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

Memory and emotion are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD), which has been linked to serotonin (5-HT) metabolism disruptions. In fact, over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) meta-bolic pathway, producing a variety of bioactive molecules. The aadat (kat2) gene encodes mito-chondrial kynurenine aminotransferase (KAT) isotype 2, responsible for kynurenic acid (KYNA) production. Little is known about its role in behavior. In CRISPR/Cas9-induced aadat knockout (kat2−/−) mice, we examined the effects on emotion, memory, motor function, Trp and its metabolite levels, enzyme activities in the plasma and the urine of 8-week-old males compared to wild-type mice. Transgenic mice showed more depressive-like behaviors in the forced swim test, but not in the tail suspension, anxiety, or memory tests. They also had fewer center field and corner entries, shorter walking distances, and fewer jumping counts in the open field test. Plasma metabolite levels are generally consistent with those of urine: KYN, antioxidant KYNs, 5-hydroxyindolacetic acid, and indole-3-acetic acid levels are lower; enzyme activities in KATs, kynureninase, and monoamine oxidase/aldehyde dehydrogenase are lower, but kynurenine 3-monooxygenase is higher; and ox-idative stress and excitotoxicity indices are higher. Transgenic mice show depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits, coupled with a decrease in KYNA, a shift of Trp metabolism toward the KYN-3-HK pathway, and a partial decrease in the gut microbial Trp-indole pathway metabolite. This is the first evidence that deleting the aadat gene causes depression-like behaviors that are unique to despair experience, which appears to be linked to excitatory neurotoxic and oxidative stresses. This may lead to the development of a double-hit preclinical model in experience-based depression, better understanding of these complex condi-tions, and more effective therapeutic strategies by elucidating the relationship between Trp me-tabolism and PTSD pathogenesis.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Major depressive disorder (MDD) and substance use disorder (SUD) are of immense medical and social concerns. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, only relatively recently the role of glia in these disorders have attracted attention. Detail understanding of the glial function in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, specific contribution of the neurotrophic factors, neuroinflammation and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes and synantocytes) on phenotypic manifestation of MDD or SUD are emphasized. In addition, potential use of this knowledge in developing novel therapeutics is touched upon.

Mood disorders are among the commonest mental disorders worldwide. Epidemiological and clinical evidence suggests that there are close links between infectious diseases and mood disorders, but the strength and direction of these association remain largely unknown. Theoretical models have attempted to explain this link based on evolutionary or immune-related factors, but these have not been empirically verified. The current study examined cross-sectional and longitudinal associations between the incidence of infectious diseases and mood disorders, while correcting for climate and economic factors, based on data from the Global Burden of Disease Studies, 1990-2019. It was found that major depressive disorder was positively associated with lower respiratory infections, while bipolar disorder was positively associated with upper respiratory infections and negatively associated with enteric and tropical infections, both cross-sectionally and over a period of thirty years. These results suggest that a complex, bidirectional relationship exists between these disorders. This relationship may be mediated through the immune system as well as through the gut-brain and lung-brain axes. Understanding the mechanisms that link these groups of disorders could lead to advances in the prevention and treatment of both.

Paenibacillus sp. tmac-D7 was isolated from coastline growing Trifolium macraei (double-head clover) root nodules from Bodega Bay, California. The draft genome is 5,567,337 bp with a G+C% of 52.4%, an N50 of 114,261 bp, and 5,282 predicted protein-coding genes. Paenibacillus, while found in many other environments, is frequently isolated from root nodules, with many acting as plant pathogen antagonists. Paenibacillus sp. tmac-D7 is the first genome of a non-rhizobial endophyte isolate from wild Trifolium macraei (double-head clover).

Canine Multiple System Degeneration (CMSD) is an early onset, progressive movement disorder affecting Kerry Blue Terriers and Chinese Crested dogs. The associated pathologic lesions include degeneration of the cerebellum, caudate nucleus and substantia nigra. CMSD is inherited as an autosomal recessive trait in both dog breeds. Previous linkage mapping localized the CMSD locus to a 15 MB region on canine chromosome 1 (CFA1). Next generation sequencing was used to generate whole genome sequences from DNA of an affected dog from each breed. The resulting sequence reads were aligned to the NCBI canine reference genome (build 3.1). Among the homozygous sequence variants within the CFA1 target region, a nonsense variant in exon 15 of SERAC1 was identified in the affected Kerry Blue Terrier, while in the Chinese Crested dog, a 4 bp deletion in the SERAC1 exon 4 acceptor splice site was found. RT-PCR showed that this deletion resulted in exon 4 skipping. Genotyping of large cohorts of Kerry Blue Terriers and Chinese Crested dogs for the respective breed-specific SERAC1 variants showed complete concordance between genotype and disease phenotype. Genotype-phenotype concordance was also observed in offspring generated by cross breeding between SERAC1-heterozygous Kerry Blue Terrier and Chinese Crested dogs, with only the compound heterozygotes exhibiting the disease phenotype, further confirming the recessive inheritance of CMSD. Variants in human SERAC1 are associated with disorders with a range of ages of disease onset and patterns of clinical signs, but that are all characterized by movement abnormalities similar to those of the dogs with CMSD. Canine CMSD could serve as a valuable model to elucidate the mechanisms underlying SERAC1-deficiency disorders and to evaluate potential therapeutic interventions.

Background: Various vitamins and minerals have been implicated in the aetiology of depression. Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomization (MR). Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566), and rMDD (cases=17,451; controls=62,482). Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g. cIVW), highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (OR_cIVW 0.90 per SD increase; 95% CI 0.85- 0.95; p=0.0003); erythrocyte copper (OR_cIVW 0.97; 95% CI 0.95- 0.99; p=0.0004); and 25(OH) vitamin D (OR_cIVW 0.81; 0.66- 0.99; p=0.04). Apparent adverse effects of increased selenium on the risk of MDD (OR_cIVW 1.03; 95% CI 1.02-1.05; p=0.0003) and rMDD (OR_cIVW 1.08; 95% CI 1.00-1.08; p=0.06), and serum magnesium on rMDD (OR_cIVW 1.21; 1.01- 1.44; p=0.04); were less consistent between methods and may be driven by pleiotropy. Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates, and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.

Bipolar disorder (BD) is a complex mental health condition characterized by alternating periods of mania and depression. This review provides a comprehensive overview of BD, focusing on its genetics, causal hypotheses, clinical signs and evolution, potential biomarkers with an emphasis on electroencephalography (EEG), and treatment options. Genetic studies have identified several susceptibility genes and polygenic risk scores, highlighting the heritable nature of BD. Various causal hypotheses, including monoamine dysregulation, kindling, circadian rhythm disruptions, and neuroinflammation, have been proposed to explain its pathophysiology. The clinical course of BD is characterized by recurrent episodes of mania/hypomania and depression, with significant heterogeneity among individuals. EEG and other biomarkers hold promise for improving diagnosis, predicting treatment response, and elucidating the neurobiological underpinnings of BD. Current treatment options include pharmacotherapy, psychotherapy, and neuromodulation techniques, which can be tailored to individual needs based on clinical presentation and response to treatment. Future research should focus on identifying more specific biomarkers, developing novel treatments, and optimizing existing therapies to improve outcomes for individuals with BD.

Transcranial magnetic stimulation, TMS, has been an innovative method of demure neuromodulation. This paper aims to delve into the different forms of its existence and to evaluate the use of TMS in five psychiatric disorders; Parkinson’s disease, schizophrenia, obsessive-compulsive disorder, major depressive disorder, and major anxiety disorder. Literature pertaining to the use of TMS in treating these specific diseases will be analyzed, and its efficacy and mechanisms will be explored. The literature will be evaluated through sources with established facts and research studies demonstrating function, potency, or inefficacy. TMS poses a method to have a more explicit effect on the regions of the brain, and the exploration of its use in the treatment of psychiatric diseases poses new possibilities in the treatment of psychiatric disorders. Venturing into the options it could have in a sole or combinatorial setting could provide penetrating insight into innovative forms of treatment and research.

People have always hoped to be able to fill an entire plane with ``single unit cells'' without periodicity. This wish was realized after the mathematician discovered a 13-sided ``single unit cell'' named `einstein'. These non-periodic tessellations generally exhibit anisotropic properties, making them superior in terms of mechanical performance compared to periodic structures. From the perspective of information entropy, the reason behind the improved mechanical properties of these structures is the higher entropy associated with non-periodic configurations. To quantify the disorder of non-periodic structures, we propose an entropy expression for the `einstein' metamaterial. To demonstrate the mechanical properties of these high-entropy structures, we fabricate specimens using 3D printing and conducte mechanical experiments. For comparative analysis, we also use ABAQUS to perform finite element analysis of the problem. The research results reveal that the mechanical properties of high-entropy structures created by the non-periodic stacking of cells are significantly improved compared to those of low-entropy structures created by periodic stacking. The conclusions drawn from the study of individual issues are generalizable and may be of assistance in future material and structural design.

Background Patients with severe dysphagia are usually fed using a nasogastric tube (NGT). Many patients who receive long-term NGT feeding are unable to obtain sufficient nutrients orally immediately after NGT removal. Thus, a transitional period involving oral diet training is required to transition from NGT feeding to exclusive oral feeding. We aimed to investigate the therapeutic effect of oral diet training in indwelling NGT patients with prolonged dysphagia. Methods A total of 175 patients who were fed using an NGT for more than 4 weeks were enrolled. Their swallowing function was evaluated by a videofluoroscopic swallowing study (VFSS). During the VFSS, patients received thick and thin barium while the NGT was insulted. Then, the patients underwent a VFSS without an NGT thirty minutes after NGT removal. If a patient had no aspiration with NGT inserted during the VFSS, oral diet training combined with NGT feeding was recommended. Results Of the 49 indwelling NGT patients who were recommended to receive oral diet training, 39 (79.6%) transitioned to exclusive oral feeding. A transition period of 2-8 weeks was required for them to achieve full oral feeding. Patients who were eligible for oral feeding trials showed no significant aspiration during the VFSS with an NGT inserted and had sufficient cough function. Patients who required prolonged NGT feeding and who could not complete oral trials showed significant aspiration during the VFSS when an NGT was inserted. Conclusion This study demonstrated that oral diet training combined with NGT feeding was safe in patients with prolonged dysphagia who had sufficient cough function and no aspiration during VFSS. We suggest that if the patient is a proper candidate for NGT removal, direct oral feeding training with an NGT inserted could be a useful therapeutic strategy during the transitional period from long-term NGT feeding to successful oral feeding.

This article presents multiple novel and compelling arguments to systematically disprove two widely accepted notions: one is that entropy is a measure of disorder, and the other is Schrödinger's notion of negative entropy (negentropy). These two notions have been cited hundreds of times annually in scientific literature for decades. To mathematically describe the second law of thermodynamics, the concept of entropy was created and defined in the 1860s as heat energy divided by thermodynamic temperature, and the entropy of an object increases when it absorbs heat. This is the uncontroversial and fundamental nature of entropy, which is pivotal to current thermodynamics and from which multiple facts are deduced. These facts consistently disprove the above two notions. Some biological facts, such as the one that life orderliness is encoded and provided by inherited genes rather than entropy decline, can also disprove Schrödinger's negentropy notion. Moreover, this article further clarifies the reasoning errors of the two notions. It also shows that the tendency of many natural or social systems to become more disordered over time does not result from the second law of thermodynamics.

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

Borderline Personality Disorder (BPD) is a complex and severe mental disorder. It is associated with greater use of medical services. It is characterized by intense fear of abandonment, recurring suicidal thoughts or self-harm, paranoid ideation or dissociation, identity difficulties, chronic feelings of emptiness, impulsive behavior and unstable moods and relationships. BPD is one of the most prevalent personality disorders with a higher diagnosis in females. For a diagnosis of BPD in patients, they must have a chronic pattern of functional impairment in addition to five of nine listed DSM-5 criteria. This review was a narrative literature search between 2000 to 2023 with a focus on BPD comorbidities. Results: Researchers observed a complex pattern of comorbidities with BPD that connects with other externalizing and internalizing disorders. BPD has a high comorbidity rate with mood disorders including bipolar I and II disorders, major depressive disorder, anxiety disorders, panic disorder alcohol use disorder, nicotine dependence, marijuana dependance, posttraumatic stress disorder, other personality disorders, binge eating disorder and ADHD. Diagnosis and management of BPD in presence of some of these disorders are discussed.

