covariates, models 1 and 2 no longer reached the level of significance. Conclusion: The risk of malnutrition diagnosed by MNA-LF was significantly less likely to occur among subjects with excess fat mass, but possibility was significantly higher in those with low total lean tissue and low gait speed after 4.1 years of follow-up in community-dwelling older adults. These results highlight that excess fat mass, low total lean tissue, and low gait speed are first than risk of malnutrition and not vice versa.

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.

Abstract Forensic institutions throughout the country house patients with severe psychiatric illness and history of criminal violations. Improved medical care, hygiene, and nutrition led to unmatched longevity in this population which previously lived on average 15 to 20 years shorter than the public at large. On the other hand, longevity has contributed to increased prevalence of age-related diseases, including neurodegenerative disorders, which complicate clinical management. Forensic institutions, originally intended for the treatment of younger individuals, are ill-equipped for the growing number of older offenders. Moreover, as antipsychotic drugs became available in 1950s and 1960s, we are observing the first generation of forensic detainees who had aged on dopamine blockers. Although the consequences of long-term treatment with these agents are unclear, schizophrenia-associated gray matter loss, may contribute to the development of early dementia. Taken together, increased lifespan and subsequent cognitive deficit observed in long-term psychiatric institutions brought forth questions and dilemmas unencountered by the previous generations of clinicians, such as: 1. Does the presence of neurocognitive dysfunction justify antipsychotic dose reduction or discontinuation despite a lifelong history of schizophrenia and violent behavior? 2. Should neurolipidomic interventions become the standard of care in elderly individuals with lifelong schizophrenia and dementia? 3. Can patients with schizophrenia and dementia meet the Dusky standard and stand trial? 4. Should neurocognitive disorders in elderly with lifelong schizophrenia be treated differently than age-related neurodegeneration? In this article, we describe strategies for potentially slowing the development of neurocognitive disorders in forensic patients with chronic mental illness by adopting a three-prong strategy: 1. Approaching lifelong psychosis from microbial and immunological perspective. 2. Identify modifiable risk factors for age-related diseases in forensic institutions. 3. Utilizing novel receptor-independent treatments for chronic psychosis.

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: The oldest old people (≥ 85 years) represent the fastest growing age group in Western populations. Knowledge on early outcomes of acute ischemic stroke (AIS) in very old female patients remains limited. Methods: We assessed gender differences and female-specific clinical data and in-hospital mortality in very old patients with AIS. Acute cerebral infarction was diagnosed in 506 very old female patients from a total of 4,600 acute cerebrovascular infarctions available in an ongoing 24-year hospital stroke data bank. A comparative analysis of vital status at discharge (alive versus dead) was performed in terms of cardiovascular risk factors, clinical data, and early outcomes. Results: The overall in-hospital mortality rate was 20.4%. In multivariate analysis, sudden onset, altered level of consciousness, and neurological, respiratory, cardiological or hemorrhagic complications, and lacunar infarcts appeared to be independent predictors of in-hospital mortality. Conclusions: Female patients ≥85 years with AIS are an unfavorable subgroup of stroke patients with a high risk of early mortality, which may be due to comorbidity, stroke subtype distribution, and higher frequency of medical complications. However, the presence of lacunar infarcts showed a significant protective effect.

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

Abstract: Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. The global prevalence of autism has increased twentyfold to thirtyfold since the earliest epidemiologic studies were conducted in the late 1960s and early 1970s. Recent reports agree on the association of ASD with the alteration of the microbiome (dysbiosis), which raises the possible role of external factors. Our study aimed at identifying antibiotic classes that might be associated with the development of ASD-related dysbiosis either promoting or inhibiting the process. Statistical comparison was made between the average yearly consumption of different antibiotic classes (1997-2020) and the number of individuals living with ASD estimated for 2023/100000 population in 30 European countries and the results were statistically analyzed. Tetracycline (J01A) showed significant positive (promoting) association with the prevalence of ASD (Pearson r: 0.373, p: 0.043. OR: 1.312, CI95%: 0.995-1.791, p: 0.065) and narrow-spectrum, beta-lactamase resistant penicillin (J01CF) (Pearson r: 0.524, p: 0.003, OR: 3.240, CI95%: 1.710-8.853, p: 0.004, Kruskal-Wallis p: 0.032). Mild, negative (inhibitory) association was observed with broad-spectrum, beta-lactamase sensitive penicillin (J01CA) (Pearson r: -0.278, p: 0.157, OR: 0.808, CI95%: 0649-0957, p: 0.028) and narrow-spectrum, beta-lactamase-sensitive penicillin (J01CE) (Pearson p: -0.032, r: 0.865, OR: 0.725, CI95%: 0.543-0.885, p: 0,009). Our findings strongly support the animal experiments when penicillin-exposed newborn mice developed "autism-like" behavior.

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

The healthy function of the vestibular system (VS) is of vital importance for individuals to carry out their daily activities independently and safely. This study carries out Tsallis entropy (TE)-based analysis on insole force sensor data in order to extract features to differentiate between healthy and VS-diseased individuals. Using a specifically developed algorithm, we detrend the acquired data to examine the fluctuation around the trend curve in order to consider the individual’s walking habit and thus increase the accuracy in diagnosis. It is observed that the TE-value increases for diseased people as an indicator of the problem of maintaining balance. As one of the main contributions of this study, in contrast to studies in the literature that focus on gait dynamics requiring extensive walking time, we directly process the instantaneous pressure values, enabling to reduce the data acquisition period significantly. The extracted feature set is then inputted into fundamental classification algorithms, with the Support-Vector-Machine (SVM) demonstrating the highest performance, achieving an average accuracy of 95%. This study constitutes a significant step of a large project aiming to identify specific VS disease together with its stage. The performance achieved in this study provides a strong motivation to further explore this topic.

