The 16p11.2 deletion is one of the most frequent recurrent copy number variations associated with a broad neurodevelopmental and phenotypic spectrum. Despite its relatively well-characterized genomic region, clinical expressivity remains highly variable, posing challenges for diagnosis and management. We conducted a retrospective single-centre study of 25 individuals with molecularly confirmed 16p11.2 deletions, including 13 males (52%), 12 females (48%), and 7 familial (28%). Both de novo and inherited cases were included. The main testing method was chromosomal microarray, although karyotyping and additional tests such as sequencing and trinucleotide repeat testing were also utilized. Comprehensive clinical data were collected from medical records, including neurodevelopmental, neuropsychiatric, metabolic, skeletal, and systemic features. The majority of the cases had the typical ~600 kilobase deletion while two had distal ~220kb deletion. One patient was found to have a double genetic diagnosis. Developmental delay was almost universal in the probands, with expressive language significantly more impaired than receptive language abilities. Intellectual disability / learning difficulties and language problems were observed in 18/25 (72%) cases. Around half of the probands showed obesity and related hyperphagia. Autism spectrum disorder, attention deficit hyperactivity disorder, stereotypic movements, and aggressive behaviour were frequently reported. Epilepsy was present in thirteen patients (52%), with electroencephalographic abnormalities supporting generalized or focal epileptiform activity. Dysmorphic facial features and skeletal anomalies such as pes equinovarus, syndactyly, and scoliosis were variably present. Brain magnetic resonance imaging revealed abnormalities in several patients, including hypoplasia of the corpus callosum and intracranial hypertension. Additional systemic findings included hepatic steatosis, constipation, and ophthalmologic anomalies. Parental testing revealed asymptomatic or mildly affected carriers in multiple cases. Our findings emphasize the broad and heterogeneous clinical spectrum of 16p11.2 deletions in a Turkish cohort. Early recognition, multidisciplinary evaluation, and family-based genetic counselling are essential for timely diagnosis and optimal care of affected individuals.
Adolescents living with HIV often experience poor antiretroviral therapy (ART) outcomes due to multiple barriers affecting medication adherence. Effective self-care interventions are needed to address these challenges. Mobile phones are widely used by the adolescent population and therefore present an opportunity to enhance ART adherence using mobile phone-based interventions. However, research on mobile phone access among adolescents living with HIV, usage patterns, and perceptions of mobile phone-based interventions is limited in Eswatini. This study aimed to explore these aspects to inform effective mobile health strategies for enhancing ART adherence among adolescents living with HIV. We conducted a qualitative study using in-depth interviews in December 2023. A total of 29 adolescents living with HIV aged 10 to 19 years and enrolled on ART were purposively sampled and interviewed from 5 Teen Clubs in the Hhohho region of Eswatini. Interviews were audio-recorded and transcribed verbatim. Topic areas covered were mobile phone accessibility, usage patterns, and perceptions on the use of mobile phones to facilitate ART adherence. The data were analyzed using the deductive-inductive coding approach. Of the 29 participants, 15 (52%) were female, and 19 (65.5%) were aged between 15 and 19 years. The study findings indicated high mobile phone access among participants, with primary usage focused on making and receiving calls, as well as engaging with social media. Three themes emerged regarding the use of gamified interventions to support ART adherence. First, the use of gamified interventions aimed at ART adherence among adolescents living with HIV was deemed feasible based on mobile phone access and past experiences with mobile games. Second, 3 main qualities of successful gamified interventions were identified as being supportive, being educational, and ensuring secure and confidential connections with other players. Finally, confidentiality and mobile phone access factors were highlighted as potential concerns when designing gamified ART adherence interventions. The findings suggest potentially high access and usage of mobile phones among adolescents living with HIV on ART in Eswatini. This provides an opportunity to leverage mobile technology to enhance ART adherence through gamified interventions. However, it is essential to carefully consider the specific needs and concerns of adolescents living with HIV in the design of these interventions to ensure their successful uptake and sustainability.
