Yale Psychiatry

TRP channels, are non-specific cationic channels that are involved in multiple physiological processes that include salivation, cellular secretions, memory extinction and consolidation, temperature, pain, store-operated calcium entry, thermosensation and functionality of the nervous system. Here we choose to look at the evidence that decisively shows how TRP channels modulate human neuron plasticity as it relates to the molecular neurobiology of sleep/circadian rhythm. There are numerous model organisms of sleep and circadian rhythm that are the results of the absence or genetic manipulation of the non-specific cationic TRP channels. Drosophila and mice that have had their TRP channels genetically ablated or manipulated show strong evidence of changes in sleep duration, sleep activity, circadian rhythm and response to temperature, noxious odours and pattern of activity during both sleep and wakefulness along with cardiovascular and respiratory function during sleep. Indeed the role of TRP channels in regulating sleep and circadian rhythm is very interesting considering the parallel roles of TRP channels in thermoregulation and thermal response with concomitant responses in growth and degradation of neurites, peripheral nerves and neuronal brain networks. TRP channels provide evidence of an ability to create, regulate and modify our sleep and circadian rhythm in a wide array of physiological and pathophysiological conditions. In the current review, we summarize previous results and novel recent advances in the understanding of calcium ion entry via TRP channels in different sleep and circadian rhythm conditions. We discuss the role of TRP channels in sleep and circadian disorders.

The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics.

Functional loss, the inability to perform necessary or desired tasks, is a common consequence of life-limiting illnesses and associated symptoms (pain, fatigue, breathlessness, etc.) and causes suffering for patients and families. Rehabilitation, a set of interventions designed to address functional loss, is recognised as essential within palliative care, as it can improve quality of life and reduce care costs. However, not everyone has equal access to rehabilitation. Despite limited life expectancy or uncertain ability to benefit from interventions, palliative rehabilitation services are often absent. This is partly due to a lack of high-quality research around optimal models of rehabilitation. Research in this area is methodologically challenging and requires multidisciplinary and cross-speciality collaboration.

Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three-SARS, SARS-CoV-2 and MERS-are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.

Healthcare professionals are known to suffer from workplace stress and burnout, which can negatively affect their empathy for patients and quality of care. While existing research has identified factors associated with wellbeing and empathy in healthcare professionals, these efforts are typically focused on the group level, ignoring potentially important individual differences and implications for individualized intervention approaches. In the current study, we implemented N-of-1 personalized machine learning (PML) to predict wellbeing and empathy in healthcare professionals at the individual level, leveraging ecological momentary assessments (EMAs) and smartwatch wearable data. A total of 47 mood and lifestyle feature variables (relating to sleep, diet, exercise, and social connections) were collected daily for up to three months followed by applying eight supervised machine learning (ML) models in a PML pipeline to predict wellbeing and empathy separately. Predictive insight into the model architecture was obtained using Shapley statistics for each of the best-fit personalized models, ranking the importance of each feature for each participant. The best-fit model and top features varied across participants, with anxious mood (13/19) and depressed mood (10/19) being the top predictors in most models. Social connection was a top predictor for wellbeing in 9/12 participants but not for empathy models (1/7). Additionally, empathy and wellbeing were the top predictors of each other in 64% of cases. These findings highlight shared and individual features of wellbeing and empathy in healthcare professionals and suggest that a one-size-fits-all approach to addressing modifiable factors to improve wellbeing and empathy will likely be suboptimal. In the future, such personalized models may serve as actionable insights for healthcare professionals that lead to increased wellness and quality of patient care.

Mindfulness describes the ability to focus on the presence, including one's thoughts and feelings. Trait mindfulness - a person's inherent tendency to be mindful - has been connected to increased subjective sleep quality, but evidence from objective EEG-based sleep measures is lacking. Here, we investigate whether objective EEG-based sleep parameters explain interindividual differences in trait mindfulness.

Primary care physicians often lack resources and training to correctly diagnose and manage chronic insomnia disorder. Tools supporting chronic insomnia diagnosis and management could fill this critical gap. A survey was conducted to understand insomnia disorder diagnosis and treatment practices among primary care physicians, and to evaluate a diagnosis and treatment algorithm on its use, to identify ways to optimize it specifically for these providers.

Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-generation antipsychotic, in an Italian sample of individuals diagnosed with schizophrenia spectrum disorder and a comorbid SUD.

Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative condition with a prevalence comparable to Alzheimer's disease for patients under 65 years of age. Limited studies have examined the association between cognition and neuroimaging in FTD using different imaging modalities.

Meditation-based interventions are novel and effective non-pharmacologic treatments for veterans with PTSD. We examined relationships between treatment response, early life trauma exposure, DNA polymorphisms, and methylation in the serotonin transporter (SLC6A4) and FK506-binding protein 5 (FKBP5) genes. DNA samples and clinical outcomes were examined in 72 veterans with PTSD who received meditation-based therapy in two separate studies of mindfulness-based stress reduction (MBSR) and Transcendental Meditation (TM). The PTSD Checklist was administered to assess symptoms at baseline and after 9 weeks of meditation intervention. We examined the SLC6A4 promoter (5HTTLPR_L/S insertion/deletion + rs25531_A/G) polymorphisms according to previously defined gene expression groups, and the FKBP5 variant rs1360780 previously associated with PTSD disease risk. Methylation for CpG sites of SLC6A4 (28 sites) and FKBP5 (45 sites) genes was quantified in DNA samples collected before and after treatment. The 5HTTLPR LL high expression genotype was associated with greater symptom improvement in participants exposed to early life trauma (p = 0.015). Separately, pre to post-treatment change of DNA methylation in a group of nine FKBP5 CpG sites was associated with greater symptom improvement (OR = 2.8, 95% CI 1.1-7.1, p = 0.027). These findings build on a wealth of existing knowledge regarding epigenetic and genetic relationships with PTSD disease risk to highlight the potential importance of SLC6A4 and FKBP5 for treatment mechanisms and as biomarkers of symptom improvement.

The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 MZ and 52 DZ twins, 69.91% females; mean age-75.79 ± 5.44) were studied. Peripheral blood gene expression was assessed using Illumina microarrays. A heritability analysis was performed using structural equation modelling. There were 5269 probes (19.9%) from 4603 unique genes (23.9%) (total 26,537 probes from 19,256 genes) that were significantly heritable (mean h = 0.40). A pathway analysis of the top 10% of significant genes showed enrichment for the immune response and ageing-associated genes. In a comparison with two other gene expression twin heritability studies using adults from across the lifespan, there were 38 out of 9479 overlapping genes that were significantly heritable. In conclusion, our study found ~24% of the available genes for analysis were heritable in older adults, with only a small number common across studies that used samples from across adulthood, indicating the importance of examining gene expression in older age groups.

Cytomegalovirus (CMV), a DNA virus that belongs to the family, infects 40-100% of people. Primary/non-primary CMV infection during pregnancy could cause fetal disabilities. After primary infection, CMV causes a latent infection and resides in cells of the myeloid compartment (CD34, monocytes). Few studies have analyzed the impact of latent CMV infections on miscarriage history, pregnancy complications, and neonatal outcomes.

Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.

Classical examples of disorders associated with body image disturbances are eating disorders (EDs) such as anorexia nervosa (AN) and bulimia nervosa (BN), as well as body dysmorphic disorder (BDD) [...].

L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research.

Intuitive eating (IE) is a non-dieting approach that promotes listening to internal cues of hunger and satiety, rather than adhering to external dietary restrictions aimed at weight loss. However, the role of IE in dieting behaviors related to weight-loss approaches is still unclear. To address this issue, the aim of this study was to compare IE levels between dieting and non-dieting individuals, exploring the relationship between IE and dieting-related psychological and physical factors. A sample of 2059 females was recruited via social media and self-reported questionnaires were administered to measure IE, eating psychopathology, self-efficacy, and quality of life. Individuals with a history of dieting exhibited lower IE levels, a higher BMI, and a greater eating psychopathology, as well as a reduced self-efficacy and quality of life, compared to non-dieters. IE showed a protective effect against dieting behaviors, with higher IE levels being associated with a lower likelihood of dieting. Additionally, higher BMI and eating psychopathology were predictors of dieting. Promoting IE could represent a relevant clinical target strategy to address disordered eating and enhance overall well-being, underscoring the need for interventions that foster a healthier relationship with food and bodily internal sensations.

Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of the cerebral cortex of fluoxetine-treated trisomic mice may provide proteomic signatures that identify therapeutic targets for DS. Subcellular fractionation of synaptosomes from cerebral cortices of age- and brain-area-matched samples from fluoxetine-treated vs. water-treated trisomic and euploid male mice were subjected to HPLC-tandem mass spectrometry. Analysis of the data revealed enrichment of trisomic risk genes that participate in regulation of synaptic vesicular traffic, pre-synaptic and post-synaptic development, and mitochondrial energy pathways during early brain development. Proteomic analysis of trisomic synaptic fractions revealed significant downregulation of proteins involved in synaptic vesicular traffic, including vesicular endocytosis (CLTA, CLTB, CLTC), synaptic assembly and maturation (EXOC1, EXOC3, EXOC8), anterograde axonal transport (EXOC1), neurotransmitter transport to PSD (SACM1L), endosomal-lysosomal acidification (ROGDI, DMXL2), and synaptic signaling (NRXN1, HIP1, ITSN1, YWHAG). Additionally, trisomic proteomes revealed upregulation of several trafficking proteins, involved in vesicular exocytosis (Rab5B), synapse elimination (UBE3A), scission of endocytosis (DBN1), transport of ER in dendritic spines (MYO5A), presynaptic activity-dependent bulk endocytosis (FMR1), and NMDA receptor activity (GRIN2A). Chronic fluoxetine treatment of Ts65Dn mice rescued synaptic vesicular abnormalities and prevented abnormal proteomic changes in adult Ts65Dn mice, pointing to therapeutic targets for potential treatment of DS.

Adolescent solitude was drastically impacted by the COVID-19 pandemic. As solitude is crucial for adolescent development through its association with both positive and negative developmental outcomes, it is critical to understand how adolescents' daily-life solitary experiences changed as a result of the pandemic.

Mental disorders in terms of depression, anxiety, and stress are one of the major causes of burden globally. Over the last two decades, the use of plant-based substances in the treatment of mental disorders in combination or not with medication has increasingly attracted the interest of the scientific research community. However, even if there is a plethora of naturally occurring bioactive compounds, most of them have low bioavailability, rendering them unable to insert into the bloodstream to exert their biological activities.