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.

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

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1,7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the Omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant n-6/n-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in either adult and pediatric populations and it has a positive and protective effect against hypertension, suggesting that ALA is an useful diet-related antihypertensive compound. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardio-protective effects.

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

Powered lower limb exoskeletons (PLLE) have attracted much interest due to their potential applications. They provide assistance for persons with disabilities to accomplish activities of daily living (ADL), and more importantly assist them in achieving their rehabilitation goals. However, still there are unclear evidences on the quality and benefits that PLLEs can deliver to patients. This is due to limited usability and performance of current PLLEs, insufficient clinical use of PLLEs for different patients with high diversity in their disability type and impairment, and also the large gap between the technological state of the art and clinical expectations. In this study, we review and analyse various factors that can improve the effectiveness of PLLEs at yielding better assistance and rehabilitation training for patients with motor impairments. First, we define a set of criteria that characterize the majority of expectations for the rehabilitation and assistance domains and we use them for evaluating PLLEs depending on the context. Then, we include the effects of control strategies and combined approaches which include auxiliary devices such as Functional electrical stimulation and smart crutches applied to PLLEs with regard to the criteria we defined.

Calcium (Ca2+) ions act as second messenger, regulating several cell functions. Mitochondria are critical organelles for the regulation of intracellular Ca2+. Mitochondrial calcium (mtCa2+) uptake is ensured by the presence in the inner mitochondrial membrane (IMM) of the mitochondrial calcium uniporter (MCU) complex, a macromolecular structure composed of pore-forming and regulatory subunits. MtCa2+ uptake plays a crucial role in the regulation of oxidative metabolism and cell death. Many evidences demonstrate that dysregulation of mtCa2+ homeostasis can have serious pathological outcomes. In this review, we briefly discuss the molecular structure and the function of the MCU complex and then we focus our attention on human diseases in which a dysfunction in mtCa2+ has been showed.

Background: This study assessed the nephrotoxicity of oral BRAF inhibitors (BRAFi), regorafenib (REG) and encorafenib (ENC), in metastatic colorectal cancer (mCRC), through an analysis of re-ports from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) da-tabase. Methods: A descriptive and disproportional analyses were performed for all reports with ENC and REG as the primary suspect. Results: A total of 379 reports had at least one renal ADR, mainly related to REG (93.1%). Potential safety signals for REG particularly included chromaturia (n = 44; ROR = 12.00, CI 95% = 8.92-16.16; IC = 2.36, IC025-IC075 = 2.06-2.66), hydronephrosis (10; 8.70, 4.67-16.19; 1.85, 1.23-2.47), nephrotic syn-drome (7; 5.73, 2.73-12.03; 1.47, 0.73-2.21), renal impairment (53; 4.16, 3.17-5.45; 1.39, 1.12-1.66), dys-uria (19; 3.06, 1.95-4.81; 1.06, 0.61-1.52), renal failure (38; 1.66, 1.20-2.28; 0.49, 0.17-0.81), and acute kidney injury (AKI) (43; 1.46, 1.08-1.97; 0.37, 0.07-0.67). For ENC, consistent disproportionalities were observed for AKI (n = 11; ROR = 3.79, CI 95% = 2.09-6.90; IC = 1.32, IC025-IC075 = 0.72-1.91) and dysuria (4; 6.50, 2.43-17.39; 1.86, 0.88-2.85). Conclusions: These findings highlighted some not extensively reported renal ADRs that required further investigations to better characterize the safety profile of BRAFi in patients with mCRC.

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising >2,000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this pa-per presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid, and is expected to continue to evolve with further development.

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

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

Diabetes and mental disorders have been recognized as two significant public health concerns globally. Recent research indicates that there is a bidirectional relationship between these two conditions, with each influencing the other's course and outcomes. Nutrition plays an essential role in the prevention and treatment of both mental disorders and diabetes. A comprehensive review of existing literature was conducted to examine the impact of anxiety and depression on the development of diabetes and the influence of diabetes on the occurrence of mental health disorders such as anxiety and depression. Additionally, the effects of nutrition on the prevention and management of mental disorders, diabetes, and related complications in at risk individuals were assessed. Our findings show that mental disorders, such as depression and anxiety increase the risk of developing type 2 diabetes and are associated with poorer glycemic control, increased diabetes-related complications, and higher mortality rates. Conversely, diabetes is also linked with an increased risk of developing mental health disorders, including depression, anxiety, and cognitive decline. The biological, psychological, and social factors that contribute to the comorbidity between these two conditions are complex and multifaceted. Therefore, an integrated approach to the management of both conditions is critical for improving patient outcomes and reducing the overall burden of disease. Nutritional interventions should be utilized to reduce the risk of diabetes in patients with anxiety and depression as well as enhance mental health in patients with diabetes.

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.

Multiple sclerosis (MS) is a persistent inflammatory disease affecting the central nervous system. Bruton's tyrosine kinase (BTK) is an enzyme crucial in the communication process of B cells, which have a significant impact on the development of MS. Recently, BTK inhibitors have emerged as a promising treatment strategy for MS due to their ability to modulate the immune system. In this study, an extensive literature search was performed utilizing multiple databases, such as PubMed, Embase, and Scopus to examine the potential use of BTK inhibitors in managing cognitive disorders experienced by individuals with MS. We found that BTK inhibitors targeting microglia offer potential advantages for managing neurodegeneration associated with cognitive impairments in MS patients by slowing down degeneration processes effectively. Their ability to impact microglial function and penetrate the CNS positions them as promising candidates for improving cognitive function. This study suggests that BTK inhibitors provide new possibilities for managing inflammatory and neurodegenerative phases of MS through their effects on microglia activation pathways. Further research and clinical trials are necessary to fully explore their efficacy in treating MS while addressing barriers related to cognitive impairment.

