Preoperative anemia, transfusions, and simple hematological parameters like red blood cell distribution width (RDW) have been associated with worse outcomes in patients undergoing transcatheter aortic valve implantation (TAVI), with some heterogeneity of results. Hemoglobin (Hb) levels are physiologically different in males and females, and sex differences are increasingly recognized to play an important role in the prognosis of many cardiovascular diseases, including aortic valve stenosis. We aimed to evaluate the prognostic role of preoperative anemia, RDW, and periprocedural transfusions in TAVI patients followed up to 2 years, especially focusing on sex-related differences. 609 patients (median age 83 years, 53.9% females) undergoing TAVI at Verona University Hospital between March 2010 and June 2019 were retrospectively evaluated. Anemia before TAVI was highly prevalent (55.0%) in our population, mostly mild to moderate. Females were less anemic than males (48.8% versus 62.3%, p = 0.001) but experienced more vascular complications and were more frequently transfused within 30 days of the procedure (43.3% versus 28.8%, p < 0.001). Overall, anemic patients at baseline had a 2-year survival lower than non-anemic patients (Log-rank 5.915, p = 0.015). Similarly, patients with baseline RDW > 15% had reduced survival at 2 years compared to patients with normal RDW (Log-rank 14.038, p < 0.001). Grouping for sex, these differences only persisted in males. Multivariable analyses showed that hematological variables, such as periprocedural transfusions and RDW, were significant predictors of 2-year mortality in males but not in females. Our study highlights significant sex-related differences in the role of hematological parameters as independent predictors of 2-year mortality after TAVI.

RNA based epigenetic modifications and their relations with chronic diseases have been widely studied. The current study aimed to determine the role of long noncoding RNA (lncRNA) TUG1 and microRNA 145 (miR-145) in the pathophysiology and progression of hypothyroidism as well as their impact on subsequent cardiovascular disorders.

Serum levels of TUG1 and miR-145 were measured in three different groups, 40 overt hypothyroid (OHT) patients, 40 subclinical hypothyroid (SHT) patients and 45 healthy controls. All individuals were subjected to a full history investigation and clinical examination. Flow mediated vasodilation of the brachial artery was measured to evaluate endothelial function. Serum samples were also tested for T4, TSH, TG, TC, HDL, LDL, HbA1c, glucose and insulin.

TUG1 level was significantly increased in OHT and SHT patients compared to the healthy controls. TUG1 correlated positively with TC, LDL levels and endothelial dysfunction, while correlated negatively with HDL. Regarding miR-145, its expression level was downregulated only in OHT patients as compared to controls and SHT patients. There were significant negative correlations with TC, LDL and endothelial dysfunction and significant positive correlation with HDL. A significant negative correlation existed between TUG1 and miR-145.

TUG1 could be considered a powerful diagnostic tool to distinguish HT patients, while miR-145 could serve as a negative independent predictor for the progression of HT among subclinical patients. TUG1/miR-145 trajectory could affect the progression of hypothyroidism and the incidence of cardiovascular diseases through impacting patients' lipid profile and endothelial integrity. They could be potential biomarkers and predictors for hypothyroidism pathophysiology.

Asian Americans underutilize mental health services, with particularly low rates among Korean American (KA) immigrants. Churches serve as central sources of support in this community, positioning clergy as critical mental health gatekeepers. Yet little is known about the factors shaping KA church leaders' readiness, perceptions, and referral behaviors. This study analyzed survey data from 93 KA church leaders across the USA to explore factors associated with readiness (comfort addressing mental health), perceptions of issues and barriers, and the action of recommending professional counseling. Using multiple regressions, we found that prior mental health training was the only significant predictor of leader readiness, with trained leaders nearly three times more likely to report higher comfort levels (OR = 2.97, p < 0.05). Perceptions of church needs varied by ministry context and personal experience: Leaders with mental health training were over six times more likely to recognize depression and suicide as key concerns (OR = 6.71, p < 0.01) and more than twice as likely to identify marriage conflict (OR = 3.11, p < 0.05). In contrast, leaders who had personally received counseling were significantly less likely to report depression and suicide as a congregational issue (OR = 0.23, p < 0.05). In the integrative model, referral behavior was shaped primarily by ministry context and stigma awareness. Leaders in Korean-speaking ministries were significantly less likely to recommend counseling (OR = 0.02, p < 0.05), while those who identified stigma as a major issue were substantially more likely to make referrals (OR = 9.50, p < 0.05). These findings highlight the central role of training, bicultural ministry contexts, and stigma recognition in shaping church leaders' engagement with mental health. The study underscores the need for culturally adapted training programs and closer collaboration between mental health professionals and immigrant churches to address persistent disparities in KA communities.

