Results from a psychometric validation study: irritable bowel syndrome patients report higher symptom burden using end-of-day versus real-time assessment.

OBJECTIVE: Real-time assessment of gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS) using the experience sampling method (ESM) is suggested as a more appropriate approach than currently used end-of-day or end-of-week reports. This psychometric evaluation study assesses the validity and reliability of a previously developed ESM-based patient-reported outcome measure (PROM) for real-time GI symptom assessment in IBS. METHODS: This multicenter validation study included 230 Rome IV IBS patients (80% female; mean age 41.2 years) in three European countries. Patients completed the electronic ESM-PROM (up to ten random moments daily, with a weekly minimum completion rate of 33%) and an end-of-day symptom diary for seven consecutive days. End-of-week questionnaires (GSRS-IBS, IBS-SSS, PHQ-9, and GAD-7) were completed at the end of the 7-day period. RESULTS: The ESM assessment had a mean completion rate of 71%. Strong and significant correlations (0.651-0.956) with moderately-to-good consistency (ICCs 0.580-0.779) were observed between ESM and end-of-day scores. However, end-of-day scores were significantly higher (Δ0.790-1.758, p<0.001) than mean daily ESM scores. Differences with end-of-week scores were more pronounced, with weaker correlations (Pearson's r 0.393-0.802). ESM-PROM exhibited moderate-to-good internal consistency (Cronbach's α 0.585-0.887) across five symptom domains. First and second half-week scores demonstrated good-to-excellent consistency (ICCs 0.871-0.958). CONCLUSIONS: Psychometric evaluation demonstrated strong validity and reliability of the ESM-PROM for real-time GI symptom assessment in IBS. In addition, the ESM-PROM provides a precise and reliable ascertainment of individual symptom pattern and trigger interactions, without the bias of peak reporting when compared to retrospective methods. This highlights its potential as a valuable tool for personalized healthcare in monitoring disease course and treatment response in IBS patients.

HLA-DR+ regulatory T cells and IL-10 are associated with success or failure of desensitization outcomes.

BACKGROUND: Omalizumab (XOLAIR®)-assisted multi-food oral immunotherapy (mOIT) has been shown to safely, effectively, and rapidly desensitize patients with multiple food allergies. In our clinical trial (NCT02626611) on omalizumab-assisted mOIT, different desensitization outcomes (success or failure of desensitization) were observed following a period of either continued or discontinued mOIT. However, the association between the immunological changes induced by omalizumab-assisted mOIT and desensitization outcomes has not yet been fully elucidated. In this study, due to the key roles of regulatory T (Treg) cells and the type 2 helper T cell (Th2) pathway in immune tolerance to food allergens, we aimed to characterize their association with the desensitization outcomes of omalizumab-assisted mOIT. METHODS: Mass cytometry and multiplex cytokine assays were performed on blood samples obtained from participants with allergies to peanut, cashew, or milk in our phase 2 clinical study (NCT02626611). Comprehensive statistical and bioinformatic analyses were conducted on high-dimensional cytometry-based single-cell data and high-throughput multiplex cytokine data. RESULTS: Our results demonstrated that the frequency of HLA-DR+ Treg cells, and the production of Th2 cytokines (IL-4, IL-5, IL-13, and IL-9) as well as the immunoregulatory cytokine IL-10 by peripheral blood mononuclear cells (PBMCs) was significantly increased in cultures with allergen compared to cultures with media alone at baseline (Week 0). We also observed increased frequency of allergen responsive HLA-DR+ Treg cells and enhanced production of IL-10 by PBMCs in participants who achieved successful desensitization compared to those with failure of desensitization. However, the production of Th2 cytokines by PBMCs did not show significant differences between participants with different desensitization outcomes (success vs. failure of desensitization), despite omalizumab-assisted mOIT inducing a significant reduction in the production of Th2 cytokines. CONCLUSIONS: We demonstrated that the frequency of HLA-DR+ Treg cells and IL-10 cytokine production by PBMCs are associated with desensitization outcomes of omalizumab-assisted mOIT. These findings suggest potential immunological parameters that could be targeted to enhance desensitization success rates.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XI - Milk supplement/replacement formulas for infants and toddlers with CMA - Systematic review.