Long COVID is a debilitating condition consisting of prolonged neurological symptoms such as cognitive impairment ('brain fog') and sleep disturbance. Symptoms may be associated with ongoing neuroinflammation from the persistence of a viral reservoir, activation of other viruses, protracted macrophagic inflammatory memory or enduring viral Spike protein that stimulates proinflammatory cytokines via toll-like receptor (TLR) signalling. Bezisterim (NE3107) is an oral, blood-brain barrier-permeable, anti-inflammatory, insulin-sensitising dehydroepiandrosterone derivative that inhibits TLR-driven neuroinflammation and is being developed for neurodegenerative diseases in which TLR-driven inflammation contributes to cognitive decline. ADDRESS-LC (NCT06847191) is a phase 2, triple-blind, placebo-controlled, randomised proof-of-concept study to evaluate the efficacy and safety of bezisterim in adults with long COVID. This multicentre study will recruit 208 adults (aged 18-69 years) with symptoms of fatigue and neurocognitive impairment for at least 3 months following an index SARS-CoV-2 infection. Individuals who meet all eligibility criteria will be randomised 1:1 to receive bezisterim 20 mg or placebo two times per day for 12 weeks. Cognition, fatigue, sleep, post-exertional malaise, quality of life and burdensome symptoms will be evaluated via several assessments, including a bespoke Cogstate Cognition Battery, Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function Short Form (SF)-8a, PROMIS Fatigue SF-13a and Patient's Global Impression of Severity, among others. The protocol has been approved by an institutional review board prior to study initiation. The study is being conducted at multiple clinical research sites across the USA. A current list of participating study sites is publicly available through the ClinicalTrials.gov registration record (NCT06847191). The study protocol has received central institutional review board approval (Advarra #Pro00081088), and participating sites obtained the necessary approvals and agreements required for study conduct and data access in accordance with applicable regulations and Good Clinical Practice guidelines. Authorised representatives of the sponsor, regulatory authorities and ethics committees may access study-related records for monitoring, auditing and regulatory purposes consistent with participant informed consent. The study will disseminate results through academic publication and conference presentations. NCT06847191.
To estimate the prevalence of cannabis use among adults attending primary care, identify the age of initiation and associated sociodemographic characteristics, and describe patterns of dependence risk. A cross-sectional descriptive study was conducted in three primary healthcare centres in the Barcelona metropolitan area. Adults aged 18 - 45 years were selected by simple random sampling. Telephone interviews used cannabis related questions from the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), validated by the World Health Organization. Cannabis use prevalence and dependence risk were analysed by sociodemographic characteristics using multiple logistic regression. Of 237 individuals contacted, 221 participated (93.25%). Among the participants, 58.8% were women, with a mean age of 33.5 years (SD = 8.1). Overall, 53.4% had used cannabis at least once in their lifetime, with a mean age of initiation of 18.4 years (SD = 4.1). Among lifetime users, 25.4% had a moderate risk of dependence. After adjustment for age and socioeconomic status, cannabis use was more likely among men than women (OR = 2.11; 95% CI: 1.21-3.72). Overall, 22.9% had used cannabis within the previous three months, and 81.5% of these users had a moderate risk of dependence. Moderate dependence risk was more frequent with lower educational attainment. Cannabis use prevalence exceeded that reported in previous studies and was higher in men. One-quarter of lifetime cannabis users had a moderate risk of dependence according to the ASSIST, particularly those with lower educational attainment.
Circadian rhythm disturbances have been implicated in several psychiatric disorders; however, circadian characteristics in pediatric obsessive-compulsive disorder (OCD) remain insufficiently investigated. Chronotype, reflecting individual differences in circadian timing, has been associated with both psychopathology and symptom severity in various psychiatric conditions. This study aimed to examine chronotype distribution in children and adolescents with OCD and to investigate the relationship between chronotype and OCD symptom severity using both psychometric assessments and biological circadian markers. This cross-sectional clinical study included 29 children and adolescents diagnosed with OCD and 30 age- and sex-matched healthy controls. Psychiatric diagnoses were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL). Chronotype was assessed using the Children's Chronotype Questionnaire (CCQ). OCD symptom severity was evaluated with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Depression and anxiety symptoms were assessed using the Children's Depression Inventory (CDI) and the Screen for Child Anxiety Related Emotional Disorders (SCARED). Sleep disturbances were evaluated using the Sleep Disturbance Scale for Children (SDSC). Morning salivary melatonin and cortisol levels were measured as endogenous circadian markers. Evening chronotype was more frequent in the OCD group compared with healthy controls (p < 0.05). Within the OCD group, participants with evening chronotype showed significantly lower CY-BOCS scores compared with non-evening chronotypes (p < 0.05). Melatonin levels were significantly higher in the evening chronotype subgroup (p < 0.05), whereas cortisol levels did not differ significantly between chronotype groups (p > 0.05). Children and adolescents with OCD appear more likely to exhibit evening chronotype characteristics. The association between chronotype and OCD severity suggests that circadian profiles may play a role in the clinical presentation of pediatric OCD. Considering chronotype characteristics during clinical assessment may contribute to a better understanding of circadian influences on OCD.
