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The article examines the crystal and molecular structure of 12-epinapelline. Previous investigations showed that the conformation of ring A in crystal structures of napelline-type alkaloids depended on the presence or absence of an intramolecular H-bond between an alpha-oriented C1 hydroxyl and the N atom. Thus, ring A in 12-epilucidusculin had the boat conformation and in acophine it adopted the twist or chair conformation.

Introduction: Obesity in prostate cancer survivors may increase mortality. Better characterization of this effect may allow better counseling on obesity as a targetable lifestyle factor to reduce mortality in prostate cancer survivors. The purpose of this study was to determine whether pre- and post-diagnostic obesity and weight change affect all-cause mortality, cardiovascular disease specific mortality, and prostate cancer specific mortality in patients with nonmetastatic prostate cancer., Patients and Methods: We performed a retrospective cohort analysis of 5,077 patients diagnosed with localized prostate cancer from 1997 to 2017 with median follow-up of 15.5 years. The Utah Population Database linked to the Utah Cancer Registry was used to identify patients at a variety of treatment centers., Results: Pre-diagnosis obesity was associated with a 62% increased risk of cardiovascular disease specific mortality and a 34% increased risk of all-cause mortality (HR 1.62, 95% CI 1.05-2.50; HR 1.34, 95% CI 1.07-1.67, respectively). Post-diagnosis obesity increased the risk of cardiovascular disease specific mortality (HR 1.83, 95% CI 1.31-2.56) and all-cause mortality (HR 1.37, 95% CI 1.16-1.64) relative to non-obese men. We found no association between pre-diagnostic obesity or post-diagnostic weight gain and prostate cancer specific mortality., Conclusion: Our study strengthens the conclusion that pre-, post-diagnostic obesity and weight gain increase cardiovascular disease and all-cause mortality but not prostate cancer specific mortality compared to healthy weight men. An increased emphasis on weight management may improve mortality for prostate cancer survivors who are obese., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To characterize the impact of nephrolithiasis diagnosis and treatment on health care utilization and identify predictors of barriers to care in the patient population., Methods: We conducted a retrospective cohort study using the All of Us Database, a National Institutes of Health database targeting recruitment of underrepresented populations. Patients with a diagnosis of kidney stones were included and matched to a control group. Primary outcomes were patients' self-reported health care access and utilization. Univariable and multivariable regression analyses were performed., Results: 9173 patients with a diagnosis of nephrolithiasis were included and matched to 9173 controls without a diagnosis of nephrolithiasis. Patients with kidney stones were less likely to have had >1 year since last provider visit (1.7% vs 3.8%, P <.001), but did not report increased delays obtaining care (31%), inability to afford care (11.4%), or higher likelihood of skipping medications (12.9%). Among patients with stones, 1208 (13.2%) had been treated surgically. On multivariable analysis, younger age, female sex, lower income, lower education, non-insured status, and lower physical and mental health were all associated with delays obtaining care, difficulty affording care, skipping medications, and/or prolonged time since seeing a provider., Conclusion: A diagnosis of nephrolithiasis and subsequent surgical intervention were not associated with an increase in patient-reported barriers to care. However, among patients with nephrolithiasis, younger, comorbid, female patients from lower socioeconomic status are at significant risk of being unable to access and utilize treatment., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Using a health systems approach to investigate low-value care (LVC) may provide insights into structural drivers of this pervasive problem., Objective: To evaluate the influence of service area practice patterns on low-value mammography and prostate-specific antigen (PSA) testing., Design: Retrospective study analyzing LVC rates between 2008 and 2018, leveraging physician relocation in 3-year intervals of matched physician and patient groups., Setting: U.S. Medicare claims data., Participants: 8254 physicians and 56 467 patients aged 75 years or older., Measurements: LVC rates for physicians staying in their original service area and those relocating to new areas., Results: Physicians relocating from higher-LVC areas to low-LVC areas were more likely to provide lower rates of LVC. For mammography, physicians staying in high-LVC areas (LVC rate, 10.1% [95% CI, 8.8% to 12.2%]) or medium-LVC areas (LVC rate, 10.3% [CI, 9.0% to 12.4%]) provided LVC at a higher rate than physicians relocating from those areas to low-LVC areas (LVC rates, 6.0% [CI, 4.4% to 7.5%] [difference, -4.1 percentage points {CI, -6.7 to -2.3 percentage points}] and 5.9% [CI, 4.6% to 7.8%] [difference, -4.4 percentage points {CI, -6.7 to -2.4 percentage points}], respectively). For PSA testing, physicians staying in high- or moderate-LVC service areas provided LVC at a rate of 17.5% (CI, 14.9% to 20.7%) or 10.6% (CI, 9.6% to 13.2%), respectively, compared with those relocating from those areas to low-LVC areas (LVC rates, 9.9% [CI, 7.5% to 13.2%] [difference, -7.6 percentage points {CI, -10.9 to -3.8 percentage points}] and 6.2% [CI, 3.5% to 9.8%] [difference, -4.4 percentage points {CI, -7.6 to -2.2 percentage points}], respectively). Physicians relocating from lower- to higher-LVC service areas were not more likely to provide LVC at a higher rate., Limitation: Use of retrospective observational data, possible unmeasured confounding, and potential for relocating physicians to practice differently from those who stay., Conclusion: Physicians relocating to service areas with lower rates of LVC provided less LVC than physicians who stayed in areas with higher rates of LVC. Systemic structures may contribute to LVC. Understanding which factors are contributing may present opportunities for policy and interventions to broadly improve care., Primary Funding Source: National Cancer Institute of the National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1456.

