Behavioral Disturbances Research Articles

Advanced paramedics' restraint decision-making when managing acute behavioural disturbance (ABD) in the UK pre-hospital ambulance setting: A qualitative investigation.

Acute behavioural disturbance (ABD), sometimes called 'excited delirium', is a medical emergency. In the UK, some patients presenting with ABD are managed by advanced paramedics (APs), however little is known about how APs make restraint decisions. The aim of this research is to explore the decisions made by APs when managing restraint in the context of ABD, in the UK pre-hospital ambulance setting. Seven semi-structured interviews were undertaken with APs. All participants were experienced APs with post-registration, post-graduate advanced practice education and qualifications. The resulting data were analysed using reflexive thematic analysis, informed by critical realism. We identified four interconnected themes from the interview data. Firstly, managing complexity and ambiguity in relation to identifying ABD patients and determining appropriate treatment plans. Secondly, feeling vulnerable to professional consequences from patients deteriorating whilst in the care of APs. Thirdly, negotiating with other professionals who have different roles and priorities. Finally, establishing primacy of care in relation to incidents which involve police officers and other professionals. A key influence was the need to characterise incidents as medical, as an enabler to establishing clinical leadership and decision-making control. APs focused on de-escalation techniques and sought to reduce physical restraint, intervening with pharmacological interventions if necessary to achieve this. The social relationships and interactions with patients and other professionals at the scene were key to success. Decisions are a source of anxiety, with fears of professional detriment accompanying poor patient outcomes. Our results indicate that APs would benefit from education and development specifically in relation to making ABD decisions, acknowledging the context of inter-professional relationships and the potential for competing and conflicting priorities. A focus on joint, high-fidelity training with the police may be a helpful intervention.

Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease

Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. To assess the safety and effectiveness of staged bilateral FUS-STN to treat PD. This prospective, open-label, case series study was conducted between June 18, 2019, and November 7, 2023, at HM-CINAC, Puerta del Sur University Hospital, Madrid, Spain, and included 6 patients with PD who had been treated with unilateral FUS-STN contralateral to their most affected body side and whose parkinsonism on the untreated side had progressed and was not optimally controlled with medication. Staged bilateral FUS-STN. Primary outcomes were assessed 6 months after the second treatment and included safety (incidence and severity of adverse events after second treatment) and effectiveness in terms of motor change (measured with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III [MDS-UPDRS III]) in the off-medication state (ie, after at least 12 hours of antiparkinsonian drug withdrawal) compared with baseline (ie, prior to the first side ablation). Secondary outcomes included motor change in patients in the on-medication state (ie, after usual antiparkinsonian medication intake), motor complications (measured with the MDS-UPDRS IV), daily living activities (measured with the MDS-UPDRS I-II), quality of life (measured with the 39-item Parkinson's Disease Questionnaire), change in dopaminergic treatment, patient's global impression of change (measured with the Global Impression of Change [PGI-C] scale), and long-term (24-month) follow-up. Of 45 patients previously treated with unilateral FUS-STN, 7 were lost to follow-up, and 4 were excluded due to adverse events. Of the remaining 34 patients, 6 (median age at first FUS-STN, 52.6 years [IQR, 49.0-57.3 years]; 3 women [50%]) experienced progression of parkinsonism on the untreated body side and were included. At the time of the first FUS-STN, patients' median duration of disease was 5.7 years (IQR, 4.7-7.3 years). The median time between procedures was 3.2 years (IQR, 1.9-3.5 years). After the second FUS-STN, 4 patients presented with contralateral choreic dyskinesia, which resolved by 3 months. Four patients developed speech disturbances, which gradually improved but remained in a mild form for 2 patients at 6 months; 1 patient experienced mild imbalance and dysphagia during the first week after treatment, which subsided by 3 months. No behavioral or cognitive disturbances were found on neuropsychological testing. For patients in the off-medication state, MDS-UPDRS III scores improved by 52.6% between baseline and 6 months after the second FUS-STN (from 37.5 [IQR, 34.2-40.0] to 20.5 [IQR, 8.7-24.0]; median difference, 23.0 [95% CI, 7.0-33.7]; P = .03). The second treated side improved by 64.3% (MDS-UPDRS III score, 17.0 [IQR, 16.0-19.5] prior to the second treatment vs 5.5 [IQR, 3.0-10.2]; median difference, 9.5 [95% CI, 3.2-17.7]; P = .02). After the second procedure, all self-reported PGI-C scores were positive. Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.