Injuries are a major cause of death and disability, but cities often lack surveillance systems that can monitor injury burden across mechanisms, severity levels, and population groups. In Spain, no comprehensive city-level injury surveillance system routinely captures the full spectrum of injuries. The Barcelona Injury Surveillance System (BISS) was developed to address this gap by integrating routine health and police data. This study aims to describe the BISS, including its scope, data sources, and public health rationale, and illustrate its utility through the analysis of recent injury data in Barcelona. We conducted a descriptive study using routinely collected emergency department, hospital discharge, mortality, and police data integrated into the BISS. We analyzed nonfatal injuries in 2024, fatal injuries in 2023, and trends from 2018 onward. Injury indicators were examined by sex, age, mechanism, type, and severity. Crude and age-adjusted rates per 100,000 residents were calculated. In 2024, BISS recorded 123,420 emergency department injury episodes and 18,749 injury-related hospitalizations; among residents, these figures were 99,379 and 14,319, respectively. In 2023, 695 injury-related deaths were recorded among residents. Nonfatal injuries were slightly more frequent in females, especially at older ages, whereas injury-related mortality was higher in males. Falls were the leading specified mechanism and were concentrated among older females, particularly those aged ≥75 years. Self-harm hospitalization rates were highest among females aged 15 years to 24 years, whereas self-harm mortality was higher in males. Road traffic injury and overall mortality rates were also higher in males. From 2018 to 2024, most nonfatal injury indicators increased after the decline observed in 2020, while road traffic injuries declined overall. BISS demonstrates the value of integrating routine health and police data to generate actionable urban injury intelligence. The findings highlight priorities for prevention, particularly falls in older females, self-harm in young females, and the persistently higher fatal injury burden among males. Integrated city-level surveillance systems such as BISS can support monitoring, equity-oriented prevention, and data-informed public health policy.
Body image is a multidimensional construct about one's appearance. Social and media factors contribute to dissatisfaction and are associated with mental health disorders. In adolescence, obesity emerges as a significant factor, with a four-fold increased risk of body dissatisfaction. Muscle dysmorphia is characterized by an obsessive pursuit of muscularity and distorted body image. A 16-year-old male with a history of obesity and depression, medically accompanied since age 10, developed obsessive behaviors around diet and exercise after weight loss and remission of depression. He adopted a "bulking and cutting" regimen and used creatine, protein, and caffeine supplements. He displayed rigid behavior, with poor insight. Given the pervasive functional impairment, he was referred to child and adolescent psychiatry. Muscle dysmorphia, classified as a body dysmorphic disorder, is underdiagnosed. Adolescent obesity may be a predisposing factor. Early recognition, particularly in adolescents with obesity and body image concerns is crucial for healthy development.
A novel dataset of 556 street art images is presented, accompanied by affective evaluations from 1,239 Portuguese and Brazilian participants. Artworks were selected to reflect themes associated with the United Nations Sustainable Development Goals. Using a stimulus-sampling design, each participant completed an online survey in which 10 randomly selected artworks were presented and reported their responses in terms of valence, arousal, and specific emotion labels (being moved, awe, inspiration, hope, sadness, fear, anger, emotional connection, reflection, awareness, and interest), as well as their interest in street art and sustainability consciousness. Multilevel analyses showed that higher interest in street art and greater sustainability consciousness were consistent predictors of more positive emotional responses to the artworks. In contrast, the effects of gender and age were negligible, and national differences emerged only for feeling moved and awe. Network analyses revealed a highly interconnected emotional structure, with three clusters: self-transcendent, epistemic, and negative emotions. Feeling moved and emotional connection occupied central bridging positions, showing both direct and indirect links across positive and negative emotion clusters. Overall, these findings indicate that street art evokes a broad range of interconnected self-transcendent, cognitive-epistemic, and negative emotions, highlighting the complexity of viewers' responses to the artworks. The dataset provides a valuable resource for research on emotional responses to street art and can support broader investigations into visual perception, aesthetic processing, and the communication of sustainability-related themes.
