Evaluating Stigmatization Toward Mental Illnesses Among Resident Physicians.

Background  Individuals with mental illness are stigmatized by peers in societal, workplace, and healthcare settings. The stigmatization individuals experience from healthcare providers is well documented and pervasive, often being a detriment to the quality of healthcare these individuals receive. Objective Recognizing and addressing stigmatization toward individuals with mental illnesses is imperative during residency training in Graduate Medical Education (GME) programs and throughout professional practice. We hope that this cross-sectional study will cultivate mindfulness and improve the healthcare outcomes of stigmatized individuals. Methodology A cross-sectional study using a web-based Attitude to Mental Illness Questionnaire (AMIQ) with additional scenarios was utilized to assess stigma among resident physicians in differing specialties in a hospital training system. The research investigators collected anonymous data on demographics, characteristics, specialties, and the AMIQ. In eight vignettes, participants responded to five items using a five-point Likert scale assessing attitudes toward individuals. Results Of the 104 resident physicians enrolled in the hospital training system where the study was conducted, 58 (56%) volunteered to participate. The participating residents markedly exhibited negative attitudes toward the individual in the vignette with multiple inpatient psychiatric admissions. Residents also exhibited more negative attitudes toward individuals with schizophrenia, self-harm by way of overdose, psychedelic users, cannabis users, and alcohol problems compared to diabetic and Christian individuals. Conclusions Residents exhibited negative attitudes toward individuals with mental illness. Additional research would further our understanding of the reasons for physician bias. Moreover, GME programs and medical educators can play a crucial role in mitigating stigma among future physicians, thereby enhancing care for individuals with mental illness.

Performance of the Quadripolar CRT-D system: 5-Year Results from the Quadripolar Pacing Post Approval Study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is associated with challenges such as elevated capture thresholds, diaphragmatic stimulation, and lead instability. OBJECTIVE: Assess the chronic safety and efficacy of the quadripolar CRT-D device system with the Quartet 1458Q Left Ventricular (LV) lead in a CRT-indicated population followed for 5 years and evaluate all-cause mortality and impact of baseline characteristics on survival through 5 years. METHODS: Patients indicated for a CRT-D system were followed every 6 months post-implant for 5 years and assessed device performance and adverse events at each visit. The three primary endpoints were freedom from quadripolar CRT-D system-related complications through 5 years, freedom from Quartet 1458Q LV lead-related complications through 5 years, and the mean programmed pacing capture threshold at 5 years. RESULTS: The study enrolled 1,970 subjects at 71 sites. The quadripolar CRT-D system was successfully implanted in 97.2% of subjects. Freedom from quadripolar CRT-D device system-related complications through 5 years was 89.7% and freedom from Quartet 1458Q LV lead-related complications through 5 years was 95.7%. 3.49 % of subjects had LV lead-related complications and an overall LV lead complication rate was 0.0122 events per subject-year. A mean LV pacing capture threshold was 1.52 ± 1.01 V at 5 years. The 5-year survival rate was 67.4%. CONCLUSION: The quadripolar CRT-D system with the Quartet 1458Q LV lead exhibited low rates of complications and stable electrical performance through 5 years of follow-up and suggested a higher 5-year survival rate compared to traditional CRT systems.

Effects of psychedelic, DOI, on nucleus accumbens dopamine signaling to predictable rewards and cues in rats.

Psychedelics produce lasting therapeutic responses in neuropsychiatric diseases suggesting they may disrupt entrenched associations and catalyze learning. Here, we examine psychedelic 5-HT2A/2C agonist, DOI, effects on dopamine signaling in the nucleus accumbens (NAc) core, a region extensively linked to reward learning, motivation, and drug-seeking. We measure phasic dopamine transients following acute DOI administration in rats during well learned Pavlovian tasks in which sequential cues predict rewards. We find that DOI (0.0-1.2 mg/kg, i.p.) increases dopamine signals, photometrically measured using GRABDA optical sensor, to rewards and proximal reward cues, but not to the distal cues that predict these events. We determine that the elevated dopamine produced by DOI to reward cues occurs independently of DOI-induced changes in reward value. The increased dopamine associated with predictable reward cues and rewards supports DOI-induced increases in prediction error signaling. These findings lay a foundation for developing psychedelic strategies aimed at engaging error-driven learning mechanisms to disrupt entrenched associations or produce new associations.