Deciphering Cognitive Impairments in Huntington's Disease: A Comparative Study of Stroop Test Variations.

Huntington's disease (HD) is a neurodegenerative disorder marked by cognitive impairment, movement abnormalities, and behavioral disturbances. The Stroop Color Word Test (SCWT) is a widely used tool to detect cognitive decline in HD. Variations in SCWT formats-horizontal (original) and vertical (Golden)-may influence performance, given HD's impact on cognitive and oculomotor abilities. This study aimed to compare the effectiveness of the horizontal and Golden vertical SCWT formats in detecting cognitive decline in HD, and to determine how performance may have been influenced by eye movement abnormalities. Forty-five participants with genetically confirmed HD were recruited. Both SCWT formats were administered to each participant in a counterbalanced fashion. Individual performance of all three sections on each format was standardized across 2 different norms. Raw and normed scores on each variation were compared and correlated with eye movement ratings on the Unified Huntington's Disease Rating Scale. The Golden variation elicited significantly slower responses, particularly in the Word Reading section, across two benchmark norms. Statistical analysis revealed significant performance differences between the two formats. Correlations between vertical eye movement ratings and performance on the Golden SCWT were highly significant, highlighting the impact of oculomotor coordination on cognitive assessments in HD. This study underscores the importance of considering test format in cognitive assessments for HD. The Golden vertical SCWT demonstrates increased sensitivity in detecting deficits in HD, possibly linked to vertical saccade abnormalities. These insights are important for improving the sensitivity of cognitive assessments and monitoring disease progression in HD research and clinical practice.

Clinical Efficacy of Psychotherapeutic Interventions for Post-Traumatic Stress Disorder in Children and Adolescents: A Systematic Review and Analysis.

Background: This systematic review aggregates research on psychotherapeutic interventions for Post-Traumatic Stress Disorder (PTSD) in children and adolescents. PTSD in this demographic presents differently from adults, necessitating tailored therapeutic approaches. In children and adolescents, PTSD arises from exposure to severe danger, interpersonal violence, or abuse, leading to significant behavioral and emotional disturbances that jeopardize long-term development. The review focuses on describing PTSD within two age groups, children (6 to 12 years) and adolescents (12 to 18 years), while evaluating the effectiveness of various clinical interventions aimed at this condition. Methods: Utilizing the PRISMA guidelines, this review systematically examines studies that assess clinical interventions for PTSD in the younger population. Results: Key symptoms of PTSD in children and adolescents include avoidance, overstimulation, flashbacks, depression, and anxiety. The review identifies several effective treatments, including Cognitive Behavioral Therapy (CBT), Trauma-Focused CBT (TF-CBT), Eye Movement Desensitization and Reprocessing (EMDR), Systemic Therapy, Play Therapy, Exposure Therapy, Relaxation Techniques, and Psychodynamic Psychotherapy. Particularly, TF-CBT is highlighted as the most effective and commonly used method in treating childhood and adolescent PTSD, as supported by most of the studies reviewed. Conclusions: A significant outcome of this study is the short-term effectiveness of CBT in reducing PTSD symptoms in children and adolescents. The findings underline the importance of psychotherapeutic interventions and mark a substantial advancement in understanding PTSD in young populations. It is crucial for practitioners to integrate various psychotherapeutic strategies into their practice to improve patient outcomes and treatment efficacy.