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Body image disturbance (BID) is a key symptom of anorexia nervosa (AN) and involves body size overestimation. Although this overestimation might be related to perceptual deficits, little is known about tactile perception in AN. To clarify the role of putative tactile deficits in BID, the present study investigated 36 adolescent female AN patients and 41 matched healthy controls (HC) using a tactile oddball paradigm during parallel EEG and MEG (EMEG) measurement. Tactile perception was behaviorally tested via the Touch Test (tactile perception threshold), a deviant count task, and a tactile stimulus discrimination task. Compared to HC participants, AN patients had similar tactile perception thresholds, but performance in the deviant count task and the tactile stimulus discrimination task was poor. Non-parametric cluster permutation tests on estimated neural source activity of evoked EMEG responses revealed that AN patients and HC did not differ regarding the neural differentiation between deviant and standard stimuli (oddball effect). However, estimated neural activity was globally reduced in the inferior temporal cortex and (by trend) in the posterior parietal cortex. These findings argue against the idea that behavioral discrimination deficits of tactile stimuli in AN are grounded in neural stimulus discrimination deficits. Instead, the overall reduced neural activity in the inferior temporal and posterior parietal cortex might reflect aberrant integration of neural tactile representations into a coherent multisensory body representation.
Learning disabilities (LD)-defined in the U.S. as specific learning disorders (e.g., dyslexia, attention-related difficulties) and distinct from intellectual disability-are associated with educational disadvantage, psychosocial stress, and constrained healthcare access. Evidence on whether adolescent LD predicts premature mortality in adulthood remains limited. To examine the association between adolescent LD and premature mortality through early to mid-adulthood and assess whether these associations differ by gender. Data were drawn from 17,478 U S. adolescents in Wave I (1994-1995) of the National Longitudinal Study of Adolescent to Adult Health, linked to National Death Index records through 2023. Cox proportional hazards models with school-clustered robust standard errors estimated hazard ratios (HR) for all-cause and cause-specific (disease, external, suicide) mortality. Sex-stratified models and LD × sex interactions assessed sex differences. Adolescents with LD had significantly elevated all-cause premature mortality (adjusted HR = 1.79 [1.47-2.18]). Associations were strongest for disease-related mortality (HR = 2.14 [1.61-2.85]) and elevated for external causes (HR = 1.57 [1.13-2.18]); suicide was non-significant. Sex-stratified analyses revealed substantially stronger effects among females than males (all-cause HR = 2.29 vs 1.58; disease-related HR = 2.87 vs 1.72); the LD × male interaction was statistically significant (p < 0.01). Adolescents with LD experience markedly elevated mortality through mid-adulthood, particularly from disease-related causes and especially among females. The findings position LD as a marker of cumulative social disadvantage shaped by stigma, exclusion, and unmet healthcare needs, calling for sustained, gender-sensitive support across educational, healthcare, and social systems.
Very preterm infants (<32 weeks gestation) have an undeveloped primary endogenous circadian rhythm and are deprived abruptly of vital maternal circadian inputs after delivery. Postnatal care in neonatal intensive care units is characterised by constant levels of lighting and noise. Stress arising from disrupted cues for circadian rhythmicity likely disrupts development of coordinated circadian rhythms critical for neurogenesis, organ growth and development. We hypothesise that cycled environmental light and noise commenced soon after birth and continued until discharge home will improve cognitive outcomes compared with infants whose postnatal care comprises constant light (bright or dim) and constant noise. Australasian multicentre, two-arm, parallel-group, prospective, randomised, open, blinded-endpoint superiority trial in 868 infants born less than 32 weeks' gestation. Infants are randomised to cycled environmental light and noise or routine care in a non-cycled hospital environment from soon after birth until discharge home. The intervention comprises wearing eye-masks and ear plugs from 20:00 to 6:00, followed by removal of these devices and exposure to normal environmental noise and 300-600 lux light from 6:00 to 20:00. The primary outcome is composite cognitive score on Bayley-4 developmental assessment at 2 years corrected postnatal age. The trial is approved by the Child and Adolescent Health Service Human Research Ethics Committee under the National Mutual Acceptance Scheme in Australia. Infants are randomised to intervention or control group after informed parental consent is obtained. Results of the CIRCA DIEM Study will be disseminated widely via presentations at local, national and international conferences, publication in international peer-reviewed journals and inclusion on the study website. Information about trial findings will also be communicated directly to the parents/guardians of trial participants through the regular study newsletter. The trial investigators will seek opportunities to communicate study results to the lay public through media and social media avenues. ANZCTRN12618000371291.
