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Abstract Antibiotics are extensively used in human medicine, aquaculture, and animal husbandry, leading to the release of antimicrobial resistance into the environment. This contributes to the rapid spread of antibiotic-resistant genes (ARGs), posing a significant threat to human health and aquatic ecosystems. Conventional wastewater treatment methods often fail to eliminate ARGs, prompting the adoption of advanced oxidation processes (AOPs) to address this growing risk. The study investigates the efficacy of visible light-driven photocatalytic systems utilizing two catalyst types (TiO2-Pd/Cu and g-C3N4-Pd/Cu), with a particular emphasis on their effectiveness in eliminating bla TEM , ermB, qnrS, tetM. intl1, 16 S rDNA and 23 S rDNA through photocatalytic ozonation and peroxone processes. Incorporating O3 into photocatalytic processes significantly enhances target removal efficiency, with the photocatalyst-assisted peroxone process emerging as the most effective AOP. The reemergence of targeted contaminants following treatment highlights the pivotal importance of AOPs and the meticulous selection of catalysts in ensuring sustained treatment efficacy. Furthermore, Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) analysis reveals challenges in eradicating GC-rich bacteria with TiO2 and g-C3N4 processes, while slight differences in Cu/Pd loadings suggest g-C3N4-based ozonation improved antibacterial effectiveness. Terminal Restriction Fragment Length Polymorphism analysis highlights the efficacy of the photocatalyst-assisted peroxone process in treating diverse samples.

Background: The consortium project INTEGRATE-ADHD compared administrative data on the presence of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with the results of a parent survey and a comprehensive clinical assessment based on the S3 guideline of the Association of the Scientific Medical Societies in Germany (AWMF). Due to the COVID-19 pandemic, the clinical assessment was carried out online. Methods: The article describes how a guideline-based clinical assessment of ADHD can be implemented in an online setting. A specially developed diagnostic matrix is presented to illustrate the assessment procedures and the diagnostic decision-making process. The matrix is intended to help the diagnostician to gain an overview of the numerous individual findings that have been collected using different assessment perspectives and methods (e.g. diagnostic interviews, rating scales, performance tests) in order to make a well-founded and transparent diagnostic decision. Discussion: The consortium project INTEGRATE-ADHD has shown that an online assessment can be implemented in a guideline-compliant manner and allows a valid clinical decision. The diagnostic strategy is discussed with reference to international guidelines and recommendations for online diagnostics (e.g. aspects of feasibility, acceptability and safety of the assessment procedures). The challenges and opportunities of using online assessments in clinical practice are also described.

Background: The study examines the psychometric properties of the ADHD section of the semi-structured diagnostic interview ILF-EXTERNAL, which was conducted online via video chat. Methods: As part of the INTEGRATE-ADHD research project, 202 children and adolescents (age M = 12.87 years, SD = 3.04, 28.2 % female) with an administrative diagnosis of ADHD registered with their health insurance company were clinically assessed for the presence of ADHD according to the German ADHD S3 guideline. Using the ILF-EXTERNAL, one parent and, from the age of eight, also the children themselves were interviewed. A proxy rating by a parent was made using the German FBB-ADHS rating scale. In a subsample (n = 65), an independent blind interviewer rated the videorecordings of the ILF-EXTERNAL parent interview to determine the interrater reliability of the ILF-EXTERNAL. Results: All ADHD symptom scales of the ILF-EXTERNAL showed good to excellent internal consistency (α = 0.89 to 0.93). Interrater reliability was high for both categorical and dimensional analyses (κ = 0.78 and κ = 0.81; ICC(1,1) = 0.97 and 0.98). High correlations of the ILF-EXTERNAL parent interview with the FBB-ADHS (r = 0.79 to r = 0.85) and with the ILF-EXTERNAL child interview (r = 0.60 to r = 0.71) demonstrated convergent validity. Conclusions: Sound psychometric properties of the ILF-EXTERNAL were also confirmed for its use in an online setting. High interrater reliabilities demonstrate the quality of the ADHD diagnostics carried out in the consortium project INTEGRATE-ADHD.

Abstract Sub-Saharan Africa (SSA) has the highest burden of neonatal hypoxic ischemic encephalopathy (HIE) in the world. However, there are few descriptions of HIE management in SSA and therapeutic hypothermia (TH) is considered controversial. A web-based survey was distributed to doctors across SSA in 2023. Adequate responses were received from 136 doctors across 43 of 48 countries. Therapeutic hypothermia was available in 13 countries, most frequently in private institutions compared to other settings (69% vs. 28%; P = 0.004). Over 90% of respondents who provided TH, appropriately cooled neonates to rectal temperatures of 33.5 °C before age 6 h, for 72 h, and 79% used automated cooling methods. Intubated ventilation and electroencephalograms were more available where TH was used (81% vs. 55%; p = 0.004 and 65% vs. 8%; p

Abstract Background The Association of American Medical Colleges suggests an Experiences-Attributes-Metrics framework for holistic review, but there is minimal research on demographic and personal characteristic attributes and the interplay between these Attributes subcategories. Understanding how personal attributes may vary among students considered represented and those considered underrepresented in one or more categories is critical to avoid unintentionally perpetuating practices that favor represented groups. This study explored differences in six personal characteristics either consistently related to academic performance or deemed positive professional traits based on diversity characteristics (categories of underrepresentation), age, and sex. Methods Three cohorts of first-year Doctor of Physical Therapy students at a single institution were invited to participate in this prospective, observational study. Participants completed six surveys: PROMIS® General Self-efficacy, PROMIS® Anxiety, 12-item Grit Scale, Perceived Stress Scale-10 (PSS-10), Brief Resilience Scale (BRS), and PROMIS® Positive Affect. T-tests and ANOVAs (or nonparametric equivalents) were used to examine differences in these measures by number of diversity characteristics, age, and sex. Multivariate linear regression was used to determine if diversity characteristics explained additional variance in each of the personal attribute scores after controlling for age and sex. Results One Hundred and Forty Five students participated (80.7% female, 77.9%

Abstract Natural compounds constitute a major resource for the development of medicines for multiple diseases. While many natural compounds show strong biological activity, the mechanisms that confer clinical benefits are often elusive and have been attributed to multiple pathways. Periplogenin (PPG), a natural compound isolated from Cortex periplocae, exhibits strong anti-tumor activities in several human cancer cell lines. However, its molecular mode of action remained unclear. In this study, we leveraged a forward genetic screening approach in DU145 prostate cancer cells to uncover the molecular target of PPG using chemical mutagenesis. Next generation sequencing revealed that a single amino acid substitution at amino acid 804 in ATP1A1 (ATPase Na + /K + Transporting Subunit Alpha 1) confers resistance to the cytotoxic activity of PPG. Mechanistically, ATP1A1 T804 forms a hydrogen bond with PPG which is abolished by the T804A substitution in ATP1A1, resulting in resistance to PPG treatment in vitro. Importantly, in vivo, PPG strongly suppressed tumor development in a DU145 xenograft model whereas DU145 xenograft tumors carrying a ATP1A1-T804A mutation were largely unaffected by the treatment. These findings demonstrate that PPG suppresses the growth of DU145 prostate cancer cells in vitro and in vivo by directly binding to ATP1A1 and highlight the power of our unbiased forward genetic screening approach to uncover direct drug target structures at single amino acid resolution.