In military flight operations, during flights, fighter pilots constantly work under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations, the Federal Aviation Administration (FAA) also recommends supplemental oxygen for flying under hypobaric conditions equivalent to higher than 3048 m altitude, and has made it mandatory for conditions equivalent to more than 3657 m altitude.

Electronic health record (EHR) transitions are known to be highly disruptive, can drastically impact clinician and staff experiences, and may influence patients' experiences using the electronic patient portal. Clinicians and staff can gain insights into patient experiences and be influenced by what they see and hear from patients. Through the lens of an emergency preparedness framework, we examined clinician and staff reactions to and perceptions of their patients' experiences with the portal during an EHR transition at the Department of Veterans Affairs (VA).

: Loneliness is prevalent among residents of long-term care settings, posing significant challenges to their mental wellbeing. Insecure attachment has been identified as a contributing factor to loneliness in this population. Previous research has suggested that meditation may have beneficial effects on mental health outcomes. This study aimed to examine the relationship between meditation, insecure attachment, and loneliness among residents of long-term care facilities in Thailand. Specifically, the study sought to investigate the moderating effect of meditation on the association between insecure attachment (both avoidance and anxiety) and loneliness. : A cross-sectional study was conducted involving 236 residents living in long-term care homes in Thailand. Participants completed self-report measures including the 18-item Revised Experience of Close Relationship questionnaire (to assess attachment anxiety and avoidance), the Inner Strength-Based Inventory (to measure meditation practice), and the 6-item Revised Version of the University of California Los Angeles Loneliness Scale. Moderation analyses were performed to explore the role of meditation in the relationship between insecure attachment and loneliness. : The mean age of participants was 73.52 years, with females accounting for 57.6% of the sample. Among the participants, 58.4% reported engaging in meditation, with practice frequency ranging from often to daily. The mean meditation score was 2.92 out of 5, indicating regular but not daily practice. Meditation was found to moderate the relationship between insecure attachment (both avoidance and anxiety) and loneliness. Specifically, the moderation effect between attachment anxiety and loneliness was significant (B = 0.44, SE = 0.21, 95% CI [0.30, 0.86]), as was the interaction effect between attachment anxiety and loneliness (B = -0.34, SE = 0.17, 95% CI [-0.67, -0.02]). : The findings suggest that the impact of meditation practice on loneliness is influenced by an individual's attachment dimension. Meditation demonstrates a moderating effect on attachment avoidance, anxiety, and loneliness, with variations observed in the direction of these effects. The clinical implications of these findings and recommendations for further research are discussed.

: The study aims to provide a comprehensive neuropsychological analysis of psychotic spectrum disorders, including schizophrenia, bipolar disorder, and depression. It focuses on the critical aspects of cognitive impairments, diagnostic tools, intervention efficacy, and the roles of genetic and environmental factors in these disorders. The paper emphasizes the diagnostic significance of neuropsychological tests in identifying cognitive deficiencies and their predictive value in the early management of psychosis. : The study involved a systematic literature review following the PRISMA guidelines. The search was conducted in significant databases like Scopus, PsycINFO, PubMed, and Web of Science using keywords relevant to clinical neuropsychology and psychotic spectrum disorders. The inclusion criteria required articles to be in English, published between 2018 and 2023, and pertinent to clinical neuropsychology's application in these disorders. A total of 153 articles were identified, with 44 ultimately included for detailed analysis based on relevance and publication status after screening. The review highlights several key findings, including the diagnostic and prognostic significance of mismatch negativity, neuroprogressive trajectories, cortical thinning in familial high-risk individuals, and distinct illness trajectories within psychosis subgroups. The studies evaluated underline the role of neuropsychological tests in diagnosing psychiatric disorders and emphasize early detection and the effectiveness of intervention strategies based on cognitive and neurobiological markers. : The systematic review underscores the importance of investigating the neuropsychological components of psychotic spectrum disorders. It identifies significant cognitive impairments in attention, memory, and executive function, correlating with structural and functional brain abnormalities. The paper stresses the need for precise diagnoses and personalized treatment modalities, highlighting the complex interplay between genetic, environmental, and psychosocial factors. It calls for a deeper understanding of these neuropsychological processes to enhance diagnostic accuracy and therapeutic outcomes.

The positive association of health with education level and socioeconomic status (SES) is well-established. Two theoretical frameworks have been delineated to understand main mechanisms leading to socioeconomic health inequalities: social causation and health selection but how these work in adolescence is poorly known. We studied if adolescent health and health behaviours predict higher education and higher SES in adulthood and if family background and school performance in adolescence explain these associations.

Urinary incontinence is highly prevalent in women while pelvic floor muscle training is recommended as the first-line therapy. However, the exact treatment regimen is poorly understood. Also, patients with pelvic floor muscle damage may have decreased muscle proprioception and cannot contract their muscles properly. Other conservative treatments including electromagnetic stimulation are suggested by several guidelines. Thus, the present study aims to compare the effectiveness of electromagnetic stimulation combined with pelvic floor muscle training as a conjunct treatment for urinary incontinence and different treatment frequencies will be investigated.

: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. : We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. : The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. : There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Sotos syndrome is a genetic disorder caused by gene (nuclear receptor binding SET domain containing protein 1) variants and characterized by overgrowth, macrocephaly, learning disabilities, and co-occurring neuropsychiatric symptoms. Literature sources published in 2002-2023 were selected and analyzed from PubMed and Google Scholar databases. Neuropsychiatric symptoms are observed among children and adolescents with Sotos syndrome. The majority have intellectual disabilities or borderline intellect. Verbal IQ is higher than performance IQ. Individuals display difficulties in expressing language. Aggression is reported by parents. Children express autistic behavior, ADHD, anxiety based on phobias, and early bedtime-wake times. Sotos syndrome is associated with neuropsychiatric disorders in children. Slow intellectual and language development, aggressive outbursts, anxiety, autism spectrum disorder, and hyperactivity are present in the newest studies. Comprehensive assistance is needed for Sotos syndrome patients in responding to areas of difficulty. There is still a lack of research on the developmental characteristics of these children and the possibilities of improving psychosocial adaptation by providing multidisciplinary long-term medical, educational, and social care.

: Inherited metabolic disorders (IEMs) can be represented in children and adolescents by psychiatric disorders. The early diagnosis of IEMs is crucial for clinical outcome and treatment. The aim of this review is to analyze the most recurrent and specific psychiatric features related to IEMs in pediatrics, based on the onset type and psychiatric phenotypes. Following the PRISMA Statement, a systematic literature review was performed using a predefined algorithm to find suitable publications in scientific databases of interest. After removing duplicates and screening titles and abstracts, suitable papers were analyzed and screened for inclusion and exclusion criteria. Finally, the data of interest were retrieved from the remaining articles. The results of this study are reported by type of symptoms onset (acute and chronic) and by possible psychiatric features related to IEMs. Psychiatric phenomenology has been grouped into five main clinical manifestations: mood and anxiety disorders; schizophrenia-spectrum disorders; catatonia; eating disorders; and self-injurious behaviors. The inclusion of a variety of psychiatric manifestations in children and adolescents with different IEMs is a key strength of this study, which allowed us to explore the facets of seemingly different disorders in depth, avoiding possible misdiagnoses, with the related delay of early and appropriate treatments.

The general movement optimality score (GMOS) quantifies the details of general movements (GMs). We recently conducted psychometric analyses of the GMOS and developed a revised scoresheet. Consequently, the GMOS-Revised (GMOS-R) instrument necessitated validation using new percentile ranks. This study aimed to provide these percentile ranks for the GMOS-R and to investigate whether sex, preterm birth, or the infant's country of birth and residence affected the GMOS-R distribution. We applied the GMOS-R to an international sample of 1983 infants (32% female, 44% male, and 24% not disclosed), assessed in the extremely and very preterm period (10%), moderate (12%) and late (22%) preterm periods, at term (25%), and post-term age (31%). Data were grouped according to the World Bank's classification into lower- and upper-middle-income countries (LMICs and UMICs; 26%) or high-income countries (HICs; 74%), respectively. We found that sex and preterm or term birth did not affect either GM classification or the GMOS-R, but the country of residence did. A lower median GMOS-R for infants with normal or poor-repertoire GMs from LMICs and UMICs compared with HICs suggests the use of specific percentile ranks for LMICs and UMICs vs. HICs. For clinical and scientific use, we provide a freely available GMOS-R scoring sheet, with percentile ranks reflecting socioeconomic stratification.

: Dual disorders (DD) entail the coexistence of a substance use disorder (SUD) and another mental health condition, often within psychotic and affective disorders. This study aims to evaluate lurasidone, an innovative atypical antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder and concurrent comorbidities of alcohol use disorder/substance use disorder (AUD/SUD). : A cohort of 23 subjects diagnosed with schizophrenia spectrum disorder and comorbid AUD/SUD underwent psychometric assessments at baseline (T0) and one-month (T1) post-lurasidone initiation. : Lurasidone exhibited significant reductions in psychopathological burden, evidenced by decreased total PANSS scores ( = 2.574, = 0.011). Positive symptoms, substance craving (VAS Craving; = 3.202, = 0.001), and aggressivity (MOAS scale; = 2.000, = 0.050) were notably reduced. Clinical Global Impression (CGI) scores significantly improved ( = 2.934, = 0.003). Quality of life enhancements were observed in SF-36 subscales (energy, emotional well-being, and social functioning) ( < 0.05) and Q-LES-Q-SF scale ( = -2.341, = 0.021). A safety analysis indicated lurasidone's good tolerability, with only 8.7% reporting discontinuation due to side effects. : This study offers initial evidence supporting lurasidone's efficacy and safety in dual diagnoses, highlighting positive effects on psychopathology, substance craving, and quality of life. These findings emphasize the need for tailored, comprehensive treatment strategies in managing the complexities of this patient population.

Academic medical institutions seek to recruit and retain a diverse workforce to foster equitable, supportive environments in which early-stage investigators, especially those who are underrepresented in medicine, can thrive. Intersectionality is a critical theoretical framework rooted in Black feminist activism and scholarship that elucidates how power and privilege are differentially structured for groups at different intersectional sociodemographic positions. As a dynamic method of analyzing multiple axes of power and inequality, intersectionality has the potential to offer a critical lens through which to view the mentor-mentee relationship. In this article, we seek to elaborate upon and extend the concept of intersectional mentoring, elucidate its essential components, and explore its application in the context of mentoring early-stage investigators in academic medicine. We propose that intersectional mentorship requires an orientation toward deep cultural humility, lifetime learning about the impact of systemic oppressions on present-day opportunities and experiences of mentees, and changing systems that perpetuate inequities by centering praxis-the application of principles of intersectionality through action to transform power dynamics in academic culture and institutions. Intersectional mentorship can help build a more equitable and representative workforce to advance intersectionally relevant and innovative approaches to achieving health equity.