Adolescent suicide remains a major public health concern in Korea, yet depressive trajectories from age 13 to emerging adulthood have rarely been examined in nationally representative seven-wave panel data. In the Korean Children and Youth Panel Survey 2018 middle-school first-grade cohort (N = 2452; age 13 at Wave 1; 80% retained at Wave 7), latent class growth analysis (LCGA) was fitted on a 9-item depression scale excluding the suicidal-ideation item and replicated in R lcmm and Mplus. Distal suicidal ideation (SI) used broad SI (E04 ≥ 2) and affirmative SI endorsement (E04 ≥ 3), with missing SI retained as missing. Distal outcomes used Bolck-Croon-Hagenaars (BCH) correction; time-to-event analysis used a class x wave Cox model with ID-level bootstrap (B = 1000). A four-class solution balanced fit, adjacent-class tests, and interpretability (BIC = 25,228; entropy = 0.66): Stable-Low (25.1%), Persistent-High (10.0%), Decreasing (29.6%), and Late-Increasing (35.3%). BCH-corrected W7 broad SI prevalence was 9.4%, 56.7%, 36.8%, and 66.2%, respectively. Odds ratios versus Stable-Low were 12.63, 5.61, and 18.86 for Persistent-High, Decreasing, and Late-Increasing. The Late-Increasing versus Persistent-High contrast was borderline (OR = 1.49, 95% CI = 1.00-2.25, p = .052), indicating two high-risk pathways rather than a definitive hierarchy. SI was measured with a single self-report item; entropy was moderate; and trajectory classes overlap calendar time with repeated SI outcomes. Persistent-High and Late-Increasing represented two high-risk pathways differing mainly in timing. Repeated assessment across adolescence may help detect late-emerging SI risk.
Few studies investigated factors that predict intensive language therapy (ILT) outcome. This study aimed to analyze multimodal neural factors that possibly underly ILT success. Lesion volume and DTI analyses were performed with 17 aphasic individuals, and complemented by fMRI analysis in 12 patients (due to drop-outs). Structural and functional data were collected at the beginning of a seven week ILT program and correlated with language changes, measured using the Aachen Aphasia Test. Additionally, all analyses were correlated with the patients' initial aphasia severity. Therapy success was associated with functional activity in right inferior and middle temporal gyri, bilateral superior frontal gyrus/ adjacent anterior cingulate cortex, and right occipital lobe (lingual gyrus, fusiform gyrus, lateral occipital cortex). Statistically uncorrected DTI analysis (p(uncorr) < .001) revealed a positive correlation between language improvement and structural integrity in the right temporal lobe and two left-hemisphere white matter clusters (frontal, parietal). Neither global nor language-specific lesion volume was correlated with therapy outcome. However, lesion volume in insula, putamen and white matter tracts was correlated with initial aphasia severity. Our preliminary results suggest a predictive role of right temporal structures and functional activation in areas associated with healthy language processing. They also indicate a contribution of functional activation in brain areas associated with cognitive control and non-linguistic semantic processing. Further, lesion volume in both global and language-specific structures proved relevant for the initial severity of aphasia but not for recovery potential following ILT. Our results should be regarded as hypothesis-generating for future research.