Severe B12 Deficiency Causing a Maturation Defect Mimicking Myelodysplastic Syndrome With Excess Blasts.

Vitamin B12 deficiency is a common condition that is often asymptomatic, though in severe cases may cause megaloblastic anemia and even neurologic symptoms. Occasionally, the clinical presentation can include pancytopenia and thus mimic a more concerning myelodysplastic syndrome (MDS) until corrected by B12 supplementation. In this unusual case, we present a patient with B12 deficiency who presents with severe macrocytic anemia, neutropenia, lymphocytosis, and a bone marrow morphology consistent with MDS.

Pilot Study by Liquid Biopsy in Gastrointestinal Stromal Tumors: Analysis of PDGFRA D842V Mutation and Hypermethylation of SEPT9 Presence by Digital Droplet PCR.

Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential for early diagnosis via liquid biopsy, focusing on the PDGFRA D842V mutation and SEPT9 hypermethylated gene. We utilized ddPCR to analyze the predominant PDGFRA mutation (D842V) in surgical tissue samples from 15 GIST patients, correlating with pathologists' diagnoses. We expanded our analysis to plasma samples to compare DNA alterations between tumor tissue and plasma, also investigating SEPT9 gene hypermethylation. We successfully detected the PDGFRA D842V mutation in GIST tissues by ddPCR. Despite various protocols to enhance mutation detection in early-stage disease, it remained challenging, likely due to the low concentration of DNA in plasma samples. Additionally, the results of Area Under the Curve (AUC) for the hypermethylated SEPT9 gene, analyzing concentration, ratio, and abundance were 0.74 (95% Confidence Interval (CI): 0.52 to 0.97), 0.77 (95% CI: 0.56 to 0.98), and 0.79 (95% CI: 0.59 to 0.99), respectively. As a rare disease, the early detection of GIST through such biomarkers is particularly crucial, offering significant potential to improve patient outcomes.

Assessing the perioperative gain of weight (Δweight) as a determinant of morbidity after kidney transplantation: a retrospective exploratory study.

Kidney transplantation (KT) is associated with a substantial risk of postoperative complications (POC) for which performant predictors are lacking. Data showed that a perioperative gain of weight (ΔWeight) was associated with higher risk of POC, but it remains unexplored in KT. This retrospective study aimed to investigate the association between ΔWeight and POC after KT. ΔWeight was calculated on postoperative day (POD) 2. POC were graded according to the Dindo-Clavien classification. Primary endpoint was overall POC. A total of 242 patients were included and 174 (71.9%) complications were reported. Patients showed a rapid gain of weight after KT. Mean ΔWeight was 7.83 kg (± 3.20) compared to 5.3 kg (± 3.56) in patients with and without complication, respectively (p = 0.0005). ΔWeight showed an accuracy of 0.74 for overall POC. A cut-off of 8.5 kg was determined. ΔWeight ≥ 8.5 kg was identified as an independent predictor of overall POC on multivariable analysis (OR 2.04; 95% CI 1.08-3.84; p = 0.025). ΔWeight ≥ 8.5 kg appeared as an independent predictor of POC after KT. These results stress the need to monitor weight in KT and to further investigate this surrogate with future studies assessing its clinical relevance.

A Novel Analog of the Natural Product Fraxinellone Protects against Endogenous and Exogenous Neurotoxicants.