Recent studies have shown that the prevalence of vegetarianism among the general population in western societies ranges between 2% and 9%. Information regarding the prevalence of vegetarianism among exercisers is lacking. The aim of the present pilot study was to determine the prevalence of vegetarianism among regular exercisers in Greek gyms, as well as assess their dietary habits, exercise habits, and attitudes toward health and environmental issues. 291 regular gym clients completed an anonymous descriptive online questionnaire containing 65 questions divided into five sections (demographic characteristics, dietary habits, physical activity, dietary supplements, environment). Thirty responders (10.3%) identified themselves as vegetarians, spanning the entire spectrum of vegetarianism, from raw vegan to semi-vegetarian. Compared to omnivores, vegetarians had lower body weight, were more concerned about their health and convinced about the health benefits of their dietary choices, were surrounded by more vegetarians socially, consumed fast food and ate out less often, used more dietary supplements, and were better informed about what a sustainable diet is (all p < 0.05). Vegetarians did not differ significantly from omnivores in demographic characteristics, alcohol consumption, smoking habits, prevalence of psychogenic eating disorders, or exercise practices (except for practicing more yoga/Pilates). In conclusion, we report, for the first time, a considerable prevalence of vegetarianism among regular exercisers in gyms. Our findings demonstrate important similarities and differences between exercising vegetarians and omnivores (partly at odds with those seen in the general population) and highlight nutritional and environmental issues on which both groups should be better educated.

Organophosphate pesticides (OPs) are toxic substances that contaminate aquatic environments, interfere with the development of the nervous system, and induce Neurodevelopmental Toxicity (NDT) in animals and humans. The canonical mechanism of OP neurotoxicity involves the inhibi-tion of acetylcholinesterase (AChE), but other mechanisms non-AChE are also involved and not fully understood. We used network toxicology and molecular docking to identify molecular targets and toxicity mechanisms common to OPs. Targets related to diazinon-oxon, chlorpyrifos oxon, and paraoxon OPs were predicted using the Swiss Target Prediction and PharmMapper databases. Targets related to NDT were compiled from GeneCards and OMIM databases. In order to construct the protein-protein interaction (PPI) network, the common targets between OPs and NDT were imported into the STRING. Networks topological analyses identified EGFR, MET, HSP90AA1, and SRC as hub nodes common to the three OPs. Using Reactome pathway and gene ontology we found that signal transduction, axon guidance, cellular responses to stress, and glutamatergic signaling activation play key roles in OP-induced NDT.

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.

Adolescents’ eating disorders and disordered eating behaviours appear to be a growing public health concern. The aetiology of these conditions is complex, as many different factors interact for their development. Among them, family factors such as parenting styles and comments regarding weight from family members are considered critical and are extensively researched. However, the impact of parental dieting has received less attention. A literature review was conducted in order to examine the relationship between parental engagement in weight-reduction dieting and their adolescent offspring’s disordered eating behaviours. The review was conducted in three databases (PubMed, Scopus and Google Scholar). A number of studies indicated that adolescents whose parents were engaged in dieting in order to lose weight are more likely to showcase disordered eating behaviours. However, research about this relationship is very scarce. More studies on the link between parental eating and dieting habits and the risk of disordered eating in adolescents are needed. Moreover, parents should be informed regarding the possible risks when they choose to follow weight-loss diets and the importance of adopting healthy eating and weight-control habits for the whole family.

A 36-year-old professional marathon runner reported sudden heart palpitations occurring during competitions, with heart rates (HR) of 230 bpm recorded on sports HR monitor (HRM) over 4 years. These episodes subsided upon the cessation of exercise. Electrocardiograms, echocardiography, and cardiac magnetic resonance imaging results were borderline for athlete's heart. Because an electrophysiology study and standard exercise tests provoked no arrhythmia, doctors suspected Munchhausen syndrome. Ultimately, an exercise test that simulated the physical effort during a competition provoked tachyarrhythmia consistent with the HRM readings. This case demonstrates the diagnostic difficulties related to exercise-induced arrhythmia and the diagnostic usefulness of sports HRMs.

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.

Polycystic ovary syndrome (PCOS) usually comes along with metabolic disturbances attributed to androgen excess and obesity, but the contribution of each has not been defined, and the occurrence of metabolic disturbances is frequently not investigated. We evaluated 99 PCOS and 41 non-PCOS women. Clinical biomarkers of glucose-, liver-, and endothelial-related metabolic alterations were measured; participants were categorized into four groups according with obesity (OB) and hyperandrogenemia (HA) statuses: Healthy (no-HA, lean), HA (HA, lean), OB (no-HA, OB), and HAOB (HA, OB). Metabolic disturbances were highly frequent in PCOS women (70%). BMI correlated with all biomarkers, while free testosterone (FT) only with glucose- and hepatic-related indicators. Despite insulin sensitivity and liver enzymes were associated with FT, women with obesity exhibited lower M [coeff = 8.56 – 0.080(FT) –3.71(Ob); p &lt;0.001)] and higher aspartate aminotransferase (coeff = 26.27 + 0.532(FT) + 8.08(Ob); p = 0.015)] than lean at the same level of FT. Women with obesity exhibited greater risk of metabolic disorders than lean, independently of hyperandrogenemia. Clinicians are compelled to search for metabolic alterations in PCOS women; obesity must be handled in all cases, but hyperandrogenemia needs to be managed also in those with glucose- or liver-related disturbances.

