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Social media use is becoming common in medical practice. Although primarily used in this context to connect physicians, social media allows users share information, to create an online profile, to learn and keep knowledge up to date, to facilitate virtual attendance at medical conferences, and to measure impact within a field. However, shared content should be considered permanent and beyond the control of its author, and typical boundaries, such as the patient-physician interaction, become blurred, putting both parties at risk. The European Association of Urology brought together a committee of stakeholders to create guidance on the good practice and standards of use of social media. These encompass guidance about defining an online profile; managing accounts; protecting the reputations of yourself and your organization; protecting patient confidentiality; and creating honest, responsible content that reflects your standing as a physician and your membership within this profession.

AimsTo develop a clinically relevant, easy to use, and validated instrument for assessing severity and bother related to urinary incontinence.MethodsSurvey items were piloted and refined following psychometric principles in five separate patient cohorts. Patient and expert endorsement of items, factor analyses, Spearman rank correlations and response distributions were employed for item selection. Formal reliability and validity evaluation were conducted for the final questionnaire items.ResultsExpert physicians and patient focus groups confirmed face and content validity for the measure. A 10-item measure called the Michigan Incontinence Symptom Index (M-ISI) was developed with two domains: a Total M-ISI Domain consisting of subdomains for stress urinary incontinence, urgency urinary incontinence, and pad use, and a Bother Domain. High construct validity was demonstrated with a Cronbach's alpha for the Total M-ISI Domain (items 1-8) of 0.90 and for the Bother Domain (items 9-10) of 0.82. Cronbach's alpha for the subdomains were all > 0.85. Construct validity, convergent and divergent validity, internal discriminant validity, and predictive validity were all robust. The minimally important difference for the measure was determined to be 4 points (out of 32) for the Total M-ISI Severity Domain, and 1-2 points (out of 8-12) for the individual subdomains.ConclusionsThe M-ISI is a parsimonious measure that has established reliability and validity on several levels and complements current clinical evaluative methods for patients with urinary incontinence.

Single-cell RNA sequencing (scRNA-seq) can resolve transcriptional features from individual cells, but scRNA-seq techniques capable of resolving the variable regions of B cell receptors (BCRs) remain limited, especially from widely-used 3′-barcoded libraries. Here, we report a method that can recover paired, full-length variable region sequences of BCRs from 3′-barcoded scRNA-seq libraries. We first verify this method (B3E-seq) can produce accurate, full-length BCR sequences. We then apply this method to profile B cell responses elicited against the capsular polysaccharide of Streptococcus pneumoniae serotype 3 (ST3) by glycoconjugate vaccines in five infant rhesus macaques. We identify BCR features associated with specificity for the ST3 antigen which are present in multiple vaccinated monkeys, indicating a convergent response to vaccination. These results demonstrate the utility of our method to resolve key features of the B cell repertoire and profile antigen-specific responses elicited by vaccination. A method that recovers full-length, paired heavy- and light-chain variable regions of B cell receptor transcripts from 3'barcoded scRNA-seq libraries reveals a convergent response to pneumococcus vaccination in rhesus macaques. [ABSTRACT FROM AUTHOR]

Abstract: Cell surface signaling (CSS) is a means of rapidly adjusting transcription in response to extracellular stimuli in Gram-negative bacteria. The pseudobactin BN7/8 uptake (Pup) system not only imports iron but also upregulates its own transcription through CSS in Pseudomonas capeferrum. In the absence of ferric pseudobactin BN7/8, the signaling components are maintained in a resting state via the formation of a periplasmic complex between the N-terminal signaling domain (NTSD) of the outer membrane iron-transporter, PupB, and the C-terminal CSS domain (CCSSD) of the sigma regulator, PupR. The previously determined 1.6 Å crystal structure of this periplasmic complex has allowed us to probe the structural and thermodynamic consequences of mutating key interfacial residues. In this report, we describe the solution structure of the PupB NTSD and use Nuclear Magnetic Resonance spectroscopy, Isothermal Titration Calorimetry, and Circular Dichroism spectroscopy together with thermal denaturation to investigate whether three PupB point mutations, Q69K, H72D, and L74A, influence the interaction merely due to the chemical nature of the amino acid substitution or also cause changes in overall protein structure. Our results demonstrate that binding to the PupR CCSSD does not alter the structure of PupB NTSD and that the individual mutations have only minor effects on structure. The mutations generally lower thermodynamic stability of the NTSD and weaken binding to the CCSSD. These findings validate the X-ray crystal structure interface, emphasizing the importance of amino acid chemical nature at the interface. [ABSTRACT FROM AUTHOR]