Patients with bipolar disorder (BD) experience more frequent and intense emotions in response to environmental conditions relative to healthy subjects, which leads to mood instability. The aim of this study was to investigate the time-course of emotion regulation strategies, distraction, and reappraisal, in euthymic BD patients using electroencephalography (EEG). Fourteen BD patients and 13 matched healthy controls took part in an experiment constituted of three conditions, i.e., a passive viewing of positive, negative, and neutral pictures and two regulation conditions, one with reappraisal strategy and the other with distraction strategy. Critically, ERP results indicated that during passive viewing, the Late Positive Potential (LPP) was larger in BD patients compared with healthy controls, but only for neutral pictures. During emotion regulation, LPP amplitude was reduced in distraction condition compared with viewing one, especially for negative emotions in both patients and controls. Importantly, LPP was reduced in reappraisal condition compared with passive viewing in an early time window for negative emotions and in a later time window for positive emotions in controls but not in patients. Our findings showed that the neurochronometry of emotion regulation is faster for negative than for positive emotion in controls but not in BD patients.

The high demands of caring for and raising a child with autism spectrum disorder on a daily basis fatally lead parents to the appearance of physical and mental fatigue. This study aimed to assess the effect of social support and spirituality on the fatigue of parents with children with autistic spectrum disorder. A cross-sectional study with a convenience sample was conducted in Schools of Special Education in Attica (Greece). The sample consisted of 123 parents who completed The Fatigue Assessment Scale (FAS), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale (FACIT Sp-12) to measure the levels of fatigue, social support, and spirituality, respectively. Demographic data were, also, recorded. Data analysis was applied using IBM SPSS 21.0. The mean age was 47.3 years old, 81.3% were women, and 38.9% stated much / very much religious. The mean of total FAS was 28.4 (SD±7.5), of total FACIT Sp-12 was 31.5 (SD±8.7), and of total MSPSS 5.1 (SD±1.1). Higher levels of total MSPSS and FACIT Sp-12 were associated with lower total FAS (r= -0.50, p &lt;0.001 and r= -0.49, p&lt;0.001 respectively). Social support and spirituality are significant predictors of fatigue.

Background and Aims: Paramedics attend an unprecedented number of drug poisoning events daily in British Columbia (BC), Canada due to the ongoing public health crisis related to an increasingly toxic and unregulated supply of illicit drugs. Paramedics have the potential to support alternative models of care to reduce harm, but their perspectives towards harm reduction initiatives are polarized. Understanding the drug-related substance use content in paramedic curriculum documents is important for deploying effective harm mitigating programs. The objective of this study was to understand what drug-related substance use content currently exists within paramedic curriculum documents in British Columbia. Methods: We performed a document analysis of curriculum documents in BC’s paramedic training institutions, the primary program textbook, and the 2011 National Occupational Competency Profile (NOCP). We used the Checklist for Assessment and Reporting of Document Analysis (CARDA) tool to perform our analysis. We analysed and coded documents both inductively and deductively and subsequently combined, refined, and used the codes to inform the development of themes via reflexive thematic analysis. Results: Of the 44 documents analysed, 22 included codes relevant to the research questions. Paramedics are primarily taught to care for people who use drugs in an acute drug-poisoning response only, with little consideration of holistic care, and no meaningful mention of harm reduction. Some stigmatizing language was found within the content. Conclusions: Many opportunities to introduce holistic models of care for people who use drugs along the entire continuum of care are unaddressed by paramedic curriculum documents in BC. Curriculum developers should include people who have lived and living experience of drug use in the co-design of educational programs involving their care. Further qualitative analyses are required to evaluate the relationship between paramedic education and provider-based stigma.

Background Posttraumatic stress disorder (PTSD) is a complex condition that represents a significant burden in terms of individual disability and societal costs. Despite decades of research investigating treatment options, PTSD remains a major cause of quality-of-life impairment. We hypothesized that patients with PTSD might benefit from peripheral somatosensory stimulation (PSS) therapy. Methods Six adult patients with clinically diagnosed PTSD were enrolled to undergo daily PSS therapy over a 4-week period. Patients completed two surveys evaluating satisfaction with treatment and overall well-being (Survey 1) and severity of PTSD symptoms (Survey 2). Survey 1 was completed weekly during the course of the study. Survey 2 was based on the 9-question National Stressful Events Survey PTSD Short Scale (NSESSS) and was completed as a baseline prior to initiation of therapy and then at the conclusion of the trial. All data were analyzed by an independent statistician. Results Six male patients were enrolled in the study; all completed the trial. All patients demonstrated a decrease in symptoms within one week of initiation of therapy. This benefit was sustained and appeared to further improve over the course of the trial. For Survey 1, the overall median scores demonstrated a significant time-dependent improvement across measurement times (p < 0.001). For Survey 2, patients had statistically significant improvements from baseline regarding feelings of being emotionally upset and being overly alert. Results from a cumulative link mixed model demonstrated that treatment yielded a 38.2-fold higher likelihood of transitioning from a higher PTSD score at baseline to a lower (improved) score at week 4. No adverse events were described by the patients. Conclusions PSS stimulation appeared to improve symptoms in all six patients with PTSD symptoms in this trial. Patients had unanimous and clinically meaningful improvement in overall PTSD symptoms with treatment. By week 4, all patients responded that they enjoyed the treatment and would like to keep their device. We suggest that further investigation into the potential usefulness of PSS therapy in patients with PTSD is warranted.

The objective of this literature review was to provide an up-to-date overview, and an analysis of the current knowledge on narcolepsy. A systematic search was conducted in different databases to identify relevant studies on various aspects of narcolepsy. The search terms included "narcolepsy," "excessive daytime sleepiness," "cataplexy," and related terms. The search was limited to studies published up until 2022. The initial screening of studies was performed based on titles and abstracts to identify potentially relevant articles. Full-text assessment was then conducted to determine the eligibility of each study for inclusion in the review. Studies were included if they provided information on the symptoms, classification, genetic aspects, impact on daily life, and gaps in knowledge regarding narcolepsy. The review reveals several important findings regarding narcolepsy: 1. the classification of narcolepsy - Type 1 narcolepsy, previously known as narcolepsy with cataplexy, and Type 2 narcolepsy, also referred to as narcolepsy without cataplexy. 2. the genetic component of narcolepsy and the complex nature of the disorder, which is characterized by excessive daytime sleepiness, disrupted sleep patterns, and potential impacts on daily life activities and social functioning. 3. the important implications for clinical practice in the management of narcolepsy. Healthcare professionals should be aware of the different types of narcolepsies and their associated symptoms, as this can aid in accurate diagnosis and treatment planning. The review underscores the need for a multidisciplinary approach to narcolepsy management, involving specialists in sleep medicine, neurology, psychiatry, and psychology. Clinicians should consider the impact of narcolepsy on a person's daily life, including their ability to work, study, and participate in social activities, and provide appropriate support and interventions. There are several gaps in knowledge regarding narcolepsy. Future research should focus on further elucidating the genetic causes of narcolepsy and exploring potential biomarkers for early detection and diagnosis. Long-term studies assessing the effectiveness of different treatment approaches, including pharmacological interventions and behavioural therapies, are needed. Additionally, there is a need for research on strategies to improve the overall well-being and quality of life of individuals living with narcolepsy, including the development of tailored support programs and interventions.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved Pharmacotherapy and Psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we reviewed clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA) assisted Psychotherapy in PTSD patients, its pharmacokinetics and current treatment guidelines for PTSD. Based on the results of the efficacy of MDMA assisted Psychotherapy from six phases II Randomized controlled trials. MDMA-assisted Psychotherapy for PTSD has received the “Breakthrough Therapy” designation from the FDA. MDMA can potentially reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e. dopamine, serotonin, norepinephrine and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.

Tourette syndrome is a complex neuropsychiatric condition that manifests in childhood and is often associated with other psychiatric comorbidities. This case describes a young male with Tourette syndrome with major depressive disorder and attention deficit hyperactivity disorder (ADHD), who experienced troublesome side-effects due to his existing medications (escitalopram, risperidone and methylphenidate). In order to control his tics, ameliorate depressive symptoms, and eliminate side-effects of stiffness and sedation, risperidone was switched to cariprazine, a third-generation antipsychotic medication with D3-D2 partial agonism. In addition, the antidepressant dose was also increased. With the new combination, the patient reported good control of his tics, together with significant improvement in depressive symptoms and no side-effects. Based on this case and the reviewed literature, cariprazine might be a viable option for patients with Tourette syndrome with other comorbid illnesses, whom are prone to side effects of medication.

Children with autism spectrum disorder (ASD) may have impaired vision from high refractive errors: near-sighted-myopia or far-sighted-hyperopia and aversion to spectacles or contact lenses. Refractive surgery can restore sharp vision and eliminate the need for spectacles or contact lenses. Restoration of sharp vision may improve ASD behaviors. Data were collated retrospectively for 267 children with refractive errors and neurodevelopmental disorders (NDD) diagnosed as ASD alone or NDD with ASD-like behaviors. Surgery was either laser photo-refractive keratectomy (PRK; 131 children), implantation of a phakic intra ocular lens (pIOL; 129 children) or removal of the crystalline lens and implantation of an IOL (refractive lens exchange, RLE; 21 children) under general anesthesia. Median age was 10.9 yrs. and median follow-up 3.1 yrs. Pre-operative refractive errors ranged from a mean +7.5 ± 0.9 D to -14.3. ± 4.8 D. Surgery corrected 87% to normal focal length (± 1 D). Visual acuity improved an average 0.6 logMAR. Social interactions and ASD behaviors improved in 55% (146/267) of the treated children (p &lt; .01), including school performance; motor skills; depth perception; repetitive or stereotyped movements; anxiety/fear; and attention. Refractive surgery improves both visual function and behaviors in the majority of highly near-sighted or far-sighted children with ASD.

Autism spectrum disorders (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by food selectivity in a significant portion of the population. The nature of this selectivity remains unclear, with hypotheses suggesting associations with sensory disorders or stereotypical and repetitive patterns of activity and interests. This study aimed to determine the prevalence and nature of food selectivity traits in individuals with ASD compared to the neurotypical population. The study involved 219 participants, with 115 diagnosed with autism and 92 without. 12 children undergoing diagnosis were excluded from the analyses. Findings revealed that food selectivity traits are more common in individuals with ASD, with differences in preferences mainly involving structure, color, taste, and serving method. Children with ASD had more food selectivity traits than those without, and certain food characteristics could alter intake as they grow. Selectivity occurred for both sensory and stereotypical reasons, but stereotypical features significantly differentiated neurotypical individuals from those with ASD.

(1) Background: Many processes play a key role in how language functions, and these processes are strongly related to reading. The aim of our research was to explore the relationship between reading impairment associated with adult acquired cognitive-linguistic impairment (aphasia) and the components of verbal working memory involved in language functioning. (2) Methods: We measured the reading abilities of a total of twenty-two adults diagnosed with aphasia using the Adult Acquired Reading Assessment. To assess working memory, we applied the measurement procedures available in Hungarian for measuring verbal working memory. Correlation analyses were performed to investigate the relationship between reading and the components of working memory involved in processing verbal information. In order to explore this relationship as comprehensively as possible, the results were analysed quantitatively through group-level analyses and qualitatively through case studies. (3) Results: The results suggest that the functioning of phonological short-term memory and verbal working memory is crucial for the reading of vowels, for certain word reading sub-processes such as reading complex words and pseudowords, and for text comprehension tasks, in particular for the processing of implicit text-level infor-mation. (4) Conclusions: The data support a strong relationship between reading and working memory, but not all mechanisms are related with the same weighting. The data will contribute to the understanding of the relationship between reading and working memory, which is important in order to see which cognitive components are dominant in reading instruction and which other cognitive mechanisms are affected in poor readers.

Toxoplasma gondii (T. gondii) is one of the most common parasites that infect humans. The parasite exists in approximately 40 million people in the United States. Latent infections are frequently associated with tissue cysts of T. gondii in the skeletal muscle and brain tissue that can lead to mental disorders, congenital disorders, and vision dysfunction. Furthermore, self-directed violence, impulsivity, and aggression are associated with T. gondii infection. Dopamine is associated with human behavior including pleasure, aggression, memory, and substance use disorder; however, the result of the studies on the association of T. gondii infection and drugs of abuse are not well understood. The frequency of substance use may be associated with substance-induced modification of dopamine-receptor densities and basal dopaminergic activity. Likewise, T. gondii can directly or indirectly influence dopaminergic activity in infected cells. Based on this hypothesis, the current paper aimed to systematically review all published literature on the association between drugs of abuse and T. gondii infection. Systematic review of controlled studies on T. gondii infection and substance use effects in adults were searched on the electronic databases. Studies have shown that individuals infected with T. gondii display increased risky behavior, such as excessive alcohol consumption. Furthermore, it was observed that T. gondii seropositive subjects had a reduced likelihood of self-reported substance use compared to T. gondii seronegative subjects. This study confirms that SUD is a potential risk factor for behavioral and psychiatric complications associated with T. gondii infection. Ultimately T. gondii infection in the context of drug dependence and the development of SUD remain to be elucidated. Therefore, it is necessary to conduct further research characterizing the mechanisms associated with dopamine metabolism of drug dependence and withdrawal in the context of a T. gondii infection, evaluating the role of inflammation, and identifying potential drug-and-sex specific underpinnings of these associations.