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

Attention Deficit-Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by motor hyperactivity, impulsivity, and inattention. MRI-based evidences support that neuroanatomical abnormalities as the volume reduction of neocortex and hippocampus are shared by several neuropsychiatric diseases as schizophrenia, autism spectrum disorder and ADHD. In addition, it is well documented the abnormal development and postnatal pruning of dendritic spines of neocortical neurons in schizophrenia, autism spectrum disorder and intellectual disability. A recent report using the prenatal nicotine exposure murine model of ADHD support a delay in spine maturation in CA1 neurons correlated with impaired working memory and hippocampal long-term potentiation (LTP). In vivo spine imaging show that dendritic spines are dynamic structures exhibiting Hebbian and homeostatic plasticity triggering intracellular cascades involving glutamate receptors, calcium influx and remodeling of F-actin network. The LTP-induced insertion of postsynaptic glutamate receptors is associated to the enlargement of spine head and long-term depression (LTD) to the spine shrinkage. In this review, we summarize recent evidence emerged from meta-analysis of brain imaging data from ADHD patients, risk loci from global genome-wide analysis and new reports focused on spine molecular structure and dynamics using in vivo imaging in neocortex and hippocampus.

Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD. We compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score &gt;5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45-7.93), SNCA_A53T_rs104893877 (8.21, 2.26-36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08-4.10), and ZNF184_rs9468199 (1.89, 1.08-3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15-0.78). The ML algorithms led to similar results. The predictive models were highly specific (95-99%) but lacked sensitivity (9-39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop RBD in PD. Additional investigations are needed.

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.

Background: Bleeding disorders can be divided into three categories: congenital coagulation disorders (CCDs), antiplatelet induced bleeding disorders (APBDs) and anticoagulant induced bleeding disorders (ACBDs). Implant placement can be challenging in this kind of patients. The aim of this study is to provide evidence on implant surgery in patient with bleeding disorders and to generate some practical recommendations for clinicians. Material &amp; Methods: Pubmed/MEDLINE, Scopus, Web of Science and Cochrane Library databases were screened. The latest search was performed in July 2022. Case Reports, Case Series, Cohort Studies, Cross-Sectional Studies, Case Control Studies, Reviews, Consensus Reports, Surveys and Animal Studies were included in the analysis. Results: Seventeen articles on CCDs were found, fourteen on APBDs, twenty-six on ACBDs. Most of these articles were case report or case series. Patients with CCDs can be treated after the infusion of the missing coagulation factor. Patients with APBDs can be treated without withdrawing the therapy. Patients with ACBDs should be treated depending on the anti-coagulative medication. Conclusion: Despite the low level of evidence, dental implants can be safely placed in patients with bleeding disorders. However, careful preoperative evaluation and the adoption of local and post-operative bleeding control measures are mandatory.

Keywords: Pain; Nociception; Disorders of Consciousness; Consciousness

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.

. 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.

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.

Depressive disorder is a disease that causes a decrease in daily function, and the prevalence of depressive disorder in Korea is the highest among OECD countries. However, due to lack of manpower and negative social awareness, timely treatment is not being performed properly. As a solution to this, AI counseling chatbots are emerging, and it is essential to use labeled datasets to create chatbots. Currently, many countries around the world, including Korea, use the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, DSM-5, but there are no nine labeled datasets according to the DSM-5 depression disorder diagnosis criteria. This study collects sympathetic datasets, analyzes morphemes using Kind Korean Morpheme Analyzer and augments and builds a word dictionary using Word2Vec. As a result, we have labeled the dataset with nine criteria for diagnosing DSM-5 depressive disorder, which will enhance the performance of the counseling chatbot.

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.

Background: According to metacognitive theory, Cognitive–Attentional Syndrome (CAS) is a transdiagnostic factor and main mechanism of psychopathology maintenance. The main goal of this study was to examine whether CAS predicted symptoms of stress and trauma-related symptomatology in the first months of the COVID-19 pandemic and three months later. Methods: Initially 1,792 participants were recruited online via social media; data was collected at two time points. Measures included the Cognitive–Attentional Syndrome Questionnaire, Adjustment Disorder – New Module 20, the International Trauma Questionnaire, and additional measures. Results: Structural equation modeling was conducted in order to determine relations between reported stressors, CAS, and symptomatology. At both time points, CAS was a significant mediator between stressors and symptoms of adjustment disorder. Despite the decrease in the intensity of adjustment disorder symptoms between waves, it was a significant predictor of other psychopathology at both time points, except for traumatic stress. Conclusions: The findings confirm the assumption that CAS is a transdiagnostic factor of psychopathology, and has a mediating role in the relationship between stressors and adjustment disorder and co-occurring symptomatology. The effect was particularly significant in the initial phase of the pandemic, which was highly stressful for many people.

-529391451442Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).0Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Abstract: SARS-CoV-2 vaccination offered the opportunity to get out of the pandemic and thereby worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe but side effects are being reported more frequently as more and more people around the world become treated. Myo-pericarditis is the major, but not the only cardiovascular complication of this vaccine, hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database emerged that heart rhythm disorders after Covid vaccination are not uncommon and deserve more clinical and scientific attention. Since Covid vaccine is the only vaccination to have been related to this side effect questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit is clearly in favor of vaccination heart rhythm disorders are not a negligible issue and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we investigated the potential mechanism for the Covid vaccine to impact on cardiac electrophysiology and cause heart rhythm disorders.

