Fused SDT/IRT Models for Mixed-Format Exams.

A psychological framework for different types of items commonly used with mixed-format exams is proposed. A choice model based on signal detection theory (SDT) is used for multiple-choice (MC) items, whereas an item response theory (IRT) model is used for open-ended (OE) items. The SDT and IRT models are shown to share a common conceptualization in terms of latent states of "know/don't know" at the examinee level. This in turn suggests a way to join or "fuse" the models-through the probability of knowing. A general model that fuses the SDT choice model, for MC items, with a generalized sequential logit model, for OE items, is introduced. Fitting SDT and IRT models simultaneously allows one to examine possible differences in psychological processes across the different types of items, to examine the effects of covariates in both models simultaneously, to allow for relations among the model parameters, and likely offers potential estimation benefits. The utility of the approach is illustrated with MC and OE items from large-scale international exams.

A Million Person Study Innovation: Evaluating Cognitive Impairment and other Morbidity Outcomes from Chronic Radiation Exposure Through Linkages with the Centers for Medicaid and Medicare Services Assessment and Claims Data.

The study of One Million U.S. Radiation Workers and Veterans, the Million Person Study (MPS), examines the health consequences, both cancer and non-cancer, of exposure to ionizing radiation received gradually over time. Recently the MPS has focused on mortality patterns from neurological and behavioral conditions, e.g., Parkinson's disease, Alzheimer's disease, dementia, and motor neuron disease such as amyotrophic lateral sclerosis. A fuller picture of radiation-related late effects comes from studying both mortality and the occurrence (incidence) of conditions not leading to death. Accordingly, the MPS is identifying neurocognitive diagnoses from fee-for-service insurance claims from the Centers for Medicare and Medicaid Services (CMS), among Medicare beneficiaries beginning in 1999 (the earliest date claims data are available). Linkages to date have identified ∼540,000 workers with available health information. Such linkages provide individual information on important co-factor and confounding variables such as smoking, alcohol consumption, blood pressure, obesity, diabetes and many other health and demographic characteristics. The total person-level set of time-dependent variables, outcomes, organ-specific dose measures, co-factors, and demographics will be massive and much too large to be evaluated with standard software. Thus, development of specialized open-source software designed for large datasets (Colossus) is nearly complete. The wealth of information available from CMS claims data, coupled with individual dose reconstructions, will thus greatly enhance the quality and precision of health evaluations for this new field of low-dose radiation and neurocognitive effects.

Maximizing Ancillary Opportunities.

In the face of increasing overhead and declining reimbursement for hand surgery services, ancillary services provide additional opportunities for revenue capture outside the standard stream of office visits and surgical billing. These additional revenue streams may allow hand surgeons to practice with less stress, improve efficiency, and create more financial security overall. Hand surgery practices are quite diverse. There are solo practitioners, hand surgery group practice, hand surgery within a specialty group (most often orthopedic surgery), multispecialty clinics, and those who are incorporated within a health system. Each of these types of practices may provide different suites of ancillary services.

Use of ICD-10-CM Codes for Adverse Social Determinants of Health Across Health Systems.

OBJECTIVE: This study investigated ICD-10-CM codes for adverse social determinants of health (SDoH) across 12 U.S. health systems by using data from multiple health care encounter types for diverse patients covered by multiple payers. METHODS: The authors described documentation of 11 SDoH ICD-10-CM code categories (e.g., educational problems or social environmental problems) between 2016 and 2021; assessed changes over time by using chi-square tests for trend in proportions; compared documentation in 2021 by gender, age, race-ethnicity, and site with chi-square tests; and compared all patients' mental health outcomes in 2021 with those of patients with documented SDoH ICD-10-CM codes by using exact binomial tests and one-proportion z tests. RESULTS: Documentation of any SDoH ICD-10-CM code significantly increased, from 1.7% of patients in 2016 to 2.7% in 2021, as did that for all SDoH categories except educational problems. Documentation was often more prevalent among female patients and those of other or unknown gender than among male patients and among American Indian or Alaska Native, Black or African American, and Hispanic individuals than among those belonging to other race-ethnicity categories. More educational problems were documented for younger patients, and more social environmental problems were documented for older patients. Psychiatric diagnoses and emergency department visits and hospitalizations related to mental health were more common among patients with documented SDoH codes. CONCLUSIONS: SDoH ICD-10-CM code documentation was infrequent and differed by population subgroup. Differences may reflect documentation practices or true SDoH prevalence variation. Standardized SDoH documentation methods are needed in health care settings.