Abstract Scandinavian electronic health-care registers provide a unique setting to investigate potential unidentified side effects of drugs. We analysed the association between prescription drugs dispensed in Norway and Sweden and the short-term risk of developing pulmonary embolism. A total of 12,104 pulmonary embolism cases were identified from patient- and cause-of-death registries in Norway (2004–2014) and 36,088 in Sweden (2005–2014). A case-crossover design was used to compare individual drugs dispensed 1–30 days before the date of pulmonary embolism diagnosis with dispensation in a 61–90 day time-window, while controlling for the receipt of other drugs. A BOLASSO approach was used to select drugs that were associated with short-term risk of pulmonary embolism. Thirty-eight drugs were associated with pulmonary embolism in the combined analysis of the Norwegian and Swedish data. Drugs associated with increased risk of pulmonary embolism included certain proton-pump inhibitors, antibiotics, antithrombotics, vasodilators, furosemide, anti-varicose medications, corticosteroids, immunostimulants (pegfilgrastim), opioids, analgesics, anxiolytics, antidepressants, antiprotozoals, and drugs for cough and colds. Mineral supplements, hydrochlorothiazide and potassium-sparing agents, beta-blockers, angiotensin 2 receptor blockers, statins, and methotrexate were associated with lower risk. Most associations persisted, and several additional drugs were associated, with pulmonary embolism when using a longer time window of 90 days instead of 30 days. These results provide exploratory, pharmacopeia-wide evidence of medications that may increase or decrease the risk of pulmonary embolism. Some of these findings were expected based on the drugs' indications, while others are novel and require further study as potentially modifiable precipitants of pulmonary embolism.

Abstract Background The use of serious games in medical education provides a bridge between rapidly developing technology and traditional health-care teaching. Building on a promising web-based serious game for reviewing and acquiring factual knowledge in dental education, the present study investigated the benefits of a dual-player mode and various game options for enhancing knowledge gain and study motivation. Methods Before the intervention, students’ dental knowledge and game experience were assessed using a pre-knowledge test and questionnaire-based self-assessment. Students in the clinical study phase (n = 57) were stratified based on prior knowledge and gender and then randomly assigned to two groups, with two player modes: single player (SP) and dual player (DP). In the SP group, each participant played alone, whereas in the DP group, the participants played against a previously determined peer. For a period of 4 weeks, the students were able to playfully acquire knowledge from the field of operative dentistry using METIS, a serious game application with three different game options (Marathon, Sprint, and Time). After the intervention phase, both groups completed a post-knowledge test. The usability of the serious game was evaluated with a self-assessment questionnaire. Results The competitive game mode (DP mode; M = 8.92, SD = 1.85) resulted in an increase in the factual knowledge test that was a mean of 2.49 points higher than the SP mode (M = 5.89, SD = 2.19; p

Abstract Inhibitory phosphatases, such as the inositol-5-phosphatase SHIP1 could potentially contribute to B-cell acute lymphoblastic leukemia (B-ALL) by raising the threshold for activation of the autoimmunity checkpoint, allowing malignant cells with strong oncogenic B-cell receptor signaling to escape negative selection. Here, we show that SHIP1 is differentially expressed across B-ALL subtypes and that high versus low SHIP1 expression is associated with specific B-ALL subgroups. In particular, we found high SHIP1 expression in both, Philadelphia chromosome (Ph)-positive and ETV6-RUNX1-rearranged B-ALL cells. As demonstrated by targeted knockdown of SHIP1 by RNA interference, proliferation of B-ALL cells in vitro and their tumorigenic spread in vivo depended in part on SHIP1 expression. We investigated the regulation of SHIP1, as an important antagonist of the AKT signaling pathway, by the B-cell-specific transcription factor Ikaros. Targeted restoration of Ikaros and pharmacological inhibition of the antagonistic casein kinase 2, led to a strong reduction in SHIP1 expression and at the same time to a significant inhibition of AKT activation and cell growth. Importantly, the tumor suppressive function of Ikaros was enhanced by a SHIP1-dependent additive effect. Furthermore, our study shows that all three AKT isoforms contribute to the pro-mitogenic and anti-apoptotic signaling in B-ALL cells. Conversely, hyperactivation of a single AKT isoform is sufficient to induce negative selection by increased oxidative stress. In summary, our study demonstrates the regulatory function of Ikaros on SHIP1 expression in B-ALL and highlights the relevance of sustained SHIP1 expression to prevent cells with hyperactivated PI3K/AKT/mTOR signaling from undergoing negative selection.

Abstract Autistic youth experience several behavioral and emotional characteristics that can predispose them to emotion dysregulation (ED). Current literature examining ED in autism spectrum disorder (ASD) is limited to parent- and self-reported measures, indicating a need for biological or physiological methods to better assess emotion regulation in ASD. Utilizing the autonomic nervous system, specifically heart rate variability (HRV), may be a promising method to objectively measure ED in ASD, given it is one of the body’s primary means of regulating physiological arousal. Our pilot study is one of the first to examine the feasibility, utility, and construct validity of HRV along with clinical measures within an intervention targeting ED-specific symptoms in ASD. Participants included 30 autistic youth ages 8–17 years who participated in the pilot study of Regulating Together, a group-based intervention targeting emotion regulation. We demonstrate HRV is feasible, demonstrates adequate test–retest reliability, and is complimentary to clinician- and parent-reported measures. Our preliminary findings also point to certain HRV profiles being indicative of long-term outcomes after receiving treatment. HRV may be a useful, objective tool in determining differential needs of long-term follow-up care for treatment maintenance at screening or baseline stages.

Abstract Background The COVID-19 pandemic has had a significant impact on mental health, with evidence suggesting an enduring mental health crisis. Studies worldwide observed increased usage of antidepressants, anxiolytics, and hypnotics during the pandemic, notably among young people and women. However, few studies tracked consumption post-2021. Our study aimed to fill this gap by investigating whether the surge in the number psychotropic drug consumers in France persisted 2 years after the first lockdown, particularly focusing on age and gender differences. Methods We conducted a national retrospective observational study based on the French national insurance database. We retrieved all prescriptions of anxiolytics, hypnotics, and antidepressants dispensed in pharmacies in France for the period 2015–2022. We performed interrupted time series analyses based on Poisson models for five age classes (12–18; 19–25; 26–50; 51–75; 76 and more) to assess the trend before lockdown, the gap induced and the change in trend after. Results In the overall population, the number of consumers remained constant for antidepressants while it decreased for anxiolytics and hypnotics. Despite this global trend, a long-term increase was observed in the 12–18 and 19–25 groups for the three drug classes. Moreover, for these age classes, the increases were more pronounced for women than men, except for hypnotics where the trends were similar. Conclusions The number of people using antidepressants continues to increase more than 2 years after the first lockdown, showing a prolonged effect on mental health. This effect is particularly striking among adolescents and young adults confirming the devastating long-term impact of the pandemic on their mental health.