A 52-y/o asymptomatic male with history of hypertension, was referred to our Heart Failure Clinic due to report of hypertrophic cardiomyopathy, TTE with an increased end-diastolic thick-ness (basal inferoseptal of 23 mm, and basal anteroseptal of 21 mm). CMR demonstrated late gadolinium enhancement at the septum, anterior, inferolateral, and inferior walls with a mid-myocardial distribution, T1 mapping which reported an average T1 of 929 ms. A next-generation sequencing panel was requested. Results demonstrated hemizygosis, in the ga-lactosidase alpha gene, consistent with Fabry Disease. The replacement of the enzyme was start-ed. Extended familial genetic counseling and testing were done.

Cognitive biases towards disorder-specific stimuli are suggested to be crucial in the development and maintenance of symptoms in adults with functional gastrointestinal disorders (FGID). Functional abdominal pain disorders (FAPD), a subtype of FGID, are common in children and adolescents, but the influence of cognitive biases is sparsely examined. The aim of this study was to 1) develop a new experimental design for assessing cognitive biases towards gastrointestinal stimuli in children and adolescents (age 8-17 years) and 2) test its feasibility on a healthy sample exploring potential sex- and age-related differences. The online experimental design – BY-FAP (Bias in Youth with Functional Abdominal Pain) includes a word task and a picture task. Stimuli in both tasks are related to general and gastrointestinal symptoms and the design includes three phases: 1) encoding, 2) free recall and 3) recognition. Results from 96 healthy participants (Mage = 12.3, 47.9% female) found no significant difference between sex or age groups in recall and recognition of either words or pictures. The results support that the design is feasible for children and adolescents. In the future, BY-FAP can be used to explore possible cognitive biases in children and adolescents with FAPD.

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.

The frequency of selected polymorphisms, one in each gene coding for proteins with antioxidative properties (CAT, SOD2, GPX1, NQO1) was compared between patients suffering from pain-related temporomandibular disorders (TMDp;n=85) and control subjects (CTR;n=85). According to the Oral Behaviours Checklist score participants were divided into high-frequency parafunction (HFP;n=98) and low-frequency parafunction (LFP;n=72) groups. In addition, we have investigated the association of selected polymorphisms with participants' psychological (anxiety, depression) and psychosomatic (hypervigilance, somatosensory amplification) characteristics. Polymorphisms rs1001179, rs4880, rs1050450, rs689452 were genotyped using the genomic DNA extracted from buccal mucosa swabs and real-time TaqMan genotyping assays. No differences in genotype distribution between TMDp patients and control subjects were found. Still, TMDp patients who were homozygous for minor allele A, related to the GPX1 polymorphism rs1050450 reported significantly more waking-state oral behaviours compared to GA+GG genotype carriers (score: 30 vs. 23, p=0.019). Frequency of genotype AA for rs1050450 polymorphism was higher in HFP compared to LFP participants (14.3% vs. 4.2%, p =0.030). Most important predictors of waking-state oral behaviours were depression, anxiety, AA genotype (rs1050450) and female sex. Explored genetic factors were not found to be significant risk factors for either TMDp or sleep-related oral behaviours. The association of waking-state oral behaviours with selected gene polymorphisms additionally supports previous assumptions that the daytime bruxism is more closely linked to various stress manifestations, which might also be reflected through the variability related to cellular antioxidative activity.

Accurate evaluation of patients with disorders of consciousness (DoC) is crucial for personalized treatment. However, misdiagnosis remains a serious issue. Neuroimaging methods could observe the conscious activity in patients who have no evidence of consciousness in behavior, and provide objective and quantitative indexes to assist doctors in their diagnosis. In the review, we discussed the current research based on the evaluation of consciousness rehabilitation after DoC using EEG, fMRI, PET, and fNIRS, as well as the advantages and limitations of each method. Nowadays single-modal neuroimaging can no longer meet the researchers` demand. Considering both spatial and temporal resolution, recent studies have attempted to focus on the multi-modal method which can enhance the capability of neuroimaging methods in the evaluation of DoC. As neuroimaging devices become wireless, integrated, and portable, multi-modal neuroimaging methods will drive new advancements in brain science research.

Brachycephalic dogs are not only affected by brachycephalic obstructive airway syndrome (BOAS), but also comprise up to 30% of canine patients seen by veterinary dermatologists, with English Bulldogs and Pugs particularly overrepresented. Some skin diseases are associated with the abnormal anatomic conformation of brachycephalic dogs, while for others there is a underlying genetic basis or a general predisposition. Anatomic alterations associated with brachycephaly, leading to fold formation of the skin and stenosis of the ear canal, together with primary immunodeficiencies described in some breeds, favor the development of pyoderma, Malassezia dermatitis and otitis externa/media. Frequently neglected but often lifelong dermatological problems of brachycephalic dogs are an important consideration when discussing genetic and medical conditions affecting the welfare of those dogs. Here we review the current state of knowledge concerning dermatological problems of brachycephalic dogs, and combine it with clinical experience in the management of these challenging disorders.

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.

Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.

Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.

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

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.

Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has increased. Currently, interest focus-es on the low-FODMAP diet (LFD), the fructose- or lactose-restricted diet (FRD or LRD), the glu-ten-free diet (GFD), and the Mediterranean diet (MD). In this review, we focus on the role of these dietary patterns in the FGIDs most commonly diagnosed in clinical practice, namely irritable bowel syndrome (IBS), functional abdominal pain (FAP), functional dyspepsia (FD), and func-tional constipation (FC). Fifteen clinical trials were systematically reviewed (both RCTs and sin-gle arm clinical trials). We demonstrated the lack of high-quality intervention trials. Based on current evidence, low-FODMAP diet, LRD, FRD, or GFD have no place in daily practice for the management of children and adolescents with FGIDs. Nevertheless, some patients with IBS or RAP may have some benefit from the use of a low-FODMAP diet or FRD/LRD. Limited data sug-gest that MD may be promising in the management of FGIDs, especially in IBS patients, but more data are required to investigate the mechanisms of its protective effects.