Glial expression of Drosophila UBE3A causes spontaneous seizures that can be modulated by 5-HT signaling.

Misexpression of the E3 ubiquitin ligase gene UBE3A is thought to contribute to a range of neurological disorders. In the context of Dup15q syndrome, additional genomic copies of UBE3A give rise to the autism, muscle hypotonia and spontaneous seizures characteristics of the disorder. In a Drosophila model of Dup 15q syndrome, it was recently shown that glial-driven expression of the UBE3A ortholog dube3a led to a "bang-sensitive" phenotype, where mechanical shock triggers convulsions, suggesting glial dube3a expression contributes to hyperexcitability in flies. Here we directly compare the consequences of glial- and neuronal-driven dube3a expression on motor coordination and seizure susceptibility in Drosophila. To quantify seizure-related behavioral events, we developed and trained a hidden Markov model that identified these events based on automated video tracking of fly locomotion. Both glial and neuronal driven dube3a expression led to clear motor phenotypes. However, only glial-driven dube3a expression displayed spontaneous seizure-associated immobilization events, that were clearly observed at high-temperature (38 °C). Using a tethered fly preparation amenable to electrophysiological monitoring of seizure activity, we found glial-driven dube3a flies display aberrant spontaneous spike discharges which are bilaterally synchronized. Neither neuronal-dube3a overexpressing flies, nor control flies displayed these firing patterns. We previously performed a drug screen for FDA approved compounds that can suppress bang-sensitivity in glial-driven dube3a expressing flies and identified certain 5-HT modulators as strong seizure suppressors. Here we found glial-driven dube3a flies fed the serotonin reuptake inhibitor vortioxetine and the 5-HT2A antagonist ketanserin displayed reduced immobilization and spike bursting, consistent with the previous study. Together these findings highlight the potential for glial pathophysiology to drive Dup15q syndrome-related seizure activity.

Monoclonal antibodies to the circumsporozoite proteins as an emerging tool for malaria prevention.

Despite various public health strategies, malaria caused by Plasmodium falciparum parasites remains a major global health challenge that requires development of new interventions. Extended half-life human monoclonal antibodies targeting the P. falciparum circumsporozoite protein on sporozoites, the infective form of malaria parasites, prevent malaria in rodents and humans and have been advanced into clinical development. The protective epitopes on the circumsporozoite protein targeted by monoclonal antibodies have been defined. Cryogenic electron and multiphoton microscopy have enabled mechanistic structural and functional investigations of how antibodies bind to the circumsporozoite protein and neutralize sporozoites. Moreover, innovations in bioinformatics and antibody engineering have facilitated enhancement of antibody potency and durability. Here, we summarize the latest scientific advances in understanding how monoclonal antibodies to the circumsporozoite protein prevent malaria and highlight existing clinical data and future plans for how this emerging intervention can be used alone or alongside existing antimalarial interventions to control malaria across at-risk populations.

Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5.

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.

Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease.

BACKGROUND: Radiolabeled antibody 131I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic. METHODS: Intraventricular radioimmunotherapy (RIT) with 925-1850 MBq (25-50 mCi) of 131I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 min, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3-10 y/o, 10-18 y/o, and 18+. RESULTS: Post-administration exposure rates for patients ranged from 0.16 to 0.46 µSv/hr/MBq at 0.3 m and 0.03-0.08 µSv/hr/MBq at 1 m. Radiation exposure precautions ranged from 1 to 10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with 131I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring. CONCLUSION: 131I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine's ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402 .

Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria.

Associations of Long-term Sleep Duration Trajectories with Overall and Cause-Specific Mortality Among Middle-to-older Aged Black and White Adults.

Background: Both short and long sleep durations are adversely associated with numerous chronic conditions, including cardiovascular disease (CVD), diabetes, hypertension, and mortality. The American Academy of Sleep Medicine recommends adults in the United States sleep at least 7 hours and less than 9 hours per night to maintain optimal health. It remains unclear how sleep duration trajectories over time are associated with mortality. Methods: This observational cohort study includes 46,928 Black and White adults (mean age: 53 ± 9 years) who enrolled in the Southern Community Cohort Study between 2002-2009 and completed a follow-up survey in 2008-2013. Participants were categorized into nine sleep duration trajectory categories based on the reported average sleep duration between study enrollment and at follow-up. Participant vital status and date and cause of death were ascertained via linkage to the National Death Index through 2022. Cox regression analysis was performed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between sleep duration trajectory and all-cause and cause-specific mortality (CVD, cancer, and neurodegenerative disease) after adjustment for sociodemographic characteristics, health behaviors, and clinical factors. Results: During a median 12.6 years of follow-up, we documented 13,579 deaths, including 4,135 from CVD, 3,067 from cancer, and 544 from neurodegenerative diseases. Compared to the optimal sleep duration trajectory (maintaining 7-9 hours), all sub-optimal trajectories were associated with significant 6 to 33% greater risk of all-cause mortality in fully adjusted models. Compared to the optimal sleep trajectory, three of the sub-optimal trajectories were associated with increased CVD mortality, with HRs ranging from 1.20 to 1.34. The short-long trajectory was associated with the greatest risk of all-cause mortality (HR:1.33; 95%CI: 1.21, 1.46) and the long-short trajectory was associated with the greatest CVD mortality risk (HR:1.34; 95%CI: 1.10, 1.65). The healthy-long trajectory was associated with the greatest risk of cancer mortality (HR: 1.19; 95%CI:1.00, 1.41). None of the sub-optimal trajectories was associated with neurodegenerative disease mortality. Conclusions: Suboptimal sleep duration trajectories were associated with increased risk of all-cause mortality as well as CVD mortality. Findings highlight the importance of maintaining healthy sleep duration throughout midlife to reduce mortality risk.

The Prevalence of Caregiving among Young People.

With the increasing number of people with chronic diseases and disabilities, the number of family members as caregivers have also been growing. Despite the attention paid to caregiving in recent years, little is known about caregiving among young people, particularly its global prevalence. The lack of information has important implications for health policy and management, resulting in the inability to form appropriate evidence-based policies and managerial decision making. This study aims to derive an estimate of the prevalence of caregiving among young people through a systematic review of the current literature. The results of this study revealed a prevalence of caregiving among younger adolescents of between 1.1% (1.06-1.14%) and 12.0% (11.02-12.98%). However, the assessment of caregiving varies across studies, and all were conducted in developed countries. These results provide information on the burden of caregiving in young people and reveal the lack of global information, calling for more research on and attention to this specific population.

A Web-Based and Mobile Intervention Program Using a Spaced Education Approach for Workplace Mental Health Literacy: Cluster Randomized Controlled Trial.