Women's experiences of military service and transition occur within a highly dominant masculinized culture. The vast majority of research on military veterans reflects men's experiences and needs. Women veterans' experiences, and therefore their transition support needs, are largely invisible. This study sought to understand the role and impact of gender in the context of the dominant masculinized culture on women veterans' experiences of military service and transition to civilian life. In-depth qualitative interviews with 22 Australian women veterans elicited four themes: (1) Fitting in a managing identity with the military; (2) Gender-based challenges in conforming to a masculinized culture-proving worthiness, assimilation, and survival strategies within that culture; (3) Women are valued less than men-consequences for women veterans, including misogyny, sexual harassment and assault, and system failures to recognize women's specific health needs and role as mothers; and (4) Separation and transition: being invisible as a woman veteran in the civilian world. Gendered military experiences can have long-term negative impacts on women veterans' mental and physical health, relationships, and identity due to a pervasive masculinized culture in which they remain largely invisible. This can create significant gender-based barriers to services and support for women veterans during their service, and it can also impede their transition support needs.

Attention-Deficit/Hyperactivity Disorder (ADHD), characterized by clinical diversity, poses diagnostic challenges often reliant on subjective assessments. Metabolomics presents an objective approach, seeking biomarkers for precise diagnosis and targeted interventions. This review synthesizes existing metabolomic insights into ADHD, aiming to reveal biological mechanisms and diagnostic potentials. A thorough PubMed and Web of Knowledge search identified studies exploring blood/urine metabolites in ADHD-diagnosed or psychometrically assessed children and adolescents. Synthesis revealed intricate links between ADHD and altered amino acid metabolism, neurotransmitter dysregulation (especially dopamine and serotonin), oxidative stress, and the kynurenine pathway impacting neurotransmitter homeostasis. Sleep disturbance markers, notably in melatonin metabolism, and stress-induced kynurenine pathway activation emerged. Distinct metabolic signatures, notably in the kynurenine pathway, show promise as potential diagnostic markers. Despite limitations like participant heterogeneity, this review underscores the significance of integrated therapeutic approaches targeting amino acid metabolism, neurotransmitters, and stress pathways. While guiding future research, this overview of the metabolomic findings in ADHD suggests directions for precision diagnostics and personalized ADHD interventions.

Mild traumatic brain injury (mTBI) affects millions of people in the U.S. Approximately 20-30% of those individuals develop adverse symptoms lasting at least 3 months. In a rat mTBI study, the closed-head impact model of engineered rotational acceleration (CHIMERA) produced significant axonal injury in the optic tract (OT), indicating white-matter damage. Because retinal ganglion cells project to the lateral geniculate nucleus (LGN) in the thalamus through the OT, we hypothesized that synaptic density may be reduced in the LGN of rats following CHIMERA injury. A modified SEQUIN (synaptic evaluation and quantification by imaging nanostructure) method, combined with immunofluorescent double-labeling of pre-synaptic (synapsin) and post-synaptic (PSD-95) markers, was used to quantify synaptic density in the LGN. Microglial activation at the CHIMERA injury site was determined using Iba-1 immunohistochemistry. Additionally, the effects of ketamine, a potential neuroprotective drug, were evaluated in CHIMERA-induced mTBI. A single-session repetitive (ssr-) CHIMERA (3 impacts, 1.5 joule/impact) produced mild effects on microglial activation at the injury site, which was significantly enhanced by post-injury intravenous ketamine (10 mg/kg) infusion. However, ssr-CHIMERA did not alter synaptic density in the LGN, although ketamine produced a trend of reduction in synaptic density at post-injury day 4. Further research is necessary to characterize the effects of ssr-CHIMERA and subanesthetic doses of intravenous ketamine on different brain regions and multiple time points post-injury. The current study demonstrates the utility of the ssr-CHIMERA as a rodent model of mTBI, which researchers can use to identify biological mechanisms of mTBI and to develop improved treatment strategies for individuals suffering from head trauma.

Inflammation processes of the central nervous system (CNS) play a vital role in the pathogenesis of several neurological and psychiatric disorders like depression. These processes are characterized by the activation of glia cells, such as microglia. Clinical studies showed a decrease in symptoms associated with the mentioned diseases after the treatment with anti-inflammatory drugs. Therefore, the investigation of novel anti-inflammatory drugs could hold substantial potential in the treatment of disorders with a neuroinflammatory background. In this in vitro study, we report the anti-inflammatory effects of a novel hexacyclic peptide-peptoid hybrid in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. The macrocyclic compound X15856 significantly suppressed Interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), c-c motif chemokine ligand 2 (CCL2), CCL3, C-X-C motif chemokine ligand 2 (CXCL2), and CXCL10 expression and release in LPS-treated BV2 microglial cells. The anti-inflammatory effects of the compound are partially explained by the modulation of the phosphorylation of p38 mitogen-activated protein kinases (MAPK), p42/44 MAPK (ERK 1/2), protein kinase C (PKC), and the nuclear factor (NF)-κB, respectively. Due to its remarkable anti-inflammatory properties, this compound emerges as an encouraging option for additional research and potential utilization in disorders influenced by inflammation, such as depression.

Age-associated deep-subcortical white matter lesions (DSCLs) are an independent risk factor for dementia, displaying high levels of CD68 microglia. This study aimed to characterize the transcriptomic profile of microglia in DSCLs and surrounding radiologically normal-appearing white matter (NAWM) compared to non-lesional control white matter. CD68 microglia were isolated from white matter groups ( = 4 cases per group) from the Cognitive Function and Ageing Study neuropathology cohort using immuno-laser capture microdissection. Microarray gene expression profiling, but not RNA-sequencing, was found to be compatible with immuno-LCM-ed post-mortem material in the CFAS cohort and identified significantly differentially expressed genes (DEGs). Functional grouping and pathway analysis were assessed using the Database for Annotation Visualization and Integrated Discovery (DAVID) software, and immunohistochemistry was performed to validate gene expression changes at the protein level. Transcriptomic profiling of microglia in DSCLs compared to non-lesional control white matter identified 181 significant DEGs (93 upregulated and 88 downregulated). Functional clustering analysis in DAVID revealed dysregulation of haptoglobin-haemoglobin binding (Enrichment score 2.5, = 0.017), confirmed using CD163 immunostaining, suggesting a neuroprotective microglial response to blood-brain barrier dysfunction in DSCLs. In NAWM versus control white matter, microglia exhibited 347 DEGs (209 upregulated, 138 downregulated), with significant dysregulation of protein de-ubiquitination (Enrichment score 5.14, < 0.001), implying an inability to maintain protein homeostasis in NAWM that may contribute to lesion spread. These findings enhance understanding of microglial transcriptomic changes in ageing white matter pathology, highlighting a neuroprotective adaptation in DSCLs microglia and a potentially lesion-promoting phenotype in NAWM microglia.

Functional neurological disorder (FND), formerly called conversion disorder, is a condition characterized by neurological symptoms that lack an identifiable organic purpose. These signs, which can consist of motor, sensory, or cognitive disturbances, are not deliberately produced and often vary in severity. Its diagnosis is predicated on clinical evaluation and the exclusion of other medical or psychiatric situations. Its treatment typically involves a multidisciplinary technique addressing each of the neurological symptoms and underlying psychological factors via a mixture of medical management, psychotherapy, and supportive interventions. Recent advances in neuroimaging and a deeper exploration of its epidemiology, pathophysiology, and clinical presentation have shed new light on this disorder. This paper synthesizes the current knowledge on FND, focusing on its epidemiology and underlying mechanisms, neuroimaging insights, and the differentiation of FND from feigning or malingering. This review highlights the phenotypic heterogeneity of FND and the diagnostic challenges it presents. It also discusses the significant role of neuroimaging in unraveling the complex neural underpinnings of FND and its potential in predicting treatment response. This paper underscores the importance of a nuanced understanding of FND in informing clinical practice and guiding future research. With advancements in neuroimaging techniques and growing recognition of the disorder's multifaceted nature, the paper suggests a promising trajectory toward more effective, personalized treatment strategies and a better overall understanding of the disorder.

Plasma levels of glial cell line-derived neurotrophic factor (GDNF), a pivotal regulator of differentiation and survival of dopaminergic neurons, are reportedly decreased in schizophrenia. To explore the involvement of GDNF in the pathogenesis of the disease, a case-control association analysis was performed between five non-coding single nucleotide polymorphisms (SNP) across the GDNF gene and schizophrenia. Of them, the 'G' allele of the rs11111 SNP located in the 3' untranslated region (3'-UTR) of the gene was found to associate with schizophrenia. In silico analysis revealed that the rs11111 'G' allele might create binding sites for three microRNA (miRNA) species. To explore the significance of this polymorphism, transient co-transfection assays were performed in human embryonic kidney 293T (HEK293T) cells with a luciferase reporter construct harboring either the 'A' or 'G' allele of the 3'-UTR of GDNF in combination with the hsa-miR-1185-1-3p pre-miRNA. It was demonstrated that in the presence of the rs11111 'G' (but not the 'A') allele, hsa-miR-1185-2-3p repressed luciferase activity in a dose-dependent manner. Deletion of the miRNA binding site or its substitution with the complementary sequence abrogated the modulatory effect. Our results imply that the rs11111 'G' allele occurring more frequently in patients with schizophrenia might downregulate GDNF expression in a miRNA-dependent fashion.

Malignant tumors are the second most common cause of death worldwide. More attention is being paid to the link between the body's impaired oxidoreductive balance and cancer incidence. Much attention is being paid to polyphenols derived from plants, as one of their properties is an antioxidant character: the ability to eliminate reactive oxygen and nitrogen species, chelate specific metal ions, modulate signaling pathways affecting inflammation, and raise the level and activity of antioxidant enzymes while lowering those with oxidative effects. The following three compounds, resveratrol, quercetin, and curcumin, are polyphenols modulating multiple molecular targets, or increasing pro-apoptotic protein expression levels and decreasing anti-apoptotic protein expression levels. Experiments conducted in vitro and in vivo on animals and humans suggest using them as chemopreventive agents based on antioxidant properties. The advantage of these natural polyphenols is low toxicity and weak adverse effects at higher doses. However, the compounds discussed are characterized by low bioavailability and solubility, which may make achieving the blood concentrations needed for the desired effect challenging. The solution may lie in derivatives of naturally occurring polyphenols subjected to structural modifications that enhance their beneficial effects or work on implementing new ways of delivering antioxidants that improve their solubility and bioavailability.

