Confronting the inevitable: When a urologist feels like a second victim.

There are many opportunities for urologists to be emotionally impacted, and possibly injured, in the regular course of their work. In particular, urologists are vulnerable to become Second Victims as a result of errors, adverse events, and distressing clinical events. This article reviews best practices that individuals, training programs, hospitals, and healthcare systems can implement to intentionally and programmatically mitigate the short and long-term effects on healthcare professionals.

Exploring the fear of clinical errors: associations with socio-demographic, professional, burnout, and mental health factors in healthcare workers - A nationwide cross-sectional study.

Background: The fear of clinical errors among healthcare workers (HCW) is an understudied aspect of patient safety. This study aims to describe this phenomenon among HCW and identify associated socio-demographic, professional, burnout and mental health factors. Methods: We conducted a nationwide, online, cross-sectional study targeting HCW in France from May to June 2021. Recruitment was through social networks, professional networks, and email invitations. To assess the fear of making clinical errors, HCW were asked: "During your daily activities, how often are you afraid of making a professional error that could jeopardize patient safety?" Responses were collected on a 7-point Likert-type scale. HCW were categorized into "High Fear" for those who reported experiencing fear frequently ("once a week," "a few times a week," or "every day"), vs. "Low Fear" for less often. We used multivariate logistic regression to analyze associations between fear of clinical errors and various factors, including sociodemographic, professional, burnout, and mental health. Structural equation modeling was used to explore how this fear fits into a comprehensive theoretical framework. Results: We recruited a total of 10,325 HCW, of whom 25.9% reported "High Fear" (95% CI: 25.0-26.7%). Multivariate analysis revealed higher odds of "High Fear" among males, younger individuals, and those with less professional experience. High fear was more notable among physicians and nurses, and those working in critical care and surgery, on night shifts or with irregular schedules. Significant associations were found between "High Fear" and burnout, low professional support, major depressive disorder, and sleep disorders. Conclusions: Fear of clinical errors is associated with factors that also influence patient safety, highlighting the importance of this experience. Incorporating this dimension into patient safety culture assessment could provide valuable insights and could inform ways to proactively enhance patient safety.

Upregulation of iNOS/NO in Cancer Cells That Survive a Photodynamic Challenge: Role of No in Accelerated Cell Migration and Invasion.

Anti-tumor photodynamic therapy (PDT) is a unique modality that employs a photosensitizer (PS), PS-exciting light, and O2 to generate cytotoxic oxidants. For various reasons, not all malignant cells in any given tumor will succumb to a PDT challenge. Previous studies by the authors revealed that nitric oxide (NO) from inducible NO synthase (iNOS/NOS2) plays a key role in tumor cell resistance and also stimulation of migratory/invasive aggressiveness of surviving cells. iNOS was the only NOS isoform implicated in these effects. Significantly, NO from stress-upregulated iNOS was much more important in this regard than NO from preexisting enzymes. Greater NO-dependent resistance, migration, and invasion was observed with at least three different cancer cell lines, and this was attenuated by iNOS activity inhibitors, NO scavengers, or an iNOS transcriptional inhibitor. NO diffusing from PDT-targeted cells also stimulated migration/invasion potency of non-targeted bystander cells. Unless counteracted by appropriate measures, all these effects could seriously compromise clinical PDT efficacy. Here, we will review specific examples of these negative side effects of PDT and how they might be suppressed by adjuvants such as NO scavengers or inhibitors of iNOS activity or expression.

Weighted Breaths: Exploring Biologic and Non-Biologic Therapies for Co-Existing Asthma and Obesity.

PURPOSE OF REVIEW: To discuss the effectiveness of biologics, some of which comprise the newest class of asthma controller medications, and non-biologics in the treatment of asthma co-existing with obesity. RECENT FINDINGS: Our review of recent preliminary and published data from clinical trials revealed that obese asthmatics respond favorably to dupilumab, mepolizumab, omalizumab, and tezepelumab, which are biologics currently indicated as add-on maintenance therapy for severe asthma. Furthermore, clinical trials are ongoing to assess the efficacy of non-biologics in the treatment of obese asthma, including a glucagon-like peptide-1 receptor agonist, a Janus kinase inhibitor, and probiotics. Although many biologics presently indicated as add-on maintenance therapy for severe asthma exhibit efficacy in obese asthmatics, other phenotypes of asthma co-existing with obesity may be refractory to these medications. Thus, to improve quality of life and asthma control, it is imperative to identify therapeutic options for all existing phenotypes of obese asthma.

