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Take Home Messages Among men with low- or intermediate-risk prostate cancer who choose active surveillance, those with suspicious magnetic resonance imaging (MRI) at the time of inclusion in active surveillance are more likely to show switch to treatment than men with nonsuspicious MRI., Background The inclusion criterion for active surveillance (AS) is low- or intermediate-risk prostate cancer. The predictive value of the presence of a suspicious lesion at magnetic resonance imaging (MRI) at the time of inclusion is insufficiently known. Objective To evaluate the percentage of patients needing active treatment stratified by the presence or absence of a suspicious lesion at baseline MRI. Design, setting, and participants A retrospective analysis of the data from the multicentric AS GAP3 Consortium database was conducted. The inclusion criteria were men with grade group (GG) 1 or GG 2 prostate cancer combined with prostate-specific antigen

Post-learning sleep plays an important role in hippocampal memory processing, including contextual fear memory (CFM) consolidation. Here, we used targeted recombination in activated populations (TRAP) to label context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons during post-learning sleep. We find that post-learning sleep deprivation (SD), which impairs CFM consolidation, selectively disrupts reactivation in inferior blade DG engram neurons. This change was linked to more general suppression of neuronal activity markers in the inferior, but not superior, DG blade by SD. To further characterize how learning and subsequent sleep or SD affect these (and other) hippocampal subregions, we used subregion-specific spatial profiling of transcripts and proteins. We found that transcriptomic responses to sleep loss differed greatly between hippocampal regions CA1, CA3, and DG inferior blade, superior blade, and hilus. Critically, learning-driven transcriptomic changes, measured 6 h following contextual fear learning, were limited to the two DG blades, differed dramatically between the blades, and were absent from all other regions. Similarly, protein abundance in these hippocampal subregions were differentially impacted by sleep vs. SD and by prior learning, with the majority of alterations to protein expression restricted to DG. Together, these data suggest that the DG plays an essential role in the consolidation of hippocampal memories, and that the effects of sleep and sleep loss on the hippocampus are highly subregion-specific, even within the DG itself.

BackgroundActive surveillance (AS) is a management option for men diagnosed with low-risk prostate cancer. Opinions differ on whether it is safe to include young men (≤60 yr) or men with intermediate-risk disease.ObjectiveTo assess whether reasons for discontinuation, treatment choice after AS, and adverse pathology at radical prostatectomy (RP; N1, or ≥GG3, or ≥pT3) differ for men ≤60 yr or those with European Association of Urology (EAU) intermediate-risk disease from those for men >60 yr or those with EAU low-risk disease.Design setting and participantsWe analyzed data from 5411 men ≤60 yr and 14959 men >60 yr, 14064 men with low-risk cancer, and 2441 men with intermediate-risk cancer, originating from the GAP3 database (21169 patients/27 cohorts worldwide).Outcome measurements and statistical analysisCumulative incidence curves were used to estimate the rates of AS discontinuation and treatment choice.Results and limitationsThe probability of discontinuation of AS due to disease progression at 5 yr was similar for men aged ≤60 yr (22%) and those >60 yr (25%), as well as those of any age with low-risk disease (24%) versus those with intermediate-risk disease (24%). Men with intermediate-risk disease are more prone to discontinue AS without evidence of progression than men with low-risk disease (at 1/5 yr: 5.9%/14.2% vs 2.0%/8.8%). Adverse pathology at RP was observed in 32% of men ≤60 yr compared with 36% of men >60 yr (p=0.029), and in 34% with low-risk disease compared with 40% with intermediate-risk disease (p=0.048).ConclusionsOur descriptive analysis of AS practices worldwide showed that the risk of progression during AS is similar across the age and risk groups studied. The proportion of adverse pathology was higher among men >60 yr than among men ≤60 yr. These results suggest that men ≤60 yr and those with EAU intermediate-risk disease should not be excluded from opting for AS as initial management.Patient summaryData from 27 international centers reflecting daily clinical practice suggest that younger men or men with intermediate-risk prostate cancer do not hold greater risk for disease progression during active surveillance.