Background: Workplace mental health is an important global health concern. objectives: This unblinded, phase-III, wait-listed cluster randomized controlled trial aimed to examine the effectiveness of a mobile health (mHealth) psychoeducation program using a spaced education approach on mental health literacy (MHL) in the workplace. The main interest of this paper was the immediate and 3-month medium-term effect of the program on the MHL of workers. The purposely built mHealth platform was also evaluated as a health-related app. Methods: The mHealth platform was designed using the principle of spaced education as a psychoeducation intervention program, with various modules of web-based and mobile materials presented to the participant in a progressive manner. Short quizzes at the end of each module ensured adequate learning, and successful completion qualified the learner to progress to the next level. The trial recruited 456 employees of specific industries with high levels of work-related stress. Participants who were nested in different offices or units were allocated into the intervention and wait-listed control groups using a block randomization process, with the office or unit as the cluster. A separate sample of 70 individual raters were used for the evaluation of the mHealth platform. The Australian National MHL and Stigma Survey and the Mobile Apps Rating Scale were completed through a web-based self-reported survey to assess MHL and evaluate the app. The trial and follow-up data were analyzed by a generalized linear latent and mixed model with adjustments for the clustering effect of work sites and repeated measures. Results: Of the 456 participants in the trial, 236 (51.8%) responded to the follow-up survey. Most MHL outcomes obtained significant results immediately after the intervention and across time. After adjusting for the clustering effect, the postintervention weighted mean scores were significantly higher in the intervention group than the control group for correct recognition of a mental health problem, help seeking, and stigmatization by 0.2 (SE 0.1; P=.003), 0.9 (SE 0.2; P<.001), and 1.8 (SE 0.4; P<.001), respectively. After adjusting for the clustering effect, significant differences across time were found in help-seeking intention (P=.01), stigmatization (P<.001), and social distancing (P<.001). The evaluation of the mHealth program resulted in average scores of the 4 major domains ranging from 3.8 to 4.2, with engagement having the lowest score. Conclusions: The mHealth psychoeducation intervention program using this platform had immediate and 3-month medium-term effects of retaining and improving MHL. The platform was evaluated to have satisfactory performance in terms of functionality, aesthetics, information content, and utility in enhancing MHL. It is anticipated that ongoing development in digital health will provide great benefits in improving the mental health of the global population.

A cultural models approach to understanding body fatness perceptions and disordered eating in young South Korean men.

OBJECTIVE: The eating disorders field has been limited by a predominant focus on White, Western women, and there is growing recognition of the need to understand cross-cultural variation in key constructs (i.e., ideal body types). A transdisciplinary, cultural models approach systematizes the incorporation of an "emic" perspective (a culture's own understandings of phenomena) into assessments of relationships between body shapes and eating disorders. METHOD: Eighty-one young South Korean men aged 19-34 years living in Seoul participated in this research. A cultural model of body fatness was identified using cultural consensus analysis during 18 months of ethnographic, mixed-methods fieldwork. Participants also completed questionnaires assessing age, height, weight, sexual identity, university prestige, body dissatisfaction, eating disorder symptoms, and cultural consonance with the Korean cultural model of the ideal male body. Variation in these factors was analyzed using a series of chi-squares and analyses of variance with the culturally defined categories of body fatness as the independent variables. RESULTS: Cultural consensus analysis found that young South Korean men are consistent in identifying categories of "too thin," "balanced," and "too fat." The "balanced" category contained the lowest proportion of high-prestige university attendees and the highest average cultural consonance. The "too fat" category was characterized by the highest levels of body dissatisfaction and dieting, as well as proportion of probable eating disorders. DISCUSSION: A cultural models approach identified culturally important factors and patterns in disordered eating among young South Korean men and may be effective for understanding eating disorders in other populations not typically studied. PUBLIC SIGNIFICANCE: This study applies a systematic, "emic" perspective to young South Korean men's body ideals. Young Korean men share a cultural model of body fatness, and this model frames how they experience risk for eating disorders. This study demonstrates a method for incorporating culture into research on eating disorder risk.

Gut resident Escherichia coli profile predicts the eighteen-month probability and antimicrobial susceptibility of urinary tract infections.