Numerous insults, both endogenous (e.g., glutamate) and exogenous (e.g., pesticides), compromise the function of the nervous system and pose risk factors for damage or later disease. In previous reports, limonoids such as fraxinellone showed significant neuroprotective activity against glutamate (Glu) excitotoxicity and reactive oxygen species (ROS) production in vitro, albeit with minimal mechanistic information provided. Given these findings, a library of novel fraxinellone analogs (including analogs 1 and 2 described here) was synthesized with the goal of identifying compounds exhibiting neuroprotection against insults. Analog 2 was found to be protective against Glu-mediated excitotoxicity with a measured EC50 of 44 and 39 nM for in vitro assays using PC12 and SH-SY5Y cells, respectively. Pretreatment with analog 2 yielded rapid induction of antioxidant genes, namely, Gpx4, Sod1, and Nqo1, as measured via qPCR. Analog 2 mitigated Glu-mediated ROS. Cytoprotection could be replicated using sulforaphane (SFN), a Nrf2 activator, and inhibited via ML-385, which inhibits Nrf2 binding to regulatory DNA sequences, thereby blocking downstream gene expression. Nrf2 DNA-binding activity was demonstrated using a Nrf2 ELISA-based transcription factor assay. In addition, we found that pretreatment with the thiol N-acetyl Cys completely mitigated SFN-mediated induction of antioxidant genes but had no effect on the activity of analog 2, suggesting thiol modification is not critical for its mechanism of action. In summary, our data demonstrate a fraxinellone analog to be a novel, potent, and rapid activator of the Nrf2-mediated antioxidant defense system, providing robust protection against insults.

Iron Chelation in Soil: Scalable Biotechnology for Accelerating Carbon Dioxide Removal by Enhanced Rock Weathering.

Enhanced rock weathering (EW) is an emerging atmospheric carbon dioxide removal (CDR) strategy being scaled up by the commercial sector. Here, we combine multiomics analyses of belowground microbiomes, laboratory-based dissolution studies, and incubation investigations of soils from field EW trials to build the case for manipulating iron chelators in soil to increase EW efficiency and lower costs. Microbial siderophores are high-affinity, highly selective iron (Fe) chelators that enhance the uptake of Fe from soil minerals into cells. Applying RNA-seq metatranscriptomics and shotgun metagenomics to soils and basalt grains from EW field trials revealed that microbial communities on basalt grains significantly upregulate siderophore biosynthesis gene expression relative to microbiomes of the surrounding soil. Separate in vitro laboratory incubation studies showed that micromolar solutions of siderophores and high-affinity synthetic chelator (ethylenediamine-N,N'-bis-2-hydroxyphenylacetic acid, EDDHA) accelerate EW to increase CDR rates. Building on these findings, we develop a potential biotechnology pathway for accelerating EW using the synthetic Fe-chelator EDDHA that is commonly used in agronomy to alleviate the Fe deficiency in high pH soils. Incubation of EW field trial soils with potassium-EDDHA solutions increased potential CDR rates by up to 2.5-fold by promoting the abiotic dissolution of basalt and upregulating microbial siderophore production to further accelerate weathering reactions. Moreover, EDDHA may alleviate potential Fe limitation of crops due to rising soil pH with EW over time. Initial cost-benefit analysis suggests potassium-EDDHA could lower EW-CDR costs by up to U.S. $77 t CO2 ha-1 to improve EW's competitiveness relative to other CDR strategies.

Emergency Medical Planning for an Ultramarathon Open Water Swim: A Case Review of "Swim Tuff".

ABSTRACT: Ultramarathon open water swimming (OWS) events are one of the toughest endurance challenges in the world. The sport has gained notoriety with athletes swimming across the English Channel, Diana Nyad swimming from Cuba to Florida, and the 5- and 10-km OWS in the Olympic schedule. The athletes who participate are exposed to dangerous conditions that expose risks inherent to the sport. The optimal time to prepare for an emergency is before it happens. The aim of this paper is to present an emergency action plan (EAP) designed for the "Swim Tuff" event, a record-breaking ultramarathon swim that took place in Rhode Island, United States. This article identifies an overview of Swim Tuff, the challenges experienced, and how the team designed and implemented risk mitigation strategies. The professionals looking over athletes completing an OWS should be educated and aware of the unique circumstances inherent to the sport.

Chronobiology of Viscum album L.: a time series of daily metabolomic fingerprints spanning 27 years.