Background: Cow's milk allergy (CMA) is the most complex and common food allergy in infants. Elimination of cow's milk from the diet and replacement with a specialized formula for infants with cow's milk allergy who cannot be breastfed is an established approach to minimize the risk of severe allergic reactions while avoiding nutritional deficiencies. Given the availability of multiple options, such as extensively hydrolyzed cow's milk-based formula (eHF-CM), aminoacid formula (AAF), hydrolyzed rice formula (HRF), and soy formula (SF), there is some uncertainty regarding which formula might represent the most suitable choice with respect to health outcomes. The addition of probiotics to a specialized formula has also been proposed as a potential approach to possibly increase the benefit. We systematically reviewed specialized formulas for infants with CMA to inform the updated World Allergy Organization (WAO) DRACMA guidelines. Objective: To systematically review and synthesize the available evidence about the use of specialized formulas for the management of individuals with CMA. Methods: We searched from inception PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations, for randomized and non-randomized trials of any language investigating specialized formulas with or without probiotics. We included all studies irrespective of the language of the original publication. The last search was conducted in January 2024. We synthesized the identified evidence quantitatively or narratively as appropriate and summarized it in the evidence profiles. We conducted this review following the PRISMA, Cochrane methods, and the GRADE approach. Results: We identified 3558 records including 14 randomized trials and 7 observational studies. Very low certainty evidence suggested that in infants with IgE-mediated CMA, eHF-CM, compared with AAF, might have higher probability of outgrowing CMA (risk ratio (RR) 2.32; risk difference (RD) 25 more per 100), while showing potentially lower probability of severe vomiting (RR 0.12, 95% CI 0.02 to 0.88; RD 23 fewer per 100, 95% CI 3 to 26) and developing food protein-induced enterocolitis syndrome (FPIES) (RR 0.15, 95% CI 0.03 to 0.82; RD 34 fewer per 100, 95% CI 7 to 39). We also found, however, that eHF-CM might be inferior to AAF in supporting a physiological growth, with respect to both weight (-5.5% from baseline, 95%CI -9.5% to -1.5%) and length (-0.7 z-score change, 95%CI -1.15 to -0.25) (very low certainty). We found similar effects for eHF-CM, compared with AAF, also in non-IgE CMA. When compared with SF, eHF-CM might favor weight gain for IgE CMA infants (0.23 z-score change, 95%CI 0.01 to 0.45), and tolerance acquisition (RR 1.86, 95%CI 1.03 to 3.37; RD 27%, 95%CI 1%-74%) for non-IgE CMA (both at very low certainty of the evidence (CoE)). The comparison of eHF-CM vs. HRF, and HRF vs. SF, showed no difference in effect (very low certainty). For IgE CMA patients, low certainty evidence suggested that adding probiotics (L. rhamnosus GG, L. casei CRL431 and B. lactis Bb-12) might increase the probability of developing CMA tolerance (RR 2.47, 95%CI 1.03 to 5.93; RD 27%, 95%CI 1%-91%), and reduce the risk of severe wheezing (RR 0.12, 95%CI 0.02 to 0.95; RD -23%, 95%CI -8% to -0.4%). However, in non-IgE CMA infants, the addition of probiotics (L. rhamnosus GG) showed no significant effect, as supported by low to very low CoE. Conclusions: Currently available studies comparing eHF-CM, AAF, HRF, and SF provide very low certainty evidence about their effects in infants with IgE-mediated and non-IgE-mediated CMA. Our review revealed several limitations in the current body of evidence, primarily arising from concerns related to the quality of studies, the limited size of the participant populations and most importantly the lack of diversity and standardization in the compared interventions. It is therefore imperative for future studies to be methodologically rigorous and investigate a broader spectrum of available interventions. We encourage clinicians and researchers to review current World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines for suggestions on how to use milk replacement formulas in clinical practice and what additional research would be the most beneficial.

Exploring the incidence of dysplasia or adenocarcinoma in early onset Barrett's esophagus.