Objective: This study aims to identify motivators influencing individuals' commitment to maintaining positive health trajectories across different demographics. The primary objective is to leverage this knowledge to enhance patient-physician relationships and improve the quality of care., Methods: A web-based survey collected data from 204 randomly selected participants aged 16 and older. The survey assessed participants' self-rated health, health-related habits, and motivators for a healthy lifestyle. Open-ended responses were included., Results: Participants had a mean self-rated health score of 6.24 (scale: one to ten). Motivation scores for health-related factors averaged 3.25 (scale: one to five), with caregiving responsibility scoring 3.07 (scale: one to five), mainly among women. Motivators related to personal productivity and values scored 3.44 (scale: one to five), while cultural or religious beliefs scored lowest at 2.89 (scale: one to five). Common themes from free responses included longevity, quality of life, personal well-being, family, independence, prevention of complications, health goals, finances, and faith, listed by frequency. Among participants, only 30% had chronic diseases, but 80% of those with chronic conditions were motivated to improve their health., Conclusion: This survey gathered valuable data on motivators for maintaining positive health trajectories. The findings have implications for improving patient-physician relationships and healthcare delivery. Understanding individuals' motivators can inform tailored interventions and personalized care approaches.

Introduction: Patients living in rural areas have worse cancer-specific outcomes. This study examines the effect of family-based social capital on genitourinary cancer survival. We hypothesized that rural patients with urban relatives have improved survival relative to rural patients without urban family., Methods: We examined rural and urban based Utah individuals diagnosed with genitourinary cancers between 1968 and 2018. Familial networks were determined using the Utah Population Database. Patients and relatives were classified as rural or urban based on 2010 rural-urban commuting area codes. Overall survival was analyzed using Cox proportional hazards models., Results: We identified 24,746 patients with genitourinary cancer with a median follow-up of 8.72 years. Rural cancer patients without an urban relative had the worst outcomes with cancer-specific survival hazard ratios (HRs) at 5 and 10 years of 1.33 (95% CI 1.10-1.62) and 1.46 (95% CI 1.24-1.73), respectively relative to urban patients. Rural patients with urban first-degree relatives had improved survival with 5- and 10-year survival HRs of 1.21 (95% CI 1.06-1.40) and 1.16 (95% CI 1.03-1.31), respectively., Conclusions: Our findings suggest rural patients who have been diagnosed with a genitourinary cancer have improved survival when having relatives in urban centers relative to rural patients without urban relatives. Further research is needed to better understand the mechanisms through which having an urban family member contributes to improved cancer outcomes for rural patients. Better characterization of this affect may help inform policies to reduce urban-rural cancer disparities., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To evaluate the interest of primary care clinicians in utilizing CDS for PSA screening. Evidence suggests that electronic clinical decision support (CDS) may decrease low-value prostate-specific antigen (PSA) testing. However, physician attitudes towards CDS for PSA screening are largely unknown., Methods: A survey was