Introduction: European mistletoe (Viscum album L.) has been gaining increasing interest in the field of oncology as a clinically relevant adjunctive treatment in many forms of cancer. In the field of phytopharmacology, harvesting time is pivotal. In the last century, a form of metabolomic fingerprinting based on pattern formation was proposed as a way to determine optimal harvesting times to ensure high quality of mistletoe as raw material for pharmaceutical use. In order to further evaluate the information obtained with this metabolomic fingerprinting method, we analysed a large time series of previously undigitised daily mistletoe chromatograms dating back to the 1950s. Methods: These chromatograms were scanned and evaluated using computerized image analysis, resulting in 12 descriptors for each individual chromatogram. We performed a statistical analysis of the data obtained, investigating statistical distributions, cross-correlations and time self-correlations. Results: The analysed dataset spanning about 27 years, contains 19,037 evaluable chromatograms in daily resolution. Based on the distribution and cross-correlation analyses, the 12 descriptors could be clustered into six independent groups describing different aspects of the chromatograms. One descriptor was found to mirror the annual rhythm being well correlated with temperature and a phase shift of 10 days. The time self-correlation analysis showed that most other descriptors had a characteristic self-correlation of ∼50 days, which points to further infradian rhythms (i.e., more than 24 h). Discussion: To our knowledge, this dataset is the largest of its type. The combination of this form of metabolomic fingerprinting with the proposed computer analysis seems to be a promising tool to characterise biological variations of mistletoe. Additional research is underway to further analyse the different rhythms present in this dataset.

Valorisation of grape stem as an alternative ingredient in rabbit feed.

Grape stem is a winery by-product that it is currently disposed as waste or at best as soil conditioner. However, it is rich in fibres and polyphenols which makes it interesting for animal feeding. In this regard, rabbit farming emerges as a target livestock farming since fibre content is essential in rabbit's diets for preventing digestive troubles and polyphenols are associated with improved performances in animals due to their antimicrobial and antioxidant activities. This study aims to assess the suitability of a grape stem-based ingredient for rabbit feeding. The stem was dried using flash drying technology to prevent rapid spoilage and stabilise the ingredient. Then, its nutritional value was evaluated resulting in a high fibre (>40%) and polyphenol (>6%) content ingredient with antioxidant and antimicrobial activity against Staphylococcus aureus. A feed efficiency trial was conducted and inclusion rates of up to 10% of grape stem-based ingredient did not affect animals' mortality, average daily feed intake, daily gain or feed conversion ratio. In conclusion, grape stem-based ingredient arises as a secondary feedstuff for cuniculture reducing the dependence on other fibre sources, such as cereals or sunflower hulls. This could also contribute to reduce the environmental footprint of the wine sector by giving a second life to an existing waste, while generating a new activity based on circular economy.

Applicability of Deep Learning to Dynamically Identify the Different Organs of the Pelvic Floor in the Midsagittal Plane.

INTRODUCTION AND HYPOTHESIS: The objective was to create and validate the usefulness of a convolutional neural network (CNN) for identifying different organs of the pelvic floor in the midsagittal plane via dynamic ultrasound. METHODS: This observational and prospective study included 110 patients. Transperineal ultrasound scans were performed by an expert sonographer of the pelvic floor. A video of each patient was made that captured the midsagittal plane of the pelvic floor at rest and the change in the pelvic structures during the Valsalva maneuver. After saving the captured videos, we manually labeled the different organs in each video. Three different architectures were tested-UNet, FPN, and LinkNet-to determine which CNN model best recognized anatomical structures. The best model was trained with the 86 cases for the number of epochs determined by the stop criterion via cross-validation. The Dice Similarity Index (DSI) was used for CNN validation. RESULTS: Eighty-six patients were included to train the CNN and 24 to test the CNN. After applying the trained CNN to the 24 test videos, we did not observe any failed segmentation. In fact, we obtained a DSI of 0.79 (95% CI: 0.73 - 0.82) as the median of the 24 test videos. When we studied the organs independently, we observed differences in the DSI of each organ. The poorest DSIs were obtained in the bladder (0.71 [95% CI: 0.70 - 0.73]) and uterus (0.70 [95% CI: 0.68 - 0.74]), whereas the highest DSIs were obtained in the anus (0.81 [95% CI: 0.80 - 0.86]) and levator ani muscle (0.83 [95% CI: 0.82 - 0.83]). CONCLUSIONS: Our results show that it is possible to apply deep learning using a trained CNN to identify different pelvic floor organs in the midsagittal plane via dynamic ultrasound.

A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis.