Equine-assisted services (EAS) are being increasingly used as complementary interventions for military veterans who have experienced trauma. However, there is limited evidence of benefit for this population and almost no literature describing desired potential outcomes and possible mechanisms of action. The aim of this article is to address these gaps by reviewing the extant literature of animal-assisted interventions in general, and equine-assisted services in particular, with the goal of providing guidance for future investigations in the field. Currently, the field is in the early stage of scientific development, but published results are promising. Interventions that enhance treatment compliance and/or outcomes could benefit this population. Preliminary results, reviewed herein, indicate that EAS interventions might benefit the military veteran population by enhancing treatment engagement and therapeutic alliance, as well as contributing to symptom reduction and resulting in various transdiagnostic benefits. It is recommended that future studies include exploration of potential beneficial outcomes discussed herein as well as investigate suggested mechanisms of action.

Over the last decades, the increased incidence of metabolic disorders such as type 2 diabetes and obesity has motivated researchers to investigate new enzyme inhibitors. In this study, the inhibitory effects of synthetic amino acid derivatives (PPC80, PPC82, PPC84, PPC89, and PPC101) on the activity of digestive enzymes was assessed by in vitro assays. The inhibitory effect was determined by the inhibition percentage and the 50% inhibitory concentration (IC50), and the mechanism of action was investigated by Lineweaver–Burk plots. PPC80, PPC82, and PPC84 inhibited pancreatic lipase (IC50 of 1.67–10.23 x 10-1 mmol/L). The activity of pancreatic α-amylase was suppressed by PPC80, PPC82, PPC84, PPC89, and PPC101 (IC50 of 1.62–5.19 x 10-1 mmol/L). Finally, PPC84, PPC89, and PPC101 also showed a potent inhibitory effect on α-glucosidase (IC50 of 0.51–3.53 x 10-1 mmol/L). PPC80 and PPC82 followed a non-competitive inhibition mechanism against pancreatic lipase, while PPC84 acted through competitive inhibition. The inhibition of pancreatic α-amylase by the derivatives was non-competitive, as well as for PPC84, PPC89 and PPC101 against α-glucosidase. The results suggest that these synthetic amino acid derivatives have inhibitory potential against digestive enzymes and may be used as therapeutic agents to control metabolic disorders.

In this review, we aimed to understand the relationship between SARS-CoV-2 infection and preeclampsia severity in infected pregnant women. Pregnant women with SARS- CoV-2 infection have been shown to have a significantly increased risk of maternal death, ICU admission, preterm delivery, and stillbirth compared with those without infection. The risk of preeclampsia also increases in pregnant women infected with SARS-CoV-2, particularly in those with severe symptoms. We emphasize the im-portance of specialized clinical management to prevent poor pregnancy outcomes in this situation. The association between COVID-19 and preeclampsia (PE) is likely due to multiple mechanisms, including the direct effects of the virus on trophoblast function and the arterial wall, acute atherosis, local inflammation leading to pla-cental ischemia, exaggerated inflammatory responses in pregnant women, SARS-CoV-2-related myocardial injury, cytokine storm, and thrombotic microan-giopathy. Emphasis has been placed on the potential impact of COVID-19 on pregnant women, specifically in relation to thrombotic complications, placental dysfunction, and cardiovascular dysfunction. Undoubtedly, one of the diagnostic tools to differentiate between COVID-19-induced preeclampsia-like syndrome and true preeclampsia is the use of biomarkers, such as the sFlt-1/PlGF ratio. We wish to highlight the potential for COVID-19-induced myocardial injury in pregnant women and the associated in-crease in maternal mortality rate. Vaccination against COVID-19 in the general population and in pregnant women in particular, drastically reduced the severity of the disease. There is an urgent need to continue the follow-up of these women and their children to detect the appearance of sequelae of the disease or peristent COVID 19

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

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.

The aim of this study was to assess the ability of multiscale sample entropy (MSE), refined composite multiscale entropy (RCMSE), and complexity index (CI) to characterize gait complexity through trunk acceleration patterns in subjects with Parkinson's disease (swPD) and healthy subjects, regardless of age or gait speed. The trunk acceleration patterns of 51 swPD and 50 HS were acquired using a lumbar-mounted magneto-inertial measurement unit during their walking. MSE, RCMSE, and CI were calculated on 2000 data points, using scale factors (τ) 1-6. Differences between swPD and HS were calculated at each τ, and the area under the receiver operating characteristics, optimal cutoff points, post-test probabilities, and diagnostic odds ratios were calculated. MSE in the antero-posterior direction at τ 4 and τ 5, and MSE in the ML direction at τ 4 outperformed the other entropy measures in terms of discriminative ability and characterized the gait of swPD with 79%, 82%, and 78% probabilities, respectively, and correlated with the motor disability, pelvic kinematics, and stance phase. Using a time series of 2000 data points, a scale factor of 4 or 5 in the MSE procedure can be considered as a marker of gait variability and complexity in swPD.

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.