Locomotor impairment is a high-prevalent and significant source of disability and significantly impacts a large population’s quality of life. Despite decades of research in human locomotion, the challenges of simulating human movement to study the features of musculoskeletal drivers and clinical conditions remain. Most recent efforts in utilizing reinforcement learning (RL) techniques are promising to simulate human locomotion and reveal musculoskeletal drives. However, these simulations often failed to mimic natural human locomotion because most reinforcement strategies have yet to consider any reference data regarding human movement. To address these challenges, in this study, we designed a reward function based on the trajectory optimization rewards (TOR), and bio-inspired rewards, which includes the rewards obtained from reference motion data captured by a single Intertial Moment Unit (IMU) sensor. The sensor was equipped on the participants’ pelvis to capture reference motion data. Also, we adapted the reward function by leveraging previous research in walking simulation for TOR. The experimental results showed that the simulated agents with the modified reward function performed better in mimicking the collected IMU data from participants, which means the simulated human locomotion was more realistic. Also, as this bio-inspired defined cost, IMU data enhanced the agent’s capacity to converge during the training process. As a result, the models’ convergence is faster than those developed without reference motion data. Consequently, human locomotion can be simulated more quicker and in a broader range of environments with a better simulation performance.

Cognitive function, arthrogryposis, obstetrics palsy, children, motor disorder

Recent research has suggested that working memory training interventions may benefit children with Developmental Language Disorder (DLD). The current study investigated a short and engaging adaptive working memory intervention that targeted executive skills and aimed to improve both language comprehension and working memory abilities in children with DLD. Forty-seven 6- to 10-year-old children with DLD were randomly allocated to an executive working memory training intervention (n=24) or an active control group (n=23). A pre-test/intervention/post-test/9-month-follow-up design was used. Outcome measures included assessments of language (to evaluate far transfer of the training) and working memory (to evaluate near transfer of the training). Hierarchical multiple regression analyses controlling for pre-intervention performance and age found group to be a significant predictor of sentence comprehension and of performance on six untrained working memory measures at post-intervention and 9-month follow-up. Children in the intervention group showed significantly higher language comprehension and working memory scores at both time points than children in the active control group. The intervention programme showed potential to improve working memory and language comprehension in children with DLD and demonstrated several advantages: it involved short sessions over a short period; caused little disruption in the school day; and was enjoyed by children.

Background: Body dysmorphic disorder (BDD) is a psychiatric disorder characterized by excessive preoccupation with imagined defects in appearance. Optical illusions induce illusory effects that distort the presented stimulus thus leading to ambiguous percepts. Using electroencephalography (EEG), we investigated whether BDD is related to differentiated perception during illusory percepts. Methods: 18 BDD patients and 18 controls were presented with 39 optical illusions together with a statement testing whether or not they perceived the illusion. After a delay period, they were prompted to answer whether the statement is right/wrong and their degree of confidence for their answer. We investigated differences of BDD on task performance and self-reported confidence and analysed the brain oscillations during decision-making using nonparametric cluster statistics. Results: Behaviorally, the BDD group exhibited reduced confidence when responding incorrectly, potentially attributed to higher levels of doubt. Electrophysiologically, the BDD group showed significantly reduced alpha power at mid-central scalp areas, suggesting impaired allocation of attention. Interestingly, the lower the alpha power of the identified cluster, the higher the BDD severity, as assessed by BDD psychometrics. Conclusions: Results evidenced that alpha power during illusory processing might serve as a quantitative EEG biomarker of BDD, potentially associated with reduced inhibition of task-irrelevant areas.

Proteolytic processing of amyloid precursor protein (APP) plays a critical role in pathogenesis of Azheimer’s disease (AD). Sequential cleavage of APP by β and γ secretases leads to generation of Aβ40 (non-amyloidogenic) and Aβ42 (amyloidogenic) peptides. Presenilin-1 (PS1) or presenilin-2 (PS2) pay a role of catalytic subunit of γ-secretase. Multiple familial AD (FAD) mutations in APP, PS1, or PS2 result in increased Aβ42:Aβ40 ratio and accumulation of toxic Aβ42 oligomers and plaques in patient brains. In this study we performed molecular modeling of APP complex with γ-secretase and analyzed potential effects of FAD mutations in APP and PS1. We noticed that all FAD mutations in APP transmembrane domain are predicted to cause an increase in the local disorder of its secondary structure. Based on structural analysis of known γ-secretase structures we proposed that APP can form a complex with γ-secretase in 2 potential conformations – M1 and M2. In conformation M1 transmembrane domain of APP forms a contact with perimembrane domain that follows the transmembrane domain 6 (TM6) in PS1 structure. In conformation M2 transmembrane domain of APP forms a contact with transmembrane domain 7 (TM7) in PS1 structure. By analyzing effects of PS1-FAD mutations on local protein disorder index, we discovered that these mutations increase conformational flexibility of M2 and reduce conformational flexibility of M1. Based on these results we proposed that M2 conformation, but not M1 conformation, of γ secretase complex with APP leads to amyloidogenic (Aβ42-generating) processing of APP. Our model predicts that APP processing in M1 conformation is favored by a curved membranes, such as membranes of early endosomes. In contrast, APP processing in M2 conformation is likely to be favored by a relatively flat memranes such as membranes of late endosomes and plasma membrane. These predictions are consistent with published biochemical analysis of APP processing at different subcellular locations. Our results suggest that specific inhibitors of Aβ42 production could be potentially developed by selectively targeting M2 conformation of γ secretase complex with APP.

The purpose of this study was to explore the association of cognition with hazardous drinking and alcohol related disorder in persons with bipolar disorder (BD). The study population included 1,268 persons from Finland with bipolar disorder. Alcohol use was assessed through hazardous drinking and alcohol related disorder including alcohol use disorder (AUD). Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Alcohol related disorder diagnoses were obtained from the national registrar data. Participants performed two computerized tasks from the Cambridge automated neuropsychological test battery (CANTAB) on tablet computer: the 5-choice serial reaction time task, or, reaction time (RT) test and the Paired Associative Learning (PAL) test. Association between RT-test and alcohol use was analyzed with log-linear regression, and eβ with 95% confidence intervals (CI) are reported. PAL first trial memory score was analyzed with linear regression, and β with 95% CI are reported. PAL total errors adjusted was analyzed with logistic regression and odds ratios (OR) with 95% CI are reported. After adjustment for age, education and housing status, hazardous drinking was associated with lower median and less variable RT in females while AUD was associated with a poorer PAL test performance in terms of the total errors adjusted scores in females. Our findings of positive associations between alcohol use and cognition in persons with bipolar disorder are unique.

Recently, ice with the stacking disorder structure, consisting of random sequences of cubic ice (Ic) and hexagonal ice (Ih) layers, is reported to be more stable than pure Ih/Ic. While, due to a much lower free energy barrier of heterogeneous nucleation, in practice, the freezing process of water is usually controlled by heterogeneous nucleation which is triggered by an external medium. Herein, molecular dynamic simulations were carried out to explore the polymorph dependence of ice on the lattice structure of substrates. It turns out that, during the nucleation stage, the polymorph of ice nuclei can be severely altered by the graphene substrate, on which the Ih was found to occupy an absolute majority in new-formed ice. This can be attributed to the structure similarity between graphene and basal face of Ih. Besides the nucleation stage, our results suggest that the substrate can not affect the polymorph of ice which is far from the graphene surface. The polymorph selectivity of graphene to Ih will diminish with the growth of ice layer.

Savouring is an emotion regulation strategy and intervention that focuses on the process of attending, intensifying and prolonging positive experiences and positive affect associated with these memories. Personal savouring involves a reflection on positive memories that are specific to the individual and do not involve others. In contrast, relational savouring entails reflecting on instances when people were responsive to the needs of their significant others. Such interventions hold potential to benefit parents of children with autism spectrum disorder (ASD). Mothers of children with ASD tend to experience higher anxiety, lower positive affect (PA) and more negative affect (NA) compared to mothers of neurotypical children, leading to a diminished overall well-being. Moreover, ASD has multiplied by up to four times in the recent decade. Thus, this paper investigates whether savouring may enhance the overall well-being of mothers of young children with ASD by increasing positive affect and decreasing negative affect. 52 mothers of neurotypical children and 26 mothers of children with ASD aged 3-7 years old were given a series of questionnaires and randomly assigned to either relational savouring or personal savouring conditions. In relational savouring, mothers were asked to reflect upon a shared positive experience with their child while in the personal savouring condition, a personal positive experience was recalled. Across mothers of children with ASD and neurotypical children, findings suggest that savouring leads to a decrease in NA (p &lt; .01) but not increases in PA. Similarly, mothers with higher levels of anxiety experience a greater decrease in NA (p &lt; .001) compared to mothers with lower levels of anxiety post-savouring. This study proposes that a brief savouring intervention may be effective among mothers of preschoolers. As lower levels of negative affect is linked to healthier psychological well-being, mothers might be able to engage in more effective and warm parenting after savouring exercises, which would cultivate positive mother-child relationships that benefit their children in the long-term.

COVID-19 induces coagulopathy at the base of SIC (sepsis-induced coagulopathy) and it is an important cause of death in the patients. Cytokine storm causes imbalance in coagulation and fibrinolytic system. A combination of hypercoagulability state, decrease or inhibition of fibrinolytic and endothelialopathy causes thromboembolic events. Underlined disease with a high rate of mortality in COVID-19 like diabetes, hypertension and some conditions like aging and obesity are the main disorders with hemostatic disturbance and increase of coagulopathy. Therefore, it seems that the combination of COVID-19 infection and these risk factors increase the risk of thromboembolic all together.

Background: CCL11 (eotaxin) is a chemokine with an important role in allergic conditions. Recent evidence indicates that CCL11 plays a role in brain disorders as well. Aims: This paper reviews the associations between CCL11 and aging, neurodegenerative, neuroinflammatory and neuropsychiatric disorders.Methods: Electronic databases were searched for original articles examining CCL11 in neuropsychiatric disorders.Results: CCL11 is rapidly transported from the blood to the brain through the brain-blood barrier. Age-related increases in CCL11 are associated with cognitive impairments in executive functions, episodic and semantic memory and, therefore, this chemokine was described as an “endogenous cognition deteriorating chemokine” (ECDC) or “accelerated brain-aging chemokine” (ABAC). In schizophrenia, increased CCL11 is not only associated with impairments in cognitive functions, but also with key symptoms including formal thought disorders. Some patients with mood disorders and premenstrual syndrome show increased plasma CCL11 levels. In diseases of old age, CCL11 is associated with lowered neurogenesis and neurodegenerative processes and, as a consequence, increased CCL11 increases risk towards Alzheimer's Disease. Polymorphisms in the CCL11 gene are associated with stroke. Increased CCL11 also plays a role in neuroinflammatory disease including multiple sclerosis. In animal models, neutralization of CCL11 may protect against nigrostriatal neurodegeneration. Increased production of CCL11 may be attenuated by glucocorticoids, minocycline, resveratrol and anti-CCL11 antibodies.Conclusion: Increased CCL11 production during inflammatory conditions may play a role in human disease including age-related cognitive decline, schizophrenia, mood disorders and neurodegenerative disorders. Increased CCL11 production is a new drug target in the treatment and prevention of those disorders.

Nanoparticles offer available tools for MDD research. In this assay, we applied CBR1 (cannabinoid receptor 1) knockout (CB1-/-) mice to study whether functionalized solid lipid nanoparticles loading with curcumin and dexanabinol (Cur/SLNs-HU-211) exhibited anti-depressant outcomes through CBR1. Wild-type (CB1+/+) animals together with CBR1 knockout (CB1-/-) animals received daily injections of Corticosterone (CORT) for 3 weeks to obtain MDD mice model, and then the therapeutic action of Cur/SLNs-HU-211 were evaluated, respectively. Our work show that Cur/SLNs-HU-211 nanoparticles in the existence of CBR1 facilitate an efficient motor function improvement in CORT-induced MDD mice model. Cur/SLNs-HU-211 nanoparticles alleviated symptoms on CB1+/+ MDD mice and resulted in dopamine and norepinephrine recovery following CORT-induced neurotoxicity. In conclusion, the possible mechanisms underlying the antidepressant effect of Cur/SLNs-HU-211 might be the induction of CB1 expression and downstream RASGEF1C and Egr1 expression, together with a significantly upregulation of neuron-specific genes in CB1+/+ mice only. In conclusion, CBR1 is necessary during the process of antidepressant activities of Cur/SLNs-HU-211 nanoparticles. This study confirms that Cur/SLNs-HU-211 nanoparticles based CBR1 in vivo targeting would be a potentially feasible and safe way to motivate future therapeutic strategies of Major Depressive Disorder.