Epstein-Barr virus (EBV) is highly prevalent worldwide and has been linked to different cancers and autoimmune disorders, including Multiple sclerosis (MS). Primary infection typically occurs during early childhood or adolescence and often goes undetected. Serological studies allow the detection of EBV-specific antibodies after infection, but venous blood collection is resource-intense and thus limits sample size. To overcome these challenges, we developed a high-throughput, semi-automated serology protocol targeting antibodies against EBV in capillary blood samples (Dried Blood Spots, DBS). Paired serum and DBS samples were obtained from 417 participants aged 18-25 years. We used Roche Elecsys® EBV nuclear antigen-1 EBNA IgG and Elecsys® EBV viral capsid antigen VCA IgG assays, established for serum, to detect antibodies against EBV anti-EBNA‑1 IgG and anti-VCA IgG in DBS. Cut-off Indices (COI) for the DBS assays were determined using a classification tree. Of the 416 valid paired serum samples, 78.6% (327/416) were anti-VCA-positive and 76.4% (318/416) anti-EBNA-positive. Discrepant results were observed in 3.6% (15/416) of participants. Based on combined assay results, 20.7% (86/416) of the samples were classified as EBV-negative. The serum COI values revealed that most of the negative cases clustered well below the cutoff, while positive cases spanned a broad range of higher values. Overall, 98.8% (326/330) of participants classified as positive based on serum testing (n = 330) were also classified as positive in DBS (n = 326), corresponding to the sensitivity of DBS relative to serum results. Likewise, 96.5% (83/86) of participants classified as serum-negative participants (n = 86) were also negative in DBS (n = 83), corresponding to the specificity of DBS relative to serum results. Among the 416 participants, only 4/330 (1.2%) were false negatives and 3/86 (3.5%) were false positives in DBS. The newly established assays were validated in a self-sampling cohort of 295 participants. We established DBS-specific cutoff values to detect antibodies against EBV in DBS, achieving high sensitivity (98.8%) and specificity (96.5%) relative to the corresponding venous blood assay. Furthermore, we derived a correction formula to convert semi-quantitative DBS values to serum-equivalents, enabling comparison with other studies and standardized datasets. The DBS-based approach allows sero-status assessment in a large population and thus e.g. simplifies the identification of suitable participants for clinical trials.
Genomic instability is increased in patients with inflammatory bowel disease (IBD), yet whether it contributes directly to disease pathogenesis remains unclear. Here, we identify RADX, a structural antagonist to RAD51 and a key regulator of replication fork stability, as a critical suppressor of intestinal inflammation by limiting innate immune sensing of replication-associated DNA damage. RADX deficiency exacerbates experimental colitis, with macrophages serving as the principal mediators of this phenotype. Mechanistically, RADX competes with the DNA sensor IFI16 for binding to single-stranded DNA (ssDNA). Loss of RADX promotes ssDNA accumulation, triggering IFI16-dependent activation of NF-κB signaling and inflammasome assembly, thereby driving intestinal inflammation. Consistent with these findings, two RADX variants identified in patients with IBD associate with reduced RADX protein expression, increased DNA damage signaling, and elevated IL-1β levels. Pharmacological inhibition of RAD51 with RI-1 alleviated colitis in both wild-type and Radx-deficient mice. Together, these findings establish a mechanistic link between genome instability and intestinal inflammation, identify a RADX-IFI16 checkpoint that restrains pathogenic innate immune activation, and nominate modulation of replication stress as a therapeutic strategy for IBD.
Management of recurrent clubfoot in walking-age children remains inconsistent, with substantial variation in treatment strategies. The role of clinical scoring systems in guiding treatment decisions in this group is unclear. This study investigated whether the video-based Pirani Böhm Sinclair (PBS)-score is associated with treatment recommendations. Fifty-five children aged 4-15 years (85 clubfeet) were video-documented. Four international paediatric orthopaedic surgeons independently assessed each case using the PBS-score and recommended management. Higher total PBS-scores were significantly associated with lower odds of recommending observation (OR 0.2, p < 0.002). A threshold around PBS-score 10 marked a consistent shift from observation to active intervention. Median PBS-scores were 8 (7-10) for observation and 13 (11-16) for active treatment. Despite this association, there was substantial variability in the type of intervention recommended. Even when specific clinical findings, such as dynamic supination, were consistently identified, this did not uniformly translate into the same surgical decision. While higher PBS-scores are associated with the decision to intervene, considerable variation in treatment choice persists. These findings highlight the lack of consensus in managing recurrent clubfoot and underscore the need for clearer indications and standardized treatment algorithms. Trial registration Clinical trial number NCT06050564, date of registration 2023-09-11.
High-quality neonatal resuscitation (NR) depends on timely execution of technical and nontechnical skills. Simulation-based training improves NR performance, but it is resource-intensive and difficult to deliver at sufficient frequency. Immersive virtual reality (VR) simulation may provide a scalable supplement to traditional mannequin-based training; however, evidence from European neonatal training settings is limited. The aim of this study is to evaluate whether immersive VR-based simulation training used as a supplement to traditional mannequin-based simulation training improves NR performance among doctors and nurses in Denmark. NEONATAL is a multicenter, individually randomized, 2-arm controlled superiority trial with a parallel-group pretest-posttest design (trial registration number ISRCTN 43822066). Resident doctors and neonatal nurses from 4 hospitals in Eastern Denmark will be randomized to either traditional mannequin-based NR training alone or traditional mannequin-based simulation training supplemented with immersive VR simulation training. Outcomes will be assessed at baseline and endline at 6 to 8 weeks using standardized neonatal simulation scenarios, validated assessment tools, and questionnaires. The study was funded in July and October 2025, as well as in January 2026. Participant recruitment began in October 2025 and was completed in December 2025, with 66 participants enrolled. Data collection was completed in February 2026. Data cleaning and analysis will take place from March to July 2026, and the results are expected to be published in autumn 2026. This study will provide data on the effectiveness, feasibility, and usability of immersive VR simulation training as a supplement to traditional mannequin-based NR training in routine clinical education. The NEONATAL study addresses an important gap in NR education by evaluating immersive VR simulation training as a supplement to traditional mannequin-based training.