Developing a multimedia patient-reported outcomes measure for low literacy patients with a human-centered design approach.

INTRODUCTION: Almost all patient-reported outcomes measures (PROMs) are text-based, which impedes accurate completion by low and limited literacy patients. Few PROMs are designed or validated to be self-administered, either in clinical or research settings, by patients of all literacy levels. We aimed to adapt the Patient Reported Outcomes Measurement Information System Upper Extremity Short Form (PROMIS-UE) to a multimedia version (mPROMIS-UE) that can be self-administered by hand and upper extremity patients of all literacy levels. METHODS: Our study in which we applied the Multimedia Adaptation Protocol included seven phases completed in a serial, iterative fashion: planning with our community advisory board; direct observation; discovery interviews with patients, caregivers, and clinic staff; ideation; prototyping; member-checking interviews; and feedback. Direct observations were documented in memos that underwent rapid thematic analysis. Interviews were audio-recorded and documented using analytic memos; a rapid, framework-guided thematic analysis with both inductive and deductive themes was performed. Themes were distilled into design challenges to guide ideation and prototyping that involved our multidisciplinary research team. To assess completeness, credibility, and acceptability we completed additional interviews with member-checking of initial findings and consulted our community advisory board. RESULTS: We conducted 12 hours of observations. We interviewed 17 adult English-speaking participants (12 patients, 3 caregivers, 2 staff) of mixed literacy. Our interviews revealed two distinct user personas and three distinct literacy personas; we developed the mPROMIS-UE with these personas in mind. Themes from interviews were distilled into four broad design challenges surrounding literacy, customizability, convenience, and shame. We identified features (audio, animations, icons, avatars, progress indicator, illustrated response scale) that addressed the design challenges. The last 6 interviews included member-checking; participants felt that the themes, design challenges, and corresponding features resonated with them. These features were synthesized into an mPROMIS-UE prototype that underwent rounds of iterative refinement, the last of which was guided by recommendations from our community advisory board. DISCUSSION: We successfully adapted the PROMIS-UE to an mPROMIS-UE that addresses the challenges identified by a mixed literacy hand and upper extremity patient cohort. This demonstrates the feasibility of adapting PROMs to multimedia versions. Future research will include back adaptation, usability testing via qualitative evaluation, and psychometric validation of the mPROMIS-UE. A validated mPROMIS-UE will expand clinicians' and investigators' ability to capture patient-reported outcomes in mixed literacy populations.

Inconsequential role for chemerin-like receptor 1 in the manifestation of ozone-induced lung pathophysiology in male mice.

We executed this study to determine if chemerin-like receptor 1 (CMKLR1), a Gi/o protein-coupled receptor expressed by leukocytes and non-leukocytes, contributes to the development of phenotypic features of non-atopic asthma, including airway hyperresponsiveness (AHR) to acetyl-ß-methylcholine chloride, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Accordingly, we quantified sequelae of non-atopic asthma in wild-type mice and mice incapable of expressing CMKLR1 (CMKLR1-deficient mice) following cessation of acute inhalation exposure to either filtered room air (air) or ozone (O3), a criteria pollutant and non-atopic asthma stimulus. Following exposure to air, lung elastic recoil and airway responsiveness were greater while the quantity of adiponectin, a multi-functional adipocytokine, in bronchoalveolar lavage (BAL) fluid was lower in CMKLR1-deficient as compared to wild-type mice. Regardless of genotype, exposure to O3 caused AHR, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Nevertheless, except for minimal genotype-related effects on lung hyperpermeability and BAL adiponectin, we observed no other genotype-related differences following O3 exposure. In summary, we demonstrate that CMKLR1 limits the severity of innate airway responsiveness and lung elastic recoil but has a nominal effect on lung pathophysiology induced by acute exposure to O3.

Multifaceted roles of cohesin in regulating transcriptional loops.