• Offering multiple strategies to facilitate cascade testing for FH as part of a comprehensive program was acceptable and feasible for probands, relatives, and healthcare professionals (HCPs). • Novel, active strategies like chatbots and direct contact were evaluated as acceptable and feasible to participants, but the more traditional packet was most often adopted among probands and relatives. • Barriers remain that need to be addressed to improve implementation and cascade testing uptake of comprehensive cascade testing programs like IMPACT-FH. • Measuring implementation outcomes from the IMPACT-FH cascade testing program can inform future implementation of similar interventions. Cascade testing can be highly effective in identifying individuals with familial hypercholesterolemia (FH) and help prevent atherosclerotic cardiovascular disease. The IMPACT-FH cascade testing program offered multiple optimized implementation strategies to improve FH cascade testing uptake. Guided by the Conceptual Model of Implementation Research, this study assessed the IMPACT-FH cascade testing program's implementation outcomes. Implementation outcomes were assessed qualitatively and quantitatively. Interviews were conducted with 33 IMPACT-FH program participants including 15 probands, 12 relatives, and 6 healthcare professionals (HCPs). Transcripts were analyzed using thematic analysis to investigate implementation outcomes. Descriptive statistics were analyzed for scaled implementation outcome measures asked after interviews. Participants described adopting strategies offered in the IMPACT-FH program because they presented an opportunity to pursue low-cost FH cascade testing. Participants identified barriers to feasibility including: the complexity of disclosing an FH result and offering strategies, inherent limitations of probands choosing strategies, confusion over testing costs, limitations sharing with relatives' clinicians, discomfort with chatbot technology, and concerns about the workload for HCPs. Participants evaluated the program positively regarding its appropriateness (Mean (M) = 4.70, Standard Deviation (SD) = 0.41), acceptability (M = 4.79, SD = 0.40), and feasibility (M = 4.24, SD = 0.53). The IMPACT-FH cascade testing program and its strategies were evaluated as valuable to adopt and highly appropriate, acceptable, and feasible by participants. Participants identified areas to enhance the program that could improve FH cascade testing uptake. [ABSTRACT FROM AUTHOR]

High levels of negative urgency imply risk for impulsive and potentially self-destructive behavior. The social consequences of these impulsive states remain poorly understood. In the present study, we examined how state-like fluctuation in negative urgency provokes day-to-day interpersonal stressors using experience sampling methods. We recruited 119 adults with a history of recurrent self-injury to complete surveys of negative urgency and interpersonal stress (i.e., exposure to criticism and rejection) 4 times per day over 14 days. Results from hierarchical linear models showed that when people experienced more negative urgency, relative to their personal norms, they were more likely than usual to encounter interpersonal stress over the next few hours. There was some evidence to suggest that this within-person connection was more pronounced for people who tended to have higher negative urgency levels in general across the experience sampling period. We interpret these findings in the context of stress generation theory, and we conclude that within-person variation in negative urgency may represent a clinically useful model of near-term risk for interpersonal dysfunction. [ABSTRACT FROM AUTHOR]

Music listening, an inherently emotional activity, is commonly used as a form of emotion regulation (ER). Although research suggests that some strategies of listening to music to regulate emotion are linked with psychological well-being and symptoms of affective disorders, the mechanisms underlying these relationships have not been thoroughly explored. The present study examined whether associations between music as ER and symptoms of depression and anxiety were mediated by individuals' use of other adaptive and maladaptive ER strategies. A nationwide online sample of US adults (n = 146) completed measures assessing their use of music as ER, other adaptive and maladaptive ER strategies, and symptoms of depression and anxiety. The results indicated that the overall use of music as ER was not directly associated with symptoms of depression and anxiety, whereas using music as discharge (venting negative emotions by listening to mood-congruent music) was positively associated with such symptoms. Mediational analyses revealed that adaptive ER mediated the relationship between overall use of music as ER and symptoms of depression and anxiety, whereas maladaptive ER mediated the relationships between discharge and symptoms. These findings suggest that people use music as ER alongside their other ER efforts, which in turn are linked with symptoms of depression and anxiety. Furthermore, although the overall use of music to regulate emotion may be beneficial for well-being via its association with adaptive ER, a more maladaptive pattern when using music for emotional discharge suggests that music plays a more nuanced role in ER and mental health. [ABSTRACT FROM AUTHOR]