Mental health practitioners in many developing countries are faced with high job demands and a lack of institutional support. Given their high levels of work-related stress, it is important to identify mechanisms that help them to maintain psychological well-being and job satisfaction. Recent research has focused on the role that positive orientation (POS) may play in mediating the negative impact of stress on individual well-being. The present study investigated whether POS predicts mental health practitioners' perceived levels of stress, mental health and job satisfaction. If POS measures a person's tendency to take a positive attitude to life and their ability to cope with difficulties, a high POS could be linked to reduced levels of stress and increased levels of job satisfaction and well-being. This study examined associations between self-reported POS and psychological outcomes in a sample of 100 Malaysian mental health practitioners. The results showed that POS significantly predicted job satisfaction positively and mental health issues and perceived stress negatively, even when socio-demographic variables were controlled. Overall, we found a strong effect of POS on individual functioning across the sample of mental health practitioners. Our results have implications for improving practitioner wellbeing and job satisfaction.

Introduction: Intensive cardiac rehabilitation (ICR) combines exercise sessions as in traditional cardiac rehabilitation (CR) with additional educational sessions focused on a heart-healthy diet and a healthy mindset. The effects of ICR, particularly outpatient Pritikin ICR, on mortality and cardiovascular outcomes have not been evaluated. Thus, the aim of our study is 1) to prospectively evaluate survival in a large cohort of patients enrolled in an outpatient Pritikin ICR program; and 2) to compare survival within a 5% Medicare sample between beneficiaries who participated in ICR versus those who did not participate in cardiac rehabilitation. Hypothesis: We hypothesize that 1) outpatient Pritikin ICR is associated with excellent survival (i.e. over 90% at 1 year) and 2) Medicare beneficiaries participating in ICR have better survival than those not participating in any cardiac rehabilitation. Methods: 1) This is a prospective longitudinal study of participants engaging in ICR at the first-ever outpatient Pritikin ICR center. For the single-center data, mortality was obtained via review of electronic medical records and direct patient follow-up for 1 year. 2) Within a 5% national Medicare sample, mortality was evaluated in all subjects utilizing a Cox proportional hazard model adjusted for age, gender, Medicaid status, number of comorbidities, and qualifying event type. The Kaplan-Meier curve is based on a subgroup matched for these same variables. Results: 1) There were 433 patients who participated in Pritikin ICR at our institution. The survival rate was 98% at 1 year. 2) In the Medicare sample, enrollees in ICR had a lower mortality than those not attending cardiac rehabilitation (HR = 0.49, 95% CI 0.28, 0.86) after adjustments; median follow-up time was 27.0 months. Conclusions: Outpatient Pritikin ICR is associated with an outstanding survival rate at 1 year. ICR in general is associated with better survival rates, even after multivariable adjustment.

The food pharmacy is an emerging program model designed to increase the access to and consumption of healthful foods, particularly fruits and vegetables. Existing research on the efficacy of the food pharmacy model shows that these programs have been effective in improving patient understanding of nutrition and removing barriers to healthy eating, and in turn may have a significant impact on diet-related health outcomes. However, efforts to date aiming to evaluate program effectiveness have been small and lack rigorous research methods. More research is needed to adequately assess the longitudinal effects of food pharmacy programs on healthful food intake and diet-related health outcomes. In this review, we outline the strengths and limitations of previous programs and explore possible options to improve the scalability and sustainability of food pharmacy programs.