Ultraviolet (UV) radiation has both harmful and beneficial effects on human health. It can cause skin damage and cancer, but also provides the primary source of vitamin D. Additionally, UV radiation affects energy metabolism in mice with metabolic diseases and has protective effects on hypertension and cardiovascular diseases.Metabolic Syndrome is a collection of metabolic dysfunctions such as dyslipidemia, hypertension, hyperglycemia, abdominal/central obesity, and insulin resistance. Chronic UVR exposure suppressed obesity and type 2 diabetes in high-fat diet-fed mice, while vitamin D supplementation did not replicate these effects. On the other hand, topical application of nitric oxide (NO) donors replicated UV effects on mice, and NO scavengers prevented the positive impact of UV. UVR may prevent the development of obesity and metabolic syndrome through mechanisms that depend on UVR-induced NO, not vitamin D. Exposure to sunshine has a protective impact on blood pressure and cardiovascular disease. Although lower vitamin D concentration is linked to increased hypertension and the incidence of CVD, oral vitamin D supplementation does not decrease blood pressure or the risk of CVD, indicating that vitamin D may not mediate the beneficial effects of sun exposure. Instead, NO plays a crucial role as an endogenous vasodilator, produced by the vascular endothelium. Solar UVA may release nitrogen oxides from skin storage into the bloodstream, lowering blood pressure and cardiovascular mortality.In conclusion, UVR exposure could be a promising non-pharmacological intervention for metabolic syndrome, hypertension, and CVD prevention, and NO may play a crucial role in mediating these effects. Further research is needed to explore the precise mechanisms and identify the optimal doses and exposure times of UVR.

Disordered eating is a serious health concern globally. The etiology is complex and multidimensional and differs somewhat for each specific eating disorder. Several risk factors have been identified which include psychological, genetic, biochemical, environmental, and sociocultural factors. Poor body image, low self-esteem, teasing, family dynamics, and exposure to media images have also been identified as risk factors. While it is enticing to consider a single behavioral risk factor, doing so fails to consider the documented environmental, social, psychological, biological, and cultural factors that contribute to the development of an eating disorder in a multidimensional and complex integration that is undoubtedly unique to everyone. Focusing only on any one factor without taking the complex etiology into account is remiss. For example, it has been suggested that the use of dietary supplements may lead to eating disorders, despite a lack of evidence to support this conjecture. Therefore, the purpose of this review is to examine the evidence-based risk factors for eating disorders and discuss why connecting dietary supplements to eating disorder etiology is not supported by the scientific literature and may interfere with treatment. Established, effective prevention and treatment approaches for eating disorders should be the focus of public health initiatives in this domain.

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.

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

Genetic sensorineural hearing loss and Meniere disease have been associated with rare variations in the coding and non-coding region of the human genome. Most of these variants are classified as likely pathogenic or variants of unknown significance and require functional validation in cellular or animal models. Given the difficulties to obtain human samples and the raising concerns about animal experimentation, human induced pluripotent stem cells emerge as cellular models to investigate the interaction of genetic and environmental factors in the pathogenesis of inner ear disorders. The generation of human sensory epithelia and neuron-like cells carrying the variants of interest may facilitate a better understanding of their role during differentiation. These cellular models will allow us to explore new strategies for restoring hearing and vestibular sensory epithelia as well as neurons. This review summarizes the use of human induced pluripotent stem cells in sensorineural hearing loss and Meniere disease and proposes some strategies for its application in clinical practice.

The mutation databases have vital importance in detecting genetic mutation and their corresponding phenotypes. The emergence of next generation sequencing genetic technologies has accelerated this process, and the growth of genetic disease identification has created a need for quality control and documentation of mutation-related information. Ethnic-specific mutation databases offer valuable information for researchers, and the article evaluates the homogeneity and effectiveness of these databases. The aim to raise awareness of NEMDBs to healthcare professionals, the general public, and researchers studying genetic disorders. The article also recommendations to improve the effectiveness of these databases.

Background: The effect of the COVID-19 pandemic has transformed medical education and is likely to have long-lasting effects on student learning, mental well-being, and eating behaviour. This study aimed to examine the learning behaviors of medical students at the American University of Integrative Sciences (AUIS), Barbados, during the COVID-19 pandemic. Methods: A cross-sectional web-based online survey was administered to medical students at AUIS from July until November 2021. The data collecting instrument recorded students’ demographic and learning behaviour information (Meo et al. 2020), and eating disorders (SCOFF questionnaire). Results: The overall response rate was 55% (n=120). In relation to learning behaviour, students agreed with the following statements: ‘deterioration in work performance and studying’ (48.4%), ‘remember subject’s contents appropriately’ (40.4%), ‘concentration on the studies’ (40.3%), ‘difficulty in performing two tasks simultaneously’ (38.7%), ‘difficulty in performing mental calculations’ (33.9%), ‘difficulty in recalling recent information’ (32.3%), and ‘difficulty in recalling old information’ (38.7%). Among the 8 dimensions of learning behaviors, deterioration in work performance or studying, and difficulties in recalling recent information were found to be significantly associated with the gender of the students. For SCOFF questionnaire, approximately 24.2% screened positive for eating disorders. Screening with the SCOFF test demonstrated that female, older (>25 years), overweight + obese, Clinical Sciences + PreMed, and non-USA-based students were at more risk of eating disorders. Conclusions: The results indicate that during the COVID-19 pandemic AUIS students have developed learning difficulties, and are likely to have eating disorders. University policymakers should take appropriate measures to support a healthy learning environment and improve students' mental well-being and eating behaviours.

Novel treatment strategies are emerging for rare, genetic diseases, resulting in clinical trials that require adequate biomarkers for the assessment of the treatment effect. For enzyme defects, biomarkers that can be assessed from patient serum, such as enzyme activity, are highly useful, but the activity assays need to be properly validated to ensure a precise, quantitative measurement. Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by the deficiency of the lysosomal hydrolase aspartylglucosaminidase (AGA). We have here established and validated a fluorometric AGA activity assay for human serum samples from healthy volunteers and AGU patients. We show that the validated AGA activity assay is suitable for the assessment of AGA activity in the serum of healthy controls and AGU patients, and it can be used for diagnostics of AGU and, potentially, for following a treatment effect.