Posterior Cortical Atrophy (PCA) is a rare form of young-onset dementia that causes early visuospatial and visuoperceptual deficits. The symptom profile of Posterior Cortical Atrophy leads to very specific care needs for those affected, who often rely on informal caregivers (including friends and family). Rare dementia support groups can be useful for both patients and their caregivers to assist with knowledge sharing, psychoeducation, and the provision of psychosocial support. Despite this, few such support groups exist. The purpose of this study was to examine a PCA support group for caregivers of individuals living with PCA. We held a structured psychoeducation support group comprised of four sessions with the aim being to provide education, strategies for the management of the disease, and peer support. Caregivers' mental health and quality of life were assessed. The results of our study showed that support group participation was a positive experience and assisted with increasing the knowledge of caregivers and fostering social connections. We suggest that peer support groups may be beneficial for both people living with PCA and their caregivers. We recommend that future quantitative and qualitative research is conducted to further assess health-promotion benefits to people living with PCA and their caregivers, and to assess their development and implementation in different contexts.

Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178-448) and 643 (502-839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42-21.00], and 15.16 [1.07-215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration.

Children with mental illness commonly live with caregivers who suffer from mental illness. Integrated mental-health-treatment approaches can provide more convenient and comprehensive care for families. This case report describes family-based treatment (FBT) for one parent/child dyad. The parent was a 37-year-old female with a history of anxiety and major depressive disorder and concern for symptoms of attention-deficit/hyperactivity disorder (ADHD). The child was an 8-year-old female with generalized anxiety disorder and concern for ADHD and behavioral problems. The parent received individual cognitive behavioral therapy (CBT) and parent management training. The child received CBT. Both also received medication management. The FBT team met regularly for coordinated treatment planning. Self-reported assessments via the Child Behavior Checklist showed meaningful improvement; anxiety decreased to nonclinical range week 12 and depression decreased to nonclinical range week 8. Clinician assessments showed improvement for both patients. Though more time intensive, FBT can yield significant improvement, particularly for children. Pragmatic approaches to treatment planning are important to minimize barriers to FBT.

Vagus nerve stimulation (VNS) represents a long-term adjunctive treatment option in patients with difficult-to-treat depression (DTD). Anti-inflammatory effects have been discussed as a key mechanism of action of VNS. However, long-term investigations in real-world patients are sparse. In this naturalistic observational study, we collected data on cytokines in peripheral blood in = 6 patients (mean age 47.8) with DTD and VNS treatment at baseline and at 6 months follow-up. We have identified clusters of peripheral cytokines with a similar dynamic over the course of these 6 months using hierarchical clustering. We have investigated cytokine changes from baseline to 6 months as well as the relationship between the cytokine profile at 6 months and long-term response at 12 months. After 6 months of VNS, we observed significant correlations between cytokines ( < 0.05) within the identified three cytokine-pairs which were not present at baseline: IL(interleukin)-6 and IL-8; IL-1β and TNF-α; IFN-α2 and IL-33. At 6 months, the levels of all the cytokines of interest had decreased (increased in non-responders) and were lower (5-534 fold) in responders to VNS than in non-responders: however, these results were not statistically significant. VNS-associated immunomodulation might play a role in long-term clinical response to VNS.

Patients with psychotic disorders 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 aimed to develop supportive tools for MHNs regarding oral health to increase sensitisation among MHNs and provide MHNs with the knowledge to recognise (potential) oral health problems in patients with a psychotic disorder. We used a human-centred design in which the user, MHNs and experts by experience were placed at 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 problems as well as needs in terms of resources, we started with focus groups ( = 9). We analysed the data thematically based on the context of patients and MHNs in practice regarding oral health, preferred oral health tools focused on MHNs, and the intended outcomes of tools. A multi-criteria decision matrix was developed and analysed ( = 9) to identify the most optimal and viable solution based on established criteria and issues that are prevalent in the work of MHNs. The most promising result was the development of a brochure with an awareness screener. The brochure with the 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 ( = 19). MHNs and experts by experience were satisfied with the tool and provided recommendations for adjustments to the content. Significant augmentations to the brochure included 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 optimise 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.

Retinal structural and functional changes in humans can be manifestations of different physiological or pathological conditions. Retinal imaging is the only way to directly inspect blood vessels and their pathological changes throughout the whole body non-invasively. Various quantitative analysis metrics have been used to measure the abnormalities of retinal microvasculature in the context of different retinal, cerebral and systemic disorders. Recently developed optical coherence tomography angiography (OCTA) is a non-invasive imaging tool that allows high-resolution three-dimensional mapping of the retinal microvasculature. The identification of retinal biomarkers from OCTA images could facilitate clinical investigation in various scenarios. We provide a framework for extracting computational retinal microvasculature biomarkers (CRMBs) from OCTA images through a knowledge-driven computerized automatic analytical system. Our method allows for improved identification of the foveal avascular zone (FAZ) and introduces a novel definition of vessel dispersion in the macular region. Furthermore, retinal large vessels and capillaries of the superficial and deep plexus can be differentiated, correlating with retinal pathology. The diagnostic value of OCTA CRMBs was demonstrated by a cross-sectional study with 30 healthy subjects and 43 retinal vein occlusion (RVO) patients, which identified strong correlations between OCTA CRMBs and retinal function in RVO patients. These OCTA CRMBs generated through this "all-in-one" pipeline may provide clinicians with insights about disease severity, treatment response and prognosis, aiding in the management and early detection of various disorders.

Adversity during infancy can affect neurobehavioral development and perturb the maturation of physiological systems. Dysregulated immune and inflammatory responses contribute to many of the later effects on health. Whether normalization can occur following a transition to more nurturing, benevolent conditions is unclear. To assess the potential for recovery, blood samples were obtained from 45 adolescents adopted by supportive families after impoverished infancies in institutional settings (post-institutionalized, PI). Their immune profiles were compared to 39 age-matched controls raised by their biological parents (non-adopted, NA). Leukocytes were immunophenotyped, and this analysis focuses on natural killer (NK) cell populations in circulation. Cytomegalovirus (CMV) seropositivity was evaluated to determine if early infection contributed to the impact of an atypical rearing. Associations with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), two cytokines released by activated NK cells, were examined. Compared to the NA controls, PI adolescents had a lower percent of CD56 NK cells in circulation, higher TNF-α levels, and were more likely to be infected with CMV. PI adolescents who were latent carriers of CMV expressed NKG2C and CD57 surface markers on more NK cells, including CD56 lineages. The NK cell repertoire revealed lingering immune effects of early rearing while still maintaining an overall integrity and resilience.

The 8p23.1 duplication syndrome is a rare genetic condition with an estimated prevalence rate of 1 out of 58,000. Although the syndrome was associated with speech and language delays, a comprehensive assessment of speech and language functions has not been undertaken in this population. To address this issue, the present study reports rigorous speech and language, in addition to oral-facial and developmental, assessment of a 50-month-old Turkish-speaking boy who was diagnosed with the 8p23.1 duplication syndrome. Standardized tests of development, articulation and phonology, receptive and expressive language and a language sample analysis were administered to characterize speech and language skills in the patient. The language sample was obtained in an ecologically valid, free play and conversation context. The language sample was then analyzed and compared to a database of age-matched typically-developing children (n = 33) in terms of intelligibility, morphosyntax, semantics/vocabulary, discourse, verbal facility and percentage of errors at word and utterance levels. The results revealed mild to severe problems in articulation and phonology, receptive and expressive language skills, and morphosyntax (mean length of utterance in morphemes). Future research with larger sample sizes and employing detailed speech and language assessment is needed to delineate the speech and language profile in individuals with the 8p23.1 duplication syndrome, which will guide targeted speech and language interventions.

This scoping review explores the use of neuromodulation techniques in individuals with cannabis use. Our goal was to determine whether cannabis use alters cortical excitation and inhibition in the context of neuromodulation and to determine whether neuromodulation affects craving and cannabis use patterns. A systematic search was conducted using PubMed, OVID Medline, and PsycINFO from inception to 20 December 2022. Our review identified ten relevant studies, eight of which used Transcranial Magnetic Stimulation (TMS), while two employed Transcranial Direct Current Stimulation (tDCS). Findings from TMS studies suggest that cannabis users exhibit altered cortical inhibition, with decreased short interval intracortical inhibition (SICI) compared to non-users. Single sessions of rTMS did not have any impact on cannabis craving. By contrast, two studies found that multiple sessions of rTMS reduced cannabis use, but these changes did not meet the threshold for statistical significance and both studies were limited by small sample sizes. The two included tDCS studies found contradictory results, with one showing reduced cannabis craving with active treatment and another showing no effect of active treatment on craving compared to sham. Future studies should further explore the effects of multiple treatment sessions and different neuromodulation modalities.

Young adults have historically high levels of cannabis use at a time which coincides with emotional and cognitive development. Age of regular onset of cannabis use and sex at birth are hypothesized to influence the relationship between cannabis use and cognition. Here we investigated past 6-month cannabis use in relation to emotional and executive functioning. We further considered age of onset and sex in subgroup analyses.

The majority of schizophrenia-affected individuals display deficiencies in multiple cognitive domains such as attention, working memory, long-term memory, and learning, deficiencies that are stable throughout the disease. The purpose of this narrative review was to examine the effect of antipsychotics on several cognitive domains affected by schizophrenia. We searched MEDLINE, Elsevier, Scopus, and DOAJ databases for randomized controlled trials and other studies investigating the effects of typical and atypical antipsychotics on cognition in patients with schizophrenia in studies conducted in the last decade. The majority of studies included in this review showed that antipsychotics (especially SGAs) have positive effects on both cognition and general psychopathology of schizophrenia. We mention that treatment with antipsychotic substances represents an ongoing effort of the researchers, who are constantly searching for the best approach to meet the mental health needs of schizophrenia patients. Even with those positive results, it should be noted that more studies are needed in order to fully observe the various effects of certain antipsychotic substances on cognition.