BACKGROUND: The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF­06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18-70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.03-6 mg) or placebo in six sequential single ascending dose (SAD) cohorts. In Part B, patients received repeat doses of subcutaneous PF-06835375 (dose range: 0.3-10 mg) or placebo on Days 1 and 29 in five multiple ascending dose (MAD) cohorts. Tetanus/Diphtheria (Td) and Meningococcal B (MenB/Trumenba™) vaccines were administered at Day 4 (Td and MenB) and Week 8 (MenB only) to assess PF-06835375 functional effects. Endpoints included treatment-emergent adverse events (TEAEs), pharmacokinetic parameters, pharmacodynamic effects on B and cTfh cells, and biomarker counts, vaccine response, and exploratory differential gene expression analysis. Safety, pharmacokinetic, and pharmacodynamic endpoints are summarized descriptively. The change from baseline of B and Tfh cell-specific genes over time was calculated using a prespecified mixed-effects model, with a false discovery rate < 0.05 considered statistically significant. RESULTS: In total, 73 patients were treated (SAD cohorts: SLE, n = 17; RA, n = 14; MAD cohorts: SLE, n = 22; RA, n = 20). Mean age was 53.3 years. Sixty-two (84.9%) patients experienced TEAEs (placebo n = 17; PF-06835375 n = 45); most were mild or moderate. Three (9.7%) patients experienced serious adverse events. Mean t1/2 ranged from 3.4-121.4 h (SAD cohorts) and 162.0-234.0 h (MAD cohorts, Day 29). B and cTfh cell counts generally showed dose-dependent reductions across cohorts (range of mean maximum depletion: 67.3-99.3%/62.4-98.7% [SAD] and 91.1-99.6%/89.5-98.1% [MAD], respectively). B cell-related genes and pathways were significantly downregulated in patients treated with PF-06835375. CONCLUSIONS: These data support further development of PF-06835375 to assess the clinical potential for B and Tfh cell depletion as a treatment for autoimmune diseases. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03334851.

Ultrasound Cut-Off Values for Rectus Femoris for Detecting Sarcopenia in Patients with Nutritional Risk.

BACKGROUND: A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures. METHODS: Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia. RESULTS: A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women (p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm2 and 3.66 cm2 for CSA, 32.57 mm and 40.21 mm for the X-axis, and 7.85 mm and 10.4 mm for the Y-axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women. CONCLUSIONS: Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice.

Comparison of outcomes and required tools between transvenous extraction of pacemaker and implantable cardioverter defibrillator leads: Insight from single high-volume center experience.

INTRODUCTION: Reports of comparison with procedural outcomes for implantable cardioverter defibrillator (ICD) and pacemaker (PM) transvenous lead extraction (TLE) are old and limited. We sought to compare the safety, efficacy, and procedural properties of ICD and PM TLE and assess the impact of lead age. METHODS: The study cohort included all consecutive patients with ICD and PM TLE in the Cleveland Clinic Prospective TLE Registry between 2013 and 2022. Extraction success, complications, and failure employed the definitions described in the HRS 2017 TLE guidelines. RESULTS: A total of 885 ICD leads, a median implant duration of 8 (5-11) years in 810 patients, and 1352 PM leads of 7 (3-13) years in 807 patients were included. Procedural success rates in ICD patients were superior to those of PM in >20 years leads but similar in ≤20 years leads. In the PM group, the complete success rate of TLE decreased significantly according to the increase of lead age, but not in the ICD group. ICD TLE required more extraction tools compared with PM TLE but cases with older leads required non-laser sheath extraction tools in both groups. The most common injury site in major complication cases differed between ICD and PM TLE, although major complication rates showed no difference in both groups (2.7% vs. 1.6%, p = .12). CONCLUSION: The procedural success rate by TLE is greater for ICD patients than PM patients with leads >20 years old but requires more extraction tools. Common vascular complication sites and the impact of lead age on procedural outcomes and required tools differed between ICD and PM TLE.

Effect of a diabetes-specific formula in non-diabetic inpatients with stroke: a randomized controlled trial.

