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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Using a behavioural intervention to target nutrition during pregnancy may be key in meeting recommendations for healthy eating. The aim was to assess the use of a short-term dietary intake measurement tool (3-day food intake record) to infer long-term habitual dietary intake during pregnancy (using a short-form food frequency questionnaire). A convenience sample (n=90) between 12- and 18-weeks’ gestation were recruited from a larger randomised controlled trial for cross-sectional analysis. Participants completed a 44-item food frequency questionnaire and 3-day food intake record. Using the participant food intake record, the investigator blindly completed a second frequency questionnaire. The frequency questionnaires were scored using Dietary Quality Scores (DQS) and compared. Aggregate data were evaluated using a Wilcoxon signed rank test, and individual-level data were evaluated using a Bland-Altman plot. No significant difference was observed in the scores (Z=-1.88, p=0.06), with small effect size (r=0.19). The Bland-Altman plot showed that comparing the DQS derived from the two different dietary assessments underestimated scores by a mean difference of 0.4 points (95% limits of agreement: -3.50 to 4.26). The data points were evenly spread suggesting no systematic variation for over- or underestimation of scores. Minimal difference was observed between the functionality of the two assessment instruments. However, the food intake record can be completed by pregnant individuals to estimate short-term nutrient intake, and then scored by the investigator to estimate long-term dietary quality. Combining these two instruments may best capture the most accurate representation of dietary habits over time.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Portable medical equipment (PME) is inconsistently cleaned and disinfected, resulting in contamination that increases the risk of healthcare-associated infections. A virtual reality PME cleaning and disinfection training module was designed and tested at multiple healthcare facilities. Barriers identified during an initial phase led to improvements in the second phase.
SHEA, in partnership with ASGE, APIC, AAMI, AORN, HSPA, IDSA, SGNA, and The Joint Commission, developed this multisociety infection prevention guidance document for individuals and organizations that engage in sterilization or high-level disinfection (HLD). This document follows the CDC Guideline for Disinfection and Sterilization in Healthcare Facilities. This guidance is based on a synthesis of published scientific evidence, theoretical rationale, current practices, practical considerations, writing group consensus, and consideration of potential harm when applicable. The supplementary material includes a summary of recommendations. The guidance provides an overview of the Spaulding Classification and considerations around manufacturers’ instructions for use (MIFUs). Its recommendations address: point-of-use treatment prior to sterilization or HLD, preparation of reusable medical devices at the location of processing, sterilization, and immediate use steam sterilization (IUSS), HLD of lumened and non-lumened devices, processing of reusable medical devices used with lubricating or defoaming agents, monitoring for effectiveness of processing, handling of devices after HLD, augments and alternatives to HLD, processing of investigational devices, tracking of reusable medical devices, and approaches to implementation.
We present a mathematical model to investigate heat transfer and mass transport dynamics in the wave-driven free-surface boundary layer of the ocean under the influence of long-crested progressive surface gravity waves. The continuity, momentum and convection–diffusion equations for fluid temperature are solved within a Lagrangian framework. We assume that eddy viscosity and thermometric conductivity are dependent on Lagrangian coordinates, and derive a new form of the second-order Lagrangian mass transport velocity, applicable across the entire finite water depth. We then analyse the convective heat dynamics influenced by the free-surface boundary layer. Rectangular distributions of free-surface temperature (i.e. a Dirichlet boundary condition) are considered, and analytical solutions for thermal boundary layer temperature fields are provided to offer insights into free-surface heat transfer mechanisms affected by ocean waves. Our results suggest the need to improve existing models that neglect the effects of free-surface waves and the free-surface boundary layer on ocean mass transport and heat transfer.
In vitro evidence of antidepressant-driven antibiotic resistance has recently been described. In this retrospective cohort study, significant associations are identified between antidepressant use and antibiotic resistance on urine cultures taken in the Emergency Department. This epidemiologic data supports previous in vitro work and raises additional questions for further study.