Exploring the genetic control of sweat gland characteristics in beef cattle for enhanced heat tolerance

BackgroundThermal stress in subtropical regions is a major limiting factor in beef cattle production systems with around $369 million being lost annually due to reduced performance. Heat stress causes numerous physiological and behavioral disturbances including reduced feed intake and decreased production levels. Cattle utilize various physiological mechanisms such as sweating to regulate internal heat. Variation in these traits can help identify genetic variants that control sweat gland properties and subsequently allow for genetic selection of cattle with greater thermotolerance.MethodsThis study used 2,401 Brangus cattle from two commercial ranches in Florida. Precise phenotypes that contribute to an animal’s ability to manage heat stress were calculated from skin biopsies and included sweat gland area, sweat gland depth, and sweat gland length. All animals were genotyped with the Bovine GGP F250K, and BLUPF90 software was used to estimate genetic parameters and for Genome Wide Association Study.ResultsSweat gland phenotypes heritability ranged from 0.17 to 0.42 indicating a moderate amount of the phenotypic variation is due to genetics, allowing producers the ability to select for favorable sweat gland properties. A weighted single-step GWAS using sliding 10 kb windows identified multiple quantitative trait loci (QTLs) explaining a significant amount of genetic variation. QTLs located on BTA7 and BTA12 explained over 1.0% of genetic variance and overlap the ADGRV1 and CCDC168 genes, respectively. The variants identified in this study are implicated in processes related to immune function and cellular proliferation which could be relevant to heat management. Breed of Origin Alleles (BOA) were predicted using local ancestry in admixed populations (LAMP-LD), allowing for identification of markers’ origin from either Brahman or Angus ancestry. A BOA GWAS was performed to identify regions inherited from particular ancestral breeds that might have a significant impact on sweat gland phenotypes.ConclusionsThe results of the BOA GWAS indicate that both Brahman and Angus alleles contribute positively to sweat gland traits, as evidenced by favorable marker effects observed from both genetic backgrounds. Understanding and utilizing genetic traits that confer better heat tolerance is a proactive approach to managing the impacts of climate change on livestock farming.

Evaluarea programului de intervenție psihologică aplicat persoanelor cu epilepsie farmacorezistentă

Drug-resistant epilepsy presents a myriad of psychological challenges, including cognitive decline, emotional and behavioral disturbances, loss of autonomy, stigma, psychosocial dysfunction, and a heightened risk of trauma and premature death, all of which significantly diminish the quality of life. This article aims to identify effective strategies for working with individuals affected by drug-resistant epilepsy and to develop a targeted psychological intervention program tailored to their unique needs. Six subjects diagnosed with drug-resistant epilepsy participated in this program. The results revealed significant improvements across multiple do mains following the intervention. There were notable enhancements in general cognitive functioning, reductions in levels of depression and anxiety, and decreases in aggressive and hostile behaviors. These positive outcomes collectively contributed to an overall increase in the quality of life for individuals grappling with drug-resistant epilepsy.

A non-microcystin-producing Microcystis wesenbergii strain alters fish food intake by disturbing neuro-endocrine appetite regulation

Cyanobacterial harmful algal blooms (cHABs) are pervasive sources of stress resulting in neurotoxicity in fish. A member of the widely distributed Microcystis genus of bloom-forming cyanobacteria, Microcystis wesenbergii can be found in many freshwater lakes, including Dianchi Lake (China), where it has become one of the dominant contributors to the lake's recurrent blooms. However, unlike its more well-known counterpart M. aeruginosa, the effects of dense non-microcystin-containing M. wesenbergii blooms are seldom studied. The disturbance of appetite regulation and feeding behaviour can have downstream effects on the growth of teleost fish, posing a significant challenge to aquaculture and conservation efforts. Here we examined the effects of M. wesenbergii blooms on the food intake of Acrossocheilus yunnanensis, a native cyprinid in southern China. This fish species has disappeared in Dianchi Lake, and its reintroduction might be negatively affected by the presence of this newly-dominant Microcystis species. We co-cultured juvenile A. yunnanensis with a non-microcystin-producing strain of M. wesenbergii at initial densities between 5 × 104 and 1 × 106 cells/mL and monitored fish feeding behaviour and changes in neurotransmitter and hormone protein levels. High-density M. wesenbergii cultures increased the feeding rate of co-cultured fish, elevating concentrations of appetite-stimulating signalling molecules (Agouti-related protein and γ-aminobutyric acid), while decreasing inhibitory ones (POMC). These changes coincided with histopathological alterations and reduced somatic indices in brain and intestinal tissues. Given this potential for detrimental effects and dysregulation of food intake, further studies are necessary to determine the impacts of chronic exposure of M. wesenbergii in wild fish.