Abstract Climate change and atmospheric deposition of nitrogen (N) and sulfur (S) impact the health and productivity of forests. Here, we explored the potential impacts of these environmental stressors on ecosystem services provided by future forests in the contiguous U.S. We found that all stand-level services benefitted (+ 2.6 to 8.1%) from reductions in N+S deposition, largely attributable to positive responses to reduced S that offset the net negative effects of lower N levels. Sawtimber responded positively (+ 0.5 to 0.6%) to some climate change, but negatively (− 2.4 to − 3.8%) to the most extreme scenarios. Aboveground carbon (C) sequestration and forest diversity were negatively impacted by all modelled changes in climate. Notably, the most extreme climate scenario eliminated gains in all three services achieved through reduced deposition. As individual tree species responded differently to climate change and atmospheric deposition, associated services unique to each species increased or decreased under future scenarios. Our results suggest that climate change should be considered when evaluating the benefits of N and S air pollution policies on the services provided by U.S. forests.

Abstract Although Eucalyptus is widely planted outside its native range for timber and pulp production, the effects of these exotic plantations on biodiversity relative to native semi-natural forests or plantations of native tree species remain incompletely understood. Here, we compare the diversity of saproxylic beetles (Coleoptera) and true bugs (Hemiptera) between non-native Eucalyptus benthamii Maiden and Cambage (Camden white gum) and native Pinus taeda L. (loblolly pine) stands on the upper Coastal Plain of South Carolina, U.S.A. We sampled insects emerging from logs of both species placed in both stand types after 1, 2, 6, and 12 months in the field. Beetle and true bug richness and diversity were both significantly lower from eucalypt than from pine wood. Moreover, the two communities were compositionally distinct. Whereas pine supported many species of host-specific phloeoxylophagous beetles, most species collected from eucalypts were mycophagous or predatory taxa capable of utilizing a wide range of hosts. Species richness did not differ between logs placed in eucalypt vs. pine stands but Shannon’s diversity was significantly higher in the eucalypt stands, possibly due to greater sun exposure in the latter. Contrary to a previous study, we found no support for the idea that eucalypt litter reduces the diversity of saproxylic insects. Our findings add to the growing body of evidence that non-native plantations are less favorable to biodiversity than those consisting of native tree species.

Abstract The cause of sudden sensorineural hearing loss (SSNHL) remains unknown in a significant number of cases, but vascular involvement in its pathophysiology has been proposed. Our study aimed to assess the incidence of stroke following idiopathic SSNHL (iSSNHL) and to evaluate associated cardiovascular risk factors and comorbidities. We extracted electronic medical record data from iSSNHL patients aged ≥ 50 years retrospectively from 84 general practices. Patients were matched for age, sex and general practice in a 1:4 ratio to controls. Primary outcome was the 5-years stroke risk following iSSNHL diagnosis. 480 iSSNHL cases could be matched to 1911 controls. The hazard ratio for iSSNHL compared with controls was 1.25 (95%CI 0.50–3.27; P = 0.646) for CVA (cerebrovascular accident) alone and 0.92 (95% CI 0.50–1.71; P = 0.804) for CVA and TIA (transient ischemic attack) combined. The hazard ratio for the interaction term between iSSNHL and age ≥ 60 years was 4.84 (95% CI 1.02–23.05; P = 0.048) for CVA and TIA combined. Patients with iSSNHL used antihypertensives and beta-blocking agents more frequently than controls (P = 0.006 and P = 0.022, respectively). In conclusion, no overall significant difference in the risk of stroke was observed, but the hazard ratio for stroke increased in iSSNHL patients aged 60 and older, suggesting potential vascular involvement in older subjects presenting with sudden sensorineural hearing loss.

Abstract Single nucleotide polymorphisms (SNPs) account for significant genomic variability in microbes, including the highly diverse gastric pathogen Helicobacter pylori. However, data on the effects of specific SNPs in pathogen-host interactions are scarce. Recent functional studies unravelled how a serine/leucine polymorphism in serine protease HtrA affects the formation of proteolytically active trimers and modulates cleavage of host cell-to-cell junction proteins during infection. A similar serine/leucine mutation in the carbohydrate binding domain of the adhesin BabA controls binding of ABO blood group antigens, enabling binding of either only the short Lewis b/H antigens of blood group O or also the larger antigens of blood groups A and B. Here we summarize the functional importance of these two remarkable bacterial SNPs and their effect on the outcome of pathogen-host interactions.

Gremlin-1 has been implicated in liver fibrosis in metabolic dysfunction-associated steatohepatitis (MASH) via inhibition of bone morphogenetic protein (BMP) signalling and has thereby been identified as a potential therapeutic target. Using rat in vivo and human in vitro and ex vivo model systems of MASH fibrosis, we show that neutralisation of Gremlin-1 activity with monoclonal therapeutic antibodies does not reduce liver inflammation or liver fibrosis. Still, Gremlin-1 was upregulated in human and rat MASH fibrosis, but expression was restricted to a small subpopulation of COL3A1/THY1+ myofibroblasts. Lentiviral overexpression of Gremlin-1 in LX-2 cells and primary hepatic stellate cells led to changes in BMP-related gene expression, which did not translate to increased fibrogenesis. Furthermore, we show that Gremlin-1 binds to heparin with high affinity, which prevents Gremlin-1 from entering systemic circulation, prohibiting Gremlin-1-mediated organ crosstalk. Overall, our findings suggest a redundant role for Gremlin-1 in the pathogenesis of liver fibrosis, which is unamenable to therapeutic targeting.

The consensus-based guideline “hand antisepsis and hand hygiene” for Germany has the following sections: Prevention of nosocomial infections by hygienic hand antisepsis, prevention of surgical site infections by surgical hand antisepsis, infection prevention in the community by hand antisepsis in epidemic or pandemic situations, hand washing, selection of alcohol-based hand rubs and wash lotions, medical gloves and protective gloves, preconditions for hand hygiene, skin protection and skin care, quality assurance of the implementation of hand hygiene measures and legal aspects. The guideline was developed by the German Society for Hospital Hygiene in cooperation with 22 professional societies, 2 professional organizations, the German Care Council, the Federal Working Group for Self-Help of People with Disabilities and Chronic Illness and their Family Members, the General Accident Insurance Institution Austria and the German-speaking Interest Group of Infection Prevention Experts and Hospital Hygiene Consultants.

Epithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of tissue injury influences early damage signaling and regenerative growth of sensory axons remains unclear. Previously we reported that thermal injury triggers distinct early tissue responses in larval zebrafish. Here, we found that thermal but not mechanical injury impairs sensory axon regeneration and function. Real-time imaging revealed an immediate tissue response to thermal injury characterized by the rapid Arp2/3-dependent migration of keratinocytes, which was associated with tissue scale ROS production and sustained sensory axon damage. Isotonic treatment was sufficient to limit keratinocyte movement, spatially restrict ROS production, and rescue sensory neuron function. These results suggest that early keratinocyte dynamics regulate the spatial and temporal pattern of long-term signaling in the wound microenvironment during tissue repair.

Abstract Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence. Understanding the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity. G protein-coupled receptors (GPCRs) are among the main modulators of metabolism and energy balance. They, for instance, regulate appetite and satiety in certain hypothalamic neurons, as well as glucose and lipid metabolism and hormone secretion from adipocytes. Mutations in some GPCRs, such as the melanocortin receptor type 4 (MC4R), have been associated with early-onset obesity. Here, we identified the adhesion GPCR latrophilin 1 (ADGRL1/LPHN1) as a member of the regulating network governing food intake and the maintenance of energy balance. Deficiency of the highly conserved receptor in mice results in increased food consumption and severe obesity, accompanied by dysregulation of glucose homeostasis. Consistently, we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from obesity. Therefore, we propose that LPHN1 dysfunction is a risk factor for obesity development.

Abstract Climate changes leading to increasingly longer seasonal drought periods in large parts of the world increase the necessity for breeding drought-tolerant crops. Cultivated potato (Solanum tuberosum), the third most important vegetable crop worldwide, is regarded as drought-sensitive due to its shallow root architecture. Two German tetraploid potato cultivars differing in drought tolerance and their F1-progeny were evaluated under various drought scenarios. Bulked segregant analyses were combined with whole-genome sequencing (BSA-Seq) using contrasting bulks of drought-tolerant and drought-sensitive F1-clones. Applying QTLseqr, 15 QTLs comprising 588,983 single nucleotide polymorphisms (SNPs) in 2325 genes associated with drought stress tolerance were identified. SeqSNP analyses in an association panel of 34 mostly starch potato varieties using 1–8 SNPs for each of 188 selected genes narrowed the number of candidate genes down to 10. In addition, ent-kaurene synthase B was the only gene present under QTL 10. Eight of the identified genes (StABP1, StBRI1, StKS, StLEA, StPKSP1, StPKSP2, StYAB5, and StZOG1) address plant development, the other three genes (StFATA, StHGD and StSYP) contribute to plant protection under drought stress. Allelic variation in these genes might be explored in future breeding for drought-tolerant potato varieties.

Objective: Time spent among the 24-h movement behaviors (physical activity [PA], sleep, sedentary behavior [SB]) in the perinatal period is important for maternal and child health. We described changes to 24-h movement behaviors and behavior guideline attainment during pregnancy and postpartum and identified correlates of behavior changes. Methods: This secondary data analysis included the standard of care group (n = 439) from the U.S.-based Lifestyle Interventions For Expectant Moms (LIFE-Moms) consortium, including persons with overweight and obesity. Wrist-worn accelerometry was used to measure movement behaviors early (9–15 weeks) and late (35–36 weeks) pregnancy, and ∼ 1-year postpartum. Sleep and moderate-to-vigorous PA (MVPA) were compared to adult and pregnancy-specific guidelines, respectively. SB was classified into quartiles. PA and SB context were quantified using questionnaires. Mixed models were used to examine changes in behaviors and guidelines and identify correlates. Results: Participants were 31.3 ± 3.5 years, 53.5 % were Black or Hispanic, and 45.1 % had overweight. Sleep duration decreased across time, but participants consistently met the guideline (range: 85.0–93.6 %). SB increased during pregnancy and decreased postpartum, while light PA and MVPA followed the inverse pattern. Participants met slightly fewer guidelines late pregnancy (1.2 ± 0.7 guidelines) but more postpartum (1.7 ± 0.8 guidelines) than early pregnancy (1.4 ± 0.8 guidelines). Black or Hispanic race/ethnicity, higher pregravid body mass index, and non-day work-shift (e.g., night-shift) were identified correlates of lower guideline adherence and varying PA and SB context. Conclusion: Perinatal interventions should consider strategies to prevent SB increase and sustain MVPA to promote guideline adherence.

Label-free techniques including Surface Plasmon Resonance (SPR) and Biolayer Interferometry (BLI) are biophysical tools widely used to collect binding kinetics data of bimolecular interactions. To efficiently analyze SPR and BLI binding kinetics data, we have built a new high throughput analysis tool named the TitrationAnalysis. It can be used as a package in the Mathematica scripting environment and ultilize the non-linear curve-fitting module of Mathematica for its core function. This tool can fit the binding time course data and estimate association and dissociation rate constants (ka and kd respectively) for determining apparent dissociation constant (KD ) values. The high throughput fitting process is automatic, requires minimal knowledge on Mathematica scripting and can be applied to data from multiple label-free platforms. We demonstrate that the TitrationAnalysis is optimal to analyze antibody-antigen binding data acquired on Biacore T200 (SPR), Carterra LSA (SPR imaging) and ForteBio Octet Red384 (BLI) platforms. The ka , kd and KD values derived using TitrationAnalysis very closely matched the results from the commercial analysis software provided specifically for these instruments. Additionally, the TitrationAnalysis tool generates user-directed customizable results output that can be readily used in downstream Data Quality Control associated with Good Clinical Laboratory Practice operations. With the versatility in source of data input source and options of analysis result output, the TitrationAnalysis high throughput analysis tool offers investigators a powerful alternative in biomolecular interaction characterization.

Objectives To explore and compare physicians’ reported moral distress in 2004 and 2021 and identify factors that could be related to these responses.Design Longitudinal survey.Setting Data were gathered from the Norwegian Physician Panel Study, a representative sample of Norwegian physicians, conducted in 2004 and 2021.Participants 1499 physicians in 2004 and 2316 physicians in 2021.Main outcome measures The same survey instrument was used to measure change in moral distress from 2004 to 2021. Logistic regression analyses examined the role of gender, age and place of work.Results Response rates were 67% (1004/1499) in 2004 and 71% (1639/2316) in 2021. That patient care is deprived due to time constraints is the most severe dimension of moral distress among physicians, and it has increased as 68.3% reported this ‘somewhat’ or ‘very morally distressing’ in 2004 compared with 75.1% in 2021. Moral distress also increased concerning that patients who ‘cry the loudest’ get better and faster treatment than others. Moral distress was reduced on statements about long waiting times, treatment not provided due to economic limitations, deprioritisation of older patients and acting against one’s conscience. Women reported higher moral distress than men at both time points, and there were significant gender differences for six statements in 2021 and one in 2004. Age and workplace influenced reported moral distress, though not consistently for all statements.Conclusion In 2004 and 2021 physicians’ moral distress related to scarcity of time or unfair distribution of resources was high. Moral distress associated with resource scarcity and acting against one’s conscience decreased, which might indicate improvements in the healthcare system. On the other hand, it might suggest that physicians have reduced their ideals or expectations or are morally fatigued.