Introduction: The rapid emergence of COVID-19 as a global crisis has led to the approval of many vaccinations, which were unfortunately associated with high complication rates due to a lack of sufficient safety studies. Objectives: The following manuscript focuses on discussing the demyelinating disorders that were noticed after COVID vaccine administration. Methods: We conducted a retrospective study using anonymous medical records from the US vaccine adverse events reporting system, complications retrieved included Acute disseminated encephalomyelitis (ADEM), Guillain Barre syndrome (GBS), and Multiple sclerosis (MS), outcome parameters were age, sex and the dose after which this complication was observed. Patients younger than 18 years-old were excluded as some of the vaccines, namely Janssen (JNJ-78436735) is not yet approved below this age. Results: Our analysis showed that demyelinating disorders were more likely to occur in patients over the age of 50 compared to other age groups, regardless of the type of vaccination, except for MS and ADEM occurrences after the Jansen vaccine. In addition, demyelinating complications were more likely to occur after the first dose of vaccination. Conclusion: Further research and observation of demyelinating diseases in different vaccinations, as well as additional in vitro studies, are recommended to further explain the pathogenesis of demyelinating disorder occurrence.

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.

Malnutrition is one of major factors of bone and cartilage disorders. Pacific cod (Gadus macrocephalus) processing waste is a cheap and highly promising source of bioactive substances, including collagen-derived peptides and amino acids, for bone and cartilage structure stabilization. Addition of these substances to a functional drink is one of the ways to achieve their fast intestinal absorption. Collagen hydrolysate was obtained via enzymatic hydrolysis, ultrafiltration, freeze-drying, and grinding to powder. The lyophilized hydrolysate was a light gray powder with high protein content (>90%), including collagen (about 85% of total protein) and a complete set of essential and non-essential amino acids. The hydrolysate was applicable as a protein food supply or a structure-forming food component due to presence of collagen fiber fragments. An isotonic fitness drink (osmolality 298.1 ± 2.1 mOsm/L) containing the hydrolysate and vitamin C as a cofactor in collagen biosynthesis was prepared. Addition of the hydrolysate did not adversely affect its organoleptic parameters. Production of such functional foods and drinks is one of the beneficial ways of fish processing waste utilization.

The physical environment is of critical importance to child development. Understanding how exposure to domains of the physical environment such as greenspace, urbanicity, air pollution or noise affects externalising problems in typical and neurodiverse children is of particular importance given the significant long-term impact of those problems. In this narrative review we investigated the evidence for domains of the physical environment that may ameliorate or contribute to the display of externalising behaviours. We have considered a broad range of study designs that include typically developing and neurodiverse children and young people aged 0-18 years. We used the GRADE system to appraise the evidence. Searches were performed in 8 databases in July 2020 and updated in June 2022. Additional articles were further identified by hand-searching reference lists of included papers. The protocol for the review was preregistered with PROSPERO. Results: We retrieved 7174 studies of which 67 are included in this review. The studies reported on green space, environmental noise and music, air pollution, meteorological effects, spatial density, urban or rural setting, and home elements (e.g., damp/sensory aspects/colour). They all used well validated parent and child reported measures of externalising problems. Most of the studies were rated as having high or probably high risk of bias. Greenspace rurality and interior design had most evidence, although the certainty of the association was low. As expected, noise, air pollution, urbanicity, spatial density, colour and humidity appeared to increase the display of externalising behaviours. There was a dearth of studies on the role of the physical environment in neurodiverse children. The studies were heterogeneous and measured a range of externalising behaviours from symptoms to full syndromes. Greenspace exposure was the most common domain studied but certainty of evidence for the association between environmental exposures and externalising problems in the child or young person was low across all domains. We found a large knowledge gap in the literature concerning neurodiverse children, which suggests that future studies should focus on these children, who are also more likely to experience adverse early life experiences including living in more deprived environments as well as being highly vulnerable to the onset of mental ill health. Such research should also aim to dis-aggregate the mechanisms of action for both environmental influences on the externalising problems the results of which may point to pathways for public health interventions and policy development to address inequities that can be relevant to ill health in neurodiverse young people.

Disruptive behaviour disorders (DBDs) in childhood, such as conduct disorder (CD) and oppositional defiant disorder (ODD) are characterized by high levels of irritability and aggression. Though psychological management is considered the first-line approach for these disorders, many children and adolescents require adjunctive pharmacotherapy for the control of specific symptoms. Several prior systematic reviews have examined the evidence for the use of antipsychotics in the symptomatic management of DBDs, but have concluded that their efficacy is marginal and limited by significant adverse effects. This paper updates existing reviews of this field by reviewing clinical trials of antipsychotics in children and adolescents with DBDs published in the period 2-1-2017 to 2-10-2022. The PubMed, Scopus and ScienceDirect databases were searched for relevant citations. Six relevant trials were identified during this period. These trials were critically evaluated in terms of outcome measures, efficacy and safety. Overall, the data from these trials suggests that certain atypical antipsychotics, such as risperidone and clozapine, are effective in the short-term management of aggression in DBDs. They have no apparent effect on cognition, but are associated with significant metabolic adverse effects. The results of these trials, and of the earlier systematic reviews, are discussed in the light of global trends towards increasing off-label prescription of antipsychotic medication in children and adolescents, and of recent literature on the neuropharmacology of aggression in this patient population. The need for rational, short-term use of these drugs is highlighted, as well as the importance of post-marketing surveillance for long-term or severe adverse events.