Characteristics of forensic psychiatric patients with a neurocognitive disorder.

Emotional and behavioural disturbances accompanying neurocognitive disorders may sometimes lead to a criminal offence. Our knowledge of this specific forensic subpopulation is lagging behind the knowledge on, and attention for, 'classic' psychiatric disorders in forensic populations. To gain knowledge on the prevalence and characteristics of individuals with neurocognitive disorders in the forensic population. This retrospective database study uses an anonymised data-set of the National Database of penitentiary psychiatric centres (PPC) (N = 8391), which collects data on all patients admitted to one of the four PPCs (mental health clinics within the prison system) in The Netherlands since May 2013. Inclusion criterion for this study was the presence of a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) or Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic code belonging to the category of neurocognitive disorders. A DSM-IV-TR or DSM-5 diagnostic code of a neurocognitive disorder was classified in 254 out of 8391 unique individuals, resulting in a prevalence of 3.0% in the total PPC population. The most prevalent diagnosis was unspecified neurocognitive disorder (59.1%). The neurocognitive disorder group significantly differed from a random control group from the database (n = 762) on demographic, clinical and criminological variables. The prevalence of neurocognitive disorders in this real-world clinical sample is remarkably lower than in two earlier studies in similar populations. Also remarkable is the relatively high prevalence of an unspecified neurocognitive disorder. These findings lead us to hypothesise that neurocognitive disorders may be underdiagnosed in this population. Forensic psychiatric settings should evaluate whether they have sufficient expertise available in neuropsychological assessment.

Distinct profiles of university students engaged in food and alcohol disturbance behaviors

ABSTRACT The present study aimed at exploring the combined effect of risk of eating disorders (ED), alcohol use, physical activity, and social and psychological traits in Food and Alcohol Disturbance (FAD) behaviors. Nine-hundred and seventy-six college students were included in the study. They were then divided into two groups based on the Compensatory Eating and Behaviors in Response to Alcohol Consumption Scale (CEBRACS): students with a FAD positive score and student with a FAD negative score. Both groups of participants were compared on the risk of ED, alcohol and physical activity variables, as well as social and psychological dimensions. A cluster analysis was performed on the FAD positive group to determine distinct subgroups and to explore the involvement of social and psychological dimensions in FAD behaviors. The comparison between FAD and non-FAD students demonstrated a more severe alcohol use, risk of ED, a higher level of impulsivity, anxiety, depression and more drinking motives as well as a lower self-esteem in students engaged in FAD behaviors compared with non-engaged students. The cluster analysis identified four clusters: the asceticism FAD subgroup, the damage control FAD subgroup, the emotional FAD subgroup and the recreational FAD subgroup. Overall, results reveal that FAD should not be considered as a unitary behavior but rather as a more complex pattern involving distinct psychological profiles.

Assessing the efficacy of ecological reserves: killer whale beach rubbing behaviour and vessel disturbance

Area-based protection is an important tool for safeguarding key habitat. Reserves that focus on mitigation of specific threats are particularly effective and are more likely to support a measurable outcome. In the marine environment, reserves that limit vessel presence have the potential to reduce disturbance to marine mammals. However, assessing the efficacy of reserves has been an ongoing challenge. Physical and acoustic disturbance from vessels is recognized as a primary threat to recovery for the northern resident killer whale (NRKW) population in Canadian Pacific waters. The Robson Bight Michael Bigg Ecological Reserve (RBMBER) was developed to support the behaviour of beach rubbing, a culturally distinct and traditionally important activity. Beach rubbing provides a rare opportunity to quantify vessel disturbance of a behaviour associated with a fixed geographic location, identifiable by visual cues, and verifiable acoustically. Observations on vessel presence, NRKW rubbing frequency, and duration were collected from a beach inside the reserve and compared to a beach in proximity to, but outside of, the RBMBER. In 2019-2022, vessel counts near the RBMBER beach were significantly lower than near the unprotected beach, and overall, rubbing occurred more frequently inside the reserve (78% of visits) than outside (35%). However, outside the reserve, concurrent vessel presence did not predict the occurrence of rubbing activity, indicating that vessel presence may negatively affect beach rubbing through long-term learned avoidance of frequently impacted areas.