Abstract Background Patients with tuberous sclerosis complex (TSC) face an increased risk of maternal health complications and worsening disease manifestations during pregnancy. There are no established consensus guidelines that address the management of pregnancy in patients with TSC and healthcare providers rely on their individual experiences and preferences to derive treatment decisions. We sought to obtain provider opinion of pregnancy related maternal complications in patients with TSC, and the common evaluation and management strategies used to address these issues. Methods We conducted a cross-sectional survey of healthcare providers with diverse areas of expertise related to the multisystem nature of involvement in TSC. Descriptive analyses were used to analyze our three primary variables: (1) provider recognition of maternal risks/complications; (2) provider recommendations before and during pregnancy; and (3) provider/clinic protocols. Results We received responses from 87 providers from 11 countries, with 40.7% (n = 35) seeing > 30 TSC patients yearly. The majority of providers (n = 70, 88.6%) deemed that a patient with TSC needed expert care beyond the standard of care for a typical pregnancy, with over 25% of providers reporting that they have seen lymphangioleiomyomatosis (LAM) exacerbation, seizures, and preterm labor in pregnant patients with TSC. Providers who managed patients treated with mTOR inhibitors (mTORi) also agreed that mTORi use should be stopped prior to pregnancy (n = 45, 68.2%) but there was uncertainty about when to stop the mTORi (one month 28.9%, two months 11.1%, three months 42.2%, and 6–12 months 2.2%). Additionally, there were mixed opinions on restarting mTORi in response to disease progression during pregnancy. When asked about provider or clinic specific protocols, 71.6% (n = 53) of providers stated that they do not have a clear protocol for management decisions for patients with TSC before or during pregnancy. Conclusion Healthcare providers recognize that patients with TSC are at an increased risk for maternal health complications during pregnancy. However, there are wide inter-individual variances in practice, especially pertaining to decisions regarding mTORi use. There is a critical need to better understand the implications of pregnancy for patients with TSC, and to draft consensus recommendations to guide management decisions.

Abstract Time-based prospective memory (TBPM) involves remembering to perform actions at specific times in the future. Several studies suggest that monetary consequences improve prospective remembering; however, the effect of monetary consequences on strategic time monitoring (i.e., clock-checking behaviour) in TBPM is still unknown. The present study investigated how the monetary costs on clock-checking affected TBPM accuracy and strategic time monitoring. Participants performed an ongoing lexical decision task while carrying out a TBPM task every two minutes. Motivational incentives were manipulated across three experimental conditions: a single-cost condition in which missed TBPM responses led to monetary deductions, a double-cost condition in which both missed responses and time monitoring led to monetary deductions, and a control condition with no monetary deductions. Overall, the findings indicated that monetary costs on clock-checking prompted more parsimonious strategic time monitoring behaviour, which negatively impacted TBPM accuracy. These results emphasize the importance of weighing the motivational aspects involved in strategic monitoring, shedding light on the complex relationship between clock-checking behaviour, its consequences, and TBPM performance.

Abstract The COVID-19 pandemic posed a global threat to nearly every society around the world. Individuals turned to their political leaders to safely guide them through this crisis. The most direct way political leaders communicated with their citizens was through official speeches and press conferences. In this report, we compare psychological language markers of four different heads of state during the early stage of the pandemic. Specifically, we collected all pandemic-related speeches and press conferences delivered by political leaders in the USA (Trump), UK (Johnson), Germany (Merkel), and Switzerland (Swiss Federal Council) between February 27th and August 31st, 2020. We used natural language analysis to examine language markers of expressed positive and negative emotions, references to the community (we-talk), analytical thinking, and authenticity and compare these language markers across the four nations. Level differences in the language markers between the leaders can be detected: Trump’s language was characterized by a high expression of positive emotion, Merkel’s by a strong communal focus, and Johnson’s and the Swiss Federal Council by a high level of analytical thinking. Overall, these findings mirror different strategies used by political leaders to deal with the COVID-19 pandemic.

Abstract Pathogens typically responsible for hospital-acquired infections (HAIs) constitute a major threat to healthcare systems worldwide. They spread via hospital (or hospital-community) networks by readmissions or patient transfers. Therefore, knowledge of these networks is essential to develop and test strategies to mitigate and control the HAI spread. Until now, no methods for comparing healthcare networks across different systems were proposed. Based on healthcare insurance data from four German federal states (Bavaria, Lower Saxony, Saxony and Thuringia), we constructed hospital networks and compared them in a systematic approach regarding population, hospital characteristics, and patient transfer patterns. Direct patient transfers between hospitals had only a limited impact on HAI spread. Whereas, with low colonization clearance rates, readmissions to the same hospitals posed the biggest transmission risk of all inter-hospital transfers. We then generated hospital-community networks, in which patients either stay in communities or in hospitals. We found that network characteristics affect the final prevalence and the time to reach it. However, depending on the characteristics of the pathogen (colonization clearance rate and transmission rate or even the relationship between transmission rate in hospitals and in the community), the studied networks performed differently. The differences were not large, but justify further studies.

Abstract Background Kidney transplantation suffers from a shortage of donor organs. Despite this, a lot of grafts are discarded due to inadequate quality. As many kidneys are afflicted by transient filtration failure early after preservation, classical renal function tests are not applicable to differentiate between prospective recovery or continuing deficit of renal function. Methods Using normothermic machine perfusion as a platform for pre-implantation evaluation of the graft, we present a novel evaluative approach based on the metabolic turnover of 13C-acetate during isolated perfusion. After injection of the tracer, 13CO2 as a metabolic end-product can be quantified by high-precision laser-based spectroscopy in the gas outflow of the oxygenator. Three groups of porcine kidneys with graduated ischemic injury were investigated. Results This quantitative approach is able to discriminate acceptable quality kidneys, most likely to recover within days from poor kidney grafts that are unlikely to regain notable glomerular function with high discriminatory power (area under the ROC curve 0.91; P

Abstract In cancer of the uterine cervix, the role of desmoplasia, i.e., peritumoral stromal remodeling characterized by fibroblast activation and increased extracellular matrix deposition, is not established. We conducted a retrospective cohort study based on data from 438 patients who had undergone surgical treatment for cervical cancer as part of the prospective Leipzig Mesometrial Resection study between 1999 and 2021. Using non-parametric tests, Kaplan–Meier plotting, and Cox regression modeling, we calculated the prognostic impact of desmoplasia and its association with other risk factors. Desmoplasia was present in 80.6% of cases and was associated with a higher frequency of lymphovascular space involvement (76.5 vs. 56.5%, p

