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Fournier gangrene (FG) is a necrotizing soft tissue infection (NSTI) of the perineum. Recent retrospective studies from quaternary centers suggest improved outcomes and a potentially less aggressive clinical course for FG than non-perineal NSTIs. However, comprehensive nationwide data remain limited.
Methods:
This retrospective cohort study analyzed the National Inpatient Sample (2016–2020) to compare outcomes between FG and non-perineal NSTIs. Adult patients undergoing surgical debridement with a diagnosis of FG or NSTI were identified using ICD-10 codes. Outcomes included in-hospital mortality, length of stay (LOS), hospital costs, and home discharge rates. Multivariable regression analyses adjusted for patient demographics, comorbidities, and hospital characteristics.
Results:
A total of 5,007 FG and 24,782 non-perineal NSTI patients were identified. Crude in-hospital mortality rates were 5.8% for FG and 5.4% for non-perineal NSTIs, with stable trends observed over five years. After adjustment, no significant difference in mortality was observed (adjusted odds ratio [aOR]: 1.04; 95% CI: 0.90–1.20). However, FG was associated with longer LOS (adjusted mean difference: 1.99 days; 95% CI: 1.53–2.46) and higher hospital costs ($37,809 higher; 95% CI: $29,540–$46,077). Home discharge rates were similar between groups (aOR: 0.97; 95% CI: 0.89–1.05).
Discussion:
Despite similar mortality rates, FG hospitalizations were associated with increased LOS and higher costs compared to non-perineal NSTIs. These findings may suggest potential nationwide disparities in FG care quality, particularly outside specialized referral centers. Further research is needed to understand if standardized care pathways tailored to FG may optimize management and reduce resource utilization.
Adverse childhood experiences (ACEs) are associated with physical and mental health difficulties in adulthood. This study examines the associations of ACEs with functional impairment and life stress among military personnel, a population disproportionately affected by ACEs. We also evaluate the extent to which the associations of ACEs with functional outcomes are mediated through internalizing and externalizing disorders.
Methods
The sample included 4,666 STARRS Longitudinal Study (STARRS-LS) participants who provided information about ACEs upon enlistment in the US Army (2011–2012). Mental disorders were assessed in wave 1 (LS1; 2016–2018), and functional impairment and life stress were evaluated in wave 2 (LS2; 2018–2019) of STARRS-LS. Mediation analyses estimated the indirect associations of ACEs with physical health-related impairment, emotional health-related impairment, financial stress, and overall life stress at LS2 through internalizing and externalizing disorders at LS1.
Results
ACEs had significant indirect effects via mental disorders on all functional impairment and life stress outcomes, with internalizing disorders displaying stronger mediating effects than externalizing disorders (explaining 31–92% vs 5–15% of the total effects of ACEs, respectively). Additionally, ACEs exhibited significant direct effects on emotional health-related impairment, financial stress, and overall life stress, implying ACEs are also associated with these longer-term outcomes via alternative pathways.
Conclusions
This study indicates ACEs are linked to functional impairment and life stress among military personnel in part because of associated risks of mental disorders, particularly internalizing disorders. Consideration of ACEs should be incorporated into interventions to promote psychosocial functioning and resilience among military personnel.
The glacial history of northeast Siberia is poorly understood compared with other high-latitude regions. Using 10Be and 26Al exposure dating together with remote sensing, we have investigated the glacial history of a remote, formerly glaciated valley in the Tas-Kystabyt Range of the Chersky Mountains in central northeast Siberia. Based on measurements from moraine boulders and bedrock samples, we find evidence for deglaciation of the valley 45.6 ± 3.4 ka ago, that is during the peak of Marine Isotope Stage 3. Satellite imagery of the range reveals at least two generations of moraines in other nearby valleys, indicating that multiple stages of glaciation took place across the Tas-Kystabyt Range. Based on calculated equilibrium-line altitudes, we speculate that the outer set of moraines is linked to the 45.6 ± 3.4 ka deglaciation event identified by our dating, while the inner generation of moraines is associated with a younger glaciation event, possibly the last glacial maximum (LGM). Thus, our results reaffirm current impressions that the maximum ice extent during the last glacial cycle was reached before the global LGM in northeast Siberia.