sent to 201 primary care clinicians, including both physicians and Advanced Practice Providers (APP), within a large academic health system. Eligible clinicians cared for male patients aged 40 to 80 years and ordered ≥5 PSA tests in the past year. Respondents were stratified into 3 groups, appropriate screeners, low-value screeners, or rare-screeners, based on responses to survey questions assessing PSA screening practices. The degree of interest in electronic CDS was determined via a composite Likert score comprising relevant survey items., Results: Survey response rate was 29% (59/201) consisting of 85% MD/DO and 15% APP respondents. All clinicians surveyed were interested in CDS (P < 0.001) without significant difference between screener groups. Clinicians agreed most uniformly that CDS be evidence-based. Clinicians disagreed on whether CDS would decrease professional discretion over patient decisions., Conclusions: Primary care clinicians are interested in CDS for PSA screening regardless of their current screening practices. Prioritizing CDS features that clinicians value, such as ensuring CDS recommendations are evidence-based, may increase the likelihood of successful implementation, whereas perceived threat to autonomy may be a hinderance to utilization., Competing Interests: Conflict of interest The authors have no competing financial interests to report in relation to the work described., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Extended prophylactic anticoagulation therapy with enoxaparin 40 mg daily is effective in reducing the incidence of venous thromboembolism (VTE) after radical cystectomy. In an effort to improve compliance, we modified our extended anticoagulation options to direct oral anticoagulants (DOAs; eg apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily). This study assesses our experience with extended VTE prophylaxis using DOAs., Methods: This is a retrospective review that included all patients who underwent radical cystectomy at our institution between January 2007 and June 2021. Multivariable logistic regression models were constructed to test the hypothesis that use of extended DOAs is similar to enoxaparin in terms of VTE events and risk of gastrointestinal bleeding., Results: In 657 patients, the median age was 71 years. Of the 101 patients who received extended VTE prophylaxis, 46 (45.5%) patients received rivaroxaban/apixaban. At 90 days of followup, 40 patients (7.2%) who did not receive extended prophylaxis on discharge developed a VTE compared to 2 patients (3.6%) in the enoxaparin group and 0 patients in the DOA group (p=0.11). Seven patients (1.3%) who did not receive extended anticoagulation developed gastrointestinal bleeding compared to 0 patients in the enoxaparin group and 1 (2.2%) in the DOA group (p=0.60). On multivariable analysis, both enoxaparin and DOAs were associated with similar reductions in the risk of developing VTE compared to controls (enoxaparin: OR 0.33, p=0.09 and DOAs: OR 0.19, p=0.15)., Conclusions: These preliminary data suggest that oral apixaban and rivaroxaban are acceptable alternatives to enoxaparin with similar safety and efficacy profiles.

This paper is a summary of the evolution of the stethoscope. It goes through the major stages of stethoscope evolution, starting with the first recorded breath sounds and going all the way to the most recent, entirely automated stethoscope pads. The iconic stethoscope has undergone many changes and evolved with the times to earn its place slung around the neck of a physician. This review traces its journey., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Choudry et al.)