Research has shown that both parenting and emotional dysregulation are associated with mental health outcomes in youth. This cross-sectional research was developed to replicate these noted findings and explore the mediating role of emotional dysregulation to explain the relationship between parenting and emotional and behavioral difficulties (internalizing and externalizing problems) in adolescents. A total of 104 adolescents (61.5% females; M = 15.62 yrs., SD = 1.38) participated in the study. Participants completed the Parental Bonding Instrument (measuring care, promotion of autonomy, and overprotection) referring to both the mother and father, the Difficulties in Emotion Regulation Scale, and the Youth Self-Report. The results showed that difficulties in emotion regulation fully mediated the relationship between overprotection (in both parents) and low maternal care with internalizing problems, on the one hand, and the relationship between maternal overprotection and low care (in both parents) with externalizing problems, on the other hand. Furthermore, emotional dysregulation partially mediated the effect of paternal care on internalizing problems. These findings help to clarify one of the mechanisms through which parenting can affect mental health in youth. Theoretical and clinical implications are discussed.

The impact of the COVID-19 pandemic on young people with eating disorders (EDs) and their families was profound, with surging rates of hospitalizations and referrals reported internationally. This paper provides an account of the additional health and social costs of ED care for young people living in Canada incurred during the COVID-19 pandemic, drawing attention to the available data to inform these estimates while noting gaps in data capacities to account for a full view of the ED system of care.

Atypical Anorexia Nervosa (AAN) is a Feeding and Eating Disorder characterized by fear of gaining weight and body image disturbance, in the absence of significantly low body weight. AAN may present specific clinical and psychopathological features. Nonetheless, the literature lacks data concerning the nutritional characteristics and body composition of children and adolescents with AAN and their variation over time.

Evidence suggests an association between exposure to electronic cigarette (e-cigarette) marketing and e-cigarette use (vaping) among adolescents. However, there is limited evidence on exposure to e-cigarette marketing and susceptibility to future vaping, especially among Black and Latino adolescents. This study aimed to examine associations between exposure to e-cigarette marketing and susceptibility to future vaping among Black and Latino adolescents in the United States (US). Participants (N = 362; equal representation between Black and Latino adolescents) completed a baseline assessment (available in English and Spanish) including sociodemographic characteristics (e.g., racial/ethnic group, age, gender, sexual orientation, etc.), exposure to e-cigarette marketing, and susceptibility to future vaping. Exposure to e-cigarette marketing was recoded and organized into two categories (high exposure = 2 to 3; low exposure = 0 to 1). Cochran-Mantel-Haenszel tests were used to evaluate the association between exposure to e-cigarette marketing and susceptibility to future vaping, stratified by racial/ethnic group. Multiple logistic regressions assessed the association between exposure to e-cigarette marketing and susceptibility to future vaping, controlling for gender, sexual orientation, grade, and academic performance within each racial/ethnic group. Black adolescents reported significantly higher frequencies of exposure to e-cigarette marketing ( = 0.005). A significant interaction was found between exposure to e-cigarette marketing and racial/ethnic group (X (1) = 6.294, = 0.012). Among Black adolescents, high exposure to e-cigarette marketing (vs. low exposure) was associated with a higher probability of susceptibility to future vaping (OR: 2.399, 95% CI 1.147-5.021, = 0.020). For Latino adolescents, exposure to e-cigarette marketing was not associated with susceptibility to future vaping (OR: 0.503, 95% CI 0.245-1.03, = 0.062). Future studies should evaluate how and where adolescents are exposed to e-cigarette marketing. Prevention efforts must include the implementation of effective counter-marketing campaigns and the reduction of exposure to e-cigarette marketing among Black and Latino adolescents.

Schizophrenia is a severe, chronic neuropsychiatric disorder characterized by symptoms that profoundly impact behavior, cognition, perception, and emotions, leading to a reduced quality of life and physical impairment. Given the complexity of schizophrenia, there is a pressing need for clinical markers and tools to predict its course, enhance disease staging, facilitate early intervention, improve differential diagnosis, and tailor individualized treatment approaches. Previous studies focused on the relationship between neurological soft signs (NSS) and factors such as age, illness duration, and symptomatology, indicating NSS as state markers improving in parallel with psychotic symptom remission or predicting treatment resistance. However, there is a lack of consensus on NSS assessment tools, hindering routine clinical monitoring despite diagnostic and prognostic potential. The present longitudinal study involved 81 psychiatric inpatients diagnosed with schizophrenia. Patients were assessed at three time points: baseline, 1 month, and 6 months. The examination included the use of scales to evaluate psychotic and neurological symptoms, as well as the identification of adverse extrapyramidal reactions caused by neuroleptic treatment. The progression of NSS was correlated to both the symptomatology and the sociodemographic data of the patients. The main findings from the present investigation revealed a statistical correlation between NSS and psychopathological symptoms, especially with negative symptoms of schizophrenia. However, it is important to note that neuroleptic side effects only had a limited impact on NSS. Therefore, instead of being linked to extrapyramidal symptoms caused by neuroleptics, NSS appears to be more frequently related with symptoms of schizophrenia. Our findings provide further support for their strong association with the course of schizophrenia, independent of treatment side effects, thus emphasizing their potential as reliable assessment tools in both research and clinical settings.

It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and β-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction.

Until recently, no disease-specific health-related quality of life (HRQoL) questionnaire existed for pediatric traumatic brain injuries (TBIs). In this revalidation study, the psychometric properties and the validity of the 35-item QOLIBRI-KID/ADO questionnaire in its final German version were examined in 300 children and adolescents. It is the first self-reported TBI-specific tool for measuring pediatric HRQoL in individuals aged between 8 and 17 years. The six-factor model fits the data adequately. The questionnaire's internal consistency was excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability, and the measure's construct validity was supported by the overlap between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. The discriminant validity tests showed that older children and girls reported a significantly lower HRQoL than comparison groups, and this was also true of children who were anxious or depressed, or who suffered from post-concussion symptoms, replicating the results of the questionnaire's first developmental study. Our results suggest that the QOLIBRI-KID/ADO is a reliable and valid multidimensional tool that can be used together with the adult version in clinical contexts and research to measure disease-specific HRQoL after pediatric TBI throughout a person's life. This may help improve care, treatment, daily functioning, and HRQoL after TBI.

Studying individuals with varying symptoms, from mild to severe, can provide valuable insights into the spectrum of cognitive outcomes after COVID-19. We investigated the cognitive performance of adults who recovered from the novel coronavirus disease (COVID-19) without prior cognitive complaints, considering mild (not hospitalized), moderate (ward), and severe (intensive care unit) symptoms.

Avoidant Restrictive Food Intake Disorder (ARFID) is a new diagnosis added to the DSM-5 characterized by pathological eating habits without body image disturbances. Previous findings demonstrated a general association between high levels of perfectionism and low levels of self-esteem in association with general eating disorders. However, research is scant when it comes to ARFID specifically. Subsequently, although self-esteem is seen to moderate the association between perfectionism and general eating disorders, this research study aims to explore the same moderation but with ARFID specifically.

Major depressive disorder is a severe mood disorder associated with a marked decrease in quality of life and social functioning, accompanied by a risk of suicidal behavior. Therefore, seeking out and adhering to effective treatment is of great personal and society-wide importance. Weight changes associated with antidepressant therapy are often cited as the reason for treatment withdrawal and thus are an important topic of interest. There indeed exists a significant mechanistic overlap between depression, antidepressant treatment, and the regulation of appetite and body weight. The suggested pathomechanisms include the abnormal functioning of the homeostatic (mostly humoral) and hedonic (mostly dopaminergic) circuits of appetite regulation, as well as causing neuromorphological and neurophysiological changes underlying the development of depressive disorder. However, this issue is still extensively discussed. This review aims to summarize mechanisms linked to depression and antidepressant therapy in the context of weight change.

The relationship between cerebral rhythms and early sensorimotor development is not clear. In recent decades, evidence revealed a rhythmic modulation involving sensorimotor processing. A widely corroborated functional role of oscillatory activity is to coordinate the information flow across sensorimotor networks. Their activity is coordinated by event-related synchronisation and desynchronisation in different sensorimotor rhythms, which indicate parallel processes may be occurring in the neuronal network during movement. To date, the dynamics of these brain oscillations and early sensorimotor development are unexplored. Our study investigates the relationship between the cerebral rhythms using EEG and a typical rhythmic movement of infants, the non-nutritive sucking (NNS) behaviour. NNS is an endogenous behaviour that originates from the suck central pattern generator in the brainstem. We find, in 17 infants, that sucking frequency correlates with beta synchronisation within the sensorimotor area in two phases: one strongly anticipating (~3 s) and the other encompassing the start of the motion. These findings suggest that a beta synchronisation of the sensorimotor cortex may influence the sensorimotor dynamics of NNS activity. Our results reveal the importance of rapid brain oscillations in infants and the role of beta synchronisation and their possible role in the communication between cortical and deep generators.

Dandy-Walker complex (DWC) consists of a continuum of brain malformations involving the posterior fossa, often leading to psychiatric manifestations during adulthood. We discussed the case of a young woman with Dandy-Walker variant (DWV) and a comorbid complex neuropsychiatric presentation, who was diagnosed with an eating disorder, obsessive-compulsive disorder, and a tic disorder. Afterwards, we conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review reappraising all evidence of psychiatric outcomes in adults with DWC. Overall, 34 studies were eligible for data extraction, comprising 36 patients. Psychiatric profiles were more common among young adult males, with DWC lesions, especially DWV subtype, being often discovered incidentally after admission to mental health inpatient facilities. Most patients were diagnosed with psychosis and bipolar disorder, often comorbid with cognitive impairment. Psychotropic polypharmacy was frequently prescribed, generally leading to complete recovery. Evidence from our case report and systematic review indicates the importance of monitoring long-term psychiatric sequelae among adult patients with DWC malformations.

Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are two common and impairing neurodevelopmental conditions with partial symptomatic overlap. The aim of this study is to systematically and meta-analytically examine the following: (i) the prevalence of an OCD diagnosis among young people with ASD, (ii) the prevalence of an ASD diagnosis among young people with OCD, and (iii) the clinical and therapeutic implications of such comorbidity.

To study sociodemographic and clinical variables, including psychiatric co-morbidities, in patients with irritable bowel syndrome.

Fatigue is a common non-motor symptom in Parkinson's disease (PD), but even so, it may still be underdiagnosed or misdiagnosed in current practice due to its non-specific manifestations. The aims of this study were to investigate the prevalence of fatigue in PD patients compared to healthy controls and to identify the main characteristics and associations of fatigue with other non-motor symptoms and the impact of fatigue on sleep disturbances in Parkinson's disease.