BACKGROUND/OBJECTIVES: In patients with acute stroke, the presence of hyperglycaemia has been associated with higher morbidity and less neurological recovery. The aim of the study was to evaluate the impact of a diabetes specific enteral nutrition (EN) formula on glycaemia, comorbidities and mortality in patients admitted with a first episode of stroke who received complete EN. METHODS: This was a prospective randomised controlled trial. Patients with acute stroke did not have diagnosis of diabetes mellitus and required nasogastric tube feeding. This study has been registered with code NCT03422900. The patients were randomised into two arms: an isocaloric isoprotein formula (control group (CG), 27 patients) vs a diabetes-specific formula (low glycaemic index carbohydrates, fibre (80% soluble) and higher lipid content) (experimental group (EG), 25 patients). Pre-EN blood glucose, hyperglycaemia during EN treatment, HbA1c, insulin use, oral route recovery, length of stay (LOS) and mortality at 30 days were collected. The complications of enteral nutrition during admission were collected as well. RESULTS: 52 patients were included, 50% females, with an age of 77.44(11.48) years; 34 (65.4%) had ischaemic stroke, with a Rankin score of 0(0-2), and a National Institute of Health Stroke Scale (NIHSS) of 19 (15-22). In CG, there were more cases of hyperglycaemia on the 5th day post-NE (13(65%) vs7(35%), p < 0.01). CG showed an OR of 7.58(1.49-39.16) (p = 0.02) for the development of hyperglycaemia. There were no differences in LOS between groups (12(8.5) days vs 14(23) days, p = 0.19) or in the death rate (10(37%) vs 10(40%), p = 0.8), although differences were found in terms of oral route recovery (EG: 11(44%) patients vs CG: 5(18.5%) patients, p = 0.04) (OR (EG): 5.53(1.25-24.47); p = 0.02). CONCLUSIONS: The use of a diabetes-specific enteral formula in non-diabetic patients admitted with acute stroke reduced the risk of developing hyperglycaemia and improved the rate of oral route recovery. Registered under ClinicalTrials.gov Identifier no. NCT03422900.

Myeloid NCOA4 sequesters KEAP1 to reduce ferroptosis for protection against salmonellosis in mice.

Salmonellosis, caused by Salmonella enterica serovar Typhimurium, is a significant global threat. Host immunity limits bacterial replication by inducing hepcidin, which degrades ferroportin, reducing iron transfer. However, this boosts macrophage iron storage, aiding intracellular pathogens like Salmonella. Mice lacking ferritin heavy chain (FTH1) in myeloid cells suffer worsened Salmonella infection. Nuclear receptor co-activator 4 (NCOA4) regulates iron release via FTH1 degradation during low iron, but its role in salmonellosis is unclear. Here, we reveal that myeloid NCOA4 deficiency augments spleen iron levels and increases cellular iron accumulation, oxidative stress, and ferroptosis in bone marrow-derived macrophages. This deficiency also increases susceptibility to Salmonella-induced colitis in mice. Mechanistically, NCOA4 suppresses oxidative stress by directly binding to the E3 ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1) and stabilizing the antioxidant transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2). Activation of NRF2 protects myeloid NCOA4 knockout mice from Salmonella-induced colitis. Antioxidant Tempol and myeloid cell-targeted curcumin offer protection against colitis in myeloid NCOA4-deficient mice. A low iron diet and ferroptosis inhibition also mitigate the heightened colitis in these mice. Overexpression of myeloid cell-specific NCOA4 confers protection against Salmonella-induced colitis via upregulating NRF2 signaling. Serum iron was reduced in myeloid NCOA4-overexpressing mice, but not in NCOA4-deficient mice. Targeted serum metabolomics analysis revealed that many lipids were decreased in myeloid NCOA4-deficient mice, while several of them were increased in myeloid NCOA4-overexpressing mice. Together, this study not only advances our understanding of NCOA4/KEAP1/NRF2/ferroptosis axis but also paves the way for novel myeloid cell-targeted therapies to combat salmonellosis.

FeverApp for Parents: A Multilingual and Socially Accountable Approach to Paediatric Fever Management in Germany.