Objectives Rheumatoid arthritis has been associated with increased fracture risk. New treatments have improved the course of the disease substantially, but it is not clear if this influences fracture risk. We examined if rheumatoid arthritis, overall and according to disease-modifying antirheumatic drugs (DMARDs), is associated with a risk of major osteoporotic fractures.Methods Overall, 92 285 participants in the population-based Nord-Trndelag Health Study (HUNT), Norway were included and linked with hospital records for a validated rheumatoid arthritis diagnosis (n=605), type of DMARD treatment and fracture diagnosis. Participants were followed up until the first major osteoporotic fracture, death, emigration or end of follow-up. Cox regression was used to estimate HRs for fractures among individuals with rheumatoid arthritis, overall and by DMARD treatment, compared with participants without rheumatoid arthritis.Results A total of 9670 fractures were observed during follow-up, of which 88 were among those with rheumatoid arthritis. Compared with the reference group of participants without rheumatoid arthritis, those with the disease had an HR of fracture of 1.41 (95% CI 1.13 to 1.74). The association was largely similar for users of csDMARDs (HR 1.44; 95% CI 1.15 to 1.81), whereas the association for bDMARD users was weaker and less precise (HR 1.19; 95% CI 0.64 to 2.21).Conclusion Participants with rheumatoid arthritis had a 40% higher risk of fracture than participants without the disease. A similar fracture risk was observed for conventional synthetic DMARD use, whereas there was weak evidence that the use of biological DMARDs may be associated with a somewhat lower fracture risk.

Objectives The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins.Methods This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel).Results Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p

Summary: Background: Lyme disease is caused by the bacteria Borreliella burgdorferi sensu lato (Bb) transmitted to humans from the bite of an infected Ixodes tick. Current diagnostics for Lyme disease are insensitive at the early disease stage and they cannot differentiate between active infections and people with a recent history of antibiotic-treated Lyme disease. Methods: Machine learning technology was utilized to improve the prediction of acute Lyme disease and identify sialic acid and galactose sugar structures (N-glycans) on immunoglobulins associated specifically at time points during acute Lyme disease time. A plate-based approach was developed to analyze sialylated N-glycans associated with anti-Bb immunoglobulins. This multiplexed approach quantitates the abundance of Bb-specific IgG and the associated sialic acid, yielding an accuracy of 90% in a powered study. Findings: It was demonstrated that immunoglobulin sialic acid levels increase during acute Lyme disease and following antibiotic therapy and a 3-month convalescence, the sialic acid level returned to that found in healthy control subjects (p

Abstract A susceptible-infectious-susceptible (SIS) model for simulating healthcare-acquired infection spread within a hospital and associated community is proposed. The model accounts for the stratification of in-patients into two susceptibility-based risk groups. The model is formulated as a system of first-order ordinary differential equations (ODEs) with appropriate initial conditions. The mathematical analysis of this system is demonstrated. It is shown that the system has unique global solutions, which are bounded and non-negative. The basic reproduction number ( $$\mathscr {R}_0$$ R 0 ) for the considered model is derived. The existence and the stability of the stationary solutions are analysed. The disease-free stationary solution is always present and is globally asymptotically stable for $$\mathscr {R}_01$$ R 0 > 1 it is unstable. The presence of an endemic stationary solution depends on the model parameters and when it exists, it is globally asymptotically stable. The endemic state encompasses both risk groups. The endemic state within only one group only is not possible. In addition, for $$\mathscr {R}_0=1$$ R 0 = 1 a forward bifurcation takes place. Numerical simulations, based on the anonymised insurance data, are also presented to illustrate theoretical results.

While SARS-CoV-2 has transitioned to an endemic phase, infections caused by newly emerged variants continue to result in severe, and sometimes fatal, outcomes or lead to long-term COVID-19 symptoms. Vulnerable populations, such as PLWH, face an elevated risk of severe illness. Emerging variants of SARS-CoV-2, including numerous Omicron subvariants, are increasingly associated with breakthrough infections. Adapting mRNA vaccines to these new variants may offer improved protection against Omicron for vulnerable individuals. In this study, we examined humoral and cellular immune responses before and after administering adapted booster vaccinations to PLWH, alongside a control group of healthy individuals. Four weeks following booster vaccination, both groups exhibited a significant increase in neutralizing antibodies and cellular immune responses. Notably, there was no significant difference in humoral immune response between PLWH and the healthy controls. Immune responses declined rapidly in both groups three months post vaccination. However, PLWH still showed significantly increased neutralizing antibody titers even after three months. These findings demonstrate the efficacy of the adapted vaccination regimen. The results suggest that regular booster immunizations may be necessary to sustain protective immunity.

Purpose Sonography training has become an important part of university medicine courses. This study explores the impact of digital and analog teaching resources on learning outcomes, knowledge retention, and student preferences and motivation in a flipped classroom setting.

Enrollment into a prospective cohort study of mother–preterm infant dyads during the COVID-19 pandemic progressed slower than anticipated. Enrollment occurred during the first week after preterm birth, while infants were still hospitalized. We hypothesized that slower enrollment was attributable to mothers testing positive for COVID-19 as hospital policies restricted them from entering the neonatal intensive care unit, thus reducing interactions with research staff. However, only 4.5% of 245 screened mothers tested COVID-19 positive. Only 24.9% of those screened, far fewer than anticipated, were eligible for enrollment. Assumptions about pandemic-related enrollment barriers were not substantiated in this pediatric cohort.

AimsGastroesophageal reflux disease (GERD) may influence the risk of atrial fibrillation (AF). We investigated the association between symptoms of GERD and AF in the Trøndelag Health Study (HUNT).MethodsThe study cohort comprised 34,120 adult men and women initially free of AF with information on GERD symptoms. Participants were followed from the baseline clinical examination (1 October 2006 to 30 June 2008) to March 31, 2018.ResultsDuring a median follow-up of 8.9 years, 1,221 cases of AF were diagnosed. When looking at the whole population, participants with much GERD symptoms did not have an increased risk of AF (HR: 1.01; CI: 95%, 0.82 to 1.24) while participants with little GERD symptoms had a 14% lower risk of AF compared those with no GERD symptoms (HR: 0.86; CI: 95%, 0.76 to 0.97). Among younger participants (ConclusionWe did not find support for a clinically important association between symptoms of GERD and AF across all age groups but for some younger people, GERD might play a role in the development of AF. However, our estimates for this age group were very imprecise and larger studies including younger individuals are warranted.