Background: Community-acquired UTI is the most common bacterial infection managed in general medical practice that can lead to life-threatening outcomes. While UTIs are primarily caused by Escherichia coli colonizing the patient's gut, it is unclear whether the gut resident E. coli profiles can predict the person's risks for UTI and optimal antimicrobial treatments. Thus, we conducted an eighteen-month long community-based observational study of fecal E. coli colonization and UTI in women aged 50 years and above. Methods and Findings: We enrolled a total of 1,804 women distributed among age groups 50-59 yo (437 participants), 60-69 yo (632), 70-79 yo (532), and above 80 yo (203), lacking antibiotic prescriptions for at least one year. The provided fecal samples were plated for the presence of E. coli and other enterobacteria resistant to trimethoprim/sulfamethoxazole (TMP/STX), ciprofloxacin (CIP) and 3rd generation cephalosporins (3GC). E. coli was also characterized as belonging to the pandemic multi-drug resistant clonal groups ST131 (subclone H30) and ST1193. Following sample collection, the women were monitored for 18 months for occurrence of UTI.E. coli was cultured from 90.8% fecal samples, with 24.1% containing bacteria resistant to TMP/STX, 19.4% to CIP, and 7.9% to 3GC. In 62.5% samples, only all-susceptible E. coli were present. Overall, there were no age-related differences in resistance prevalence. However, while the total E. coli H30 and ST1193 carriage rates were similar (4.3% and 4.2%, respectively), there was a notable increase of H30 carriage with age (P = .001), while carriage decreased with age for ST1193 (P = .057).Within 18 months, 184 women (10.2%) experienced at least one episode of UTI - 10.9% among the gut E. coli carriers and 3.0% among the non-carriers (P=.0013). The UTI risk among carriers of E. coli H30 but not ST1193 was significantly above average (24.3%, P = .0004). The UTI probability increased with age, occurring in 6.4% of 50-59 yo and 19.7% of 80+ yo (P<.001), with the latter group being especially at high risk for UTI, if they were colonized by E. coli H30 (40.0%, P<.001).E. coli was identified in 88.1% of urine samples, with 16.1% resistant to TMP/STX, 16.1% to CIP, 4.2% to 3GC and 73.1% to none of the antibiotics. Among tested urinary E. coli resistant to antibiotics, 86.1% matched the resistance profile of E. coli in the fecal samples, with the clonotyping and whole genome sequencing confirming the matching strains' identity. Positive predictive value (PPV) of using gut resistance profiles to predict UTI pathogens' susceptibility to TMP/STX, CIP, 3GC and all three antibiotics were 98.4%, 98.3%, 96.6% and 95.3%, respectively. Corresponding negative predictive values (NPV) were 63.0%, 54.8%, 44.4% and 75.8%, respectively. The AUC ROC curve values for the accuracy of fecal diagnostic testing for the prediction of UTI resistance ranged .86-.89. The fecal test-guided drug-bug mismatch rate for empirical (pre-culture) prescription of TMP-SXT or CIP is reduced to ≤2% in 89.6% of patients and 94.8% of patients with an optional 3GC prescription. Conclusion: The resistance profile and clonal identity of gut colonizing E. coli, along with the carrier's age, can inform personalized prediction of a patients' UTI risk and the UTI pathogen's antibiotic susceptibility within an 18-month period.

Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease.

Background: Radiolabeled antibody 131I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic. Methods: Intraventricular radioimmunotherapy (RIT) with 925-1850 MBq (25-50 mCi) of 131I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 minutes, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3-10 y/o, 10-18 y/o, and 18+. Results: Post-administration exposure rates for patients ranged from 0.16-0.46 µSv/hr/MBq at 1 ft and 0.03-0.08 µSv/hr/MBq at 1 m. Radiation exposure duration ranged from 1-10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with 131I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring. Conclusion: 131I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine's ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402.

Glial expression of Drosophila UBE3A causes spontaneous seizures modulated by 5-HT signaling.