Take Home Message Risks of upgrading and disease progression were higher among African than among Caucasian men on active surveillance for prostate cancer. Transitioning to treatment without progression was highest among Asian men. Understanding of the reasons for these differences requires further investigation., Background Studies of active surveillance (AS) for prostate cancer (PCa) have focussed predominantly on Caucasian populations. Little is known about the experience of Asian men, while suitability for men of African descent has been questioned. Objective To compare baseline characteristics, follow-up, and outcomes for men on AS for PCa, according to ethnicity. Design, setting, and participants The study cohort included 13 centres from the GAP3 consortium that record ethnicity (categorised broadly as Caucasian/white, African/Afro-Caribbean/black, Asian, mixed/other, and unknown). Men with biopsy grade group >2, prostate-specific antigen (PSA) >20 ng/ml, T stage ≥cT3, or age >80 yr were excluded. Outcome measurements and statistical analysis Clinical characteristics, follow-up schedules, outcome status, and reasons for discontinuation were compared across ethnic groups. Risk of upgrading, potential disease progression (grade group ≥3 or T stage ≥3), suspicious indications (any upgrading, number of positive cores >3, T stage ≥cT3, PSA >20 ng/ml, or PSA density >0.2 ng/ml/cc2), and conversion to treatment were assessed using mixed-effect regression models. Results and limitations The eligible cohort (n = 9158) comprised 83% Caucasian men, 6% men of African descent, 5% Asian men, 2% men of mixed/other ethnicity, and 4% men of unknown ethnicity. Risks of suspicious indicators (hazard ratio = 1.27; 95% confidence interval [CI] 1.12–1.45), upgrading (odds ratio [OR] = 1.40; 95% CI 1.14–1.71), and potential progression (OR = 1.46; 95% CI 1.06–2.01) were higher among African/black than among Caucasian/white men. Risk of transitioning to treatment did not differ by ethnicity. More Asian than Caucasian men converted without progression (42% vs 26%, p < 0.001). Heterogeneity in surveillance protocols and racial makeup limit interpretation. Conclusions This multinational study found differences in the risk of disease progression and transitioning to treatment without signs of progression between ethnic groups. Further research is required to determine whether differences are due to biology, sociocultural factors, and/or clinical practice. Patient summary This international study compared prostate cancer active surveillance outcomes by ethnicity. Risks of upgrading and disease progression were higher among African than among Caucasian men. Transitioning to treatment without progression was highest among Asian men. Understanding of these differences requires further investigation.

Background A von Hippel Lindau (VHL) mutation or functional inactivation occurs in the a large proportion of patients with clear-cell renal cell carcinoma (ccRCC), which results in the dysregulation of a number of key cellular functions. A high throughput screen and candidate compound assessment revealed that agents with proteasome inhibition properties were able to stabilize point-mutated VHL and restore some of its functions. Patients and Methods Nine patients with histologically confirmed metastatic ccRCC with disease progression during at least 1 previous systemic therapy were treated with carfilzomib at a dose of 20 mg/m2 over 30 minutes via intravenous (I.V.) infusion on days 1 and 2 and a dose of 56 mg/m2 over 30 minutes via I.V. infusion on days 8, 9, 15, and 16 of each 4-week cycle. Results The study was stopped after 9 patients were enrolled because of futility. Of the 9 patients treated in the study, all patients had disease progression within 4 months, with a median time of 1.8 months (95% confidence interval, 0.8-3.6 months). No patient showed a response according to Response Evaluation Criteria In Solid Tumors. Three patients showed a best response of stable disease. The most common side effects were musculoskeletal pain, elevated creatinine level, anemia, hyperkalemia, leukopenia, lymphopenia, and fatigue. Conclusion Although the negative safety and efficacy results of this study do not favor the use of carfilzomib for the treatment of ccRCC, previous studies have shown selected patients achieved partial or complete response to this class of agent. Further preclinical investigations to evaluate the molecular characteristics of the patients who respond to proteasome inhibitors will better characterize the underlying mechanism of response, and might allow for the selection of an appropriate patient population in future studies.

This chapter will include most important anatomical landmarks and differential diagnosis of middle mediastinum across various imaging modalities.

This chapter will include most important anatomical landmarks and differential diagnosis of posterior mediastinum across various imaging modalities. The key questions included are common questions asked during the rotation as well as questions that will help differentiate disease processes that may look very similar at an initial glance. Many of the questions will include high-yield differential diagnosis for common findings in imaging.

The increased amount of virtual care during the COVID-19 pandemic has exacerbated the challenge of providing appropriate medical board oversight to ensure proper quality of care delivery and safety of patients. This is partly due to the conventional model of each state medical board (SMB) holding responsibility for medical standards and oversight only within the jurisdiction of that state board and partly due to regulatory waivers and reduced enforcement of privacy policies. Even with a revoked license in one state, significant number of physicians have continued to practice by obtaining a medical license in a different state. Individualized requests were sent to 63 medical boards with questions related to practice of telemedicine and digital health by debarred or penalized medical doctors. The responses revealed major deficiencies and the urgent need to adopt a nationwide framework and to create an anchor point to serve as the coordinator of all relevant information related to incidents of improper medical practice. The ability to cause damage to large number of patients is significantly more now. Federal and state agencies urgently need to provide more attention and funding to issues related to quality of care and patient care in the changing ecosystem that includes medical specialists at a distance and the use of evolving digital health services and products. The creation, maintenance, and use of an integrated information system at national and multinational levels is increasingly important.