Adverse drug events (ADEs) are a leading cause of preventable patient harm in hospitals. Because they are often recorded only in clinical free-text documents, retrieval and quantification are significantly limited. Automating ADE detection with natural language processing (NLP) is promising. Recent work shows that bidirectional encoder representations from transformers (BERT)-based models outperform bidirectional long short-term memory (Bi-LSTM) models and even larger generative pretrained transformers while being more computationally efficient. However, most ADE-NLP research focuses on the English language, often applies metrics less suitable for rare outcomes such as ADEs, and lacks external validation.

To evaluate four transformer models for the detection of ADEs by reusing Dutch clinical free-text documents and create a benchmark with realistic clinical scenarios, appropriate performance measures, and external validation.

We used three anonymized datasets: (1) Dutch ADE corpus with 102 densely annotated progress notes of patients admitted to the intensive care unit (ICU) from one Dutch academic hospital, (2) ICU AKI corpus with 411 sparsely annotated ICU notes from the same hospital, and (3) WINGS corpus with 100 discharge letters of internal medicine patients from two Dutch non-academic hospitals, labeled for ADE presence. A Bi-LSTM model and four transformer-based Dutch or multilingual encoder models (BERTje, RobBERT-base, MedRoBERTa.nl, NuNER) were trained for named entity recognition (NER) and relation classification (RC) using the Dutch ADE corpus. We used fivefold cross validation with 60%/20%/20% train/validation/test splits and performed hyperparameter tuning on the first fold for NER and across all folds for RC. We evaluated our ADE RC models internally using gold standard (two-step task) and predicted entities (end-to-end task). In addition, all models were externally validated using WINGS Corpus on detecting ADEs at the document level. We report both micro- and macro-averaged F1 scores, to account for ADE rarity.

In our internal validation, MedRoBERTa.nl achieved the best performance, with macro-averaged F1 score of 0.63 using gold standard entities and 0.62 using predicted entities, while all models reached micro-averaged F1 scores ± 0.99. MedRoBERTa.nl also performed the best in our external validation, with recall range 0.67-0.74 using predicted entities (end-to-end task), meaning that between 67% and 74% of discharge letters with ADEs were detected.

The Dutch domain-specific MedRoBERTa.nl showed the best performance in detecting ADEs in Dutch clinical texts, and in line with previous studies in English language settings, outperformed Bi-LSTM. The inclusion of external validation highlights its generalization potential. Our findings also underline the need for further model improvement and use of performance measures suited to rare outcomes such as ADEs, as micro-averaged F1 scores inflate performance compared with macro-averaged F1 scores. We provide a robust and clinically meaningful benchmark approach for NLP-based ADE detection in clinical free-text documents. Our approach can serve as a guidance for future NLP benchmarks in ADE domain.

Therapeutic communication is essential to nursing practice, yet many pre-licensure nursing students report discomfort applying these skills in clinical settings. Standardized patient (SP) simulation offers a controlled environment for practicing communication, yet qualitative research describing students' perceptions of these experiences remains limited. This study explored undergraduate nursing students' perspectives on small-group, communication-focused SP simulations within a psychiatric-mental health nursing course.

As part of a larger program evaluation, six in-person focus groups were conducted with 47 Bachelor of Science in Nursing students following participation in two series of SP simulations across nine scenarios. Discussions were audio-recorded, transcribed, and analyzed using inductive thematic content analysis. An audit trail and team debriefing supported rigor and consistency.

Three themes emerged. First, students reported that SP simulations increased their comfort and confidence in therapeutic communication, providing a safe space to practice navigating emotionally charged conversations and building rapport. Second, the simulations evoked ambiguity regarding the psychiatric-mental health nurse's role, as students struggled to differentiate therapeutic communication from psychotherapy and acknowledged real-world time constraints that limit such interactions. Third, students identified high-quality, instructive feedback, particularly during debriefing, as essential to learning and expressed a desire for more structured guidance from SPs and faculty.