The Mexican dataset of a repetitive transcranial magnetic stimulation clinical trial on cocaine use disorder patients: SUDMEX TMS

Cocaine use disorder (CUD) is a global health problem with severe consequences, leading to behavioral, cognitive, and neurobiological disturbances. While consensus on treatments is still ongoing, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising approach for medication-resistant disorders, including substance use disorders. In this context, here we present the SUDMEX-TMS, a Mexican dataset from an rTMS clinical trial involving CUD patients. This longitudinal dataset comprises 54 CUD patients (including 8 females) with data collected at five time points: baseline (T0), two weeks (T1), three months (T2), six months (T3) follow-up, and twelve months (T4) follow-up. The clinical rTMS treatment followed a double-blinded randomized clinical trial design (n = 24 sham/30 active) for 2 weeks, followed by an open-label phase. The dataset includes demographic, clinical, and cognitive measures, as well as magnetic resonance imaging (MRI) data collected at all time points, encompassing structural (T1-weighted), functional (resting-state fMRI), and multishell diffusion-weighted (DWI-HARDI) sequences. This dataset offers the opportunity to investigate the impact of rTMS on CUD participants, considering clinical, cognitive, and multimodal MRI metrics in a longitudinal framework.

AAV-Mediated Restoration of Dystrophin-Dp71 in the Brain of Dp71-Null Mice: Molecular, Cellular and Behavioral Outcomes.

A deficiency in the shortest dystrophin-gene product, Dp71, is a pivotal aggravating factor for intellectual disabilities in Duchenne muscular dystrophy (DMD). Recent advances in preclinical research have achieved some success in compensating both muscle and brain dysfunctions associated with DMD, notably using exon skipping strategies. However, this has not been studied for distal mutations in the DMD gene leading to Dp71 loss. In this study, we aimed to restore brain Dp71 expression in the Dp71-null transgenic mouse using an adeno-associated virus (AAV) administrated either by intracardiac injections at P4 (ICP4) or by bilateral intracerebroventricular (ICV) injections in adults. ICP4 delivery of the AAV9-Dp71 vector enabled the expression of 2 to 14% of brain Dp71, while ICV delivery enabled the overexpression of Dp71 in the hippocampus and cortex of adult mice, with anecdotal expression in the cerebellum. The restoration of Dp71 was mostly located in the glial endfeet that surround capillaries, and it was associated with partial localization of Dp71-associated proteins, α1-syntrophin and AQP4 water channels, suggesting proper restoration of a scaffold of proteins involved in blood-brain barrier function and water homeostasis. However, this did not result in significant improvements in behavioral disturbances displayed by Dp71-null mice. The potential and limitations of this AAV-mediated strategy are discussed. This proof-of-concept study identifies key molecular markers to estimate the efficiencies of Dp71 rescue strategies and opens new avenues for enhancing gene therapy targeting cognitive disorders associated with a subgroup of severely affected DMD patients.

The treatment of behavioural and psychological symptoms in dementia: pragmatic recommendations.

Behavioural and psychological symptoms of dementia (BPSD) are a clinical challenge for the lack of a sound taxonomy, frequent presentation with comorbid BPSD, lack of specific pharmacologic interventions, poor base of methodologically sound evidence with randomized clinical trials, contamination from the treatment of behavioural disturbances of young and adult psychiatric conditions, and small efficacy window of psychotropic drugs. We present here a treatment workflow based on a concept-driven literature review based on the notions that (i) the aetiology of BPSD can be mainly neurobiological (so-called 'primary' symptoms) or mainly environmental and functional ('secondary' symptoms) and that this drives treatment; (ii) the clinical efficacy of psychotropic drugs is driven by their specific profile of receptor affinity; (iii) drug treatment should follow the rules of 'start low-go slow, prescribe and revise'. This article argues in support of the distinction between primary and secondary BPSD, as well as their characteristics, which until now have been just sketchily described in the literature. It also offers comprehensive and pragmatic clinician-oriented recommendations for the treatment of BPSD.