Background: Complications are a practical consideration for elective magnetic resonance imaging (MRI) studies performed under general anaesthesia but relatively little is known about their distribution and risk factors. Objectives: To describe the incidence of complications associated with MRI performed under general anaesthesia at a large referral facility and evaluate potential risk factors for these complications. Study design: Retrospective case–control study. Methods: Patient information and details of the MRI procedure were collected retrospectively from medical records of all horses that had undergone an MRI under general anaesthesia at the University of Pennsylvania, New Bolton Center, between September 2005 and April 2012. Complications and categorical variables were examined by chi‐squared or Fisher's exact tests as appropriate. A mixed‐effects logistic regression approach was used to evaluate associations between explanatory variables and the outcome variable (complications or pyrexia). A univariable screen was used to select variables (likelihood ratio test p < 0.2) for inclusion in the multivariable analysis. Statistical significance was inferred when p ≤ 0.05. Results: Complications were noted after MRI in 51 (17.4%) of 293 events eligible for inclusion. Complications included pyrexia (n = 35), pneumonia (n = 14), colic (n = 10), facial/nerve paralysis (n = 6), diarrhoea (n = 4), and other (n = 3). The odds of developing a post‐anaesthetic complication were significantly decreased in horses that received peri‐anaesthetic antimicrobials (OR 0.29, 95% CI 0.14–0.63, p = 0.002). Increased age (OR 0.87, 95% CI, 0.76–0.99, p = 0.03) and peri‐anaesthetic antimicrobial administration (OR 0.23, 95% CI 0.08–0.65, p = 0.005) were associated with a decreased odds of developing pyrexia. Main limitations: Single centre retrospective design. Conclusions: Potential complications including pyrexia, pneumonia and colic should be recognised when pursuing MRI under general anaesthesia. The administration of peri‐anaesthetic antimicrobials decreased the odds of a complication and warrants consideration, particularly in horses that might be classified as high risk. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8+ T cell differentiation in response to chronic antigen stimulation is highly complex, and it remains unclear precisely which T cell differentiation states at which anatomic sites are critical for the response to ICB. We identified an intermediate-exhausted population in the white pulp of the spleen that underwent substantial expansion in response to ICB and gave rise to tumor-infiltrating clonotypes. Increased systemic antigen redirected differentiation of this population toward a more circulatory exhausted KLR state, whereas a lack of cross-presented tumor antigen reduced its differentiation in the spleen. An analogous population of exhausted KLR CD8+ T cells in human blood samples exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen for the differentiation and expansion of T cell clonotypes in response to ICB. Editor's summary: T cell dysfunction is a defining feature of many tumor types, but how tumor-specific T cells progress to a terminally exhausted state and which populations are targeted by immune checkpoint blockade (ICB) remains incompletely understood. Using single-cell transcriptomics, Morgan et al. profiled T cell differentiation states across different anatomical sites including tumors, draining lymph nodes, and the white pulp of the spleen from tumor-bearing mice treated with ICB. A population of splenic intermediate-exhausted T cells supplied most of the ICB-elicited tumor-specific T cell response, which required low levels of cross-presented tumor antigen in the spleen. Together, these findings identify the spleen as an important site for generating a tumor-specific T cell response after ICB. —Claire Olingy [ABSTRACT FROM AUTHOR]