In 2013, the Chicago Public Schools district received funding from the Division of Adolescent and School Health at the Centers for Disease Control and Prevention (CDC) to implement a series of strategies aimed to reduce HIV, STIs (sexually transmitted diseases), and related risk behaviors among students. One such set of strategies included "safe and supportive environments" (SSE), aimed to support lesbian, gay, bisexual, transgender, questioning, and other LGBTQ+ students. SSE strategies included professional development and technical assistance provided to K-12 school staff (teachers, administrators, social workers, etc.) to implement the following practices: support for transgender and gender nonconforming students in accordance with district guidelines, use of LGBTQ+ inclusive curricula, posting of signs and symbols of support, and creation of Genders and Sexualities Alliance student clubs. To monitor progress and performance, both quantitative and qualitative process measure data were collected. Quantitative data consisted of key metrics such as number of staff trained and surveillance data collected through school health profiles in collaboration with the CDC. Qualitative data were gathered to understand barriers and facilitators to implementation of SSE practices via interviews with 55 school staff members and four focus groups with 31 high school students. Results indicated an increased uptake of all SSE activities across the 5-year funding period. Findings also reveal additional needed supports, such as increased availability and offering of professional development for all staff, support for staff in engaging parents, and ensuring the LGBTQ+ inclusive sexual health education curriculum is experienced as such by students. Current work to address these needs is described.

In the past there have been a multitude of studies that ardently support the role of arginase II (Arg II) in vascular and endothelial disorders; however, the regulation and function of Arg II in autoimmune diseases has thus far remained unclear. Here we report that a global Arg II null mutation in mice suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. During EAE, both Arg I and Arg II were induced in spinal cords, but only Arg II was induced in spleens and splenic dendritic cells (DCs). DC activation by lipopolysaccharide (LPS), CD40L or TLR8 agonist significantly enhanced Arg II expression without affecting Arg I expression. Conversely, DC differentiating cytokines [IL-4 and granulocyte macrophage-colony-stimulating factor (GM-CSF)] yielded opposite effects. In addition, Arg I and Arg II were regulated differentially during Th1 and Th17 cell polarization. Arg II deficiency in mice delayed EAE onset, ameliorated clinical symptoms and reduced myelin loss, accompanied by a remarkable reduction in the EAE-induced spinal cord expression of Th17 cell markers (IL-17 and RORγt). The abundance of Th17 cells and IL-23 + cells in relevant draining lymph nodes was significantly reduced in Arg II knockout mice. In activated DCs, Arg II deficiency significantly suppressed the expression of Th17-differentiating cytokines IL-23 and IL-6. Interestingly, Arg II deficiency did not lead to any compensatory increase in Arg I expression in vivo and in vitro. In conclusion, Arg II was identified as a factor promoting EAE likely via an Arg I-independent mechanism. Arg II may promote EAE by enhancing DC production of Th17-differentiating cytokines. Specific inhibition of Arg II could be a potential therapy for multiple sclerosis., (© 2018 John Wiley & Sons Ltd.)

For many who pertain to particular theological paradigms, their faith cannot be compartmentalised, but is mobilised to inform all aspects of their being, most notably their ethical and moral persuasions. As clinicians, the concept that there are good and bad deaths is already known; understanding the origin and depth of non-physical suffering, and aiming to alleviate it is not possible without learning the individual experiences and beliefs that go with it. Spiritual care forms a fundamental consideration in the endeavor to address the holistic experience of those patients receiving palliative care. Good palliative care seeks to promote the wellbeing and priorities of those with faltering health in a way that continues to support individualised notions of self-determination. The last few decades have resulted in a multicultural and multi-ethnic patient population. Addressing the spiritual and physical needs of patients allows healthcare professionals to deliver truly holistic care. Exploring and understanding the specific nuances of the five major religions of the UK provides healthcare professionals the opportunity to comfort the religiously observant patient at the end of life., (© Royal College of Physicians 2018. All rights reserved.)

We propose a stochastic framework to analyze and compare differences in human motions for applications in injury prevention, rehabilitation, sports training and performance research. Human motions are modeled as Hidden Markov Models and the differences between the motions are measured using the Kullback-Leibler distance metric. The distance metric is recomputed with degrees of freedom excluded to determine which degree of freedom most influences the difference between a set of motions. The proposed system is tested on a human motion dataset consisting of lifting movements under differing load weights and ankle bracing conditions. Results indicate that the algorithm is capable of successfully determining which joints are impacted and ranking them according to importance.