Cohesin is required for chromatin loop formation. However, its precise role in regulating gene transcription remains largely unknown. We investigated the relationship between cohesin and RNA Polymerase II (RNAPII) using single-molecule mapping and live-cell imaging methods in human cells. Cohesin-mediated transcriptional loops were highly correlated with those of RNAPII and followed the direction of gene transcription. Depleting RAD21, a subunit of cohesin, resulted in the loss of long-range (>100 kb) loops between distal (super-)enhancers and promoters of cell-type-specific genes. By contrast, the short-range (<50 kb) loops were insensitive to RAD21 depletion and connected genes that are mostly housekeeping. This result explains why only a small fraction of genes are affected by the loss of long-range chromatin interactions due to cohesin depletion. Remarkably, RAD21 depletion appeared to up-regulate genes located in early initiation zones (EIZ) of DNA replication, and the EIZ signals were amplified drastically without RAD21. Our results revealed new mechanistic insights of cohesin's multifaceted roles in establishing transcriptional loops, preserving long-range chromatin interactions for cell-specific genes, and maintaining timely order of DNA replication.

Menstrual health and hygiene knowledge among post menarche adolescent school girls in urban and rural Tanzania.

Adolescent girls' capacity to lead healthy lives and perform well in school has been hampered by their lack of awareness about menstruation and the requirements for its hygienic management. Lack of enabling infrastructure, improper menstrual supplies, and limited socioeconomic support for good menstrual health and cleanliness are characteristics of schools in Africa South of the Sahara. We evaluated school-age girls' knowledge of menstrual hygiene and identified bottlenecks that could affect policy and programming for menstrual health and hygiene. A school-based cross-sectional study involved 8,012 adolescent school girls in the age group of 11-18 years (mean age = 14.9 years). The study evaluated students' knowledge of menstrual health and hygiene (MHH) from the viewpoints of schools and communities using a combination of qualitative and quantitative approaches. Data was collected using self-administered surveys, focus group discussions, in-depth interviews, and site observations. Girls' older age (AOR = 1.62, P 0.001), having a female guardian (AOR = 1.39: P = 001), and having a parent in a formal job (AOR = 1.03: P 0.023) were positively associated with Menstrual health and Hygiene Knowledge. MHH knowledge levels varied significantly between girls attending government (53.3) and non-government schools (50.5%, P = 0.0001), although they were comparable for girls attending rural and urban schools. Only 21% of the study's schools had at least one instructor who had received training in MHH instruction for students. We have established that the majority of adolescent girls in schools have inadequate knowledge on menstrual health and hygiene, and that school teachers lack the skills to prepare and support young adolescents as they transition into puberty. Concerted actions aimed at building supportive policy are paramount, for school-aged teenagers to learn about and reap the long-term advantages of good menstrual health practices.

Advancing Fluoride-Ion Batteries with a Pb-PbF2 Counter Electrode and a Diluted Liquid Electrolyte.

Fluoride ion batteries (FIB) are a promising post lithium-ion technology thanks to their high theoretical energy densities and Earth-abundant materials. However, the flooded cells commonly used to test liquid electrolyte FIBs severely affect the overall performance and impede comparability across different studies, hindering FIB progress. Here, we report a reliable Pb-PbF2 counter electrode that enables the use of two-electrode coin cells. To test this setup, we first introduce a liquid electrolyte that combines the advantages of a highly concentrated electrolyte (tetramethylammonium fluoride in methanol) while addressing its transport and high-cost shortcomings by introducing a diluent (propionitrile). We then demonstrate the viability of this system by reporting a BiF3-Pb-PbF2 cell with the highest capacity retention to date.

Role Preferences in Medical Decision Making: Relevance and Implications for Health Preference Research.