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.
Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.
Aims
The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.
Method
This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.
Results
Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.
Conclusions
Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.
The RDA for dietary protein is likely insufficient for individuals with cystic fibrosis (CF). This study sought to characterise protein intake and diet quality in adults with cystic fibrosis (awCF), before and after elexacaftor/tezacaftor/ivacaftor (ETI) therapy, compared with healthy controls. Dietary intake was assessed by diet diary in awCF at baseline (BL, n 40) and at follow-up > 3 months post ETI therapy (follow-up (FUP), n 40) and in age-matched healthy controls (CON, n 80) free from known disease at a single time point. Protein intake dose and daily distribution, protein quality, protein source and overall diet quality were calculated for each participant. Both CON (1·39 (sd 0·47) g·kg–1·day–1) and CF (BL: 1·44 (sd 0·52) g·kg–1·day–1, FUP: 1·12 (sd 0·32) g·kg–1·day–1) had a higher mean daily protein intake than the protein RDA of 0·75g·kg–1·day–1. There was a significant reduction in daily protein intake in the CF group at FUP (P = 0·0003, d = 0·73), with levels below the alternative suggested dietary intake of ≥ 1·2 g·kg–1·day–1. There were no sex differences or noticeable effects on protein quality or source following the commencement of ETI therapy when compared with CON (all P > 0·05), although overall diet quality decreased between time points (P = 0·027, d = 0·57). The observed reduction in daily protein intake in the present cohort emphasises the importance of ensuring appropriate dietary protein intake to promote healthy ageing in adults with CF. More research is needed to evidence base dietary protein requirements in this at-risk population.
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.
Natural disasters are becoming more frequent. The crises that follow are becoming more impactful along with diverse emergency-prone hazards and security contexts. EMTs play a crucial role in emergency and disaster response offering timely medical assistance, stabilizing patients, and ensuring safe transport to medical facilities. EMTs must have public health competencies to evaluate, prioritize, and resource all types of medical and public health emergencies.
Objectives:
Define the essential competencies for leading/coordinating actions between public health and disaster medicine to reliably prepare EMTs for lasting success.
Method/Description:
We hosted an international colloquium targeted at EMT capacity building and training.
Results/Outcomes:
EMTs work in environments with limited resources, including medical supplies, equipment, personnel, which impacts their ability to provide care. EMTs provide care to individuals and communities during recovery and provide medical assistance for displaced individuals, addressing acute health concerns and chronic conditions. They empower individuals and communities to take active roles in their recovery fostering empowerment, preparedness, and cohesion. EMTs ensure continuity of care and effectively address emerging health concerns.
Conclusion:
Continued investment is needed in public health training, resources, and support systems to enhance the effectiveness of EMTs in disaster management: 1) training equips EMTs with critical team competencies, 2) adequate resources, including medical supplies, equipment/transportation, are essential for EMTs, 3) investment in mental health support systems to address the psychological impacts of disaster response and recovery, 4) funding research initiatives and embracing technological advancements helps identify best practices and develop evidence-based protocols, 5) establish (international) regulatory framework, registration, and individual competency certification to professionalize EMT cadre.
Interventions to foster inclusive learning environments may benefit college STEMM instructors (NASEM, 2019). We investigated the impact of a social inclusion intervention (SII) on scientific self-efficacy, identity, community values, and persistence intentions in a large and diverse sample of biomedical college instructors (n = 116) in the USA. The results indicated that the SII group developed stronger scientific community values than the control group, and the effect was the strongest for instructors who had initially expressed lower values. From a mentoring perspective, the intervention helps boost feelings of community values, which is linked to increased persistence in STEMM careers.