BACKGROUND: Currently data on the risk of progression to and lifetime risk of cancer are not available for patients with young onset Barrett's esophagus (BE). Our aim was to obtain epidemiologic data on the incidence of dysplasia or adenocarcinoma in young onset BE in the Netherlands by collecting data on all histologically confirmed cases over a prolonged period of 25 years between January 1, 1991 and December 31, 2015. METHODS: Data were obtained from the Dutch National Pathology Registry. Patients were included if there was a suspicion of BE visualized in the esophagus during the endoscopic examination in combination with a concordant histologic diagnosis of intestinal metaplasia. RESULTS: 231 patients with early onset BE were identified (median age 26 years [range 0-29 years]), with 17 progressing to dysplasia (6 prevalent and 11 incident). For the patients with incident dysplasia, the median surveillance time between the diagnosis of early onset BE and diagnosis of dysplasia was 5 years (range 0-16 years). The incidence rate of dysplasia was 7.3 per 1000 person-years. There were three patients who developed adenocarcinoma (1 prevalent and 2 incident), who were diagnosed at ages 28, 35, and 36 years. The incidence rate of adenocarcinoma was 1.3 per 1000 person-years. CONCLUSIONS: In this 25-year period, 231 patients were diagnosed with early onset BE in the Netherlands, with 17 patients progressing to dysplasia and three developing adenocarcinoma. This corresponded to incidence rates of 7.3 per 1000 person-years for dysplasia and 1.3 per 1000 person-years for adenocarcinoma.

The effect of microbiome-modulating therapeutics on glucose homeostasis in metabolic syndrome: A systematic review, meta-analysis, and meta-regression of clinical trials.

BACKGROUND: Metabolic syndrome (MetS) is a chronic disorder featuring overweight/obesity, high blood pressure, and dysfunction of lipid and carbohydrate metabolism. Microbiome-modulating probiotics, prebiotics, synbiotics and fecal microbiota transplant (FMT) are promising adjunct therapies for improving parameters of glucose homeostasis and insulinemia. METHODS: We conducted a comprehensive systematic review, meta-analyses, and meta-regressions to investigate the effect of the abovementioned microbiome therapies on various biomarkers after screening clinical trials published through April 2023. We pooled data using random effects meta-analyses, reporting them as mean differences (MDs) with 95 % confidence intervals (CIs), and conducting univariate linear model meta-regressions. RESULTS: Data from 21 trial comparisons across 19 studies (n = 911) revealed that, compared to placebo/control, microbiome-modulating therapies were associated with statistically significant changes in fasting plasma glucose (MD: 4.03 mg/dL [95%CI: 6.93; -1.13]; p effect = 0.006, I2 = 89.8 %), and fasting insulin (MD: 2.56 µU/mL [95%CI: 4.28; -0.84]; p effect = 0.004, I2 = 87.9 %), but not insulin resistance or sensitivity indices and HbA1c. Age, baseline BMI, baseline biomarker value, pro/synbiotic dosage, trial duration, nutraceutical type, and WHO region were factors affecting the efficacy of these interventions at producing changes in biomarkers, signaling the potential role of personalized precision medicine adjunct therapy for deranged glucose homeostasis in patients with MetS. Nevertheless, presence of heterogeneity calls for further investigation before their clinical application. CONCLUSIONS: Probiotics, prebiotics, synbiotics and FMT supplementation improved fasting glucose and insulin in patients with MetS. Further large-scale and high-quality trials are required before potential clinical applications.

[Low and very low cholesterol levels: what we need to know]. / Livelli di colesterolo bassi e molto bassi: cosa è necessario sapere.