Health preference research (HPR) is being increasingly conducted to better understand patient preferences for medical decisions. However, patients vary in their desire to play an active role in medical decisions. Until now, few studies have considered patients' preferred roles in decision making. In this opinion paper, we advocate for HPR researchers to assess and account for role preferences in their studies, to increase the relevance of their work for medical and shared decision making. We provide recommendations on how role preferences can be elicited and integrated with health preferences: (1) in formative research prior to a health preference study that aims to inform medical decisions or decision makers, (2a) in the development of health preference instruments, for instance by incorporating a role preference instrument and (2b) by clarifying the respondent's role in the decision prior to the preference elicitation task or by including role preferences as an attribute in the task itself, and (3) in statistical analysis by including random parameters or latent classes to raise awareness of heterogeneity in role preferences and how it relates to health preferences. Finally, we suggest redefining the decision process as a model that integrates the role and health preferences of the different parties that are involved. We believe that the field of HPR would benefit from learning more about the extent to which role preferences relate to health preferences, within the context of medical and shared decision making.

Cholesterol Hydroperoxide Co-trafficking in Testosterone-generating Leydig Cells: GPx4 Inhibition of Cytotoxic and Anti-steroidogenic Effects.

Trafficking of intracellular cholesterol (Ch) to and into mitochondria of steroidogenic cells is required for steroid hormone biosynthesis. This trafficking is typically mediated by one or more proteins of the steroidogenic acute regulatory (StAR) family. Our previous studies revealed that 7-OOH, a redox-active cholesterol hydroperoxide, could be co-trafficked with Ch to/into mitochondria of MA-10 Leydig cells, thereby inducing membrane lipid peroxidation (LPO) which impaired progesterone biosynthesis. These negative effects of 7-OOH were inhibited by endogenous selenoperoxidase GPx4, indicating that this enzyme could protect against 7-OOH-induced oxidative damage/dysfunction. In the present study, we advanced our Leydig focus to cultured murine TM3 cells and then to primary cells from rat testis, both of which produce testosterone. Using a fluorescent probe, we found that extensive free radical-mediated LPO occurred in mitochondria of stimulated primary Leydig cells during treatment with liposomal Ch+7-OOH, resulting in a significant decline in testosterone output relative to that with Ch alone. Strong enhancement of LPO and testosterone shortfall by RSL3 (a GPx4 inhibitor) and reversal thereof by Ebselen (a GPx4 mimetic), suggested that endogenous GPx4 was playing a key antioxidant role. 7-OOH in increasing doses was also cytotoxic to these cells, RSL3 exacerbating this in Ebselen-reversable fashion. Moreover, GPx4 knockdown increased cell sensitivity to LPO with reduced testosterone output. These findings, particularly with primary Leydigs (which best represent cells in intact testis) suggest that GPx4 plays a key protective role against peroxidative damage/dysfunction induced by 7-OOH co-trafficking with Ch.

Caregiver-reported quality of communication in pancreatic and periampullary cancer.

BACKGROUND: Communication between caregivers and clinical team members is critical for transitional care, but its quality and potential impact on outcomes are not well understood. This study reports on caregiver-reported quality of communication with clinical team members in the postpancreatectomy period and examines associations of these reports with patient and caregiver outcomes. METHODS: Caregivers of patients with pancreatic and periampullary malignancies who had undergone pancreatectomy were surveyed. Instrument measures assessed care experiences using the Caregiver Perceptions About Communication with Clinical Team Members (CAPACITY) instrument. The instrument has two main subscales: communication, assessing the extent to which providers helped caregivers comprehend details of clinical visits, and capacity, defined as the extent to which providers assessed whether caregivers were able to care for patients. RESULTS: Of 265 caregivers who were approached, 240 (90.6%) enrolled in the study. The mean communication and capacity subscale scores were 2.7 ± 0.6 and 1.5 ± 0.6, respectively (range, 0-4 [higher = better]). Communication subscale scores were lower among caregivers of patients who experienced (vs. those who did not experience) a 30-day readmission (2.6 ± 0.5 vs. 2.8 ± 0.6, respectively; p = .047). Capacity subscale scores were inversely associated with restriction in patient daily activities (a 0.04 decrement in the capacity score for every 1 point in daily activity restriction; p = .008). CONCLUSIONS: After pancreatectomy, patients with pancreatic and periampullary cancer whose caregivers reported worse communication with care providers were more likely to experience readmission. Caregivers of patients with greater daily activity restrictions were less likely to report being asked about the caregiver's skill and capacity by clinicians. PLAIN LANGUAGE SUMMARY: This prospective study used a validated survey instrument and reports on the quality of communication between health care providers and caregivers as reported by caregivers of patients with pancreatic and periampullary cancer after pancreatectomy. In an analysis of 240 caregivers enrolled in the study, lower communication scores (the extent to which providers helped caregivers understand clinical details) were associated with higher odds of 30-day patient readmission to the hospital. In addition, lower capacity scores (the extent to which providers assessed caregivers' ability to care for patients) were associated with greater impairment in caregivers. The strikingly low communication quality and capacity assessment scores suggest substantial room for improvement, with the potential to improve both caregiver and patient outcomes.