The corticobasal syndrome (CBS) is a complex asymmetric movement disorder, with cognitive impairment. Although commonly associated with the primary 4-repeat-tauopathy of corticobasal degeneration, clinicopathological correlation is poor, and a significant proportion is due to Alzheimer's disease (AD). Synaptic loss is a pathological feature of many clinical and preclinical tauopathies. We therefore measured the degree of synaptic loss in patients with CBS and tested whether synaptic loss differed according to β-amyloid status.

Methamphetamine is a highly stimulating psychoactive drug that causes life-threatening addictions and affects millions of people around the world. Its effects on the brain are complex and include disturbances in the neurotransmitter systems and neurotoxicity. There are several known treatment methods, but their effectiveness is moderate. It must be emphasised that no drugs have been approved for treatment. For this reason, there is an urgent need to develop new, effective, and safe treatments for methamphetamine. One of the potential treatments is mindfulness meditation. In recent years, this technique has been researched extensively in the context of many neurological and psychiatric disorders.

Understanding the organization of neural processing is a fundamental goal of neuroscience. Recent work suggests that these systems are organized as a multiscale hierarchy, with increasingly specialized subsystems nested inside general processing systems. Current neuroimaging methods, such as independent component analysis (ICA), cannot fully capture this hierarchy since they are limited to a single spatial scale. In this manuscript, we introduce multiresolution hierarchical principal components analysis (hPCA) and compare it to ICA using simulated fMRI datasets. Furthermore, we describe a parametric statistical filtering method developed to focus analyses on biologically relevant features. Lastly, we apply hPCA to the Human Connectome Project (HCP) to demonstrate its ability to estimate a hierarchy from real fMRI data. hPCA accurately estimated spatial maps and time series from networks with diverse hierarchical structures. Simulated hierarchies varied in the degree of branching, such as two-way or three-way subdivisions, and the total number of levels, with varying equal or unequal subdivision sizes at each branch. In each case, as well as in the HCP, hPCA was able to reconstruct a known hierarchy of networks. Our results suggest that hPCA can facilitate more detailed and comprehensive analyses of the brain's network of networks and the multiscale regional specializations underlying neural processing and cognition.

Transcranial magnetic stimulation coupled with electroencephalography (TMS-EEG) allows for the study of brain dynamics in health and disease. Cranial muscle activation can decrease the interpretability of TMS-EEG signals by masking genuine EEG responses and increasing the reliance on preprocessing methods but can be at least partly prevented by coil rotation coupled with the online monitoring of signals; however, the extent to which changing coil rotation may affect TMS-EEG signals is not fully understood. Our objective was to compare TMS-EEG data obtained with an optimal coil rotation to induce motor evoked potentials (M1) while rotating the coil to minimize cranial muscle activation (M1). TMS-evoked potentials (TEPs), TMS-related spectral perturbation (TRSP), and intertrial phase clustering (ITPC) were calculated in both conditions using two different preprocessing pipelines based on independent component analysis (ICA) or signal-space projection with source-informed reconstruction (SSP-SIR). Comparisons were performed with cluster-based correction. The concordance correlation coefficient was computed to measure the similarity between M1 and M1 TMS-EEG signals. TEPs, TRSP, and ITPC were significantly larger in M1 than in M1 conditions; a lower CCC than expected was also found. These results were similar across the preprocessing pipelines. While rotating the coil may be advantageous to reduce cranial muscle activation, it may result in changes in TMS-EEG signals; therefore, this solution should be tailored to the specific experimental context.

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health. Finally, the review discusses public health initiatives and efforts to reduce the hazards of synthetic cathinones, including harm reduction methods, education, and current clinical management strategies.

Obsessive-compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insights of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas the severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need for additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and an extraordinary supply of essential resources.

Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex (L-DLPFC) for enhancing cognitive flexibility based on performance on a cognitive task. First, forty healthy participants had their single target site at the L-DLPFC determined based on each individual's performance on a random letter generation task. Participants then received, in a cross-over single-blinded experimental design, a single session of intermittent theta burst stimulation (iTBS) to their individualised DLPFC target site, an active control site and sham iTBS. Following each treatment condition, participants completed the Task Switching task and Colour-Word Stroop test. There was no significant main effect of treatment condition on the primary outcome measure of switch reaction times from the Task Switching task [F = 1.16 (2, 21.6), = 0.33] or for any of the secondary cognitive outcome measures. The current results do not support the use of our novel individualised targeting methodology for enhancing cognitive flexibility in healthy participants. Research into alternative methodological targeting approaches is required to further improve rTMS's cognitive enhancing effects.

General food frequency questionnaires (FFQs) have not been tailored for or validated in individuals with psychiatric disorders. Given the unique eating behaviors of patients with serious mental illnesses (SMIs), custom-made tools are needed. Therefore, we developed and validated an FFQ customized to individuals with SMIs. A total of 150 adults with SMIs (schizophrenia, bipolar disorder, or major depression) were recruited from Bahrain. The participants completed the 50-item Dietary Intake Evaluation Questionnaire for Serious Mental Illness (DIETQ-SMI) FFQ and a 3-day food record (FR). The validity of the FFQ was assessed by comparing nutrient intake to FR intake using correlation and reliability statistics. The DIETQ-SMI demonstrated a good ranking validity compared to the FR based on correlation coefficients (rho 0.33 to 0.92) for energy and macro- and micronutrients. The FFQ had high internal consistency (McDonald's omega = 0.84; Cronbach's alpha = 0.91) and test-retest reliability (ICC > 0.90). The FFQ tended to estimate higher absolute intakes than the FR but adequately ranked the intakes. The FFQ value was correlated with the FR for all the items ( < 0.001). The DIETQ-SMI is a valid and reliable FFQ for ranking dietary intake in individuals with an SMI. It can help assess nutritional status and, subsequently, guide interventions in high-risk psychiatric populations.

Posttraumatic stress disorder (PTSD) is a widespread fear-related psychiatric affection associated with fear extinction impairments and important avoidance behaviors. Trauma-related exposure therapy is the current first-hand treatment for PTSD, yet it needs to be improved to shorten the time necessary to reach remission and increase responsiveness. Additional studies to decipher the neurobiological bases of extinction and effects on PTSD-like symptoms could therefore be of use. However, a PTSD-like animal model exhibiting pronounced PTSD-related phenotypes even after an extinction training directly linked to the fearful event is necessary. Thus, using a contextual fear conditioning model of PTSD, we increased the severity of stress during conditioning to search for effects on extinction acquisition and on pre- and post-extinction behaviors. During conditioning, mice received either two or four electrical shocks while a control group was constituted of mice only exposed to the context. Stressed mice exhibited important fear generalization, high fear reaction to the context and selective avoidance of a contextual reminder even after the extinction protocol. Increasing the number of footshocks did not induce major changes on these behaviors.

Head and neck cancer (HNC) is associated with significant morbidity globally, with smoking recognized as a key risk factor. This study investigates the interplay between smoking and inflammatory biomarkers in HNC development. The study involved 50 HNC patients, divided into smoking and non-smoking groups, and a control group of 30 healthy individuals. Serum levels of 48 cytokines, chemokines, growth factors, and other inflammatory markers were meticulously assessed. Significant differences in the levels of an extensive panel of inflammatory markers were observed between the patient groups and healthy controls. Elevated macrophage colony-stimulating factor (M-CSF) in both HNC groups implicated increased activity in pathways known for immunomodulation, proliferation, and angiogenesis during HNC cancerogenesis. In contrast, non-smokers with HNC demonstrated higher levels of interleukin 10 (IL-10) and interleukin 15 (IL-15), suggesting a more robust immune response. Platelet-derived growth factor BB (PDGF-BB) levels were particularly high in smokers with HNC. Smoking seems to alter the levels of crucial biomarkers in HNC, potentially affecting disease progression and responses to treatment. The data indicate that smokers may experience a more aggressive cancer phenotype, while non-smokers maintain a profile suggestive of a more active and effective immune response against HNC.

Mean platelet volume (MPV), which represents the average platelet size in femtoliters, has emerged as a reliable biomarker in several systemic and chronic disorders. However, its relationship with disease characteristics in large series of patients with systemic lupus erythematosus (SLE) has not been exhaustively studied to date. In the present work, we aimed to analyze how disease characteristics, including disease activity and cumulative damage, relate to MPV in a well-characterized series of SLE patients. In total, 179 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood counts including MPV were assessed. Linear multivariable analysis was performed to evaluate the relationship between MPV and SLE disease characteristics, including composite scores of disease activity and damage. MPV was significantly lower in patients with SLE compared to controls after multivariable analysis (beta coefficient, -0.7 [95% confidence interval, -1.1 to -0.3)] fL, < 0.001). Although the SLEDAI disease activity index was not related to MPV, the SLICC score measuring cumulative disease damage was significantly associated with lower MPV values after adjustment for covariates. Elements of the SLICC score that were associated with lower MPV levels were those pertaining to the kidney, peripheral vascular, and musculoskeletal manifestations of the disease. In conclusion, MPV is lower in patients with SLE compared to matched controls. This MPV downregulation is primarily due to the renal, peripheral vascular and musculoskeletal manifestations of the disease. MPV may represent a biomarker of accrual disease damage in SLE.

The e4 allele of the apolipoprotein E gene is the strongest genetic risk factor for sporadic Alzheimer's disease. Nevertheless, how is regulated is still elusive. In a -eQTL analysis, we found a genome-wide significant association between transmembrane protein 106B () genetic variants and cortical mRNA levels in human brains. The goal of this study is to determine whether TMEM106B is mis-regulated in Alzheimer's disease or in other neurodegenerative conditions. Available genomic, transcriptomic and proteomic data from human brains were downloaded from the Mayo Clinic Brain Bank and the Religious Orders Study and Memory and Aging Project. An in-house mouse model of the hippocampal deafferentation/reinnervation was achieved via a stereotaxic lesioning surgery to the entorhinal cortex, and mRNA levels were measured using RNAseq technology. In human temporal cortices, the mean TMEM106B expression was significantly higher in Alzheimer's disease compared to cognitively unimpaired individuals. In the mouse model, hippocampal reached maximum levels during the early phase of reinnervation. These results suggest an active response to tissue damage that is consistent with compensatory synaptic and terminal remodeling.