Measuring behavioural disturbances exhibited by children and adolescents in post‐traumatic amnesia: Development of a scale

AbstractBehavioural disturbances are often observed, but (to our knowledge) not systematically assessed, in children who are in post‐traumatic amnesia (PTA) following traumatic brain injury (TBI). Therefore, we aimed to develop a prototype scale that measures the full range of behavioural disturbances exhibited by school‐aged children in PTA. Quantitative and qualitative feedback was collected via online surveys. First, experts (n = 7) evaluated the relevance and developmental appropriateness of 37 behavioural items, extracted from the scoping literature review. Second, clinicians (n = 20) evaluated the preliminary scale for its suitability (acceptability, feasibility and usability). Analyses included descriptive statistics and qualitative analyses. First, experts eliminated nine items, adjusted the wording of three retained items and categorised 18 of the remaining 28 items into one of eight categories. Ten items were not consistently categorised. All experts highlighted that the scale needed to be short and easy to administer. Hence, categorised items were bundled, arriving at an 18‐item preliminary scale. Second, clinicians deemed the preliminary scale highly suitable, easy to implement and addressing a gap in current clinical practice. The layout of the scale and wording of three items was modified according to qualitative feedback, arriving at an 18‐item prototype. To our knowledge, this is the first scale designed to assess the full range of behavioural disturbances in children in PTA. The scale has the potential to systematically assess behaviour and streamline documentation of behavioural recovery in this population, inform management and rehabilitation, track responses to interventions and facilitate discussion with affected families.

The effect of weighted blankets on sleep and related disorders: a brief review.

Sleep disorders such as insomnia can lead to a range of health problems. The high risk of side effects and drug abuse of traditional pharmacotherapy calls for a safer non-pharmacotherapy. To examine the use and efficacy of weighted blankets in improving sleep and related disorders in different populations and explore the possible mechanisms. A literature search was conducted using PubMed, Embase, Web of Science, MEDLINE, Cochrane Library and CNKI databases. Eligible studies included an intervention with weighted blankets and outcomes covering sleep and/or related disorders (behavioral disturbance, negative emotions and daytime symptoms). Studies using other deep pressure, compression, or exercise-related interventions were excluded. Most of the included studies showed that weighted blankets could effectively improve sleep quality and alleviate negative emotions and daytime symptoms in patients with sleep disorders, attention deficit hyperactivity disorder, autism spectrum disorder, and other related disorders, with a possible mechanism of deep pressure touch. Weighted blankets might be a promising tool for sleep interventions among individuals with sleep disorders in clinical settings. More high-quality and large-scale randomized controlled trials are needed to further validate the safety and efficacy of weighted blankets and explore precise mechanisms.

The Effect of Shift Working on Dietary Patterns of Healthcare Practitioners during the COVID-19 Pandemic: A Cross-Sectional Study.

Background and Objectives: Health professionals' working schedules often do not allow them to follow a balanced way of life, and the nature of their work can affect their weight and eating habits. The aim of the present study is to shed some light on the impact of night shift working on the dietary practices of healthcare practitioners in Greece. Materials and Methods: This was a cross-sectional study. With the use of an administered questionnaire several parameters were assessed, including anthropometric characteristics, weight history, as well as nutritional habits of the same group of participants during night shifts and when at regular working hours. Moreover, nutritional beliefs of the subjects were recorded, as well as the level of adherence to the Mediterranean diet. Results: It was observed that in all food groups, including water, used to compare the nutritional patterns of the participants during night shifts and when working regular hours, statistical differences were noted (p = 0.001). Furthermore, the participants who reported a higher adherence to the Mediterranean diet and self-reported healthier nutritional habits, had a statistically lower weight compared to the participants that rarely followed the specific model or reported unhealthier eating routine (p = 0.010 and p = 0.015, respectively). Conclusions: We conclude that shift-working healthcare professionals are associated with disturbed eating behaviours leading to the high consumption of unhealthy food. The implementation of interventions that will concentrate on educating health workers on balanced nutrition and improving physical environment (i.e., food availability, healthier food choices) seems to be of great importance.