Due to the growing evidence of clinical benefits conferred by the reduction of low-density lipoprotein cholesterol (LDL-C) levels, the availability of multiple effective lipid-lowering agents, and guideline recommendations, clinicians not infrequently have to manage patients with low or very low LDL-C levels. In clinical practice it is essential to consider that, when LDL-C plasma concentrations are low, the Friedewald formula commonly used for LDL-C level calculation is less accurate, hence risk assessment should be integrated by using different methods for LDL-C level quantification and other parameters, such as non-high-density lipoprotein cholesterol and, where possible, apolipoprotein B, should be measured. As regards the clinical impact of low LDL-C levels, genetically determined hypocholesterolemia forms provide reassuring data on the effects of this condition in the long term, except for the forms with extremely low or undetectable LDL-C levels. Evidence from clinical studies that used highly effective lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 inhibitors, goes in the same direction. In these studies, the incidence of non-cardiovascular adverse events in patients who reached very low LDL-C levels was similar to that in the placebo arm. Overall, the fear of adverse effects should not deter intensive lipid-lowering treatment when indicated to reduce the risk of cardiovascular events.

Stool-Based Testing for Post-Polypectomy Colorectal Cancer Surveillance Safely Reduces Colonoscopies: The Molecular Stool Testing for Colorectal Cancer Surveillance Study.

BACKGROUND & AIMS: Colonoscopy-based surveillance to prevent colorectal cancer (CRC) causes substantial burden for patients and health care. Stool tests may help to reduce surveillance colonoscopies by limiting colonoscopies to individuals at increased risk of advanced neoplasia. METHODS: This cross-sectional observational study included individuals aged 50-75 years with surveillance indication. Before bowel preparation, participants collected samples for a multitarget stool DNA test and 2 fecal immunochemical tests (FITs). Test accuracy was calculated for all surveillance indications. For the post-polypectomy indication only, which is the most common and is associated with a relatively low CRC risk, long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test's positivity threshold to obtain strategies at least as effective as colonoscopy surveillance. RESULTS: There were 3453 individuals with results for all stool tests and colonoscopy; 2226 had previous polypectomy, 1003 had previous CRC, and 224 had a familial risk. Areas under the receiver operating characteristic curve for advanced neoplasia were 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test, 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR (Eiken Chemical Co, Tokyo, Japan) and 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold (Sentinel, Milan, Italy). Stool-based post-polypectomy surveillance strategies at least as effective as colonoscopy surveillance reduced the number of colonoscopies by 15%-41% and required 5.6-9.5 stool tests over a person's lifetime. Multitarget stool DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs. CONCLUSIONS: This study found that stool-based post-polypectomy surveillance strategies can be safe and cost-effective, with potential to reduce the number of colonoscopies by up to 41%. CLINICALTRIALS: gov, Number: NCT02715141.

Artificial Intelligence Tools in Pediatric Urology: A Comprehensive Review of Recent Advances.

Artificial intelligence (AI) is providing novel answers to long-standing clinical problems, and it is quickly changing pediatric urology. This thorough analysis focuses on current developments in AI technologies that improve pediatric urology diagnosis, treatment planning, and surgery results. Deep learning algorithms help detect problems with previously unheard-of precision in disorders including hydronephrosis, pyeloplasty, and vesicoureteral reflux, where AI-powered prediction models have demonstrated promising outcomes in boosting diagnostic accuracy. AI-enhanced image processing methods have significantly improved the quality and interpretation of medical images. Examples of these methods are deep-learning-based segmentation and contrast limited adaptive histogram equalization (CLAHE). These methods guarantee higher precision in the identification and classification of pediatric urological disorders, and AI-driven ground truth construction approaches aid in the standardization of and improvement in training data, resulting in more resilient and consistent segmentation models. AI is being used for surgical support as well. AI-assisted navigation devices help with difficult operations like pyeloplasty by decreasing complications and increasing surgical accuracy. AI also helps with long-term patient monitoring, predictive analytics, and customized treatment strategies, all of which improve results for younger patients. However, there are practical, ethical, and legal issues with AI integration in pediatric urology that need to be carefully navigated. To close knowledge gaps, more investigation is required, especially in the areas of AI-driven surgical methods and standardized ground truth datasets for pediatric radiologic image segmentation. In the end, AI has the potential to completely transform pediatric urology by enhancing patient care, increasing the effectiveness of treatments, and spurring more advancements in this exciting area.

Synthesis and dengue inhibition potential of new uridine derivatives: The DENV 2 inhibitors.