The effect dietary FODMAPs (fermentable oligo-, di- and mono-saccharides and polyols) in healthy adults is poorly documented. This study compared specific effects of low and moderate FODMAP intake (relative to typical intake) on the faecal microbiome, participant-reported outcomes and gastrointestinal physiology. In a single-blind cross-over study, 25 healthy participants were randomised to one of two provided diets, ‘low’ (LFD) <4 g/d or ‘moderate’ (MFD) 14-18 g/d, for 3 weeks each, with ≥2-week washout between. Endpoints were assessed in the last week of each diet. The faecal bacterial/archaeal and fungal communities were characterised in 18 participants in whom high quality DNA was extracted by 16S rRNA and ITS2 profiling, and by metagenomic sequencing. There were no differences in gastrointestinal or behavioural symptoms (fatigue, depression, anxiety), or in faecal characteristics and biochemistry (including short-chain fatty acids). Mean colonic transit time (telemetry) was 23 (95% confidence interval: 15, 30) h with the MFD compared with 34 (24, 44) h with LFD (n=12; p=0.009). Fungal diversity (richness) increased in response to MFD, but bacterial richness was reduced, coincident with expansion of the relative abundances of Bifidobacterium, Anaerostipes, and Eubacterium. Metagenomic analysis showed expansion of polyol-utilising Bifidobacteria, and Anaerostipes with MFD. In conclusion, short-term alterations of FODMAP intake are not associated with symptomatic, stool or behavioural manifestations in healthy adults, but remarkable shifts within the bacterial and mycobiome populations were observed. These findings emphasise the need to quantitatively assess all microbial Domains and their interrelationships to improve understanding of consequences of diet on gut function.
Double-diffusive convection can arise when the fluid density is set by multiple species which diffuse at different rates. Different flow regimes are possible depending on the distribution of the diffusing species, including salt fingering and diffusive convection. Flows arising from diffusive convection commonly exhibit step-like density profiles with sharp density interfaces separated by well-mixed layers. The formation of density layers is also seen in stratified turbulence, where a framework based on sorted density coordinates (Winters & D’Asaro 1996 J. Fluid Mech.317, 179–193) has been used to diagnose layer formation (Zhou et al. 2017 J. Fluid Mech.823, 198–229; Taylor & Zhou 2017 J. Fluid Mech.823, R5). In this framework, the evolution of the sorted density profile can be expressed solely in terms of the eddy diffusivity, $\kappa _e$. Here, we use the same framework to diagnose layer formation in two-dimensional simulations of double-diffusive convection. We show that $\kappa _e$ is negative everywhere, with the antidiffusive effect strongest in ‘well-mixed’ layers where a positive diffusion coefficient may be expected. By considering a decomposition of the budget of the square of the Brunt-Väisälä frequency $\partial N^2_*/\partial t$, we demonstrate that the density layers are maintained by fundamentally different processes than in single-component stratified turbulence. In more complicated flows where stratified turbulence and double-diffusive convection can coexist, this framework could provide a method to distinguish between the mechanisms responsible for generating density layers.
This is a study of the dynamics of partisan polarization in the United States. It has three objectives: (1) to identify and explain why some Republicans and Democrats – but not others – have polarized, particularly over the last twenty years; (2) to demonstrate that they have done so not on this or that issue but systematically, programmatically – domain versus issue sorting; and (3) to bring into the open profound asymmetries in polarization between the two parties, not least that Republicans polarized early and thoroughly on issues of race, while Democrats in the largest number stayed neutral or even conservative until only recently. Emerging from the reasoning and results is a revised theory of party identification that specifies the conditions under which ordinary Republicans and Democrats can become ideological partisans – real-life conservatives and liberals in their behavior – in the choices they make on candidates, policies, and parties.
Cophinforma spp. are gall-inducing fungi that can infect the highly invasive Brazilian peppertree (Schinus terebinthifolia Raddi), in its introduced range in southern Florida, USA. A classical biological control agent, the thrips Pseudophilothrips ichini, has been released to mitigate the invasive potential of S. terebinthifolia. We investigated the synergistic potential of thrips feeding damage and gall formation on S. terebinthifolia management program success. A group of potted S. terebinthifolia saplings were inoculated with Cophinforma. Galled, symptomatic and ungalled, asymptomatic saplings were then paired in laboratory cages for a two-choice test with 40 P. ichini adults. Galled and ungalled plants were assessed for dead stem tips and necrotic stem tissue, with and without thrips present. Larval F1 thrips were also counted on each plant. Thrips feeding damage significantly increased the number of dead tips and extent of stem necrosis. Regardless of thrips presence, stem tip mortality and extent of necrosis were not significantly different between galled and ungalled plant pairs. Additionally, the maximum number of F1 larvae counted on stems did not differ between those on galled versus ungalled plants. Gall growth on heavily thrips-damaged plants nearly stopped, while galls continued to grow on plants with little thrips damage. While our results suggest the Cophinforma galls do not impact damage potential or plant preference from P. ichini, more work is needed to understand other factors that may contribute to at least additive impacts on S. terebinthifolia in the field, such as more advanced stages of the fungal infection on mature plants and prolonged thrips feeding damage.