Japanese encephalitis virus NS1 and NS1' protein disrupts the blood-brain barrier through macrophage migration inhibitory factor-mediated autophagy.

Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases. The nonstructural protein 1 (NS1) is a multifunctional protein of flavivirus that can be secreted by infected cells and circulate in the host bloodstream. NS1' is an additional form of NS1 protein with 52 amino acids extension at its carboxy-terminal and is produced exclusively by flaviviruses in the JEV serogroup. In this study, we demonstrated that the secreted form of both NS1 and NS1' can disrupt the blood-brain barrier (BBB) of mice, with NS1' exhibiting a stronger effect. Using the in vitro BBB model, we found that treatment of soluble recombinant JEV NS1 or NS1' protein increases the permeability of human brain microvascular endothelial cells (hBMECs) and leads to the degradation of tight junction proteins through the autophagy-lysosomal pathway. Consistently, NS1' protein exhibited a more pronounced effect compared to NS1 in these cellular processes. Further research revealed that the increased expression of macrophage migration inhibitory factor (MIF) is responsible for triggering autophagy after NS1 or NS1' treatment in hBMECs. In addition, TLR4 and NF-κB signaling was found to be involved in the activation of MIF transcription. Moreover, administering the MIF inhibitor has been shown to decrease viral loads and mitigate inflammation in the brains of mice infected with JEV. This research offers a novel perspective on the pathogenesis of JEV. In addition, the stronger effect of NS1' on disrupting the BBB compared to NS1 enhances our understanding of the mechanism by which flaviviruses in the JEV serogroup exhibit neurotropism.IMPORTANCEJapanese encephalitis (JE) is a significant viral encephalitis worldwide, caused by the JE virus (JEV). In some patients, the virus cannot be cleared in time, leading to the breach of the blood-brain barrier (BBB) and invasion of the central nervous system. This invasion may result in cognitive impairment, behavioral disturbances, and even death in both humans and animals. However, the mechanism by which JEV crosses the BBB remains unclear. Previous studies have shown that the flavivirus NS1 protein plays an important role in causing endothelial dysfunction. The NS1' protein is an elongated form of NS1 protein that is particularly produced by flaviviruses in the JEV serogroup. This study revealed that both the secreted NS1 and NS1' of JEV can disrupt the BBB by breaking down tight junction proteins through the autophagy-lysosomal pathway, and NS1' is found to have a stronger effect compared to NS1 in this process. In addition, JEV NS1 and NS1' can stimulate the expression of MIF, which triggers autophagy via the ERK signaling pathway, leading to damage to BBB. Our findings reveal a new function of JEV NS1 and NS1' in the disruption of BBB, thereby providing the potential therapeutic target for JE.

Differences in Well-Being at School Between Young Students With and Without a Refugee Background.

Students with a refugee background are a vulnerable group in education. Adverse experiences and unsafe circumstances that they encounter prior, during and after their flight can place a great burden on their mental health and psychological well-being. Little is known about the psychological well-being of young refugee students in kindergarten and early years of primary school. The current study examined the psychological well-being of 4- to 8-year-old students with a refugee background residing in the Netherlands (n = 136), compared to Dutch peers without a refugee background (n = 406). Primary school teachers completed three questionnaires which assessed multiple indicators of their students' psychological well-being: Strengths and Difficulties Questionnaire (SDQ), Social-Emotional Questionnaire (SEV) and Risk and Protective factors Trauma Observation School Situations (RaPTOSS). In line with the hypothesis, results showed overall lower psychological well-being among refugee students compared to non-refugee students. Teachers observed more total difficulties in socio-emotional functioning, anxious and mood disturbing behavior, ADHD symptoms, problematic social behavior and post-traumatic stress symptoms (small effects), and less developed trauma protective factors and prosocial behavior (medium effects) among students with a refugee background compared to their non-refugee peers. However, the findings also demonstrated that half of the refugee students did not have any scores that fall in the clinical range of the psychological and behavioral problems assessed. The results underline the need to promote protective factors such as positive self-image, self-regulation skills, safety and relations in the classroom and prosocial behavior among students with a refugee background.