Dengue is an important arboviral infection worldwide for which presently there is no specific medicine. Evidence suggests there are four serotypes of dengue virus (DENV1-4), of which DENV 2 is considered to cause the most sever dengue. Therefore, this study was aimed to develop the new uridine derivatives (NUDs) against dengue virus (DENV 2). In current study 2-(3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-4-((substituted cyclohexa-2,5-dienylidene)methyl)-1,2,4-triazine-3,5(2H,4H)-dione (2a-f), were obtained via reaction of substituted uridine (1) and different aromatic aldehydes separately. Synthesized NUDs were further characterized using FTIR, 1H & 13C-NMR, mass and element analysis data. Characterized NUDs were assessed for their inhibition potential against DENV 2. Synthesized NUDs were also evaluated for their cytotoxicity towards Vero cells by MTT assay method. This investigation successfully synthesized NUDs 2a-f and reported their high inhibitory activity against DENV 2. The synthesized NUDs exhibited negligible cytotoxicity. High anti-viral activity against DENV 2 serotype and least/no cytotoxicity of NUDs suggests their importance in the treatment of dengue. Present study recommends that in future these NUDs must be investigated for their clinical importance to establish them as a choice for dengue treatment.

Aspiring to clinical significance: Insights from developing and evaluating a machine learning model to predict emergency department return visit admissions.

Return visit admissions (RVA), which are instances where patients discharged from the emergency department (ED) rapidly return and require hospital admission, have been associated with quality issues and adverse outcomes. We developed and validated a machine learning model to predict 72-hour RVA using electronic health records (EHR) data. Study data were extracted from EHR data in 2019 from three urban EDs. The development and independent validation datasets included 62,154 patients from two EDs and 73,453 patients from one ED, respectively. Multiple machine learning algorithms were evaluated, including deep significance clustering (DICE), regularized logistic regression (LR), Gradient Boosting Decision Tree, and XGBoost. These machine learning models were also compared against an existing clinical risk score. To support clinical actionability, clinician investigators conducted manual chart reviews of the cases identified by the model. Chart reviews categorized predicted cases across index ED discharge diagnosis and RVA root cause classifications. The best-performing model achieved an AUC of 0.87 in the development site (test set) and 0.75 in the independent validation set. The model, which combined DICE and LR, boosted predictive performance while providing well-defined features. The model was relatively robust to sensitivity analyses regarding performance across age, race, and by varying predictor availability but less robust across diagnostic groups. Clinician examination demonstrated discrete model performance characteristics within clinical subtypes of RVA. This machine learning model demonstrated a strong predictive performance for 72- RVA. Despite the limited clinical actionability potentially due to model complexity, the rarity of the outcome, and variable relevance, the clinical examination offered guidance on further variable inclusion for enhanced predictive accuracy and actionability.

Evaluation of Anal Position Indexes from Anal Dimple and Neoanus at Sphincter Muscle Complex in Children with High Anorectal Malformations in Kano, Nigeria.

BACKGROUND: Anorectal malformations (ARMs) comprise a spectrum of congenital anomalies that continue to present a challenge to patients, caregivers and paediatric surgeons. The main objective of this study was to determine the anal position index (API) from anal dimple and neoanus at the sphincter muscle complex in children with high ARM. METHODS: Using a cross-sectional study design, the API was assessed from anal dimple and neoanus at the sphincter muscle complex in children with high ARM. All eligible children with high ARM who presented to AKTH during the study period were recruited into the study. RESULTS: Forty eligible patients with an age range of 8 months to 108 months were recruited. Twenty-five were males (62.5%) with a male: female ratio of 1.7:1. The mean pre-operative API using anal dimple was 0.47 ± 0.05, while that of the post-operative API using neoanus was 0.53 ± 0.04. There was a statistically significant difference between the two indices (t = -11.8, P < 0.01). There was also a statistically significant difference amongst male and female indices P < 0.05, but there were no significant differences between different age groups. CONCLUSION: This study has shown that there was a statistically significant difference between the pre-operative API and post-operative API; thus, the position of the anal dimple does not significantly predict the central position of the sphincter muscle complex.

Using hardystonite as a biomaterial in biomedical and bone tissue engineering applications.