A major subglacial lake, Lake Snow Eagle (LSE), was identified in East Antarctica by airborne geophysical surveys. LSE, contained within a subglacial canyon, likely hosts a valuable sediment record of the geological and glaciological changes of interior East Antarctica. Understanding past lake activity is crucial for interpreting this record. Here, we present the englacial radiostratigraphy in the LSE area mapped by airborne ice-penetrating radar, which reveals a localized high-amplitude variation in ice unit thickness that is estimated to be ∼12 ka old. Using an ice-flow model that simulates englacial stratigraphy, we investigate the origin of this feature and its relationship to changes in ice dynamical boundary conditions. Our results reveal that local snowfall redistribution initiated around the early Holocene is likely the primary cause, resulting from a short-wavelength (∼10 km) high-amplitude (∼20 m) ice surface slope variation caused by basal lubrication over a large subglacial lake. This finding indicates an increase in LSE water volume during the Holocene, illustrating the sensitivity in volume of a major topographically constrained subglacial lake across a single glacial cycle. This study demonstrates how englacial stratigraphy can provide valuable insight into subglacial hydrological changes before modern satellite observations, both for LSE and potentially at other locations.
Objectives/Goals: This study investigates the contribution of the stool secretome (the soluble factors secreted by microbes into extracellular space) to in vitro α-synuclein (αSyn) oligomerization using stool cultures from patients with multiple system atrophy (MSA), a rare neurodegenerative disease hallmarked by pathologic αSyn aggregates. Methods/Study Population: Stool samples from MSA patients (n = 20), household controls (n = 20), and healthy controls (n = 20) will be cultured using an adapted dilution-to-extinction approach. The goal is to reduce microbial complexity progressively to produce random secretome combinations that may affect αSyn oligomerization differentially. The original inoculant and dilutions will be cultured anaerobically to collect conditioned media (CM) enriched with microbial secretomes. CM will be used to expose a fluorescence resonance energy transfer (FRET) biosensor assay and a Gaussia luciferase protein complementation assay – both modified to quantify αSyn-αSyn interaction indicating oligomerization. Any CM-altering αSyn oligomerization will undergo multiomic characterization to identify potential causative agent(s). Results/Anticipated Results: Specific microbe-produced molecules from the literature are anticipated to modulate αSyn oligomerization, identified by targeted, reductionist studies that selected and tested separately single microbial factors on αSyn aggregation in vitro and in vivo. From these studies, lipopolysaccharide and bacterial amyloid protein are expected to increase αSyn oligomerization, while short-chain fatty acids, such as butyrate, are expected to interfere with and decrease oligomerization. As a complementary systemic approach, this study’s agnostic methods involving MSA stool culture combined with the proposed dilution-to-extinction method are expected to identify additional MSA stool secretome components modulating αSyn oligomerization that might otherwise be missed in earlier reductionist approaches. Discussion/Significance of Impact: Completion of this reverse-translational work will aid in discovering MSA stool secretome components modulating αSyn oligomerization. Identification of specific factors contributing to pathologic αSyn behavior might set the stage for patient screenings for identified stool markers and could lead to microbiome-based interventions for MSA.
Understanding the development and use of musical instruments in prehistory is often hampered by poor preservation of perishable materials and the relative rarity of durable examples. Here, the authors present a pair of third-millennium BC copper cymbals, excavated at Dahwa, Oman. Although they are the only well-contextualised examples from Arabia, the Dahwa cymbals are paralleled by contemporaneous examples from the Indus Valley and images in Mesopotamian iconography. Not only do the cymbals add to the body of evidence interpreted in terms of Indus migrants in Early Bronze Age Oman, they also suggest shared musical and potentially ritual practices around the Arabian Gulf at that time.
Paediatric ventricular assist device patients, including those with single ventricle anatomy, are increasingly managed outside of the ICU. We used retrospective chart review of our single centre experience to quantify adverse event rates and ICU readmissions for 22 complex paediatric patients on ventricular assist device support (15 two ventricles, 7 single ventricle) after floor transfer. The median age was 1.65 years. The majority utilised the Berlin EXCOR (17, 77.3%). There were 9 ICU readmissions with median length of stay of 2 days. Adverse events were noted in 9 patients (41%), with infection being most common (1.8 events per patient year). There were no deaths. Single ventricle patients had a higher proportion of ICU readmission and adverse events. ICU readmission rates were low, and adverse event rates were comparable to published rates suggesting ventricular assist device patients can be safely managed on the floor.