(1) Objective: This systematic review explores the intricate relationship between cyberbullying and non-suicidal self-injury (NSSI) in adolescents, acknowledging the dynamic nature of these phenomena in the evolving landscape of technology and social norms. (2) Methods: PubMed/MEDLINE, Web of Science, and EMBASE were searched, and 14 studies were selected based on the eligibility criteria, focusing on participants aged 10 to 19, cyberbullying roles, and NSSI as the predictor and outcome variables, respectively. (3) Results: Internalizing symptoms, specifically depression and anxiety, emerged as the most prominent mediators. However, factors such as externalizing symptoms, stress, and negative emotional responses (emotion reactivity, negative emotions) were also identified to play a significant role in the relationship between cyberbullying and NSSI. On the other hand, protective factors against the negative impact of cyberbullying on NSSI risk, such as strong peer connections and school engagement, were identified. (4) Discussions: This review underscores the multidimensional nature of the cyberbullying-NSSI association, emphasizing the roles of potential risk factors such as internalizing and externalizing symptoms, stress, and negative emotional response. Internalizing symptoms played a central role as pathways between cyberbullying victimization and NSSI. Additionally, social factors, including peer connections and school engagement, were found to act as protective elements. (4) Conclusion: Continuous investigation is crucial in order to adapt interventions to the evolving technological and social landscape. The study advocates for targeted interventions that prioritize positive social connections to mitigate the impact of cyberbullying on adolescent well-being.

Cancers and neurological disorders are two major types of diseases in humans. We developed the concept called the "Aberrant Cell Cycle Disease (ACCD)" due to the accumulating evidence that shows that two different diseases share the common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncoprotein activation and tumor suppressor (TS) inactivation, which are associated with both tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase/oncogene inhibition and TS elevation) can be leveraged for neurological treatments. MicroRNA (miR/miRNA) provides a new style of drug-target binding. For example, a single tumor suppressor miRNA (TS-miR/miRNA) can bind to and decrease tens of target kinases/oncogenes, producing much more robust efficacy to block cell cycle re-entry than inhibiting a single kinase/oncogene. In this review, we summarize the miRNAs that are altered in both cancers and neurological disorders, with an emphasis on miRNA drugs that have entered into clinical trials for neurological treatment.

Children from vulnerable backgrounds often have insecure attachment or disorganized attachment, which are related to psychological troubles, and such children need interventions to help them heal. The attachment system reorganizes in middle childhood, and other important adults play a considerable role in children's lives. Thus, it is essential to weigh the impact of psychosocial interventions, while the main focus of the intervention is the staff member's direct work with the child through a trusting relationship. The primary purpose of this study is to investigate whether children's attachment security and mental health outcomes change after participating in a trauma-informed, attachment-based, Trust-Based Relational Intervention (TBRI) provided in a daycare center. It was a case-series study involving twelve children aged 8-11 years. The child attachment interview (CAI), CBCL/6-18, TRF/6-18, and clinical interviews for parents and children were used, measuring the change between the TBRI implementation in the daycare center and after one year. For ten participants, we noticed an improvement in mental health; for seven participants, security scales improved; for two participants, their disorganized attachment changed into insecure-dismissing. We have preliminary evidence that vulnerable children may benefit in terms of attachment security and mental health from the trusting relationship that staff build using the TBRI.

Among the most vulnerable to the health-harming effects of heat are people experiencing homelessness. However, during the 2021 Heat Dome, the deadliest extreme heat event (EHE) recorded in Canada to date, people experiencing homelessness represented the smallest proportion of decedents (n = 3, 0.5%)-despite the impacted region (British Columbia) having some of the highest rates of homelessness in the country. Thus, we sought to explore the 2021 Heat Dome as a media-based case study to identify potential actions or targeted strategies that were initiated by community support agencies, individuals and groups, and communicated in the news during this EHE that may have aided in the protection of this group or helped minimize the mortality impacts. Using media articles collated for a more extensive investigation into the effects of the 2021 Heat Dome (n = 2909), we identified a subset which included content on people experiencing homelessness in Canada (n = 274, 9%). These articles were thematically analysed using NVivo. Three main themes were identified: (i) public warnings issued during the 2021 Heat Dome directly addressed people experiencing homelessness, (ii) community support services explicitly targeting this population were activated during the heat event, and (iii) challenges and barriers faced by people experiencing homelessness during extreme heat were communicated. These findings suggest that mass-media messaging and dedicated on-the-ground initiatives led by various organizations explicitly initiated to support individuals experiencing homelessness during the 2021 Heat Dome may have assisted in limiting the harmful impacts of the heat on this community.

The pathophysiological mechanisms underlying migraine are more difficult to investigate in children than in the adult population. Abnormal cortical excitability turns out to be one of the most peculiar aspects of migraine, accounting for the manifestations of migraine attacks. Recently, visual cortical excitability has been explored effectively in adult migraineurs with a technique based on cross-modal audio-visual illusions (with sound-induced flash illusions (SIFIs) being reduced in migraineurs compared to non-migraineur subjects). On such a basis, in this study, we investigated visual cortical excitability in children with migraine using SIFIs using combinations of visual and sound stimuli presented randomly. We evaluated 26 children with migraine without aura and 16 healthy children. Migraineurs did not differ from the age-matched healthy subjects regarding fission or fusion illusions but perceived more flashes in trials of multiple flashes with or without beeps. The higher number of SIFIs in migraineur children compared to adults may be due to a greater propensity of visual stimulation to be driven by auditory stimuli (i.e., acoustic dominance). The increased ability to perceive flashes reveals a hyperfunctional visual cortex, demonstrating that the use of SIFIs is a valid tool for assessing visual cortical responsiveness even in pediatric migraine.

Syndromic autism refers to autism spectrum disorder diagnosed in the context of a known genetic syndrome. The specific manifestations of any one of these syndromic autisms are related to a clinically defined genetic syndrome that can be traced to certain genes and variants, genetic deletions, or duplications at the chromosome level. The genetic mutations or defects in single genes associated with these genetic disorders result in a significant elevation of risk for developing autism relative to the general population and are related to recurrence with inheritance patterns. Additionally, these syndromes are associated with typical behavioral characteristics or phenotypes as well as an increased risk for specific behavioral or psychiatric disorders and clinical findings. Knowledge of these associations helps guide clinicians in identifying potentially treatable conditions that can help to improve the lives of affected patients and their families.

This study examined associations between COVID-19-related anxiety and sleep in middle-aged and older adults and tested whether these varied by age or sex. In June/July 2020, middle-aged/older adults aged 50+ ( = 277, 45% women, M = 64.68 ± 7.83) in the United States completed measures of sleep and COVID-19-related anxiety. Multiple regressions examined whether anxiety was independently associated with or interacted with age or sex in its associations with sleep health, controlling for age, education, medical conditions, sleep/pain medication use, and COVID-19 status. Greater COVID-19 anxiety was associated with worse sleep quality and daytime dysfunction. COVID-19-related anxiety interacted with age (not sex) in associations with total sleep time and sleep efficiency. Greater anxiety was associated with shorter total sleep time and lower sleep efficiency in oldest-older adults (~73 years old) and youngest-older adults (~65 years old) but not middle-aged adults (~57 years old). In mid to late life, older adults may be most vulnerable to the impact of COVID-19-related anxiety on sleep health. Social and behavioral (e.g., knowledge on age-related vulnerability to COVID-19 risk/morbidity/mortality, uncertainty, and changes to daily routines) and physiological factors (sleep disruption and age-related autonomic dysfunction) may underlie these associations. Interventions that mitigate negative pandemic-related psychological and sleep outcomes may be particularly relevant for older adults.

: The pandemic has proven to be a particular challenge for healthcare workers, not only in the professional but also individual sense. The COVID-19 pandemic negatively influenced their well-being and caused psychological distress. Undoubtedly, direct contact with sick patients, the fight against the pandemic, and observing the epidemiological situation influenced the attitudes of this group towards COVID-19 and vaccinations. The aim of the study was to analyse the level of anxiety among healthcare workers during the COVID-19 pandemic and to assess attitudes towards vaccinations against COVID-19. : The cross-sectional study followed the recommendations of STROBE (Strengthening the Reporting of Observational Studies in Epidemiology). A convenience purposive sampling method was used and the study was led among nurses and doctors employed in healthcare facilities. The study used a survey and the Trait Anxiety Scale SL-C. : The study included 385 participants, with an average age of 48.41 ± 6.76 years. The nurses constituted 55% of the study group and the doctors 45%. A total of 70% of healthcare workers had over 10 years of work experience. Over half of the subjects (57%) became infected with COVID-19. A total of 85% of respondents have received vaccination. A total of 71% of respondents believe vaccinations are harmless. Frequently, the participants assessed their level of anxiety as moderate. : Almost all surveyed doctors chose to be vaccinated, while the percentage of vaccinated nurses was significantly lower. As a result, it is possible to conclude that the employment position has a significant influence on the decision to get vaccinated against COVID-19. In self-assessment during the COVID-19 pandemic, most healthcare professionals experienced a moderate level of anxiety. Receiving the COVID-19 vaccination reduced the level of anxiety.

: Medical students represent the ideal target group for promoting mental health and mental wellbeing, being exposed to specific risk factors, such as the content of medical training, the exposure to sickness and death, and a stressful academic routine. Medical students report high levels of cynicism and emotional exhaustion, which represent two of the essential features of burnout syndrome. In this systematic review, studies assessing the levels of burnout among medical students through validated tools worldwide were analyzed. : A systematic review has been performed in order to identify studies: (1) focusing on samples of medical students; (2) evaluating burnout syndrome using validated tools; (3) providing prevalence data on burnout; and (4) written in English. : Out of the 5547 papers initially obtained, 64 were finally included in the analysis. The sample sizes ranged from 51 to 2682 participants. Almost all studies had a cross-sectional design; the Maslach Burnout Inventory and its related versions were the most frequently used assessment tools. The prevalence of burnout, which was stratified based on gender and academic stage, ranged from 5.6 to 88%. Burnout was mostly predicted by thoughts of stopping medical education, negative life events, lack of support, dissatisfaction, and poor motivation. : The prevalence of burnout syndrome in medical students is quite heterogeneous, reaching a peak of 88% in some countries. However, several predictors have been identified, including negative life events or poor motivation. These findings highlight the need to develop preventive interventions targeting the future generation of medical doctors, in order to improve their coping strategies and resilience styles.