There is a rapid spread of antibiotic resistance in the environment. However, the impact of antibiotic resistance in drinking water is relatively underexplored. Thus, this study aimed to quantify antibiotic resistance genes (ARGs) and antibiotic residues in two drinking water production facilities (NW-E and NW-C) in North West Province, South Africa and link these parameters to bacterial communities. Physicochemical and ARG levels were determined using standard procedures. Residues (antibiotics and fluconazole) and ARGs were quantified using ultra-high performance liquid chromatography (UHPLC) chemical analysis and real-time PCR, respectively. Bacterial community compositions were determined by high-throughput 16S rRNA sequencing. Data were analysed using redundancy analysis and pairwise correlation. Although some physicochemical levels were higher in treated than in raw water, drinking water in NW-E and NW-C was safe for human consumption using the South African Water Quality Guideline (SAWQG). ARGs were detected in raw and treated water. In NW-E, the concentrations of ARGs (sul1, intl1, EBC, FOX, ACC and DHA) were higher in treated water than in raw water. Regarding antimicrobial agents, antibiotic and fluconazole concentrations were higher in raw than in treated water. However, in NW-C, trimethoprim concentrations were higher in raw than in treated water. Redundancy analysis showed that bacterial communities were not significantly correlated (Monte Carlo simulations, p-value >0.05) with environmental factors. However, pairwise correlation showed significant differences (p-value

BackgroundCardiovascular discharge diagnoses may serve as endpoints in epidemiological studies if they have a high validity. Aim was to study if diagnoses-specific characteristics like type, sub-categories, and position of cardiovascular diagnoses affected diagnostic accuracy.MethodsPatients (n = 7,164) with a discharge diagnosis of acute myocardial infarction, heart failure or cerebrovascular disease were included. Data were presented as positive predictive values (PPV) and sensitivity.ResultsPPV was high (≥88%) for acute myocardial infarction (n = 2,189) (except for outpatients). For heart failure (n = 4,026) PPV was 67% overall, but higher (>99%) when etiology or echocardiography was included. For hemorrhagic (n = 257) and ischemic (n = 1,034) strokes PPVs were 87% and 80%, respectively, with sensitivity of 79% and 75%. Transient ischemic attacks (n = 926) had PPV 56%, but sensitivity 86%. Primary diagnoses showed higher validity than subsequent diagnoses and inpatient diagnoses were more valid than outpatient diagnoses (except for transient ischemic attack). The diagnoses of acute myocardial infarction and heart failure where most valid when placed at cardiology units, while ischemic stroke when discharged from an internal medicine unit.ConclusionsThe diagnoses of acute myocardial infarction and stroke had excellent validity when placed during hospital stays. Similarly, heart failure diagnoses had excellent validity when echocardiography was performed before placing the diagnosis, while overall the diagnoses of heart failure and transient ischemic attack were less valid. In conclusion, the results indicate that cardiovascular diagnoses based on objective findings such as acute myocardial infarction and stroke have excellent validity and may be used as endpoints in clinical epidemiological studies with less rigid validation.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

BackgroundJuvenile antisocial behavior can have long-lasting and devastating effects for juveniles themselves, victims, and society. Evidence-based treatment is vital. Forensic Outpatient Systemic Therapy (Forensische Ambulante Systeem Therapie; FAST) is a promising treatment for juveniles showing severe antisocial behavior including aggression, (domestic) violence, and delinquent behavior. FAST has a flexible intensity and length, addresses individual and systemic risk and protective factors, and is responsive to the abilities of the client (system), intervention characteristics all considered crucial for effective treatment. The current study will investigate whether FAST is effective in reducing aggression of the juvenile, reaching client formulated subgoals, and improving family functioning. Processes of change will be examined, as well as mediation by reaching client formulated subgoals and improved family functioning.MethodsA Multiple Case Experimental Design (MCED) with an ABC design will be performed (A = baseline, B = intervention, and C = follow-up). Juveniles with primary aggression and/or anger problems (N = 15) and their caregiver(s) will be recruited. Data collection will consist of self-report questionnaires and case file analysis. Participants fill out frequent short self-report questionnaires (twice a week during phase A, every other week during phase B, and every week during phase C) and two main questionnaires at the start of the intervention and immediately after intervention end, thereby covering a period of 5 to 11 months. Both visual and statistical analyses will be performed.DiscussionThis study will generate robust knowledge and inform clinical practice on the effectiveness, processes of change, and mediating mechanisms of FAST, aiming to improve the treatment of future families within youth forensic care.Trial registrationThis trial was registered at ClinicalTrials.gov on 28/08/2023, protocol ID 60-63600-98-1138a.

The NIMH-funded Multilevel Community-Based Mental Health Intervention to Address Structural Inequities and Adverse Disparate Consequences of COVID-19 Pandemic on Latinx Immigrants and African Refugees study aims to advance the science of multilevel interventions to reduce the disparate, adverse mental health, behavioral, and socioeconomic consequences of the COVID-19 pandemic that are a result of complex interactions between underlying structural inequities and barriers to health care. The study tests three nested levels of intervention: 1) an efficacious 4-month advocacy and mutual learning model (Refugee and Immigrant Well-being Project, RIWP); 2) engagement with community-based organizations (CBOs); and 3) structural policy changes enacted in response to the pandemic. This community-based participatory research (CBPR) study builds on long-standing collaboration with five CBOs. By including 240 Latinx immigrants and 60 African refugees recruited from CBO partners who are randomly assigned to treatment-as-usual CBO involvement or the RIWP intervention and a comparison group comprised of a random sample of 300 Latinx immigrants, this mixed methods longitudinal waitlist control group design study with seven time points over 36 months tests the effectiveness of the RIWP intervention and engagement with CBOs to reduce psychological distress, daily stressors, and economic precarity and increase protective factors (social support, access to resources, English proficiency, cultural connectedness). The study also tests the ability of the RIWP intervention and engagement with CBOs to increase access to the direct benefits of structural interventions. This paper reports on the theoretical basis, design, qualitative and quantitative analysis plan, and power for the study.

Medical simulation offers a controlled environment for studying challenging clinical care situations that are difficult to observe directly. Overdose education and naloxone distribution (OEND) programs aim to train potential rescuers in responding to opioid overdoses, but assessing rescuer performance in real-life situations before emergency medical services arrive is exceedingly complex. There is an opportunity to incorporate individuals with firsthand experience in treating out-of-hospital overdoses into the development of simulation scenarios. Realistic overdose simulations could provide OEND programs with valuable tools to effectively teach hands-on skills and support context-sensitive training regimens. In this research, semi-structured interviews were conducted with 17 individuals experienced in responding to opioid overdoses including emergency department physicians, first responders, OEND program instructors, and peer recovery specialists. Two coders conducted qualitative content analysis using open and axial thematic coding to identify nuances associated with illicit and prescription opioid overdoses. The results are presented as narrative findings complemented by summaries of the frequency of themes across the interviews. Over 20 hours of audio recording were transcribed verbatim and then coded. During the open and axial thematic coding process several primary themes, along with subthemes, were identified, highlighting the distinctions between illicit and prescription opioid overdoses. Distinct contextual details, such as locations, clinical presentations, the environment surrounding the patient, and bystanders' behavior, were used to create four example simulations of out-of-hospital overdoses. The narrative findings in this qualitative study offer context-sensitive information for developing out-of-hospital overdose scenarios applicable to simulation training. These insights can serve as a valuable resource, aiding instructors and researchers in systematically creating evidence-based scenarios for both training and research purposes.