Transdermal alcohol biosensors have the ability to detect the alcohol that emanates from the bloodstream and diffuses through the skin. However, they have suffered from long-term fouling of the sensor element and drift in the resulting sensor readings over time. Here, we report a disposable cartridge platform that solves the problem of sensor fouling, and an enzymatic detection pathway that minimizes baseline drift for sensitive detection. Laboratory characterization of the enzymatic alcohol sensor demonstrates a linear sensor range of between 0 and 50 mM. Further, we show continuous transdermal alcohol data recorded with a human subject over 48 hours.

Background: India has one-fifth of the world's population and the number of people suffering from mental illness is assumed to be huge considering the contribution of mental disorders to the overall burden of the disease being 13.9 %. Objectives of Study: To estimate prevalence and patterns of mental illnesses to assess the current mental health services and systems in the Madhya Pradesh. Material and Methods: Multi-stage, stratified, random cluster sampling technique, with random selection based on probability proportionate to size at each stage. A total of 3240 individuals aged 18 years and above were interviewed. Both quantitative and qualitative methods were employed. A set of 10 instruments including Mini International Neuro-psychiatric Interview were utilized. Results: The overall weighted prevalence for any mental illness was 16.7% lifetime and 13.9% current. Treatment-gap for all mental health problems is as high as 91% in the state along with huge socioeconomic impact of mental illness. Conclusions: This huge burden of mental, behavioural and substance use disorders, in Madhya Pradesh, calls for immediate attention of political leaders, policy makers, health professionals, opinion-makers and society at large. It is hoped that the data from the study will inform mental health policy and legislation and help shape mental health care delivery systems in the country.

The focus of this study was to investigate how individuals with bipolar disorder integrate auditory and visual speech information compared to non-disordered individuals and whether there were any differences in auditory and visual speech integration in the manic and depressive episodes in bipolar disorder patients. It was hypothesized that bipolar groups’ auditory-visual speech integration would be less robust than the control group. Further, it was predicted that those in the manic phase of bipolar disorder would integrate visual speech information more than their depressive phase counterparts. To examine these, the McGurk effect paradigm was used with typical auditory-visual speech (AV) as well as auditory-only (AO) speech perception on visual-only (VO) stimuli. Results. Results showed that the disordered and non-disordered groups did not differ on auditory-visual speech (AV) integration and auditory-only (AO) speech perception but on visual-only (VO) stimuli. The results are interpreted to pave the way for further research whereby both behavioural and physiological data are collected simultaneously. This will allow us understand the full dynamics of how, actually, the auditory and visual (relatively impoverished in bipolar disorder) speech information are integrated in people with bipolar disorder.

A probabilistic description is essential for understanding the dynamics of stochastic systems far from equilibrium, given uncertainty inherent in the systems. To compare different Probability Density Functions (PDFs), it is extremely useful to quantify the difference among different PDFs by assigning an appropriate metric to probability such that the distance increases with the difference between the two PDFs. This metric structure then provides a key link between stochastic systems and information geometry. For a non-equilibrium process, we define an infinitesimal distance at any time by comparing two PDFs at times infinitesimally apart and sum these distances in time. The total distance along the trajectory of the system quantifies the total number of different states that the system undergoes in time, and is called the information length. By using this concept, we investigate the information geometry of non-equilibrium processes involved in disorder-order transitions between the critical and subcritical states in a bistable system. Specifically, we compute time-dependent PDFs, information length, the rate of change in information length, entropy change and Fisher information in disorder-to-order and order-to-disorder transitions, and discuss similarities and disparities between the two transitions. In particular, we show that the total information length in order-to-disorder transition is much larger than that in disorder-to-order transition, and elucidate the link to the drastically different evolution of entropy in both transitions. We also provide the comparison of the results with those in the case of the transition between the subcritical and supercritical states and discuss implications for fitness.

Current agriculture intensifies crop cultivation to meet food demand, leading to unsustainable use of chemical fertilizers. This study investigates a few physiological and agronomic responses of common wheat following the inoculation with plant growth-promoting bacteria to reduce nitrogen inputs. A field trial was conducted in 2022-23, in Legnago (Verona, Italy) on Triticum aestivum var. LG-Auriga comparing full (180 kg ha-1) and reduced (130 kg ha-1) N doses, both with and without foliar application at end tillering of the N-fixing bacterium Methylobacterium symbioticum. Biofertilization did not improve shoot growth, while it seldom increased root length density in the arable layer. It delayed leaf senescence, prolonged photosynthetic activity, amplified stomatal conductance and PSII efficiency under reduced N dose. Appreciable ACC-deaminase activity of such bacterium disclosed augmented nitrogen retrieval and reduced ethylene production, explaining ameliorated stay-green. Yield and testing weight were unaffected by biofertilization, while both glutenin-to-gliadin and HMW-to-LMW ratios increased together with dough tenacity. It is concluded that Methylobacterium symbioticum can amplify nitrogen metabolism at reduced nitrogen dose, offering a viable approach to reduce chemical fertilization under suboptimal growing conditions for achieving a more sustainable agriculture. Further research over multiple growing seasons and soil types is necessary to corroborate these preliminary observations.

Protein 53 (P53) shows different functions either to support or to contrast malignant growth. P53 history tells that discoveries of molecular features have contributed to the emergence of P53 functions. Conversely, the shift of paradigms demonstrates that P53 functions coexist even if are in conflict with one another. Since 1979, five paradigms have been assembled then deconstructed by taking into account P53 functions of viral protein, oncogene, tumor suppressor gene, transcription factor, apoptotic factor. By summarizing the past five disassembled P53 paradigms, in this investigation the current paradigm involving P53 in the modulation of a composite bio-morphological entity namely, tumor immune microenvironment (TIME) is analyzed. The aims of this investigation were to provide an overview of solid and validated knowledge occurring in all P53 paradigms and to determine P53 abilities to modify TIME through manipulation of viruses. As a result, definitive P53 evidence concerns its genetic localization, amino acids composition, its isoforms and subcellular expression in organelles. P53 “mutome” assembles all mutations affecting this complex protein. Lastly, both categories of tumor promoting and non-oncogenic viruses related to P53 were scrutinized. In conclusion, paradigms teach that P53 is undruggable because its drugs inevitably target all P53 functions.

Despite several studies on learner-to-teacher workplace violence and harassment, the problem persists in some South African schools. Learner-to-teacher violence and harassment is a form of workplace violence and harassment as schools are workplaces for teachers. Learner-to-teacher violence and harassment is therefore an important occupational health and safety issues for teachers. The employer is obliged to provide a safe working environment for the teachers to enable quality teaching and learning in the schools. The purpose of this interpretative phenomenological study was to explore and describe the lived experiences of high school teachers who have been targets of workplace violence and harassment perpetrated by learners at selected schools in Limpopo province of South Africa. Many teachers were willing to share their lived-experiences but due to data saturation, only eleven participated after being selected through purposive sampling from seven high schools under a particular circuit. Research ethics of voluntary participation, informed consent, ethical clearance and gatekeeper permission were observed. Data was collected through semi-structured interviews using an interview guide. Interviews were audio-taped, and field notes were also taken. Voice recordings were transcribed verbatim and analysed using interpretative phenomenological analysis into themes and sub-themes. Findings were confirmed by an independent coder to achieve trustworthiness. Teachers experienced physical workplace violence and harassment, verbal workplace violence and harassment as well as nonverbal workplace violence and harassment from learners. Learner-to-teacher workplace violence and harassment affects teachers emotionally and in turn affects quality teaching and learning in the schools. Some teachers propose involvement of community policing forum, strengthening of School Governing Bodies as well as reducing overcrowding in the classroom as possible solutions to deal with learner-to-teacher bullying.

Autism Spectrum Disorder etiopathogenesis is still unclear and no effective preventive and treatment measures have been identified. Research has focused on the potential role of neuroinflammation and kynurenine pathway. Here we review the nature of these interactions. Pre-natal or neonatal infections would induce microglial activation, with secondary consequences on behavior, cognition and neurotransmitter networks. Peripherally, higher levels of pro-inflammatory cytokines and anti-brain antibodies have been identified. Increased frequency of autoimmune diseases, allergies, and recurring infections have been demonstrated both in autistic patients and in their relatives. Genetic studies, also, have identified some important polymorphisms in chromosome loci related to human leukocyte antigen (HLA) system. The persistence of immune-inflammatory deregulation would lead to mitochondrial dysfunction and oxidative stress, creating a self-sustaining cytotoxic loop. Chronic inflammation activates kynurenine pathway with increase in neurotoxic metabolites and excitotoxicity, causing long-term changes in glutamatergic system, trophic support and synaptic function. Furthermore, overactivation of kynurenine’s branch induces depletion of melatonin and serotonin worsening ASD symptoms. In this scenario, kynurenine pathway appears as a pharmacological target to treat and prevent ASD. Thus, in genetically predisposed subjects aberrant neurodevelopment may derives from a complex interplay between inflammatory process, mitochondrial dysfunction, oxidative stress and kynurenine pathway overexpression. To validate previous hypothesis a new translational research approach is necessary.

Bipolar disorder is a debilitating psychiatric condition characterized by recurrent episodes of mania and depression, affecting millions worldwide. While pharmacotherapy remains the cornerstone of treatment, a significant proportion of patients exhibit inadequate response or intolerable side effects to conventional medications. In recent years, neuromodulation techniques have emerged as promising adjunctive or alternative treatments for bipolar disorder. We performed a narrative review to provide a comprehensive overview of the current literature on neuromodulation interventions in bipolar disorder across the course of lifespan. Specifically, it examines the efficacy, safety, and mechanisms of action of various neuromodulation strategies, including, among others, transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), deep brain stimulation (DBS), and it describes the therapeutic experiences across the different ages of illness. Additionally, this review discusses the clinical implications, challenges, and future directions of the integration, in the clinical practice, of neuromodulation into the management of bipolar disorder. By synthesizing evidence from different studies, this review aims to inform clinicians, researchers, and stakeholders about the evolving landscape of neuromodulation treatments and their potential role in improving outcomes for individuals with bipolar disorder.

A cross-sectional study was organised to investigate the range, prevalence, and associated factors for occupational health problems related to dental practice among Cambodian dentists; Participants underwent a face-to-face interview to explore dentists work-related health problems; 106 Cambodian dentists participated in this study, 68.9% were male. Ages ranged from 29 to 71 years, averaging 36.1 years, with the majority (77.4%) in the 29-40 age group. They had 5 to 18 years of practice experience, and worked an average of 52.2 hours per week. Commonly reported health issues included back pain (88.7%), headaches (81.1%), shoulder pain (78.3%), arm/hand pain (57.5%), and eye problems (48.1%). 38.7% of participants felt stressed and 19.8% depressed. Some reported suicidal thoughts and taking medication for depression. Despite these challenges, 91.5% enjoyed practicing dentistry; Findings highlight the need for interventions and strategies to address the physical and mental well-being of Cambodian dentists. By addressing these issues, steps can be taken to enhance the working conditions and professional satisfaction of dental professionals, ultimately benefiting both the practitioners and their patients.

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

This study explores the efficacy of using EEG-based parameters to diagnose bipolar disorder. A synthetic dataset was generated, including both correctly diagnosed and misdiagnosed cases, simulating realistic clinical conditions. EEG features such as theta-alpha mean, beta band mean, and coherence measures were used to train a multi-layer perceptron (MLP) model. The model achieved a validation accuracy of 92%, demonstrating strong potential for EEG-based diagnostics. However, challenges such as standardization of electrode configurations and addressing equipment differences are crucial for broader applicability and validity of the findings in diverse clinical settings.