Misexpression of the E3 ubiquitin ligase UBE3A is thought to contribute to a range of neurological disorders. In the context of Dup15q syndrome, excess genomic copies of UBE3A is thought to contribute to the autism, muscle tone and spontaneous seizures characteristic of the disorder. In a Drosophila model of Dup 15q syndrome, it was recently shown glial-driven expression of the UBE3A ortholog dube3a led to a "bang-sensitive" phenotype, where mechanical shock triggers convulsions, suggesting glial dube3a expression contributes to hyperexcitability in flies. Here we directly compare the consequences of glial- and neuronal-driven dube3a expression on motor coordination and neuronal excitability in Drosophila. We utilized IowaFLI tracker and developed a hidden Markov Model to classify seizure-related immobilization. Both glial and neuronal driven dube3a expression led to clear motor phenotypes. However, only glial-driven dube3a expression displayed spontaneous immobilization events, that were exacerbated at high-temperature (38 °C). Using a tethered fly preparation we monitored flight muscle activity, we found glial-driven dube3a flies display spontaneous spike discharges which were bilaterally synchronized indicative of seizure activity. Neither control flies, nor neuronal- dube3a overexpressing flies display such firing patterns. Prior drug screen indicated bang-sensitivity in glial-driven dube3a expressing flies could be suppressed by certain 5-HT modulators. Consistent with this report, we found glial-driven dube3a flies fed the serotonin reuptake inhibitor vortioxetine and the 5HT 2A antagonist ketanserin displayed reduced immobilization and spike bursting. Together these findings highlight the potential for glial pathophysiology to drive Dup15q syndrome-related seizure activity.

The association between Long-COVID symptomology, perceived symptom burden and mental health in COVID-19 patients in Shijiazhuang, China: a population-based health survey.

Background: Long-COVID (LC) refers to post-acute COVID-19 symptoms that can last for months or longer after the initial infection, affecting the physical health of infected patients. This study aims to investigate the association between the symptomology of LC and the mental health of patients in China. It also aims to examine the relationship between the perceived symptom burden and mental health of these patients. Methods: A population-based stratified cluster sample was recruited, using a standard sampling procedure, from a prefecture-level city in Northern China. Participants included patients who had tested positive for COVID-19 after December 2022. LC symptomology was assessed using a LC symptoms checklist where the perceived symptom burden was measured by the included 5-point Likert scales. Mental health of patients was measured using the Depression, Anxiety, and Stress Scale (DASS), the original Connor-Davidson Resilience Scale (CD-RISC), and the Duke-UNC Functional Social Support Questionnaire (DUFSS). Data were analysed using multiple linear regression models. Results: About 25% of respondents, experienced COVID symptoms lasting longer than two months that could only be explained by the infection. Post-exertional malaise (22.2%) and fatigue (21.2%) were the most common symptoms. After controlling for potential confounding variables, LC symptomology was significantly and positively associated with depression (t=2.09, p=0.037) and anxiety (t=4.51, p<0.001), but not stress. Perceived symptoms burden was also positively and significantly related to depression (ß=0.35, p<0.001), anxiety (ß=0.54, p<0.001), and stress (ß=0.35, p<0.001), suggesting a dose-response relationship between perceived symptom burden and mental ill health. Conclusion: This study highlights the importance of recognising the risk of LC, patients' perception of the symptom burden and its potential impact on mental health. Healthcare professionals should be aware of the complexity of psychological comorbidities among infected patients reporting prolonged symptoms, and be able to give advice regarding long-term management of the symptoms.

A Rare Presentation of Idiopathic Unilateral Hypertrophic Olivary Degeneration.

Hypertrophic olivary degeneration (HOD) is a rare form of trans-synaptic degeneration affecting the inferior olivary nucleus (ION). Its classical description involves a lesion in the Guillain-Mollaret triangle (GMT), characteristic imaging findings, and associated oculopalatal tremor. However, understanding of this disease entity is incomplete, as its overall rarity has limited strong classification. Case reports and small studies indicate that a variety of presentations can occur, including non-existent or non-classical lesions as well as variations in physical symptoms. Here we report the exceedingly rare case of idiopathic, nonlesional, unilateral HOD in a female patient.