Screening Second Victims for Emotional Distress: Assessment of the Clinimetric Properties of the WITHSTAND-PSY Questionnaire.

INTRODUCTION: Adverse events (AEs) are a leading cause of patient morbidity and mortality, greatly impacting healthcare providers' well-being (second victim (SV) phenomenon). Since it is not accurately captured by existing psychometric instruments, we developed a clinimetric instrument for assessing SVs' emotional distress before and after an AE. METHODS: Content validity and clinical utility of the WITHSTAND-PSY Questionnaire (WS-PSY-Q) were examined using cognitive interviews. Rasch analysis (n = 284) was applied for clinimetric assessment (i.e., construct, concurrent, and clinical validity, internal consistency), considering two crucial psychological facets of the SV phenomenon (1st: emotional impact of the AE, 2nd: current emotional state). RESULTS: The Rasch partial credit model was used. The 1st facet demonstrated overall acceptable clinimetric properties with the subscale anxiety meeting clinimetric threshold values (e.g., all items with ordered thresholds, Loevinger's coefficient h ≥ 0.40; Person Separation Reliability Index (PSI) = 0.7). The 2nd facet showed overall better clinimetric properties for both subscales (e.g., h ≥ 0.40, PSI = 0.82 and 0.79, respectively; receiver operating characteristic area of 0.80 and 0.86, respectively). For both datasets, item fit statistics, except those for item 19, were within the critical range (z-score < ±2.5), and meaningful differential functioning analysis was observed for only 4 (out of 24) items. Local dependency was not observed, except for two item couples in the depression subscales. CONCLUSIONS: The WS-PSY-Q is the first clinimetric tool assessing SVs' emotional distress. It should be regarded as part of the armamentarium used by clinicians to assess in-depth healthcare providers' psychological reactions in the aftermath of an AE to mitigate burnout and allostatic overload.

Hyper-Aggressiveness of Bystander Cells in an Anti-Tumor Photodynamic Therapy Model: Role of Nitric Oxide Produced by Targeted Cells.

When selected tumor cells in a large in vitro population are exposed to ionizing radiation, they can send pro-survival signals to non-exposed counterparts (bystander cells). If there is no physical contact between irradiated and bystander cells, the latter respond to mediators from targeted cells that diffuse through the medium. One such mediator is known to be nitric oxide (NO). It was recently discovered that non-ionizing anti-tumor photodynamic therapy (PDT) can also elicit pro-survival/expansion bystander effects in a variety of human cancer cells. A novel silicone ring-based approach was used for distinguishing photodynamically-targeted cells from non-targeted bystanders. A key finding was that NO from upregulated iNOS in surviving targeted cells diffused to the bystanders and caused iNOS/NO upregulation there, which in turn stimulated cell proliferation and migration. The intensity of these responses depended on the extent of iNOS/NO induction in targeted cells of different cancer lines. Moreover, the responses could be replicated using NO from the chemical donor DETA/NO. This review will focus on these and related findings, their negative implications for clinical PDT, and how these might be averted by using pharmacologic inhibitors of iNOS activity or transcription.

Complex haploinsufficiency in pluripotent cells yields somatic cells with DNA methylation abnormalities and pluripotency induction defects.