Communication-focused SP simulations effectively enhance therapeutic communication skills among pre-licensure nursing students. To optimize learning, faculty should intentionally clarify nursing role boundaries and strengthen debriefing structures. Findings highlight the importance of targeted feedback and instructional support in maximizing the educational value of SP-based simulation.

The retina-an extension of the central nervous system-contains microglia that survey and respond to injury or pathogens. In response to their environmental milieu, these cells accumulate autofluorescent material likely reflective of cellular debris. Measuring these autofluorescence changes may be a useful tool for early diagnosis of brain-related inflammatory conditions or diseases by imaging the eye. To assess this, we gave Wistar rats a systemic immune challenge with lipopolysaccharide (LPS; 250 µg/kg, intraperitoneally) and examined autofluorescence characteristics of the microglia in brain and eye using confocal microscopy. Initial flow cytometry experiments verified that isolated microglia are highly autofluorescent compared to cells in immune-related organs such as spleen. In immunolabelled brain sections (arcuate, hippocampus, retrosplenial cortex), astrocytes, neurons, and microglia all displayed significant autofluorescence, with microglia displaying greatest levels. LPS led to predicted changes in microglial morphology in the brain and this was accompanied by an increase in the number of individual autofluorescent aggregates but a reduction in the total volume, indicative of changes in the dynamics of the material. While there were similarities in the microglial response to LPS in the retina, and the total volume of autofluorescence aggregates was also reduced, retinal autofluorescence changes did not simply predict those seen in brain. These findings suggest that the relationship between immune challenge states and autofluorescence accumulation is dynamic and complex. Understanding the role of microglia in accumulating and metabolising this autofluorescent material may assist our understanding of disease states and how they influence retina and brain.

Reduced hippocampal volumes are frequently observed in psychiatric disorders and have been linked to childhood adversity. Conversely, physical activity is associated with increased hippocampal volumes. This study aimed to integrate these risk and protective factors in young people by examining both group-level differences and dimensional associations.

We investigated the associations between hippocampal subfield volumes, early-stage psychiatric symptoms, childhood adversity and cardiorespiratory fitness as a proxy measure for long-term physical activity (VO₂max/kg), using multi-level models. The sample included 122 participants aged 16-24 years, categorized into a symptom and healthy control group. A transdiagnostic approach was employed to capture the heterogeneous and pluripotent nature of early-stage symptomatology.

No significant group differences in overall or subfield hippocampal volumes were observed between participants with early-stage psychiatric symptoms and healthy controls. However, within the symptom group, reduced CA1 subfield volumes showed clear associations with more childhood adversity, depressive and PTSD symptoms. In contrast, cardiorespiratory fitness was associated with greater right CA1 volume. Moreover, the negative association between depressive symptoms and overall hippocampal volume was moderated by cardiorespiratory fitness, being significant only in individuals with low fitness levels.

These findings indicate that the CA1 volumetric variation may be influenced by environmental risk and protective factors. Future research should explore these dynamics longitudinally, accounting for the type, severity and duration of both psychiatric symptoms and childhood adversity.

The purpose of the study is to establish prevalence of separate components of subjective psychological problems among adolescents aged 15-18 years, to identify dynamics of the prevalence of factors of psychological problems over the past decade and to characterize perception by parents of children aged 10-14 years the crisis psychological situations of their child in the Republic of Belarus. The data of surveys of representative Republican samples of adolescents of age of 15-18 years carried out in 2022-2023 (n=1254) and in 2010-2011 (n=949) were analyzed. The following factors were considered: self-assessment of health, emotional psychological characteristics of personality of adolescents as parameters of subjective psychological well-being/problematic condition. The results of survey of the Republican representative sample of parents of adolescents aged 10-14 years (n=1230) that was carried out in 2022-2023 were used to analyze opinions of parents about crisis psychological situations in life of their child. The study confirms the widespread prevalence in adolescent environment of indicators of condition of subjective psychological problems, the intensity of which increases in the interim of 15-18 years as they are becoming adult. The risk groups of condition of subjective psychological problems subjective disadvantage are individuals residing in rural areas and male youths. As regarding male youths, the tendency was revealed concerning deterioration of self-assessment of health and an increase of prevalence of factors of condition of subjective psychological problems during 2010-2023. According opinions of of adolescents themselves and their parents, extremely low demand for help from school psychologists, pedagogues and other workers of social psychological services of educational institutions in cases of crisis psychological situation of adolescent remained during 2010-2023.