Maternal health and nutrition in early pregnancy play a vital role in the growth and development of the foetus. During this time, macro and micronutrients contribute to nutritional programming, which helps form the foundations of the foetus’s life course health outcomes. This study aimed to investigate dietary habits, macro and micronutrient intake, micronutrient status, and folic acid supplement adherence among Emirati pregnant women in their first trimester. Data were collected according to the UAE-BCS study protocol, which was set up to investigate maternal nutrition, health, child growth, and developmental outcomes within the first 1000 days. Pregnant Emirati women with singleton pregnancies within their first trimester of pregnancy (between 8 and 12 weeks of gestation) were enrolled. The 24-hour food recall method was administered to collect dietary intake. The maternal mean average age was 29 years. Participants had high adherence to supplementation during pregnancy compared to preconception. The mean energy intake was 1345kcal, and 56% of participants consumed saturated fats above the acceptable macronutrient distribution ranges (AMDR), while 94% consumed below AMDR for total fibre. The consumption of micronutrients was below the recommended dietary allowance (RDA). Biochemical results show a high prevalence of low haemoglobin (74%) and deficiencies in vitamin D (39%) and vitamin E (96%). There is a need for research into dietary patterns and influences in pregnant women in the UAE. Furthermore, investigations of knowledge practices and attitudes towards supplementation and the factors contributing to folic acid supplement use are needed to inform government strategies and interventions.
Limited access to multiple sclerosis (MS)-focused care in rural areas can decrease the quality of life in individuals living with MS while influencing both physical and mental health.
Methods:
The objectives of this research were to compare demographic and clinical outcomes in participants with MS who reside within urban, semi-urban and rural settings within Newfoundland and Labrador. All participants were assessed by an MS neurologist, and data collection included participants’ clinical history, date of diagnosis, disease-modifying therapy (DMT) use, measures of disability, fatigue, pain, heat sensitivity, depression, anxiety and disease activity.
Results:
Overall, no demographic differences were observed between rural and urban areas. Furthermore, the categorization of primary residence did not demonstrate any differences in physical disability or indicators of disease activity. A significantly higher percentage of participants were prescribed platform or high-efficacy DMTs in semi-urban areas; a higher percentage of participants in urban and rural areas were prescribed moderate-efficacy DMTs. Compared to depression, anxiety was more prevalent within the entire cohort. Comparable levels of anxiety were measured across all areas, yet individuals in rural settings experienced greater levels of depression. Individuals living with MS in either an urban or rural setting demonstrated clinical similarities, which were relatively equally managed by DMTs.
Conclusion:
Despite greater levels of depression in rural areas, the results of this study highlight that an overall comparable level and continuity of care is provided to individuals living with MS within rural and urban Newfoundland and Labrador.
Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization.
Method:
This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care.
Results:
Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy.
Discussion:
The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy.
Conclusion:
This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.
The recent expansion of cross-cultural research in the social sciences has led to increased discourse on methodological issues involved when studying culturally diverse populations. However, discussions have largely overlooked the challenges of construct validity – ensuring instruments are measuring what they are intended to – in diverse cultural contexts, particularly in developmental research. We contend that cross-cultural developmental research poses distinct problems for ensuring high construct validity owing to the nuances of working with children, and that the standard approach of transporting protocols designed and validated in one population to another risks low construct validity. Drawing upon our own and others’ work, we highlight several challenges to construct validity in the field of cross-cultural developmental research, including (1) lack of cultural and contextual knowledge, (2) dissociating developmental and cultural theory and methods, (3) lack of causal frameworks, (4) superficial and short-term partnerships and collaborations, and (5) culturally inappropriate tools and tests. We provide guidelines for addressing these challenges, including (1) using ethnographic and observational approaches, (2) developing evidence-based causal frameworks, (3) conducting community-engaged and collaborative research, and (4) the application of culture-specific refinements and training. We discuss the need to balance methodological consistency with culture-specific refinements to improve construct validity in cross-cultural developmental research.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Anhedonia characterizes major depressive episodes in bipolar depression and is associated with more severe illness/poor prognosis. These post hoc analyses assess effect of cariprazine 1.5 and 3 mg/d on anhedonia symptoms in patients with bipolar I depression.
Methods
Data were pooled from 3 randomized, double-blind, placebo-controlled bipolar I depression trials in cariprazine. Cariprazine 1.5 and 3 mg/d versus placebo were evaluated in patient subgroups stratified by median baseline MADRS anhedonia score (higher anhedonia=score ≥19; lower anhedonia=score <19). Outcomes included mean change from baseline to week 6 in MADRS total and anhedonia factor score (sum of apparent sadness, reported sadness, concentration, lassitude, and inability to feel items). The proportion of patients with week 6 anhedonia factor response (≥50% improvement from baseline) was also determined. Changes from baseline were analyzed using a mixed-effect model for repeated measures.