A complete knockout of a single key pluripotency gene may drastically affect embryonic stem cell function and epigenetic reprogramming. In contrast, elimination of only one allele of a single pluripotency gene is mostly considered harmless to the cell. To understand whether complex haploinsufficiency exists in pluripotent cells, we simultaneously eliminated a single allele in different combinations of two pluripotency genes (i.e., Nanog+/-;Sall4+/-, Nanog+/-;Utf1+/-, Nanog+/-;Esrrb+/- and Sox2+/-;Sall4+/-). Although these double heterozygous mutant lines similarly contribute to chimeras, fibroblasts derived from these systems show a significant decrease in their ability to induce pluripotency. Tracing the stochastic expression of Sall4 and Nanog at early phases of reprogramming could not explain the seen delay or blockage. Further exploration identifies abnormal methylation around pluripotent and developmental genes in the double heterozygous mutant fibroblasts, which could be rescued by hypomethylating agent or high OSKM levels. This study emphasizes the importance of maintaining two intact alleles for pluripotency induction.

Preventing Avoidable Rehospitalizations through Standardizing Management of Chronic Conditions in Skilled Nursing Facilities.

OBJECTIVES: This study evaluated the impact of standardized care protocols, as a part of a quality improvement initiative (J10ohns Hopkins Community Health Partnership, J-CHiP), on hospital readmission rates for patients with a diagnosis of congestive heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD) after being discharged to skilled nursing facilities (SNFs). DESIGN: A retrospective study comparing 30-day hospital readmission rates the year before and 2 years following the implementation of the care protocol interventions. SETTINGS AND PARTICIPANTS: Patients discharged from Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center to the participating SNFs diagnosed with CHF and/or COPD. METHODS: The standardized protocols included medical provider or nurse assessments on SNF admission, multidisciplinary care planning, and medication management to avoid unplanned readmissions to the hospital. Descriptive analyses were conducted to illustrate the 30-day readmission rates before and after protocol implementation. RESULTS: There were 1128 patients in the pre-J-CHiP cohort and 2297 patients in the J-CHiP cohort. About half of the patients with a recorded diagnosis of CHF without COPD had the standardized protocol initiated, whereas 47% of the patients with a recorded diagnosis of COPD without CHF had the standardized protocol initiated. Of patients with recorded diagnoses of COPD and CHF, 49% had both protocols initiated. A reduction in the readmission rate was observed for patients with COPD protocols, from 23.5% in 2011 to 12.1% in 2015. However, fluctuations in the readmission rates were observed for patients who initiated the CHF protocols. CONCLUSIONS AND IMPLICATIONS: There were improvements in the readmission rates in this study, especially for patients who had initiated standardized care protocols in the SNFs. Our findings demonstrate great value in standardizing care management and strengthening collaboration with chronic care settings to facilitate a smooth transition of medically complex patients discharged from large health care systems. Future interventions could consider assessing nonclinical factors that may impact preventable hospital readmissions.

Genomic predictions to leverage phenotypic data across genebanks.

Genome-wide prediction is a powerful tool in breeding. Initial results suggest that genome-wide approaches are also promising for enhancing the use of the genebank material: predicting the performance of plant genetic resources can unlock their hidden potential and fill the information gap in genebanks across the world and, hence, underpin prebreeding programs. As a proof of concept, we evaluated the power of across-genebank prediction for extensive germplasm collections relying on historical data on flowering/heading date, plant height, and thousand kernel weight of 9,344 barley (Hordeum vulgare L.) plant genetic resources from the German Federal Ex situ Genebank for Agricultural and Horticultural Crops (IPK) and of 1,089 accessions from the International Center for Agriculture Research in the Dry Areas (ICARDA) genebank. Based on prediction abilities for each trait, three scenarios for predictive characterization were compared: 1) a benchmark scenario, where test and training sets only contain ICARDA accessions, 2) across-genebank predictions using IPK as training and ICARDA as test set, and 3) integrated genebank predictions that include IPK with 30% of ICARDA accessions as a training set to predict the rest of ICARDA accessions. Within the population of ICARDA accessions, prediction abilities were low to moderate, which was presumably caused by a limited number of accessions used to train the model. Interestingly, ICARDA prediction abilities were boosted up to ninefold by using training sets composed of IPK plus 30% of ICARDA accessions. Pervasive genotype × environment interactions (GEIs) can become a potential obstacle to train robust genome-wide prediction models across genebanks. This suggests that the potential adverse effect of GEI on prediction ability was counterbalanced by the augmented training set with certain connectivity to the test set. Therefore, across-genebank predictions hold the promise to improve the curation of the world's genebank collections and contribute significantly to the long-term development of traditional genebanks toward biodigital resource centers.