Widespread adoption for substitutes of artificial bone grafts based on proper bioceramics has been generated in recent years. Among them, calcium-silicate-based bioceramics, which possess osteoconductive properties and can directly attach to biological organs, have attracted substantial attention for broad ranges of applications in bone tissue engineering. Approaches exist for a novel strategy to promote the drawbacks of bioceramics such as the incorporation of Zn2+, Mg2+, and Zr4+ ions into calcium-silicate networks, and the improvement of their physical, mechanical, and biological properties. Recently, hardystonite (Ca2ZnSi2O7) bioceramics, as one of the most proper calcium-silicate-based bioceramics, has presented excellent biocompatibility, bioactivity, and interaction. Due to its physical, mechanical, and biological behaviors and ability to be shaped utilizing a variety of fabrication techniques, hardystonite possesses the potential to be applied in biomedical and tissue engineering, mainly bone tissue engineering. A notable potential exists for the newly developed bioceramics to help therapies supply clinical outputs. The promising review paper has been presented by considering major aims to summarize and discuss the most applicable studies carried out for its physical, mechanical, and biological behaviors.

Intelligent Tutoring Systems, Generative Artificial Intelligence (AI), and Healthcare Agents: A Proof of Concept and Dual-Layer Approach.

This study introduces a novel methodology for enhancing intelligent tutoring systems (ITS) through the integration of generative artificial intelligence (GenAI) and specialized AI agents. We present a proof of concept (PoC) demo that implements a dual-layer GenAI validation approach that utilizes multiple large language models to ensure the reliability and pedagogical integrity of the AI-generated content. The system features role-specific AI agents, a GenAI-powered scoring mechanism, and an AI mentor that provides periodic guidance. This approach demonstrates capabilities in dynamic scenario generation and real-time adaptability while addressing key challenges in AI-driven education, such as personalization, scalability, and domain-specific knowledge integration. Although exemplified here through a case study in healthcare root cause analysis, the methodology is designed for broad applicability across various fields. Our findings suggest that this approach has significant potential for advancing adaptive learning and personalized instruction while raising important considerations regarding ethical AI application in education. This work provides a foundation for further research into the efficacy and impact of GenAI-enhanced ITS on learning outcomes and instructional design across diverse educational domains.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update - XVI - Nutritional management of cow's milk allergy.

Cow's milk allergy (CMA) is one of the most common presentations of food allergy in early childhood. Management of CMA involves individualized avoidance of cow's milk and other mammalian milk and foods containing these. Optimal elimination of cow's milk avoidance includes: label reading; information about safe and nutritious substitute foods; appropriate choice of infant formula or a plant-based food; establishing tolerance to baked milk and monitoring nutritional intake and growth. Substitute formulas are divided into soy formula (not hydrolyzed), milk-based extensively hydrolyzed formulas, rice based extensive, and partially hydrolyzed formulas and amino acid-based formulas. The use of other mammalian milks is not recommended for the management of cow's milk allergy due to a high level of cross-reactivity and nutritional concerns. For toddlers who are eating well, children, and adults, a suitable plant-based beverage may be a suitable alternative to a specialized formula, following careful nutritional considerations. Families need to be instructed on finding suitable nutritious foods and how to prepare suitable meals at home. Individuals with CMA also need to know how to identify and treat acute severe reactions.

Cellulose nanofibers of oil palm fronds as a filler in nanocomposite coating for corrosion protection of copper.

Cellulose nanofibers (CNF) create a physical barrier preventing contact with corrosive substances and improving corrosion prevention. Oil palm fronds (OPF), the primary source of underused biomass waste from plantations, were processed into CNF. The OPF-CNF, mixed with hydroxyethyl cellulose as the matrix, forms a nanocomposite. Corrosion analysis using electrochemical methods demonstrated that copper coated with cellulose-rich nanocomposite containing 5 % CNF had a significantly decreased corrosion rate with an efficiency of 97.92 %. This CNF-based coating, combining barrier and passivation mechanisms, enhances performance, providing a competitive, eco-friendly alternative to conventional coatings.

Oral rabies vaccination of foxes in Türkiye, 2019-2022.