Policymakers and practitioners are increasingly focused on achieving health equity and meeting the specific health needs of diverse populations, including vulnerable groups such as children. To address these challenges, the Fever App for Parents has emerged as a solution to guide parents through the complexities of managing fever in their children by improving fever management in children through real-time data collection and comprehensive educational support. This systematic approach aims to reduce unnecessary medical interventions and overuse of antibiotics, thereby improving the overall quality of pediatric care and reducing parental anxiety. In Germany, almost every second child aged 0-10 is a child with migration status and/or migration experience. This means that the parents of these children also need to be targeted in fever management and informed about the correct behavior in case of fever. This information will also be monitored anonymously to provide a feedback loop on the parent's experience with the menu navigation and information design. The FeverApp provides parents with a structured, step-by-step guide to accurately track their child's temperature and medication intake to encourage adherence to established fever management protocols. This study examines how the FeverApp embodies the principles of social responsibility through its multilingualism and digital development stages that incorporate user feedback. It shows why this app can be a resource to promote health equity through social responsibility in medical education and practice for parents, but also what barriers need to be considered at different stages of app development for parents from different cultural backgrounds to enable informal medical learning through apps.

Intracerebral Hemorrhage in a Patient With Newly Diagnosed Immune Thrombocytopenic Purpura Precipitated by a Viral Illness.

Intracerebral hemorrhage (ICH) is a rare and severe complication of immune thrombocytopenic purpura (ITP) that can be spontaneous. Viral illnesses, other infections, autoimmune disorders, and medications can cause ITP. ITP causes a significant decrease in platelet levels, increasing bleeding risk. ITP can be treated by steroids, intravenous immunoglobulin, plasmapheresis, platelet transfusion, biological agents, and splenectomy. ICH treatment involves the treatment of underlying ITP, as well as any neuro-interventional procedures needed. In this case report, we look at the presenting symptoms and treatment course of an interesting case of ICH in a patient who developed ITP after a viral upper respiratory infection.

Evolution and Prognosis of Tricuspid and Mitral Regurgitation Following Cardiac Implantable Electronic Devices. A Systematic Review and Meta-analysis.

BACKGROUND: Significant changes in tricuspid regurgitation (TR) and mitral regurgitation (MR) post-cardiac implantable electronic devices (CIED) are increasingly recognized. However, uncertainty remains as to whether risk of CIED-associated TR and MR differs with right ventricular pacing (RVP) via CIED with trans-tricuspid RV leads, compared to cardiac resynchronization therapy (CRT), conduction system pacing (CSP), and leadless pacing (LP). AIMS: Synthesize extant data on risk and prognosis of significant post-CIED TR and MR across pacing strategies. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases published until October 31st, 2023. Significant post-CIED TR and MR were defined as ≥ moderate. RESULTS: Fifty-seven TR studies (N=13,723 patients) and 90 MR studies (N =14,387 patients) were included. For all CIED, risk of post-CIED TR increased (pooled odds ratio (OR)=2.46 and 95% CI=1.88-3.22), while risk of post-CIED MR reduced (OR=0.74, 95% CI=0.58-0.94) after 12 and 6 months of median follow-up respectively. RVP via CIED with trans-tricuspid RV leads was associated with increased risk of post-CIED TR (OR=4.54, 95% CI=3.14-6.57) and post-CIED MR (OR=2.24, 95% CI=1.18-4.26). Binarily, CSP did not alter TR risk (OR=0.37, 95% CI=0.13-1.02), but significantly reduced MR (OR =0.15, 95% CI=0.03-0.62). CRT did not significantly change TR risk (OR=1.09, 95% CI=0.55-2.17), but significantly reduced MR with prevalence pre-CRT of 43%, decreasing post-CRT to 22% (OR =0.49, 95% CI=0.40-0.61). There was no significant association of LP with post-CIED TR (OR=1.15, 95% CI=0.83-1.59) or MR (OR=1.31, 95% CI=0.72-2.39). CIED-associated TR was independently predictive of all-cause mortality (pooled hazard ratio (HR)=1.64, 95% CI=1.40-1.90) after median of 53 months. MR persisting post-CRT independently predicted all-cause mortality (HR=2.00, 95% CI=1.57-2.55) after 38 months. CONCLUSIONS: Our findings suggest that, when possible, adoption of pacing strategies which avoid isolated trans-tricuspid RV leads may be beneficial in preventing incident or deteriorating atrioventricular valvular regurgitation and might reduce mortality.