Abstract Background There is accumulating evidence for a link between trauma exposure, posttraumatic stress disorder (PTSD) and diminished health status. To assess PTSD-related biological burden, we measured biological factors that comprise metabolic syndrome, an important established predictor of morbidity and mortality, as a correlate of long-term health risk in PTSD. Methods We analyzed clinical data from 253 male and female veterans, corresponding to five factors linked to metabolic syndrome (systolic and diastolic blood pressure, waist-to-hip ratio and fasting measures of high-density lipoprotein (HDL) cholesterol, serum triglycerides and plasma glucose concentration). Clinical cut-offs were defined for each biological parameter based on recommendations from the World Health Organization and the National Cholesterol Education Program. Controlling for relevant variables including sociodemographic variables, alcohol/substance/nicotine use and depression, we examined the impact of PTSD on metabolic syndrome using a logistic regression model. Results Two-fifths (40%) of the sample met criteria for metabolic syndrome. Of those with PTSD (n = 139), 43% met criteria for metabolic syndrome. The model predicted metabolic syndrome well (-2 log likelihood = 316.650, chi-squared = 23.731, p = 0.005). Veterans with higher severity of PTSD were more likely to meet diagnostic criteria for metabolic syndrome (Wald = 4.76, p = 0.03). Conclusion These findings provide preliminary evidence linking higher severity of PTSD with risk factors for diminished health and increased morbidity, as represented by metabolic syndrome.

OBJECTIVES/GOALS: Antibiograms are used to guide empiric antibiotic selection. However, it is unclear if antibiotic profiles differ between symptomatic urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB). We aimed to compare antibiotic susceptibility profiles of urinary E. coli isolates from patients with a symptomatic UTI to those with ASB. METHODS/STUDY POPULATION: We conducted a cohort study of 1,140 urinary E. coli isolates from unique patients that received care through Vanderbilt University Medical Center (VUMC) from Nov 2020 – Jun 2021. We included any patient that was seen at VUMC as an inpatient, outpatient or at the emergency department with ≥ 105 colony forming units/mL E. coli detected from a clinical urine specimen. Chart abstractions were performed to capture reported UTI symptoms and demographic information. Descriptive statistics were conducted to compare antibiotic susceptibility profiles (i.e., susceptible, intermediate, resistant) between symptomatic and ASB groups. The risk of detection of a multidrug-resistant organism (MDRO) (intermediate, or resistant to at least one antibiotic in three or more classes) was assessed between groups. RESULTS/ANTICIPATED RESULTS: Among 1,140, 1,018 (89%) and 122 (11%) were symptomatic and ASB, respectively. When comparing symptomatic and ASB, the median ages were 50 and 46. Groups had similar proportions of no indwelling catheter (94% v. 95%) and without diabetes (87% v. 88%). The collection setting between inpatient, emergency department, and outpatient were similar with most being outpatient (79% v. 83%). The proportion of patients who were pregnant, immuno compromised, or had a structural/functional urinary tract abnormality were higher in the symptomatic group. The proportion of isolates resistant and susceptible to tested antibiotics were similar between groups, with only ciprofloxacin showing slightly higher resistance among ASB (16% v. 25%). The risk of MDRO detection was similar between groups (RR: 0.858, 95% CI: 0.64, 1.15). DISCUSSION/SIGNIFICANCE: Antibiotic susceptibility comparison demonstrated similar profiles, which suggests antibiogram use as appropriate to guide ASB treatment. Results offer insight on whether traditional methods for assessing antibiotic susceptibility on population-levels could benefit from further refinement by patient-specific clinical parameters.

A global outbreak of predominantly sexually transmitted mpox infections, outside endemic regions, was reported in May 2022. Thereafter, risk groups were vaccinated against smallpox, a structurally related orthopoxvirus. In the current study, we analyzed T cell responses against peptides derived from orthopoxviruses in 33 HIV-positive patients after two vaccinations against smallpox and in 10 patients after mpox infection. We established an ELISpot assay, detecting either the secretion of the pro-inflammatory cytokine interferon (IFN)-γ or interleukin (IL)-2. After vaccination, 21 out of 33 patients (64%) showed specific IFN-γ secretion and 18 (55%) specific IL-2 secretion, defined as >3-fold higher specific value than negative control and at least 4 spots above the negative control. After mpox infection, all patients showed specific IFN-γ secretion and 7 out of 10 (70%) IL-2 secretion. In vaccinated patients, IFN-γ responses were significantly lower than in patients with mpox infection (median response 4.5 vs. 21.0 spots, p < 0.001). The same trend was observed for IL-2 responses. After mpox infection, IL-2 ELISpot results positively correlated with CD8+ T cells (p < 0.05). Thus, T cell responses were detectable in two thirds of HIV-positive patients after vaccination and were even more abundant and vigorous after mpox infection.

Secondary metabolites and phytochemicals in plant-based diets are known to possess properties that inhibit the development of several diseases including a variety of cancers of the aerodigestive tract. Berries are currently of high interest to researchers due to their high dietary source of phytochemicals. Black raspberries (BRB), Rubus occidentalis, are of special interest due to their rich and diverse composition of phytochemicals. In this review, we present the most up-to-date preclinical and clinical data involving berries and their phytochemicals in the chemoprevention of a variety of cancers and diseases. BRBs possess a variety of health benefits including anti-proliferative properties, anti-inflammatory activity, activation of pro-cell-death pathways, modulation of the immune response, microbiome modulation, reduction in oxidative stress, and many more. However, little has been done in both preclinical and clinical settings on the effects of BRB administration in combination with other cancer therapies currently available for patients. With the high potential for BRBs as chemopreventive agents, there is a need to investigate their potential in combination with other treatments to improve therapeutic efficacy.

Functional and motility-related gastrointestinal (GI) disorders affect nearly 40% percent of the population. Disturbances of GI myoelectric activity have been proposed to play a significant role in these disorders. A significant barrier to usage of these signals in diagnosis and treatment is the lack of consistent relationships between GI myoelectric features and function. A potential cause of this issue is the use of arbitrary classification criteria, such as percentage of power in tachygastric and bradygastric frequency bands. Here we applied automatic feature extraction using a deep neural network architecture on GI myoelectric signals from free-moving ferrets. For each animal, we recorded during baseline control and feeding conditions lasting for 1 h. Data were trained on a 1-dimensional residual convolutional network, followed by a fully connected layer, with a decision based on a sigmoidal output. For this 2-class problem, accuracy was 90%, sensitivity (feeding detection) was 90%, and specificity (baseline detection) was 89%. By comparison, approaches using hand-crafted features (e.g., SVM, random forest, and logistic regression) produced an accuracy from 54% to 82%, sensitivity from 46% to 84% and specificity from 66% to 80%. These results suggest that automatic feature extraction and deep neural networks could be useful to assess GI function for comparing baseline to an active functional GI state, such as feeding. In future testing, the current approach could be applied to determine normal and disease-related GI myoelectric patterns to diagnosis and assess patients with GI disease.