Objective: To establish whether hypomagnesemia at admission predicts excessive morbidity, particularly cardiac arrhythmias, and mortality in patients with acute myocardial infarction., Methods: We compared hypomagnesemic and normomagnesemic patients with acute myocardial infarction in 517 patients admitted to the coronary care unit. The serum magnesium concentration, along with a large array of other parameters, was measured on admission to the emergency department. Other baseline attributes and variables related to the patients' hospital course were used to compare the 2 groups., Results: The 132 patients (25.9%) with low serum magnesium concentrations at admission (mean +/- SD, 0.61 +/- 0.06 mmol/L [1.48 +/- 0.15 mg/dL]) were comparable to the patients with normal serum magnesium concentrations (0.81 +/- 0.11 mmol/L [1.96 +/- 0.26 mg/dL]) except for a higher rate of prehospital use of diuretic agents (32.6% vs 22.5%, P = .02) and earlier presentation after onset of symptoms (mean +/- SD, 3.2 +/- 4.1 vs 4.8 +/- 6.6 hours, P = .003). There was no correlation between serum magnesium and potassium concentrations in the emergency department (r = 0.14). No difference was detected between the hypomagnesemic and normomagnesemic cohorts in rates of total mortality (18.9% vs 18.5%, P = .91), cardiac mortality (15.2% vs 15.3%, P = .99), atrial fibrillation (13.6% vs 13.8%, P = .97), ventricular tachycardia (18.2% vs 15.3%, P = .44), or ventricular fibrillation (15.2% vs 13.5%, P = .63). Management of the 2 cohorts was not different, except for higher rates of use of magnesium (17.4% vs 1.3%, P < .001) and potassium (59.8% vs 42.1%, P < .001) supplements and antiarrhythmic drugs (62.9% vs 48.7%, P = .005) in the hypomagnesemic patients. An endogenous rise in serum magnesium level was documented in a subgroup of 161 patients who had a repeated measurement (0.74 +/- 0.12 mmol/L [1.79 +/- 0.29 mg/dL] in the emergency department vs 0.77 +/- 0.09 mmol/L [1.88 +/- 0.23 mg/dL] in the coronary care unit, P < .001)., Conclusions: We conclude that hypomagnesemia is seen in approximately one fourth of patients with myocardial infarction, is not linked to hypokalemia, has some relationship to preadmission use of diuretic agents, is associated with early presentation to the hospital, and is not a predictor of increased morbidity or mortality.

Background: The past literature has long ago identified painless myocardial infarction as a clinical entity; however, the term has been applied, often loosely, to denote diagnosis of infarction made at autopsy, or during routine electrocardiography, or at presentation with atypical symptoms. Many of the old studies were retrospective or included patients who could not contribute a reliable history., Methods: Systematic interviews of 517 consecutive patients with an acute myocardial infarction admitted to the Coronary Care Unit were carried out; a large array of data was collected prospectively while the patients were taken care of in the hospital., Results: A reliable history of symptoms at the inception of the clinical episode could be provided by 501 patients; 40 patients (8.0%) presented with painless (not silent) infarction, while the remaining 461 had pain. Multivariate analysis revealed that painless presentation of myocardial infarction correlated positively with age (OR 1.05, CI 1.02-1.08) and admission Killip class (OR 2.58, CI 2.16-2.97), and negatively with history of prior angina (OR 0.16, CI 0.15-064); also it was not a predictor of increased rate of mortality or life-threatening arrhythmias., Conclusions: Presentation with painless myocardial infarction occurs in older patients with increased degrees of pulmonary congestion on admission, and less frequent rate of prior angina than the ones encountered in patients with pain; however such presentation is not an independent predictor of worse than expected in-hospital outcome.