Effects of fluorene-9-bisphenol exposure on anxiety-like and social behavior in mice and protective potential of exogenous melatonin.

Fluorene-9-bisphenol (BHPF) is widely used in the manufacture of plastic products and potentially disrupts several physiological processes, but its biological effects on social behavior remain unknown. In this study, we investigated the effects of BHPF exposure on anxiety-like and social behavior in female mice and the potential mechanisms, thereby proposing a potential therapy strategy. We exposed female Balb/c mice to BHPF by oral gavage at different doses (0.5, 50 mg/kg bw/2-day) for 28 days, which were found BHPF (50 mg/kg) exposure affected motor activity in the open field test (OFT) and elevated cross maze (EPM), resulting in anxiety-like behaviors, as well as abnormal social behavioral deficits in the Social Interaction Test (SIT). Analysis of histopathological staining results showed that BHPF exposure caused damage to hippocampal neurons in the CA1/CA3/DG region and decreased Nissl pyramidal neurons in the CA1/CA3 regions of the hippocampus, as well as a decrease in parvalbumin neuron expression. In addition, BHPF exposure upregulated the expression of excitatory and inhibitory (E/I) vesicle transporter genes (Vglut1, Vglut2, VGAT, GAD67, Gabra) and axon growth gene (Dcc) in the mouse hippocampus. Interestingly, behavioral disturbances and E/I balance could be alleviated by exogenous melatonin (15 mg/kg bw/2-day) therapy. Our findings suggest that exogenous melatonin may be a potential therapy with protective potential for ameliorating or preventing BHPF-induced hippocampal neuronal damage and behavioral disturbances. This study provided new insight into the neurotoxicological effects on organisms exposed to endocrine-disrupting chemicals and aroused our vigilance in current environmental safety about chemical use.

Differential diagnosis between frontotemporal dementia and bipolar disorder, review and case report

IntroductionDementia can present with psychiatric symptoms even before the cognitive impairment, which makes difficult to establish an adequate diagnosis. There have described symptoms of this type in vascular dementia, frontotemporal dementia, Alzheimer disease and Lewy bodies dementia. Frontotemporal dementia has a prevalence of 9-20% and it`s the third in frequency among degenerative dementia. It appears before the age of 65 years old and is more common in men. Two variants have been described, linguistic and behavioral. The behavioral one has usually an initial psychiatric presentation, with behavioral disorders, disinhibition and personality changes. Therefore it`s important to make an adequate differential diagnosis with late onset bipolar disorder.ObjectivesTo review about frontotemporal dementia and its differential diagnosis with late onset bipolar disorder.MethodsWe carry out a literature review about frontotemporal dementia and its differential diagnosis with late onset bipolar disorder, accompanied by a clinical description of one patient with behavioral disturbance and language disorder.Results A 59-year-old female was admitted to the short-term hospitalization unit from the emergency department due to behavior disorder. She had no relevant personal or familiar psychiatric history up to two years before when she received diagnosis of bipolar disorder. She presented behavioral disorganization, psychomotor restlessness, verbal aggressiveness, verbiage, insomnia and decreased intake. Psychopathological examination became difficult due to her language disorder since she presented an incoherent speech with paraphasias and loss of the common thread. Neurological study guided diagnosis to frontotemporal dementia even though they left the psychopharmacological treatment to our discretion. Olanzapine 5 mg twice a day was initiated, and behavioral improvement was observed. However, the patient maintained a significant functional impairment.ConclusionsPsychiatric presentation is frequent in dementia, even before cognitive failures which makes essential an exhaustive differential diagnosis. It`s important to consider the diagnosis of frontotemporal dementia in those patients who debut with behavioral disturbance in the 50s. Psychopharmacological treatment is only symptomatic so functional recovery should not be expected.Disclosure of InterestNone Declared