Teledentistry offers possibilities for improving efficiency and quality of care and supporting cost-effective healthcare systems. This umbrella review aims to synthesize existing systematic reviews on teledentistry and provide a summary of evidence of its clinical- and cost-effectiveness. A comprehensive search strategy involving various teledentistry-related terms, across seven databases, was conducted. Articles published until 24 April 2023 were considered. Two researchers independently reviewed titles, abstracts and full-text articles. The quality of the included reviews was critically appraised with the AMSTAR-2 checklist. Out of 749 studies identified, 10 were included in this umbrella review. Two reviews focusing on oral-health outcomes revealed that, despite positive findings, there is not yet enough evidence for the long-term clinical effectiveness of teledentistry. Ten reviews reported on economic evaluations or costs, indicating that teledentistry is cost-saving. However, these conclusions were based on assumptions due to insufficient evidence on cost-effectiveness. The main limitation of our umbrella review was the critically low quality of the included reviews according to AMSTAR-2 criteria, with many of these reviews basing their conclusions on low-quality studies. This highlights the need for high-quality experimental studies (e.g., RCTs, factorial designs, stepped-wedge designs, SMARTs and MRTs) to assess teledentistry's clinical- and cost-effectiveness.

Pathogenic variants have been reported in probands with broad phenotypic presentations, including intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, seizures, congenital anomalies, and other skeletal, muscular, and sleep differences. Here, we review previously published individuals with pathogenic variants and report three further probands with novel variants and previously unreported phenotypic features, including mixed receptive language disorder and gait disturbances. These novel data from the Brain Gene Registry, an accessible repository of clinically derived genotypic and phenotypic data, have allowed for the expansion of the phenotypic and genotypic spectrum of this condition.

Artificial intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use, ChatGPT holds a prominent position, using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for generating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT integration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex datasets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.

Assessment of health-related quality of life (HRQoL) after pediatric traumatic brain injury (TBI) has been limited in children and adolescents due to a lack of disease-specific instruments. To fill this gap, the Quality of Life after Traumatic Brain Injury for Children and Adolescents (QOLIBRI-KID/ADO) Questionnaire was developed for the German-speaking population. Reference values from a comparable general population are essential for comprehending the impact of TBI on health and well-being. This study examines the validity of the German QOLIBRI-KID/ADO in a general pediatric population in Germany and provides reference values for use in clinical practice. Overall, 1997 children and adolescents aged 8-17 years from the general population and 300 from the TBI population participated in this study. The questionnaire was tested for reliability and validity. A measurement invariance (MI) approach was used to assess the comparability of the HRQoL construct between both samples. Reference values were determined by percentile-based stratification according to factors that significantly influenced HRQoL in regression analyses. The QOLIBRI-KID/ADO demonstrated strong psychometric properties. The HRQoL construct was measured largely equivalently in both samples, and reference values could be provided. The QOLIBRI-KID/ADO was considered reliable and valid for assessing HRQoL in a general German-speaking pediatric population, allowing for clinically meaningful comparisons between general and TBI populations.

22q11.2 Deletion Syndrome (22q11.2DS), the most common chromosomal microdeletion, presents as a heterogeneous phenotype characterized by an array of anatomical, behavioral, and cognitive abnormalities. Individuals with 22q11.2DS exhibit extensive cognitive deficits, both in overall intellectual capacity and focal challenges in executive functioning, attentional control, perceptual abilities, motor skills, verbal processing, as well as socioemotional operations. Heterogeneity is an intrinsic factor of the deletion's clinical manifestation in these cognitive domains. Structural imaging has identified significant changes in volume, thickness, and surface area. These alterations are closely linked and display region-specific variations with an overall increase in abnormalities following a rostral-caudal gradient. Despite the extensive literature developing around the neurocognitive and neuroanatomical profiles associated with 22q11.2DS, comparatively little research has addressed specific structure-function relationships between aberrant morphological features and deficient cognitive processes. The current review attempts to categorize these limited findings alongside comparisons to populations with phenotypic and structural similarities in order to answer to what degree structural findings can explain the characteristic neurocognitive deficits seen in individuals with 22q11.2DS. In integrating findings from structural neuroimaging and cognitive assessments, this review seeks to characterize structural changes associated with the broad neurocognitive challenges faced by individuals with 22q11.2DS.

The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus-like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.

New Psychoactive Substances (NPS) are modifying the drug scenario worldwide and have become a public health concern because of their toxicological profiles and their harmful physical/psychological effects. 3-Methoxy-Phencyclidine (3-MeO-PCP), a non-competitive antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors, belongs to the phencyclidine-like subfamily of arylcyclohexylamines and has gained attention for its toxic, sometimes fatal, effects. Despite several cases of intoxication and death reported in the literature, little is known about substance-induced psychotic disorders (SIP) and potential cognitive impairment following 3-MeO-PCP intake. This literature review aimed to summarize available evidence about 3-MeO-PCP mechanisms of action and physical and psychotropic effects and to spread preliminary findings about persistent psychotic symptoms and impaired cognitive functioning. Additionally, the case of an SIP is reported in a 29-year-old man with small oral intakes of 3-MeO-PCP over two weeks until a high dose ingestion. Psychometric and neuropsychological assessment and brain [F]-fluorodeoxyglucose positron emission tomography integrated with computed tomography were used to support clinical description. Identifying and addressing the characteristic clinical features and neural substrates of NPS-induced psychoses might help clinicians with a more precise differentiation from other psychotic disorders. Although further studies are required, phenotyping the cognitive profile of NPS users might provide targets for tailored therapeutic approaches.

The COVID-19 pandemic has been particularly challenging for the mental health of African American (AA) birthing people. The pandemic necessitated shifting mental health care to online interventions. The goals of this study were to (1) describe an adapted evidence-based group preventive intervention for AA mothers with young children within a pediatric setting and (2) evaluate the feasibility, acceptability, and preliminary effectiveness of this virtual intervention. Phase 1 describes the adaptation of the HealthySteps Mom's Virtual Wellness Group, including eight weekly sessions based on the Mothers and Babies Course. Phase 2 was a mixed-methods, pre-post intervention design. Six AA mothers with young children completed questionnaires related to depression, anxiety, and parenting competence at three time points: pre-intervention (T1), post-intervention (T2), and 3 months post-intervention (T3). The participants also completed a focus group post-T2 to gather qualitative feedback regarding the intervention. The median scores for depression were lower at T2 and increased at T3, and for anxiety, they increased at T2 and decreased at T3. The median scores for parenting competence increased across the three time points. The participants attended a mean of 7.2 sessions (SD = 0.74). The qualitative results indicate that the participants gained a sense of empowerment, enjoyed connecting with other mothers, and acquired information. This pilot study suggests that a virtual intervention is feasible, acceptable, and can increase parenting competence and support among AA mothers with young children.

In a digitally oriented society, smartphones provide continual online accessibility to daily life while simultaneously predisposing adolescents to engage in prolonged connections for various purposes, thus escalating the risk of Internet addiction (IA). Cognitive processes such as multitasking and attentional shifting are frequently associated with smartphone activities. Additionally, online engagements may serve as emotional strategies for regulating negative states (e.g., boredom and distress), redirecting attention towards more gratifying activities, such as social media contents. This study delves into cognitive-emotional processes (i.e., emotion regulation, attention impulsiveness, online vigilance, and multitasking) and emotional/behavioural factors (i.e., emotional problems, conduct problems, hyperactivity/inattention, peer relationships, and prosocial behaviours) that may be implicated in smartphone activities and technology addiction among adolescents. A community sample of Italian high school students (N = 676; 42.2% females) completed the Smartphone Distraction Scale (SDS), the Strength and Difficulties Questionnaire (SDQ) for internalising/externalising symptoms and the Internet Addiction Test (IAT) to assess the presence and severity of IA. The scores on the SDS were found to be positively associated with IA levels. Furthermore, students exhibiting higher internalising/externalising symptoms, particularly those with traits of attention deficit hyperactivity disorder (ADHD), are more likely to manifest problematic smartphone usage. The implications for screening adolescents more susceptible to developing IA symptoms and for implementing preventive interventions are discussed.

Research on mental health and psychosocial support (MHPSS) interventions within refugee and migrant communities has increasingly focused on evaluating implementation, including identifying strategies to promote retention in services. This study examines the relationship between participant characteristics, study setting, and reasons for intervention noncompletion using data from the Entre Nosotras feasibility trial, a community-based MHPSS intervention targeting refugee, migrant, and host community women in Ecuador and Panama that aimed to promote psychosocial wellbeing. Among 225 enrolled women, approximately half completed the intervention, with varying completion rates and reasons for nonattendance across study sites. Participants who were older, had migrated for family reasons, had spent more time in the study community, and were living in Panamá (vs. Ecuador) were more likely to complete the intervention. The findings suggest the need to adapt MHPSS interventions to consider the duration of access to the target population and explore different delivery modalities including the role of technology and cellular devices as reliable or unreliable source for engaging with participants. Engaging younger, newly arrived women is crucial, as they showed lower completion rates. Strategies such as consulting scheduling preferences, providing on-site childcare, and integrating MHPSS interventions with other programs could enhance intervention attendance.

Perinatal stress is associated with altered placental methylation, which plays a critical role in fetal development and infant outcomes. This proof-of-concept pilot study investigated the impact of lifetime trauma exposure and perinatal PTSD symptoms on epigenetic regulation of placenta glucocorticoid signaling genes ( and Lifetime trauma exposure and PTSD symptoms during pregnancy were assessed in a racially/ethnically diverse sample of pregnant women ( = 198). Participants were categorized into three groups: (1) No Trauma (-T); (2) Trauma, No Symptoms (T - S); and (3) Trauma and Symptoms (T + S). Placental tissue was analyzed via bisulfite pyrosequencing for degree of methylation at the promoter and regulatory regions. Analyses of covariance were used to test group differences in percentages of and methylation overall and at each CpG site. We found a significant impact of PTSD symptoms on placental methylation. Compared to the -T group, the T + S group had greater methylation overall and at CpG6, CpG8, CpG9, and CpG13, but lower methylation at CpG5. The T + S group had significantly higher N methylation overall and at CpG8 compared to the T - S group. There were no differences between the T - S group and - T group. Additionally, no group differences emerged for methylation. Pregnant trauma survivors with PTSD symptoms exhibited differential patterns of placental methylation compared to trauma survivors without PTSD symptoms and pregnant women unexposed to trauma. Results highlight the critical importance of interventions to address the mental health of pregnant trauma survivors.