Objective-Most women stop using hormonal contraceptives due to changes in their mood. The evidence regarding the association of hormonal contraception with depression shows mixed results. Therefore, we aim to establish the association between the use of hormonal contraception and depressive symptoms. Method- This cross-sectional study was conducted on 326 women of reproductive age using hormonal contraceptives for a week to one year referred to as "hormonal contraceptive (HC) users" (n=165), and those using non-hormonal methods and not using contraceptives referred to as "HC non-users" (n=161). Beck's depression inventory (BDI-II) was used to measure depression. Result-There was no discernible difference in mean Beck's depression inventory score and degree of depression between the two groups. However, individual symptoms of depression such as sadness(p=0.01), reduced libido(p=0.0002) feelings of pessimism (p=0.02), and failure (p=0.003) were found to be significantly high in the HC user group. Conclusion- We conclude that there was no significant difference in mean depression scores between groups. However, few individual symptoms of depression were high in HC users suggesting depression as a potential side effect of hormonal contraceptive use.

This survey of research literature is an overview of the current state of science addressing DSM-5 diagnostic criteria as it relates to identifying Autism Spectrum Disorder (ASD) in young children. Selected sources are of high quality and have been published since 2020 in peer-reviewed journals relevant to children’s health. The narrative is organized from the earliest to the most recent publications and is divided into sections around categories and themes that highlight the main arguments, findings, and controversies identified by researchers. There are indications in the literature that while ASD can be identified and differentiated from other developmental disorders in young children, doing so requires that clinicians who have relied on the DSM-5 should also use multiple measures, including other formalized screening tools as assessments that gather observational input from parents and caregivers, as well as findings from physical examinations, laboratory investigations, and magnetic resonance imagining (MRI). This high level of corroboration points to an emerging diagnosis paradigm through which transdiagnostic approaches to early diagnosis and intervention may exist.

We present a case of adult-onset systemic chronic active EBV disease (CAEBV) in a 40-year-old woman with chronic HBV hepatitis. Initial symptoms resembled a viral illness, progressing to recurrent fever, transaminitis, and anasarca. Investigations revealed high-level EBV viremia and an abnormal T-cell population in liver and bone marrow, indicative of CAEBV. Liver biopsy showed CD3+ T-cells lacking TCRbeta and displaying dim/negative CD5, with elevated EBV-infected T-cells. Next-generation sequencing identified rare variants in CREBBP, SPEN, TP73, and PLCG2, suggesting potential contributions to disease pathogenesis. This case underscores diagnostic challenges and management complexities of adult-onset CAEBV, particularly with underlying chronic HBV infection. Genomic profiling offers crucial insights into the molecular landscape of rare lymphoid malignancies, highlighting the importance of personalized treatment strategies. The distinct immunophenotypic features underscore the heterogeneity in EBV-associated T-cell LPDs, urging further research for optimized clinical management

Type2 diabetes(T2D) is a pervasive modern disease, classified as a metabolic disorder marked by hyperglycemia, hyperinsulinemia, and life-long threatening cardiovascular morbidities. Subclinical inflammation stands as the primary pathogenetic factor propelling T2D progression, correlated with heightened levels of proinflammatory cytokines. Immune cells serve as the prominent sources of cytokine production, and under diabetic conditions, they tend toward a proinflammatory phenotype, fostering chronic inflammation. This review zeroes in on the disrupted homeostasis characteristic of diabetic conditions, encompassing cytokines, hormones, and their interplay with altered immune function, all contributing to the onset of diabetic cardiovascular complications.

Abstract: (1) Background: The occurrence of youth aggression has aroused widespread concern, and we would like to explore the reasons for it from both the family and individual sides of the youth. This study constructed a chain mediation model based on Bandura's Social Learning Theory to explore the mechanism of internet gaming disorder and avatar identification in it; (2) Methods: We conducted a randomized survey involving 973 adolescents from various middle schools in China. We used the Harsh Parenting Scale, the Online Gaming Disorder Scale, the Incarnate Identity Scale, and the Buss-Perry Aggression Scale to conduct a randomized survey. Empirical analyses were conducted using SPSS 25.0 and Amos 24.0 software to examine the mediating role of online gaming barriers and avatar identity; (3) Results: There was a two-by-two significant positive correlation between harsh parenting, internet gaming disorder, avatar identification and aggression. The me-diation model between harsh parenting, internet gaming disorder, avatar identification and ag-gression was well fitted ( χ2/df=7.268, GFI=0.961, AGFI=0.923, IFI=0.970, CFI=0.970, TLI=0.951, RMSEA=0.080).; (4) Conclusions: Parental harsh parenting affects adolescent aggression not only through the separate mediating roles of internet gaming disorder and avatar identification, but also through the chain mediating roles of internet gaming disorder and avatar identification.

This study presents a computational simulation to explore the distinctive patterns of neural connectivity in Autism Spectrum Disorder (ASD), focusing on the concepts of spatial and topological proximities. ASD is characterized by unique cognitive and behavioral profiles, often attributed to atypical neural development and connectivity. Our simulation employs a two-pronged approach: first, by modeling spatial proximity through the generation of clustered 3D node positions, we mimic the observed over-connectivity in localized brain regions in ASD. Second, we construct a topological network to represent the complex interplay of under-connectivity and over-connectivity in functional brain networks, a hallmark of ASD's neural landscape. The spatial model demonstrates pronounced clustering, reflecting the structural brain differences and atypical growth patterns reported in neuroimaging studies of individuals with ASD. In contrast, the topological model reveals a network with a mix of sparse and dense connections, simulating the diverse and often contradictory findings of functional connectivity in ASD, such as reduced long-range connections and increased local connections. Our simulation provides a visual and conceptual framework for understanding the altered neural connectivity in ASD. It underscores the importance of considering both physical (spatial) and functional (topological) aspects of brain connectivity to grasp the full extent of neurodevelopmental deviations in ASD. This approach not only aids in elucidating the neural underpinnings of ASD's core symptoms but also offers a foundation for developing targeted interventions. Future research, integrating more complex and individual-specific data, could further refine this model, enhancing our understanding of ASD's neural dynamics and contributing to personalized therapeutic strategies.

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

We investigated if the abnormal sleep-wake rhythms in infants are related to the future development of autism spectrum disorder (ASD), using questionnaire from September to October 2016. The parents of a total 160 children with ASD (male, n=123; female, n=37) recruited from the two hospitals in K and H cities and as a control group, 145 children (male, n=75; female, n=70) recruited from four nursery schools in T city. Fisher’s exact test was used for the comparison of categorical variables. The associations of bedtime and waking time on weekdays and holidays in infancy, at 1-3≦ (1-3) years of age and at 3-5 ≦ (3-5)years of age with the prevalence of ASD were analyzed using a multivariable logistic regression analysis. Especially by 3 years of age, the following factors were associated with an increased risk of developing ASD in the future: 1) short sleep (<8h), 2) long time to fall asleep (>60min), 3) sleep onset time after 22:00h, 4) wake-up time after 07:00h and/or 08:00h on weekdays and holidays, respectively, 5) frequent (>3 times) and long-term awakening (>60min). Misalignment and/or shift of the sleep-wake circadian rhythm in infant may be one of the precursors and/or risk factor to the future development of ASD.

Background Binge eating disorder (BED) is the most common eating disorder, categorized in DSM-V, but many patients are not diagnosed, because of the difficulty to consider BED distinct condition from obesity. Its identification is important for targeting individuals at high risk of obesity, adverse metabolic pattern, and cardiovascular disease. In this review we have highlighted the main aspects of screening, diagnosis and treatment of patients with BED and Obesity.

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.

Myofascial pain is the most common cause of chronic pain in the masticatory region and can be assessed through clinical analysis and muscle palpation. Generally, it appears with headache and orofacial pain associated with sensitive points (trigger points) due to the excessive contraction of the masticatory muscle fibres. The study aims to evaluate how a correct treatment of myofascial pain can improve the life quality of the affected patients. In this case series, 300 patients with myofascial pain were divided into two groups: 150 with intra- and extra-articular disorder and 150 with the only extra-articular disorder. Each group included 75 males and 75 females. All the patients were treated with gnathological therapy through passive aligners and biofeedback exercises for 4 months. They underwent pain assessment (through a visual analogue scale and muscular palpation test) before, during and after the treatment, and nuclear magnetic resonance of the temporomandibular joint before and after the gnathological treatment. The treatment considerably reduced the pain in all patients, without drugs, in 4 months, according to the visual analogue scales and the palpation test. The temporomandibular magnetic resonance in each patient was similar before and after the gnathological treatment. The improvement in pain did not depend on a change in the relationship between the articular condyle and the disc.

The idealized rhombohedral unit cell of boron carbide is formed by a 12-atom icosahedron and a 3-atom linear chain. Phase transitions are second order and caused by the exchange of B and C sites or by vacancies in the structure. Nevertheless, the impact of such minimal structural changes on the properties can be significant. As the X-ray scattering cross sections of B and C atoms are very similar, the capability of X-ray fine structure investigation is restricted. Phonon spectroscopy helps closing this gap. Phase transitions known to date have been identified due to significant changes of properties: (1) The phase transition near the chemical composition B8C by clear change of the electronic structure; (2) The endothermic temperature-dependent phase transition at 712 K by the according change of specific heat; (3) The high-pressure phase transition at 33.2 GPa by the drastic change of optical appearance from opacity to transparency. These phase transitions affect IR- and Raman-active phonons and other solid-state properties. The phase transitions at B~8C and 712 K mean that a well-defined distorted structure is converted into another one each. In the high-pressure phase transition, an apparently well-defined distorted structure changes into a highly ordered one. In all these cases, the distribution of polar C atoms in the icosahedra plays a crucial role.

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, bioinformatics, and databases. We analyzed the raw DNA sequencing files on the Variantyx® (Framingham, MA, USA) bioinformatics platform for the last 50 autism patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, very rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) heterozygous de novo, 3 X-linked, 4 autosomal recessive, 2 autosomal dominant, and 1 heteroplasmic mtDNA variants. De novo variants in genes associated with ASD were far more likely to be Qualified than non-Qualified (control group, P = 0.002), validating that most are indeed disease causal. Only 14/34 (41%) of PDV cases had the variant listed on the laboratory report, and reanalysis increased diagnostic yield from 28% to 68%. The “missed” cases predominately included genes with zero (14 cases) to ≤5 prior reported case reports. Many cases both with and without a PDV had inherited Qualifying variants in known ASD-associated genes, suggesting polygenic inheritance. Thirty-three participants (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. Many are de novo and represent un/under-published conditions.

Febrile seizure (FS), which occurs as a response to fever, is the most common seizure that occurs in infants and young children. FS is usually accompanied by diverse neuropsychiatric symptoms including impaired social behaviors; however, no causative link between FS and autism spectrum disorder (ASD) has yet been established. Here, we provide evidence linking FS occurrence with ASD pathogenesis in rats. We developed an FS juvenile rats model and found ASD-like abnormal behaviors including deficits in social novelty, repetitive behaviors, and hyperlocomotion. In addition, FS model juvenile rats showed enhanced levels of gliosis and inflammation in the hippocampal CA2 region and cerebellum. Furthermore, abnormal levels of social and repetitive behaviors persisted in adults FS model rats. These findings suggest that occurrence of FS in infants can cause behavioral endophenotypes of ASD.

Background and objectives: Huntington disease (HD) is characterized by motor, cognitive and psychiatric manifestations and is caused by an expansion of CAG repeats over 35 triplets on the huntingtin (HTT) gene. However, expansions in the range 27-35 repeats (intermediate allele) can be associated with pathological phenotypes. The onset of HD is conventionally defined by the onset of motor symptoms, but psychiatric disturbances can precede the motor phase by up to twenty years. The aims of the present study are to identify HD patients in the pre-motor phase of the disease among patients diagnosed with bipolar disorders and to evaluate any differences between bipolar patients carrying normal HTT allele and patients with expanded HTT gene. Methods: We assessed the HTT genotype in an Italian cohort of 69 patients affected by bipolar disorder type 1 and type 2. Results: No patient was found to be a carrier of the pathological HTT allele, but 10% of bipolar subjects carried an intermediate allele. Carriers of the intermediate allele were older at onset of psychiatric symptoms than non-carriers. Conclusion: The pathological HTT gene was not associated with bipolar disorder, while we found a higher frequency of the intermediate allele among the bipolar population with respect to healthy controls.