This study includes the long-term benefit-harm analysis of population-wide colorectal cancer (CRC) screening strategies commissioned by the Austrian National Committee for Cancer Screening (ANCCS). In addition, we present the related cost-effectiveness analysis.

Using a validated decision-analytic Markov state transition model, we evaluated 17 by the ANCCS suggested CRC-screening strategies differing in tests (fecal-immunochemical test (FIT), guaiac-based fecal occult blood test (gFOBT), colonoscopy (COL)), age at start (40,45,50 years) and end (COL: 65,70,75 years, FIT/gFOBT 75 years), and intervals (2,5,10 years). Positive FIT/gFOBT tests are followed by colonoscopy. Evaluated outcomes included health benefits (life-years gained (LYG), CRC-cases/CRC-deaths avoided), harms (severe colonoscopy complications, psychological harms due to positive test results (PTR), additional colonoscopies), stepwise evaluated incremental harm-benefit ratios (IHBR), and incremental cost-effectiveness ratios (ICER). We applied the Austrian healthcare system perspective, a lifelong-time horizon and conducted sensitivity analyses.

The most effective colonoscopy-based screening strategy is colonoscopy at age 40/50/60/70 (449 LYG per 1000 individuals) with an IHBR of 3 PTR/LYG compared to COL45/55/65 (ICER: 13,032 Euro/LYG vs. COL45/55/65/75). The most effective fecal blood-test-based strategy is annual FIT testing starting at age 40 years (488 LYG per 1000 individuals) and an IHBR of 30 PTR/LYG compared to FIT40+2y (biennial FIT starting age 40). All biennial FIT-based screening strategies represent alternative options on the harm-benefit efficiency frontier with IHBR of PTR/LYG: 2 (FIT50+2y vs. no screening), 5 (FIT45+2y vs. FIT50+2y), and 7 (FIT40+2y vs. FIT45+2y). The cost-effectiveness analyses provided stepwise ICERs ranging from 3391 Euro/LYG (FIT45+2y vs. FIT50+2y) to 47,812 Euro/LYG (FIT40+1y vs. FIT40+2y).

Our decision analysis shows benefit-harm and cost-effectiveness trade-offs. In the consensus meeting of the ANCCS, colonoscopy- and FIT-based screening starting at age 45 were selected as suggested screening strategies, accounting for benefit-harm balance, evidence level, and implementation aspects.

The identification of tumor-generated DNA must be accurate, minimally invasive, and precise, as it forms a fundamental aspect of effective cancer diagnosis, prognosis, and customized treatment plans. Recent advances in synthetic biology have pioneered the creation of genetically engineered bacteria as innovative biosensors capable of detecting tumor-derived DNA directly in situ. This review explores key developments in designing these microbial sentinels to pinpoint oncogenic DNA alterations, particularly emphasizing KRAS mutations that drive many cancers. By leveraging natural competence and horizontal gene transfer, in combination with CRISPR-Cas tools for selective targeting and integration of mutant DNA sequences, engineered bacteria can distinguish between tumor and wild-type DNA and produce observable reporter outputs. We further elaborate on various molecular engineering strategies using unique genetic circuits, homologous recombination, multiplexed CRISPR systems and safety circuits to improve specificity, sensitivity and biosafety. An additional perspective in the discussion incorporates diverse bacterial species and various cancer types, with a specific emphasis on colorectal and gastrointestinal cancers, while also considering possible applications to other solid tumors. Detection modalities encompass in vitro assays, organoid models, in vivo mouse models, and non-invasive stool sampling, offering an impressive range of platforms for validating biosensors. The positive aspects of these approaches, such as real-time detection, affordability, programmability, and reduced invasiveness, need to be balanced with their negative aspects concerning biosafety, colonization efficiency, and detection sensitivity limitations. Looking forward, this review delves into the translational potential of engineered bacterial biosensors for clinical cancer diagnostics, their integration with therapeutic delivery systems, and future directions that involve multiplexed detection and the incorporation of digital health. Indubitably, engineered bacterial tumor DNA biosensors represent a key fusion of microbiology, synthetic biology, and oncology, aimed at revolutionizing the diagnosis and management of cancers.