Obsessive-compulsive disorder (OCD) frequently emerges during adolescence, a critical period of brain network maturation. Although altered functional and structural connectivity have been reported separately in adolescent OCD, structural-functional connectivity (SC-FC) coupling, which reflects how white matter architecture shapes functional organization, remains unexplored. Fifty adolescents with OCD and 53 healthy control participants underwent multimodal neuroimaging. SC-FC coupling was quantified across 246 brain regions and large-scale networks. Group differences were examined using general linear models, and associations with symptom severity were assessed using partial correlations. Machine learning evaluated prediction of diagnosis and symptom severity. Spatial correlation analyses linked coupling alterations to neurotransmitter systems and transcriptional signatures. Adolescents with OCD exhibited elevated SC-FC coupling, most prominently within the default mode network (DMN, t = 3.563, p < 0.001). DMN coupling was positively associated with compulsive symptom severity (ρ = 0.436, p = 0.002). SC-FC coupling discriminated patients from controls with 66.0% accuracy (area under the curve = 0.691, p = 0.003) and predicted symptom severity (r = 0.426, p = 0.002). Spatial association analyses linked SC-FC coupling alterations to normative dopaminergic and cholinergic molecular architectures. Transcriptomic analyses identified genes enriched for synaptic, neurodevelopmental, and signaling-related processes, with preferential expression in excitatory and inhibitory neurons. These findings demonstrate that adolescent OCD is characterized by SC-FC coupling alterations embedded within specific neurochemical and transcriptional architectures, suggesting that SC-FC coupling may serve as a systems-level marker linking brain organization, molecular substrates, and clinical manifestations.
This study retrospectively evaluates the microbiological profile, antibiotic susceptibility patterns, and the effectiveness of empirically initiated antibiotic therapies in children with perforated appendicitis, based on intraoperative peritoneal fluid culture and antibiogram results. A total of 154 pediatric patients (97 boys, 57 girls; mean age 9.15 ± 4.08 years) underwent surgery for perforated appendicitis between 2014 and 2020. Before surgery, patients received one of three empirical antibiotic combinations: (1) Ampicillin/sulbactam, metronidazole, and amikacin; (2) ceftriaxone and metronidazole; (3) cefotaxime and metronidazole. Peritoneal fluid samples collected intraoperatively were cultured, and microbial growth and susceptibility profiles were analyzed. A total of 167 strains were isolated. The most common microorganisms were Escherichia coli (79.0%), Pseudomonas aeruginosa (13.8%), Klebsiella pneumoniae (2.4%), Enterobacter cloacae (1.8%), Enterococcus raffinosus (2.4%), and Staphylococcus hominis (0.6%). Before surgery, Combination 1 was administered to 97 patients (63.0%), Combination 2 to 38 patients (24.7%), and Combination 3 to 19 patients (12.3%). Antibiotic susceptibility of the isolated microorganisms was as follows. E. coli: ampicillin/sulbactam 23%, ceftriaxone 60%, cefotaxime 92%, amikacin 99%. P. aeruginosa: ampicillin/sulbactam 8%, ceftriaxone 16%, cefotaxime 0%, amikacin 99%. K. pneumoniae: ceftriaxone 75%, cefotaxime 75%, amikacin 100%. E. raffinosus: ceftriaxone 33%, cefotaxime 100%, amikacin 100%. Postoperative modification of empirical therapy was required in 102 cases (66.2%) Conclusions. High resistance rates to commonly used empirical antibiotics were observed among isolated microorganisms, highlighting the need for regular revision of empirical treatment protocols and greater reliance on intraoperative culture results in pediatric perforated appendicitis.