Obesity has become a global epidemic, contributing to the development of numerous chronic diseases, including diabetes, chronic kidney disease (CKD) and cardiovascular disorders. MicroRNAs (miRNAs) have emerged as key regulators in various biological processes, including metabolism, inflammation, and tissue remodeling, making them pivotal players in obesity-related pathologies. This review aims to provide comprehensive insights into the roles of miRNAs in obesity, with a particular emphasis on their involvement in the pathogenesis of CKD and cardiovascular disorders. We highlight the involvement of specific miRNAs in adipose tissue development, energy homeostasis, inflammation, and insulin resistance, contributing to the pathogenesis of obesity. Moreover, we explore the impact of miRNAs on renal fibrosis, and inflammation, giving clues on their roles in the development and progression of CKD. Additionally, we discuss the influence of miRNAs on endothelial dysfunction, atherosclerosis, and cardiac remodeling, emphasizing their contribution to obesity-related cardiovascular disorders. Understanding the regulatory functions of miRNAs in these interconnected conditions holds promise for improved diagnosis, prognosis, and therapeutic interventions. Indeed, miRNAs are potential diagnostic biomarkers for obesity-related diseases although challenges remain to be elucidated before their clinical translation. Furthermore, we highlight the emerging strategies that target miRNAs as therapeutic interventions to mitigate the detrimental effects of obesity on kidney and cardiovascular health.

Sex/gender (S/G) differences in ASD language profiles have been poorly investigated. The present study aims to explore whether male (M) and female (F) children with ASD and with normal non-verbal cognitive abilities differ in their linguistic profiles. A sample of 76 Italian children with ASD (range: 4.9 – 8 years), including 50 M and 26 F, was retrospectively recruited. Language profiles were analyzed using standardized tests for the evaluation of receptive and expressive vocabulary as well as grammar. Grammatical comprehension was the most impaired domain compared to the other language measures in both M and F children. Comparing language profiles between S/G, F showed significantly better scores than M in grammatical production (p=.002), and M showed better active negative sentences comprehension (p=.035). Moreover, comparing the language profiles between M and F with receptive disorder, F had significantly worse grammatical comprehension and better grammatical production than M. Even among children without receptive disorder, F had significantly higher grammatical production scores. The S/G differences in language profile, particularly better expressive language in F than M, can partially contribute to the delayed ASD diagnosis or underdiagnosis of F without intellectual disability. Finally, our results document the importance of accurately investigating both expressive and receptive abilities in children with ASD.

Frontal incomes play an important role in human behavioral regulation and can be a determinant of eating behavior. The aim of this study was to analyse the frontal incomes in obese patients with and without Binge Eating Disorder (BED), compared to normoweight (NW) subjects and to analyse the effect of sex and binge disorder on quality of life, with age and BMI as covariates. A total of 114 participants comprised three different groups (obese with BED, obese without BED and NW) completed the Frontal Assessment Battery (FAB) and Impact of Weight on Quality of Life (IWQOL-lite). The results showed that obese patients, with and without BED, have poorer frontal functioning than NW persons. Obese patients with BED have lower performance in frontal income than obese patients without BED. Male participants have a higher perception of quality of life in all dimensions, with women showing lower values in self-esteem and sex life. Obese with BED show greater weaknesses in physical function. These results suggest that low frontal incomes and worse quality of life characterize obese patients, more evident in obese patients with BED.

Children with Autism Spectrum Disorder have deficits in social interaction and expressing and understanding emotions. Many robots for children with ASD have been proposed. However, few studies were found about how to design a social robot for children with ASD. Studies reviewed employed non-experimental studies to evaluate a social robot, but the methodology to design a social robot is rare. This study proposes a design path for a social robot for emotional communi-cation for children with ASD, following User-Centered Design approach. This design path is ap-plied with a study case, evaluated with an expert group on psychologist, human-robot interaction, human-computer interaction, and parents of children with ASD. Results show than following the design path proposed to design a social robot to communication emotions for children ASD is favorable.

To evaluate the impact of a new Substance Use Disorder (SUD) education program on medical students' representations, we selected the Substance Abuse Attitude Survey (SAAS) questionnaire, which we adapted to our curriculum and cultural context. To validate this adapted version, we conducted an exploratory factor analysis following the administration of our 29-items bSAAS questionnaire to 657 medical students in Belgium (response rate: 71,1%). 23 items correlated to 3 factors namely "Stereotypes and moralism", "Treatment optimism" and "Specialised treatment" were retained (70% of total variance explained, Cronbach's alpha= 0.80) and constituted the new questionnaire called beSAAS. The factor "Specialised treatment", stood out from previous studies which could be explained by our target population and the impact of the formal, informal, and hidden curriculum in medical education. This study highlighted certain factors influencing stereotypical representations such as age, gender, origin, and personal or professional experience with substance use. Our study allowed us to retain the beSAAS as a good questionnaire to evaluate SUD stigma and highlighted interesting findings to improve SUD training in medicine. Further studies are needed to complete its validity and reliability.

Background: To assess the prevalence of Hypertension (HTN) in Burning Mouth Syndrome (BMS) patients and to investigate its relationship with sociodemographic factors, pain and the psychological profile. Methods: A case-control study was conducted by enrolling 242 BMS patients and 242 controls matched for age and gender. Sociodemographic and clinical characteristics were recorded, and all the participants completed the numeric rating scale (NRS), the short-form of the McGill pain questionnaire (SF-MPQ), the Hamilton rating scale for anxiety and depression (HAM-A, HAM-D), the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS). Results: The BMS patients presented a statistically significant higher prevalence of HTN compared to the controls (55% versus 33.5%; p-value: &lt;.001**) and higher median scores of the NRS, SF-MPQ, HAM-A, HAM-D, PSQI and ESS (p &lt; .001**). Multivariate regression analysis in the BMS patients indicated positive correlations between HTN and age, systemic diseases, drug consumption and anxiety (p-value: &lt;.001**) and these predictors were responsible for 11.3% of the HTN variance in the BMS patients, when considered together. Conclusions: The prevalence of HTN was significantly higher in the BMS patients, since ageing, the presence of comorbidities, drug consumption and anxiety were potential predictors. Further studies are needed to better investigate the relationship between BMS and HTN.

Contemporary research has found that people with autism spectrum disorder (ASD) exhibit aberrant immunological function, with a shift toward increased cytokine production and unusual cell function. Microglia and astroglia were found to be significantly activated in immuno-cytochemical studies, and cytokine analysis revealed that the macrophage chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and transforming growth factor β-1 (TGFB-1), all generated in the neuroglia, constituted the most predominant cytokines in the brain. Taurine (2-aminoethanesulfonic acid) is a promising therapeutic molecule able to increase the activity of antioxidant enzymes and ATPase, which may be protective against aluminum-induced neurotoxicity. It can also stimulate neurogenesis, synaptogenesis, and reprogramming of proinflammatory M1 macrophage polarization by decreasing mitophagy (mitochondrial autophagy) and raising the expression of the markers of the anti-inflammatory and pro-healing M2 macrophages, such as macrophage mannose receptor (MMR, CD206) and IL-10, while lowering the expression of the M1 inflammatory factor genes. Taurine also induces autophagy, which is a mechanism that is impaired in microglia cells and is critically associated with the pathophysiology of the ASD. We hypothesize here that taurine could reprogram the metabolism of M1 macrophages that are overstimulated in the nervous system of people suffering from ASD, thereby decreasing the neuroinflammatory process, neuronal death, and improving cognitive functions. Therefore, we think that taurine can serve as an important lead for the development of novel drugs for the ASD treatment.

(1) Background: tuberculosis (TB) is considered one of the leading causes of death by a single in-fectious agent worldwide. This study aimed to identify hotspots of people diagnosed with tu-berculosis and abusive use of alcohol, tobacco and other drugs in communities through a geo-spatial intelligence application; (2) Methods: ecological study with a spatio-temporal approach. We considered tuberculosis cases diagnosed and registered in the Notifiable Diseases Information System, which presented information on alcoholism, smoking, and other drugs. Spatial Variations in Temporal Trends (SVTT) and scan statistics were applied for the identification of Hotspots; (3) Results: of 29.499 cases of tuberculosis were identified. And when we applied the STTT for al-coholism, three Hotspots were detected, one of which was protective (RR: 0.08 – CI95%: 0.02 – 0.32) and two at risk (RR:1.42 – CI95%: 1.11 – 1.73; RR: 1.39 - CI95%: 1.28 – 1.50). Regarding smoking, two risk clusters were identified (RR: 1.15 - CI95%: 1.01 – 1.30; RR: 1.68 - CI95%: 1.54 – 1.83). For other drugs, a risk cluster was found (RR: 1.13 - CI95%: 0.99 – 1.29) and two protections (RR: 0.70 - CI95%: 0.63 – 0.77; RR: 0.76 – CI95%: 0.65 – 0.89); (4) Conclusions: it was evidenced in the communities a problem of TB and drug addiction. Use disorder perhaps in a person's brain and behavior and leads to an inability to continue their treatment, putting the community at risk for TB.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. Neurobiologically, ADHD impairments arise from abnormalities in different circuits involving the prefrontal cortex. In face of high rates of diagnosis, alternative/complementary pharmacological therapeutic approaches for ADHD are needed. Although the number of publications that study the potential effects of caf-feine consumption on ADHD treatment have been accumulating over the last years, and caffeine has recently been used in ADHD research in the context of animal models, an updated evi-dence-based systematic review on the effects of caffeine on ADHD-like symptoms in animal stud-ies is missing. To provide insight and value at the preclinical level, a systematic review based on PRISMA guidelines was performed for all publications available up to September 1, 2021. Caffeine treatment increases attention, improves learning, memory and olfactory discrimination, without altering blood pressure and body weight. These results are supported at the neuronal level. Nonetheless, the implication of caffeine in modulating ADHD-like symptoms of hyperactivity and impulsivity is contradictory, raising discrepancies that require further clarification. Our results strengthen the hypothesis that caffeine cognitive effects found in animal models could be trans-lated to human ADHD, particularly during adolescence.

The present study aimed to investigate the effect of a motor skills training program in children with DCD considering their gender. The Movement Assessment Battery for Children (MABC-2) classified the children and assessed skill changes over time. The study was implemented at four kindergartens in the Khorezm region of Uzbekistan. In the study, all children had DCD (5.17 ± 0.70 years; 10 girls), and all indicators on MABC-2 were less than 16 percent. Participants were divided into an experimental group (n=17) receiving ten weeks of motor skills training program for 45 min twice per week, the control group (n=7) proceeded with exercises of everyday living. All children in the experimental group had a significant increase in total percentile rank of MABC-2 and concerning each domain (manual dexterity; throwing and catching; balance). In the control group, a significant decrease in the total percentile rank of MABC-2 and each domain of MABC-2 was observed. The effectiveness of the intervention program was similar across both genders. The study supports that a period of 10 weeks of a motor skills training program can increase the quality of children's motor coordination and represent a valuable procedure for physical education specialists to enhance motor skills for children with DCD.

Term vascular dysfunctional refers to a wide spectrum of vascular abnormalities including pathogenesis of tumors, their proliferation and leading to malfunctioned conditions. The treatment of most of the vascular anomalies including peripheral arterial disease and cardiac disease is multi factor procedure which include the embolic therapy, laser-based treatments and coagulation are all plating important role in managing the disease associated with vascular breakdown. The research proposal defines the treatment and diagnosis procedures involved in treatment of vascular abnormalities with a deep emphasis on techniques, efficiency and complications resulted from various other procedure and use of mapping and sequencing techniques based on genetics of variants of selected genes PIk3CA which will ultimately be more effective.

Today, rupture of the anterior cruciate ligament is the most common heavy injury in athletes, but it can also occur in sedentary subjects. Its treatment, always adapted to the lifestyle, age and will of the patient, often remains surgical. However, despite its frequency and universality, there are still walking disorders following the operation. These disorders sometimes persist for several months, or even several years after surgery. The present study is therefore interested in determining the risk factors linked to walking disorders following reconstruction of the anterior cruciate ligament. The objective of this study is to determine what risk factors associated with walking disorders are after reconstruction of the anterior cruciate ligament by hamstring graft. This study focused on factors that may exist at 3 and 6 months postoperatively. Two populations participated in this study, a healthy population and a population having benefited from reconstruction of the anterior cruciate ligament. The operated test group is divided into two subgroups, one with a postoperative period of 3 months and the second at 6 months. All subjects were subjected to the same protocol, their gait on the treadmill was analyzed and evaluated with an Optogait® analysis system. A univariate analysis was carried out first. Then, a multivariate analysis by adjustment method was carried out in order to eliminate the potential confounding factors. The comparison of the results between the populations in the univariate analysis shows an absence of significant results however there are trends. The statistical results of the multivariate analysis showed interactions in the two subgroups of the operated population.In fact, it turns out that at 3 months there is a tendency to worse gait disorders in subjects with a high BMI reflecting overweight, when an associated surgical procedure has taken place on the meniscus, in subjects over 35 years of age and males. On the other hand, at 6 months, the tendency to worsening is visible only in the strata represented by subjects with a BMI corresponding to overweight, as well as in subjects having benefited from a meniscal suture associated with ACL reconstruction. .The results of the present study show that there are certain factors which tend to increase the risk of these walking disorders after reconstruction of the anterior cruciate ligament by hamstring graft, these factors are different depending on the time postoperative.

Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common variants which differ across populations and hence do not fully account for HbF variation. To investigate rare and common variants influencing HbF levels in SCD, we performed targeted next generation sequencing covering exonic and other significant fetal hemoglobin-associated loci, including BCL11A, MYB, HOXA9, HBB, HBG1, HBG2, CHD4, KLF1, MBD3, ZBTB7A and PGLYRP1. Results revealed a range of functionally relevant genetic variants. Notably, there were significantly more deletions in individuals with high HbF levels (11% vs 0.9%). We identified frameshift deletion in individuals with high HbF levels and frameshift insertions in individuals with low HbF. CHD4 and MBD3 genes, interacting in the same sub-network, were identified to have a significant number of pathogenic or non-synonymous mutations in individuals with low HbF levels, suggesting an important role of epigenetic pathways in the regulation of HbF synthesis. This study provides new insights in selecting essential variants associated with extreme HbF levels in SCD.

For the past several decades, abdominal prenatal ultrasonography has been the most significant technology in obstetrics with a long-established application. However, the frequency, exposure time, thermal and cavitation exposure indices, and increased acoustic output of the ultrasonic waves may be harmful to the embryo/fetus and might increase susceptibility to Autism Spectrum Disorder (ASD). The increase in the prevalence of ASD is associated with an affluent ethnicity, high socioeconomic status, and high parental education where prenatal ultrasonography is readily available and affordable. Enhanced biophysical adverse effects may link the analogous increase in prenatal ultrasonography and autism, and prenatal ultrasonography may emerge as a risk factor for autism. Radiography usage provides historical evidence for this fact: the predominant past opinion was that exposure to X-rays during pregnancy caused no significant risk to a fetus. However, the association between X-ray exposure and childhood leukemia was only established 40 years after X-ray use began. This review focuses on excessive PUS usage and ASD development. Public Abstract Advancements in medical technology over the past several decades have made prenatal ultrasound more frequently accessible to expecting mothers during their pregnancy, especially for the affluent. A parallel development in health care is the increase in autism diagnoses (Autism Spectrum Disorder, or ASD) in children of affluent families. There is a general lack of studies of the impact of prenatal ultrasound on fetuses, especially around varying attributes such as frequency, duration of exposure, and thermal and cavitation indices. There is also a historical precedent set, where exposing fetuses to X-rays was not found to be harmful until it was linked to the development of childhood leukemia decades later. This paper seeks to establish a need to further study these attributes of prenatal ultrasound overuse and their possible impact on a developing fetus, with a special focus on the occurrence of Autism.

Objective: To determine demographic predictors and comorbidities in hospitalized children with conduct disorder. Methods: A retrospective analysis was performed using Nationwide Inpatient Sample (2012–2014). All patients were ≤18 years and cases with primary diagnosis of conduct disorder (N = 32345) and a comparison group with another psychiatric diagnosis (N = 410,479) were identified using ICD-9-CM diagnosis codes. A logistic regression model was used to generate the Odds Ratio (OR) between both groups. Results: Children <11 years old have five times greater chances of admission for conduct disorder than adolescent (OR 5.339). African American males are more likely to be admitted for conduct disorder. Children with conduct disorder from low-income families have a 1.5 times higher likelihood for inpatient admission compared to high-income families. These children have about eleven times higher odds of comorbid psychosis (OR 11.810) and seven times for depression (OR 7.093) compared to the comparison group. Conclusion: Conduct disorders are more debilitating for children and families than many providers realize. African American male under 11 years is at the highest risk for inpatient management for conduct disorder. These patients have a higher risk of comorbid psychosis and depression which may further deteriorate the severity of illness and require acute inpatient care.

Autism spectrum disorder (ASD) refers to the diverse range of neurodevelopmental disorders accompanying impairments in social interaction, difficulties in communication, and stereotyped or repetitive behaviors. Unlike the older term, autism, the newer term, ASD, better reflects the broad range of autistic symptoms and denotes a single diagnostic category of autism accompanied by numerous conditions. The pineal hormone melatonin is a well-known neuroprotectant and circadian entrainer. This hormone crosses the placenta and enters the fetal circulation, then conveys photoperiodic information to the fetus during pregnancy. These actions enable normal sleep patterns and circadian rhythms, followed by normal neurodevelopment. Melatonin also reduces oxidative stress, which is harmful to the central nervous system. Therefore, melatonin acts as a neuroprotectant and circadian entrainer, and may reduce the risk of neurodevelopmental disorders such as ASD.

Neuropsychiatric disorders are worldwide public-health concern. Schizophrenia is one of the well-known neuropsychiatric disorders, which may affect millions globally. Maternal immune activation might be one of the key factor for the development of neuropsychiatric disorders. Previously, a mouse model of neuropsychiatric disorders has originally been made, in which poly-I:C, sodium dextran sulfate (DSS) and κ-carrageenan (CGN) were used for the maternal immune activation of mice. In the neuropsychiatric disorder mice, a significant link between biochemical changes of p62 and/or GLAST in the mouse brain and the alteration of experimental behaviors. Therefore, potential therapeutic study has been achieved for the development of effective treatment against neuropsychiatric disorders with using butyric acid, trehalose, piceid, and biochanin A. As a result, some of the combination with these orally available molecules could be effective for the improvement of behavioral alterations as well as biochemical changes of p62 and/or GLAST in the mouse brain. Importantly, the correlation between behavioral score and p62/GLAST protein expression has been again recognized. The significant correlation between pathological behavior and the biochemical alterations would contribute to develop further innovative therapeutics for vaious psychiatric disorders.

Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world’s population. PTSD is associated with several medical and neurological comorbidities. It has been suggested that these are due to accelerated aging, and that changes in telomere length (TL) and telomerase enzyme activity may serve as biomarkers of this process. Early research in this field suggested that TL was significantly reduced in PTSD. The current review was conducted to provide a critical analysis of recent clinical and translational research on telomere length and telomerase in PTSD. The results of 26 clinical studies suggest that TL in PTSD is highly variable, and may be influenced by methodological, demographic, trauma-related and psychosocial factors. There is no evidence for altered telomerase activity in PTSD, though this was hypothesized by earlier workers in the field. Translational research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL in PTSD depends on several variables that are specific to individuals and groups. Other markers of cellular aging, such as epigenetic changes, may be more specific indices of accelerated aging in patients with PTSD.

Opioids have served as a cornerstone in pain management for decades. However, the emergence of increasingly potent synthetic analogs brings forth a range of side effects, including respiratory depression, tolerance, dependence, constipation, and, more importantly, the development of severe and debilitating opioid use disorder (OUD). Search for therapeutics to mitigate OUD has been challenging and this has called for novel approaches that include design of small molecules targeting neuronal circuits involved in addiction (opioid, dopamine, serotonin, norepinephrine, and glutamate receptors, etc.) and development of biologics that target circulating opioids/opiates. In this review, we retrieved and discussed over two dozen of relevant patents filed in the past twelve (12) years that focus on novel approaches to produce therapeutics for OUD. The current review excluded patents on biologics and concentrated on small molecules, which will be discussed separately in a subsequent sequel. The chemical entities disclosed were highlighted and specific examples were provided where necessary. Although the number of patents in the realm of drug discovery for OUD is currently limited, we foresee a continued expansion in the quest for therapeutics for OUD in the years to come.

Causation concepts for work-related musculoskeletal disorders vary among authors and academic disciplines. Major causation concepts are single-event and repetitive motion. The aim of this short communication is to share findings from a recent survey, conducted by the U.S. Bureau of Labor Statistics of United States employers about work-related musculoskeletal cases, and more specifically, about whether the employers regard the cause of their employee’s musculoskeletal problem as being from a single exposure or from multiple exposures. Recommendations are offered for using terminology consistent with employer understandings.

The prevalence of patients on buprenorphine therapy presenting for elective surgery has increased. Buprenorphine is a widely used medication for management of patients with chronic pain. It is also used for maintenance therapy for patients with a history of opioid use disorder (OUD). Due to lack of standardized protocol for managing patients on buprenorphine peri-operatively, we performed a retrospective analysis to compare pain score outcomes and post-operative opiate requirements between patients who continued versus discontinued buprenorphine. We identified 35 patients, 11 continued buprenorphine and 24 discontinued buprenorphine. The average Post-Anesthesia Care Unit (PACU) pain score was 7.54 for those who discontinued pre-operative buprenorphine and 5.59 for those who continued (P value 0.0339). The average post-operative Morphine Milligram Equivalent (MME) use was 86.13 for those who continued pre-operative buprenorphine and was 107.70 for those who discontinued buprenorphine (P value 0.6439). The results from our study correlate with several previous studies which showed lower PACU pain scores in patients who continued buprenorphine. There is a benefit of decreased pain post-operatively when pre-operative buprenorphine is continued and having a decrease in relapse in those with a history of OUD.

Temporomandibular disorders (TMDs) refer to a group of conditions that affect the temporomandibular joint, causing pain and dysfunction in the jaw joint and related muscles. The diagnosis of TMDs typically involved clinical assessment through operator-based physical examination, self-reported questionnaire and imaging studies. To objectivize the measurement of TMD, this study aims at investigating on the feasibility to use machine-learning algorithms fed with data gathered from low-cost and portable instruments to discriminate the presence of TMD in adult subjects. Through this aim, the experimental protocol involved fifty participants, equally distributed between TMD and healthy subjects, acting as control group. The diagnosis of TMD has been performed by a skilled operator through the typical clinical scale. Participants underwent to a baropodometric analysis by using a pressure matrix and the evaluation of the cervical mobility through inertial sensors. Nine machine-learning algorithms belonging to support vector machine, k-nearest neighbours and decision tree were compared. The k-nearest neighbours based on cosine distance was found as the best performing, achieving performance of 0.94, 0.94 and 0.08 for the accuracy, F1-score and G-index, respectively. These findings open the possibility to use such methodology to support the diagnosis of TMDs in clinical environments.

Patients with a psychotic disorder frequently report oral health problems, while mental health nurses (MHNs) seem not to be fully aware of these problems and the risk factors. Therefore, this study aims to develop supportive tools for MHNs regarding oral health to increase sensitization among MHNs and to provide MHNs with knowledge to recognize (potential) oral health problems in patients with a psychotic disorder. We used a human-centered design in which the user, MHNs as well as experts by experience, were placed in the centre of the research process. Problems and needs in MHNs working with patients with a psychotic disorder were addressed. To identify key issues of problem as well as the needs in terms of resources, we started with focus groups (n = 9). We analysed the data thematically based on context of patients and MHNs in practice regarding oral health, preferred oral health tools focused on MHN, and intended outcomes of tools. A Multi Criteria Decision Matrix was developed and analysed (n = 9) to identify the most optimal and viable solution based on established criteria and issues that are prevalent in the work of MHNs. Most promising result was the development of a brochure with an awareness screener. The brochure with awareness screener was developed as a low-fidelity prototype for MHNs regarding oral health in patients with a psychotic disorder, based on the latest scientific evidence. After testing it, the feasibility was tested through semi-structured interviews (n=19). MHNs and experts by experience were satisfied with the tool and provided recommendations for adjustments to the content. Significant augmentations to the brochure include a clinical lesson and a toothbrush with toothpaste for patients. We can conclude that a brochure with an awareness screener is feasible for MHNs. Future steps aiming to further refine and optimize care processes for oral health tools in MHNs, should take refining eligibility criteria for psychiatric populations and the language level of the target group of a tool into account.

To explore the relevant factors that affect the efficacy of consciousness-regaining therapy (CRT)for prolonged disorder of consciousness(pDOC),a retrospective analysis was conducted on the case data of 114 patients with pDOC admitted to department of functional neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022. Basic information on the cases,data on pDOC disease assessment, consciousness-regaining therapy methods, and efficacy evaluation were collected. A total of 114 patients were grouped and compared based on the efficacy at the end of treatment. Among them, there were 61 cases in the ineffective group and 53 cases in the effective group. There was no statistically significant difference (P&gt;0.05) between the two groups in terms of gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of consciousness-regaining therapy , and duration of consciousness-regaining therapy(P&gt;0.05). However, there were statistically significant differences (P&lt;0.05) in terms of secondary hydrocephalus, , consciousness-regaining therapy methods, CRS-R grading before treatment, and GOSE score at 6 months after treatment. Binary logistic regression analysis showed that the type of therapy (OR=0.169, 95% CI: 0.057-0.508) was a related factor affecting the efficacy of consciousness-regaining therapy (P&lt;0.05).Compared with non-invasive therapy, personalized awakening therapy using various invasive consciousness-regaining therapy methods can help improve the efficacy of therapy for pDOC.