Background: Rabies in Turkey is maintained by dogs, but following a sustained spill-over, red fox mediated rabies had spread from the Aegean region to the central part of Türkiye. During the past four years from 2019 to 2023 large scale efforts used oral rabies vaccination (ORV) to control rabies in red foxes. Here, we present the results of the largest ORV campaign on the Asian continent. Methods: ORV campaigns were carried out twice a year in spring and autumn with a targeted bait density of 20-23 baits/km2. Monitoring of ORV campaigns included the GIS-based analyses of bait distribution, the assessment of bait uptake through biomarker detection and the determination of seroconversion (sero-positivity in ELISA) in the target species collected within the vaccination area. For determination of fox rabies incidence in vaccination areas as the main indicator of the performance of the ORV campaigns, epidemiological data was obtained from the national passive surveillance program. Results: Aerial bait distribution was highly accurate, with >99 % of baits being recorded from targeted zones, thus meeting the desired bait densities. Although the overall bait uptake (28.1 %; 95 %CI: 23.2-32.8) and seroprevalance (36.3 %; 95 %CI: 30.0-43.2) were low, rabies incidence drastically decreased in ORV areas and rabies was eliminated from western and central parts of Turkey, with no reported cases in foxes from ORV areas in 2022 and 2023. Conclusions: A large-scale ORV campaign against fox rabies using high quality vaccine baits and the GIS-aided and monitored bait distribution was able to control fox mediated rabies in the western and central parts of Türkiye. Rabies control both in dogs and foxes should be expanded to cover also the eastern parts of Türkiye, to become eventually rabies free.

Anti-aging and immunomodulatory role of caffeine in Drosophila larvae.

Drug repurposing is a promising approach to identify new pharmacological indications for drugs that have already been established. However, there is still a limitation in the availability of a high-throughput in vivo preclinical system that is suitable for screening and investigating new pharmacological indications. The aim of this study was to introduce the application of Drosophila larvae as an in vivo platform to screen drug candidates with anti-aging and immunomodulatory activities. To determine whether Drosophila larvae can be utilized for assessing anti-aging and immunomodulatory activities, phenotypical and molecular assays were conducted using wildtype and mutant lines of Drosophila. The utilization of mutant lines (PGRP-LBΔ and Psh[1];;ModSP[KO]) mimics the autoinflammatory and immunodeficient conditions in humans, thereby enabling a thorough investigation of the effects of various compounds. The phenotypical assay was carried out using survival and locomotor observation in Drosophila larvae and adult flies. Meanwhile, the molecular assay was conducted using the RT-qPCR method. In vivo survival analysis revealed that caffeine was relatively safe for Drosophila larvae and exhibited the ability to extend Drosophila lifespan compared to the untreated controls, suggesting its anti-aging properties. Further analysis using the RT-qPCR method demonstrated that caffeine treatment induced transcriptional changes in the Drosophila larvae, particularly in the downstream of NF-κB and JAK-STAT pathways, two distinct immune-related pathways homologue to humans. In addition, caffeine enhanced the survival of Drosophila autoinflammatory model, further implying its immunosuppressive activity. Nevertheless, this compound had minimal to no effect on the survival of Staphylococcus aureus-infected wildtype and immunodeficient Drosophila, refuting its antibacterial and immunostimulant activities. Overall, our results suggest that the anti-aging and immunosuppressive activities of caffeine observed in Drosophila larvae align with those reported in mammalian model systems, emphasizing the suitability of Drosophila larvae as a model organism in drug repurposing endeavors, particularly for the screening of newly discovered chemical entities to assess their immunomodulatory activities before proceedings to investigations in mammalian animal models.

How do emotional intelligence, resilience, and parental employment affect anxiety and depression levels among Sudanese adolescents?