Results
There were 760 patients in the higher anhedonia subgroup (placebo=249, cariprazine: 1.5 mg/d=261; 3 mg/d=250) and 623 patients in the lower anhedonia subgroup (placebo=211, cariprazine: 1.5 mg/d=200; 3 mg/d=212). Mean baseline MADRS total score was higher in the higher anhedonia subgroup (total=33.6) than in the lower anhedonia subgroup (total=27.6). Change from baseline to week 6 in MADRS total score was greater for both cariprazine doses versus placebo in the higher anhedonia subgroup (least squares mean difference [LSMD] and 95% confidence interval [CI]: 1.5 mg/d=-3.01 [-4.84, -1.19], P=.0012; 3 mg/d: -3.26 [-5.12, -1.40], P=.0006); in the lower anhedonia subgroup, cariprazine 1.5 mg/d was statistically significant versus placebo (-2.61 [-4.28, -0.93], P=.0024). In the higher anhedonia subgroup at week 6, change from baseline in anhedonia factor score was significant versus placebo for both cariprazine doses (1.5 mg/d=-1.97 [-3.13, -0.81], P=.0009; 3 mg/d=-2.07 [-3.26, -0.89], P=.0006); in the lower subgroup, the difference was significant versus placebo for cariprazine 1.5 mg/d (-1.70 [-2.77, -0.62], P=.0021). After adjusting for changes in other depressive symptoms, LSMDs versus placebo in the anhedonia factor score remained significant for cariprazine 1.5 mg/d (-1.21 [-2.05, -0.36], P=.0052) and 3 mg/d (-1.00 [-1.86, -0.14], P=.0233) in the higher anhedonia subgroup, and for 1.5 mg/d (-1.06 [-1.92, -0.19], P=.0164) in the lower subgroup. In the higher anhedonia subgroup, rates of anhedonia factor response were greater versus placebo (31.7%) for cariprazine 1.5 mg/d (44.8%, P=.0028) and 3 mg/d (45.6%, P=.0019); in the lower subgroup, response rates were 39.3% for placebo, 48.0% for 1.5 mg/d, and 46.7% for 3 mg/d. Adverse events in ≥5% cariprazine and twice placebo were nausea, akathisia, restlessness, and EPS.
Importance
Those with bipolar depression and anhedonia cariprazine demonstrated a potent antidepressant and antianhedonic effect in higher/lower anhedonia subgroups.
Funding
AbbVie
This data was previously presented at the European College of Neuropsychopharmacology (ECNP) Congress; Barcelona, Spain; October 7 – 10, 2023.
The study objective was to develop and validate a clinical decision support system (CDSS) to guide clinicians through the diagnostic evaluation of hospitalized individuals with suspected pulmonary tuberculosis (TB) in low-prevalence settings.
Methods:
The “TBorNotTB” CDSS was developed using a modified Delphi method. The CDSS assigns points based on epidemiologic risk factors, TB history, symptoms, chest imaging, and sputum/bronchoscopy results. Below a set point threshold, airborne isolation precautions are automatically discontinued; otherwise, additional evaluation, including infection control review, is recommended. The model was validated through retrospective application of the CDSS to all individuals hospitalized in the Mass General Brigham system from July 2016 to December 2022 with culture-confirmed pulmonary TB (cases) and equal numbers of age and date of testing-matched controls with three negative respiratory mycobacterial cultures.
Results:
104 individuals with TB (cases) and 104 controls were identified. Prior residence in a highly endemic country, positive interferon release assay, weight loss, absence of symptom resolution with treatment for alternative diagnoses, and findings concerning for TB on chest imaging were significant predictors of TB (all P < 0.05). CDSS contents and scoring were refined based on the case–control analysis. The final CDSS demonstrated 100% sensitivity and 27% specificity for TB with an AUC of 0.87.
Conclusions:
The TBorNotTB CDSS demonstrated modest specificity and high sensitivity to detect TB even when AFB smears were negative. This CDSS, embedded into the electronic medical record system, could help reduce risks of nosocomial TB transmission, patient-time in airborne isolation, and person-time spent reviewing individuals with suspected TB.