The IMPACT-FH study implemented strategies (packet, chatbot, direct contact) to promote family member cascade testing for familial hypercholesterolemia (FH). We evaluated the impact of genetic counseling (GC) on medical outcomes, strategy selection, and cascade testing. Probands (i.e., patients with FH) were recommended to complete GC and select sharing strategies. Comparisons were performed for both medical outcomes and strategy selection between probands with or without GC. GEE models for Poisson regression were used to examine the relationship between proband GC completion and first-degree relative (FDR) cascade testing. Overall, 46.3% (81/175) of probands completed GC. Probands with GC had a median LDL-C reduction of −13.0 mg/dL (−61.0, 4.0) versus −1.0 mg/dL (−16.0, 17.0) in probands without GC (p = 0.0054). Probands with and without GC selected sharing strategies for 65.3% and 40.3% of FDRs, respectively (p < 0.0001). Similarly, 27.1% of FDRs of probands with GC completed cascade testing, while 12.0% of FDRs of probands without GC completed testing (p = 0.0043). Direct contact was selected for 47 relatives in total and completed for 39, leading to the detection of 18 relatives with FH. Proband GC was associated with improved medical outcomes and increased FDR cascade testing. Direct contact effectively identified FH cases for the subset who participated. [ABSTRACT FROM AUTHOR]

Scholars have documented harm associated with positive stereotypes about groups that experience inequality. We surveyed five samples from the United States to explore antecedents to dominant group endorsement of positive stereotypes about women, gay men, Asian Americans, Black Americans, and Native Americans. We found more liberal participants, and those with more close contact with members of these groups, were more internally motivated to respond without prejudice, which was then associated with greater endorsement of positive stereotypes about women, gay men, Black Americans, and Native Americans. In contrast, more conservative participants were more likely to believe in system legitimacy, which was then associated with greater endorsement of positive stereotypes about women and Asian Americans. We theorize that positive stereotypes are used by dominant group members in divergent ways, sometimes to legitimate inequality and other times with concern about inequality. The latter likely involves naivety regarding the harmful nature of positive stereotypes. [ABSTRACT FROM AUTHOR]

Physical activity is associated with improvements in both health and longevity and is highly recommended for older adults. Public health and nonprofit organizations have invested considerable efforts to promote physical activity among this population. The present manuscript describes the specifics of the first university-based adult fitness program (Lifetime Fitness Program) and how this program promotes healthy aging through physical activity while serving as an important venue for experiential learning among students. Thus, the goal of this paper is to provide a "road map" to guide strategies and methods to promote physical activity and healthy aging in an academic setting and provide students with meaningful experiential learning opportunities. [ABSTRACT FROM AUTHOR]

Superconducting transition-edge sensors (TESs) used in X-ray and γ -ray microcalorimeters suffer degraded performance if cooled in a magnetic field B sufficient to trap flux in the sensors. We report measurements of γ -ray TESs before and after implementing measures to reduce stray B fields from sources inside and outside the cryostat. These measurements showed a correlation between anomalous features in TES current–voltage (IV) curves and degraded energy resolution. After reducing internal sources of stray B field and improving shielding against external sources, both IV curves and energy resolution improved. Finally, we placed magnetized screws with remnant fields ∼ 10 μ T near similar γ -ray TESs in a different type of detector package and observed the same effects. [ABSTRACT FROM AUTHOR]

Objectives To characterize the role of pathology explanation clinics (PECs) in prostate cancer care and determine their impact on patients, urologic oncologists, and quality of care. Methods Semistructured interviews with 10 patients with newly diagnosed prostate cancer were conducted before and after a PEC pilot and at the 1- and 6-month follow-up visits. Information about participants' cancer knowledge and anxiety were collected quantitatively. Documented pathologist communications and proper review of outside biopsy slides were collected. Semistructured interviews were also completed with participating urologic oncologists following the pilot. Results Pathology explanation clinics improved participants' understanding of their diagnosis, cognitively and emotionally supporting them first in their urologic oncology visit and later in making an informed treatment decision. Mean knowledge scores were high, and a minority of participants had prostate cancer anxiety. Urologic oncologists noted improved understanding and reduced anxiety among participants, enabling nuanced conversations about prognosis and management during the visit. By ensuring review of outside biopsy slides and communication of clinically significant or unexpected diagnoses, PECs supported high-quality care and patient safety. Conclusions In this small pilot, PECs positively affected patients with prostate cancer, their clinicians, and the overall care system. Additional studies in larger populations and diverse settings will be useful. [ABSTRACT FROM AUTHOR]