BACKGROUND: Adolescents are often sensitive to emotions and vulnerable to psychiatric issues, including suicidal tendencies. Emotional intelligence is believed to play a significant role in resilience, which acts as a protective factor for mental well-being. The study investigated the level of emotional intelligence, resilience, depression, and anxiety in Sudanese adolescents and the relationship between these factors. METHODS: A cross-sectional study was conducted among four high schools and included a total of 392 adolescents who completed a self-administered questionnaire consisting of the 30-item trait; Emotional Intelligence Questionnaire- short form (TEQ-SF), Brief Resilience Scale-6 (BRS-6) and Patient Health Questionnaire-4 (PHQ-4). RESULTS: Emotional intelligence levels were moderate to high (M = 131.53 ± SD 22.16). While resilience levels were low to normal (M = 3.20 ± SD 0.51). Levels of anxiety were present in 89% of students while levels of depression were present in 78% of students and both were positively correlated (r = 0.540). Emotional intelligence and resilience were positively correlated (r = 0.272, p < 0.0005). Also, Resilience was positively correlated with levels of anxiety (r = 0.105) and the latter had a significant negative association with academic performance (r = - 0.102). Parents' status significantly contributed to predicting resilience levels (p-value = 0.011), with an unstandardized beta coefficient of 0.368. The mothers' unemployment (r = - 0.100) and the father's employment (r = 0.105) were significantly linked to lower anxiety levels. CONCLUSION: The high prevalence of anxiety and depression levels among Sudanese adolescents is influenced by parental separation and employment. Improving students' mental health is crucial as it is linked to enhancing their academic performance. This underscores the importance of addressing mental well-being alongside educational outcomes.

Feline acute patient physiologic and laboratory evaluation scores and other prognostic factors in cats with first-time diabetic ketoacidosis.

BACKGROUND: Acute Patient Physiologic and Laboratory Evaluation (APPLE) scores have not been reported in cats with diabetic ketoacidosis (DKA). HYPOTHESIS: In cats with DKA, APPLE scores will be significantly higher in non-survivors compared with survivors and these scores will predict mortality. ANIMALS: Sixty-eight cats with DKA. METHODS: Retrospective study. The APPLE scores, blood glucose concentration (BG), venous pH, and ketone concentrations were compared between survivors and non-survivors. Simple logistic regression was used to determine if these variables predict the binary variable of survival or non-survival, and if they did, an empirical optimal cut point for mortality prediction was calculated. RESULTS: The APPLEfast and APPLEfull scores were significantly higher in non-survivors (30 cats; 24.6 ± 7.4 and 45.2 ± 7.3 , respectively) compared with survivors (38 cats; 20.9 ± 6.2 and 41.7 ± 6.5 ; P = .01 and P = .02, respectively). The APPLEfast (P = .03) but not the APPLEfull scores (P = .06) predicted mortality. For every 1 unit increase in the APPLEfast score, the odds of death increased by 1.08 (95% confidence interval [CI], 1.006-1.17; P = .03). Median BG was significantly higher in non-survivors (431 mg/dL; range, 260-832 mg/dL) compared with survivors (343 mg/dL; range, 256-738 mg/dL; P = .01) and BG predicted mortality (P = .02). For every 1 mg/dL increase in BG, the odds of death increased by 1.004 (95% CI, 1.0006-1.008). Empirical optimal cut points for APPLEfast and BG mortality prediction were 24.5 and 358 mg/dL, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The APPLEfast score and BG predict mortality in cats with DKA and can be used to stratify populations by risk of mortality in clinical trials of DKA in cats.

Maximizing Minimally Invasive Cardiac Surgery With Enhanced Recovery (ERAS).

We convened a group of cardiac surgeons, intensivists, and anesthesiologists with extensive experience in minimally invasive cardiac surgery (MICS) and perioperative care to identify the essential elements of a MICS program and the relationship with Enhanced Recovery After Surgery (ERAS). The MICS incision should minimize tissue invasion without compromising surgical goals. MICS also requires safe management of hemodynamics and preservation of cardiac function, which we have termed myocardial management. Finally, comprehensive perioperative care through an ERAS program should be provided to allow patients to achieve optimal recovery. Therefore, we propose that MICS requires 3 elements: (1) a less invasive surgical incision (non-full sternotomy), (2) optimized myocardial management, and (3) ERAS. We contend that the full benefit of MICS can be achieved only by also utilizing an ERAS platform.