Advanced paternal age increases the risk of transmitting de novo germline mutations, particularly missense mutations activating the receptor tyrosine kinase (RTK) signaling pathway, exemplified by the FGFR3 mutation linked to achondroplasia (ACH). This risk is attributed to the expansion of spermatogonial stem cells carrying the mutation, forming sub-clonal clusters in the ageing testis, thereby increasing the frequency of mutant sperm and the number of affected offspring from older fathers. While prior studies proposed a correlation between sub-clonal cluster expansion in the testis and elevated mutant sperm production in older donors, limited data exist on the universality of this phenomenon. Our study addresses this gap by examining the testis expansion patterns, as well as increases of mutations in sperm for two FGFR3 variants: c.1138G>A (p.G380R) and c.1948A>G (p.K650E)- associated with ACH or thanatophoric dysplasia (TDII), respectively. Unlike the ACH mutation, which showed sub-clonal expansion events in an aged testis and a significant increase of mutant sperm with the donor’s age, the TDII mutation formed sub-clonal clusters, but exhibited reduced transmission into sperm and no significant age-related increase. The mechanism behind this divergence remains unclear, suggesting potential pleiotropic effects of aberrant RTK signaling in the male germline, possibly hindering differentiation requiring meiosis. This study provides further insights into transmission risks of micro-mosaics associated with advanced paternal age in the male germline.

Reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) manifest in individuals facing attachment system chal-lenges, particularly observed in minors under protective measures. The lack of standardized tools for assessing these difficulties and uncertainty about the most effective instruments from a psychometric perspective prompted this study. Using the COSMIN checklist, we systematically reviewed instruments assessing RAD, adhering to PRISMA and COSMIN guidelines. Examined tools included the Disturbance Attachment Inter-view, Preschool Age Psychiatric Assessment, Relationship Patterns Questionnaire, Assessment of RAD and DSED, Development and Well-Being Assessment, and Reactive Attachment Disorder Question-naire. Of the 11 articles analyzed, results highlight a research emphasis on internal consistency, structural and construct validity, sidelining other properties. While the instruments demonstrate strong structural validity, excellent internal consistency, and generally satisfactory error measurement results, the study concludes a dearth of investigations into psychometric properties for children and adolescents under protective measures.

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

Adult patients with Autism Spectrum Disorder (ASD) exhibit a range of behaviours that can be disruptive to the medical care of themselves and other patients and as a result, are at higher risk of being sedated. The aim of the present study was to determine whether patients with ASD presenting to hospital for acute psychiatric crises re-ceive more sedative medications compared to similar patients without ASD. 43 adult patients with a previous di-agnosis of ASD who were referred to the mental health team at a single, large emergency department in metro-politan Victoria over the year of 2021 were identified and matched with an equal number of controls within the same cohort. Sedative medications were converted to diazepam and chlorpromazine equivalent doses and com-pared using repeated measures T-tests. Patients with ASD received 5.1mg more diazepam-equivalent benzodiaz-epines on average compared to matched controls (95%CI: 0.41-9.71). This difference was statistically significant (T=2.20, df=42, p=0.034). There was no significance difference in chlorpromazine-equivalent antipsychotic doses. Clinicians should be aware of the higher dose of sedatives, and consider other means of behavioural management in these patients.

Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by persistent deficits in social interaction and communication manifests in early childhood and is followed by restricted and stereotyped behaviors, interests or activities in adolescence and adulthood (DSM-V). Although genetics and environmental factors have been implicated, the exact causes of ASD have yet to be fully characterized. New evidence suggests that dysbiosis or perturbation in gut microbiota (GM) and exposure to lead (Pb) may play important roles in ASD etiology. Pb is a toxic heavy metal that has been linked to a wide range of negative health outcomes including anemia, encephalopathy, gastroenteric diseases and more importantly cognitive and behavioral problems inherent to ASD. Pb exposure can disrupt GM, which is essential for maintaining overall health. GM, consisting of trillions of microorganisms, has been shown to play a crucial role in the development of various physiological and psychological functions. GM interacts with the brain in a bidirectional manner referred to as “Gut-Brain Axis (GBA).” In this review, following a general overview of ASD and GM, the interaction of Pb with GM in the context of ASD is emphasized. Potential exploitation of this interaction for therapeutic purposes is also touched upon.

Introduction: Mucopolysaccharidosis type I (MPSI) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and nonspecific symptoms resulting in high morbidity and mortality. The incidence of MPSI in US is estimated to be 0.26:100,000, however, it is unknown in Kuwait. This pilot study was undertaken to screen MPSI in all Kuwaiti neonates born at Farwaniya Hospital over a period of 12-months. This study examined the incidence of MPSI in a major center in Kuwait for inclusion in the national newborn screening program to enable its early detection and adequate treatment. Methods: All Kuwaiti neonates born at Farwaniya Hospital, Kuwait from December 2021 to December 2022, were screened for MPSI. The screening consisted of determining IDUA enzyme activity in dried blood spots (DBS)-derived samples by Tandem Mass Spectrometry. A follow-up genetic analysis of IDUA gene is planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. Results: A total of 618 newborns, including 331 (54%) males and 287 (46%) females, were screened. Twenty of them had deficient IDUA enzyme activity but showed negative genetic testing for IDUA. However, we have diagnosed one additional female baby with MPSI, who belonged to Farwaniya Hospital, but the parents chose to deliver in a private hospital. She presented at age three months with recurrent upper airway infections, snoring and extensive Mongolian spots. The molecular study revealed previously reported pathogenic nonsense variant in IDUA c.1882C>T; p.(Arg628Ter), associated with severe phenotype. That being included, MPSI is estimated to be about 0.3% among tested females and 0.2% of all screened cases in Kuwait. Conclusion: Our study is the first to evaluate the incidence of MPSI in Kuwait. Given the single center, small number of screened babies and the short study duration thus far, it is premature to calculate the incidence of MPSI. It is anticipated that as the study continues and more infants are examined, we would be able to estimate the incidence of this disease in our population correctly. Further studies including screening newborns in all maternity hospitals in Kuwait are needed to calculate the actual incidence of MPSI. Our data supports including MPSI in national newborn screening program to allow early initiation of treatment and thus improve disease outcome.

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.

The Speer allergic tension-fatigue syndrome (SATFS) is a classic syndrome characterized by allergy-like symptoms, muscle tension, headache, chronic fatigue, and a particular behavior. The particular behavior displayed includes symptoms such as hyperkinesis, hyperesthesia (i.e., insomnia), restlessness, and distractibility, among others. Interestingly, these symptoms are very similar to recent descriptions of attention deficit hyperactivity disorder (ADHD), the most prevalent neurodevelopmental disorder worldwide, which is characterized by inattention, hyperactivity and impulsivity. Although the exact cause of ADHD remains unknown, it has been proposed that deficiency of the enzyme diamine oxidase (DAO), which metabolizes histamine, may be involved in the development of ADHD. Our conceptual paper suggests that DAO enzyme deficiency may be involved in the development and severity of ADHD. Histamine, which is metabolized by DAO, plays an important role in the regulation of attention, memory and cognition. Therefore, decreased DAO activity could lead to an accumulation of histamine, which could contribute to ADHD symptoms. This study provides a theoretical framework for the relationship between DAO deficiency and ADHD, which could have important implications for the diagnosis and treatment of the disorder. Further empirical studies are needed to confirm our hypothesis and explore the clinical implications of the relationship between DAO deficiency, histamine, and ADHD.

In recent years, there has been a rise in the prevalence of autism spectrum disorder (ASD). The diagnosis of ASD requires behavioral observation and standardized testing completed by highly trained experts. Early intervention for ASD can begin as early as 1-2 years of age, but ASD diagnoses are not typically made until ages 2-5 years, thus delaying the start of intervention. There is an urgent need for non-invasive biomarkers to detect ASD in infancy. While previous research using physiological recordings has focused on brain-based biomarkers of ASD, this study investigated the potential of electrocardiogram (ECG) recordings as an ASD biomarker in 3-6-month-old infants. We recorded heart activity of infants at typical and elevated familial likelihood for ASD during naturalistic interactions with objects and caregivers. After obtaining the ECG signals, features such as heart rate variability (HRV) and sympathetic and parasympathetic activities were extracted from them. Then we evaluated the effectiveness of multiple machine learning classifiers for the classification of ASD likelihood. Our findings support our hypothesis that infant ECG signals contain a significant amount of information about ASD familial likelihood. Among the various machine learning algorithms tested, XGBoost performed best according to sensitivity (0.76±0.12), f1-score (0.75±0.12), precision (0.79±0. 12), classification accuracy (0.77±0.12, p-value = 0.01) and AUC (0.76±0.12, p-value = 0.02). These results suggest that ECG signals contains relevant information about the likelihood of an infant to develop ASD. Future studies should consider the potential of information contained in ECG, and other indices of autonomic control, for the development of biomarkers of ASD in infancy.

Background and Objectives: Light therapy (LT) is used as an adjunctive treatment for sleep problems. This study evaluates the impact of LT on sleep quality and sleep-related parameters in patients with sleep disorders. Materials and Methods: We performed a pilot randomized, open-label clinical trial. Fourteen patients aged 20–60 years with sleep disorders for more than three months were randomized into the control and LT groups (1:1 ratio). The LT group was instructed to use a device that provides bright LT (6000 K, 380 lux, wavelength 480 nm) for at least 25 minutes before 09:00 am for two weeks. A self-reported questionnaire was used to evaluate circadian preference, mood, and sleep-related parameters. We analyzed serum cortisol levels and clock genes expression. Results: The Epworth Sleepiness Scale (ESS), insomnia severity index, and Pittsburgh Sleep Quality index were significantly improved within the LT group only after the two-week period. When comparing the two groups, only the change in ESS significant was significant (mean difference; control: -0.14 vs LT: -1.43, p=0.021) after adjusting for baseline characteristics. There were no significant differences in serum cortisol or clock genes expression. Conclusions: LT can improve daytime sleepiness in patients with sleep disorders; however, further well-designed studies are warranted to confirm its efficacy.

While shoulder injuries represent the musculoskeletal disorders (MSDs) most encountered in physical therapy, there is no consensus on their management. As attempts to provide standardized and personalized treatment, a robot-ic-assisted device combined with EMG biofeedback specifically dedicated to shoulder MSDs has been developed. The aim of this study was to determine the efficacy of an 8-week rehabilitation program (≈3 sessions a week) using a ro-botic-assisted device combined with EMG biofeedback (RA-EMG group) in comparison with a conventional program (CONV group) in patients presenting with shoulder MSDs. This study is a retrospective cohort study including data from 2010 to 2013 on patients initially involved in a physical rehabilitation program in a private clinic of Chicoutimi (Canada) for shoulder MSDs. Shoul-der flexion strength and range of motion were collected before and after the rehabilitation program. Forty-four patients participated in a conventional pro-gram using dumbbell (CONV group) while 72 of them completed a program on robot-assisted device with EMG and visual biofeedback (RA-EMG group), whereby both programs consisted in 2 sets of 20 repetitions at 60% of maximal capacity. Results showed that the RA-EMG had significantly greater benefits than the Conv group for shoulder flexion strength (+103.1% vs 67%, p = 0.016) and range of motion (+14.4% vs 6.1%, p = 0.046). The current retrospective co-hort study showed that a specific and tailored rehabilitation program with constant effort by automatic adjustment of the level of resistance was able to potentiate strength and range of motion shoulder flexion after an 8-week reha-bilitation period in comparison with a conventional approach in patients with shoulder MSDs. This study provides new insight on shoulder MSD rehabilita-tion and future research should be pursued to determine the added potential of this approach for abduction and external rotation with a randomized controlled design.

Virtual reality (VR) technology gains theoretical support from rehabilitation and pedagogical theories and offers a variety of capabilities in educational and interventional contexts with affordable products. VR is attracting increasing attention in the medical and healthcare industry as it provides fully interactive three-dimensional simulations of real-world settings and social situations, which are particularly suitable for cognitive and performance training including social and interaction skills. The worldwide rising trend in the prevalence of autism spectrum disorder calls for innovative and efficacious techniques for assessment and treatment. The article offers a summary of current perspectives and evidence-based applications of VR technology as an educational and intervention tool for individuals with autism spectrum disorder, with a primary focus on social communication including social functioning, emotion recognition, and speech and language. Technology- and design-related limitations as well as the disputes over the application of virtual reality to autism research and therapy are discussed and future directions of this emerging field are highlighted with regards to application expansion and improvement, technology enhancement, and the development of brain-based research and theoretical models.