This research builds on the work of D.K. Gode and Shyam Sunder who demonstrated the existence of a strong relationship between market institutions and the ability of markets to seek equilibrium—even when the agents themselves have limited intelligence and behave with substantial randomness. The question posed is whether or not market institutions account for the operation of the law of supply and demand in markets populated by humans with no role required of human rationality. Are institutions responsible for the operations of the law of supply and demand or are behavioral principles also at work? Experiments with humans and simulations with robots both conducted in conditions in which major institutional and structural aids to convergence were removed, produced clear answers. Human markets converge, while robot markets do not. The structural and institutional features certainly facilitate convergence under conditions of substantial irrationality, but they are not necessary for convergence in markets in which agents have the rationality of humans.
To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates—clusters of symptoms that occur within individuals over time.
Methods
Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18–35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed.
Results
Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates.
Conclusions
Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.
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.
Sea-ice floating in the Arctic ocean is a constantly moving, growing and melting layer. The seasonal cycle of sea-ice volume has an average amplitude of $10\,000\,\mathrm{km}^3$ or 9 trillion tonnes of sea ice. The role of dynamic redistribution of sea ice is observable during winter growth by the incorporation of satellite remote sensing of ice thickness, concentration and drift. Recent advances in the processing of CryoSat-2 radar altimetry data have allowed for the retrieval of summer sea-ice thickness. This allows for a full year of a purely remote sensing-derived ice volume budget analysis.
Here, we present the closed volume budget of Arctic sea ice over the period October 2010–May 2022 revealing the key contributions to summer melt and minimum sea-ice volume and extent. We show the importance of ice drift to the inter-annual variability in Arctic sea-ice volume and the regional distribution of sea ice. The estimates of specific areas of sea-ice growth and melt provide key information on sea-ice over-production, the excess volume of ice growth compared to melt. The statistical accuracy of each key region of the Arctic is presented, revealing the current accuracy of knowledge of Arctic sea-ice volume from observational sources.
Lewy body dementias (LBD) are the second most common dementia. Several genes have been associated with LBD, but little is known about their contributions to LBD pathophysiology. Each gene may transcribe multiple RNA, and LBD brains have extensive RNA splicing dysregulation. Hence, we completed the first transcriptome-wide transcript-level differential expression analysis of post-mortem LBD brains for gaining more insights into LBD molecular pathology that are essential for facilitating discovery of novel therapeutic targets and biomarkers for LBD. We completed transcript-level quantification of next-generation RNA-sequencing data from post-mortem anterior cingulate (ACC) and dorsolateral prefrontal cortices (DLPFC) of people with pathology-verified LBD (LBD = 14; Controls = 7) using Salmon. We identified differentially expressed transcripts (DET) using edgeR and investigated their functional implications using DAVID. We performed transcriptome-wide alternative splicing analysis using DRIMseq. We identified 74 DET in ACC and 96 DET in DLPFC after Benjamini-Hochberg false discovery rate (FDR) correction (5%). There were 135 and 98 FDR-corrected alternatively spliced genes in ACC and DLPFC of LBD brains, respectively. Identified DET may contribute to LBD pathology by altering DNA repair, apoptosis, neuroplasticity, protein phosphorylation, and regulation of RNA transcription. We confirm widespread alternative splicing and absence of chronic neuroinflammation in LBD brains. Transcript-level differential expression analysis can reveal specific DET that cannot be detected by gene-level expression analyses. Therapeutic and diagnostic biomarker potential of identified DET, especially those from TMEM18, MICB, MPO, and GABRB3, warrant further investigation. Future LBD blood-based biomarker studies should prioritise measuring the identified DET in small extracellular vesicles.