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Abstract Background Functional somatic symptoms (FFS) and bodily distress disorders are highly prevalent across all medical settings. Services for these patients are dispersed across the health care system with minimal conceptual and operational integration, and patients do not currently access therapeutic offers in significant numbers due to a mismatch between their and professionals’ understanding of the nature of the symptoms. New service models are urgently needed to address patients’ needs and to align with advances in aetiological evidence and diagnostic classification systems to overcome the body–mind dichotomy. Method A panel of clinical experts from different clinical services involved in providing aspects of health care for patients with functional symptoms reviewed the current care provision. This review and the results from a focus group exploration of patients with lived experience of functional symptoms were explored by the multidisciplinary expert group, and the conclusions are summarised as recommendations for best practice. Results The mapping exercise and multidisciplinary expert consultation revealed five themes for service improvement and pathway development: time/access, communication, barrier-free care, choice and governance. Service users identified four meta-themes for best practice recommendations: focus on healthcare professional communication and listening skills as well as professional attributes and knowledge base to help patients being both believed and understood in order to accept their condition; systemic and care pathway issues such as stronger emphasis on primary care as the first point of contact for patients, resources to reduce the length of the patient journey from initial assessment to diagnosis and treatment. Conclusion We propose a novel, integrated care pathway for patients with ‘functional somatic disorder’, which delivers care according to and working with patients’ explanatory beliefs. The therapeutic model should operate based upon an understanding of the embodied nature of patient’s complaints and provide flexible access points to the care pathway.

The global aging population presents economic, social, and cultural challenges, accentuated by the rise of age-related chronic conditions. Physical activity emerges as a crucial component for elderly well-being, countering sedentary lifestyles and comorbidities. Motivation, habit formation, and cultural integration are key to sustaining exercise behavior. Practices like yoga, tai chi, and qigong, deeply rooted in tradition, offer holistic benefits for the elderly. Research underscores their positive impact on physical and mental health, particularly in improving balance and reducing falls. However, awareness of their advantages needs amplification. To foster adoption and sustainability, targeted awareness campaigns, community programs, healthcare integration, intergenerational involvement, and accessibility enhancements are proposed. By combining these strategies, therapeutic exercises can be seamlessly integrated into elderly lifestyles, promoting long-term health and well-being.

Abstract Background The rising incidence of infective endocarditis (IE) among people who inject drugs (PWID) has been a major concern across North America. The coincident rise in IE and change of drug preference to hydromorphone controlled-release (CR) among our PWID population in London, Ontario intrigued us to study the details of injection practices leading to IE, which have not been well characterized in literature. Methods A case–control study, using one-on-one interviews to understand risk factors and injection practices associated with IE among PWID was conducted. Eligible participants included those who had injected drugs within the last 3 months, were > 18 years old and either never had or were currently admitted for an IE episode. Cases were recruited from the tertiary care centers and controls without IE were recruited from outpatient clinics and addiction clinics in London, Ontario. Results Thirty three cases (PWID IE+) and 102 controls (PWID but IE-) were interviewed. Multivariable logistic regressions showed that the odds of having IE were 4.65 times higher among females (95% CI 1.85, 12.28; p = 0.001) and 5.76 times higher among PWID who did not use clean injection equipment from the provincial distribution networks (95% CI 2.37, 14.91; p

Leukocytoclastic vasculitis (LCV) is a rare vascular inflammatory condition that affects post-capillary venules. Its incidence in the pediatric population is unknown. However, its incidence has been shown to increase with age. The causes of LCV can be varied, ranging from drugs to infections to systemic disease. LCV as a presenting symptom of inflammatory bowel disease (IBD) is rare, especially in the pediatric population. A 15-year-old female with a family history of systemic lupus erythematosus was transferred to our hospital with a month-long history of rash, joint swelling and tenderness, periorbital edema, weight loss, and diarrhea. She presented with the objective findings of a biopsy showing LCV and a computed tomography scan read that was concerning for IBD versus infectious colitis. She had a thorough workup, involving both the rheumatology and gastroenterology services, and was ultimately found to have Crohn’s disease. This case reveals the importance of recognition of a constellation of symptoms in IBD even when they are not classical in nature at initial presentation.

Purpose: Despite increasing use, proton therapy (PT) remains a relatively limited resource. The purpose of this study was to assess clinical and demographic differences in PT use for prostate cancer compared to intensity modulated radiation therapy (IMRT) at a single institution. Methods and materials: All patients with low- and intermediate-risk prostate cancer (N = 633) who underwent definitive radiation therapy between 2010 and 2015 were divided into PT (n = 508) and IMRT (n = 125) comparison groups and compared using χ2 and independent sample t tests. Univariable and multivariable logistic regression analyses were conducted to assess the associations between PT use and demographic, clinical, and treatment characteristics. Results: The PT and IMRT cohorts varied by age, race, poverty, distance, treatment year, and treating physician. Patients who underwent IMRT were more likely to be older (mean age, 66 vs. 68 years), black (51% vs. 75%), and living in poverty or close to the facility (mean distance between residence and facility, 90 vs. 21 miles; P < .05). Prostate-specific antigen, prostate volume, and International Index of Erectile Function were significantly higher in the IMRT cohort (P < .05), but insurance type, risk group, tumor stage, Gleason score, and patient-reported urinary and bowel scores did not differ significantly (P > .05). Patients who underwent PT were more likely to receive hypofractionated therapy and less likely to receive androgen deprivation therapy (P < .01). On multivariable analysis, black (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.15-0.57) and other race (OR, 0.42; 95% CI, 0.20-0.90); distance (OR, 1.14; 95% CI, 1.06-1.24); treatment years 2011 (OR, 4.87; 95% CI, 2.23-10.6), 2012 (OR, 8.27; 95% CI, 3.43-19.9), and 2014 (OR, 4.44; 95% CI, 1.94-10.2) relative to 2010; and a single treating physician (OR, 0.38; 95% CI, 0.18-0.81) relative to the reference physician with the highest rate of use were associated with PT use, whereas clinical factors such as prostate-specific antigen, prostate volume, International Index of Erectile Function, and androgen deprivation therapy were not. Conclusion: Sociodemographic disparities exist in PT use for prostate cancer at an urban academic institution. Further investigation of potential barriers to access is warranted to ensure equitable distribution across all demographic groups.

Purpose: There is growing evidence supporting incorporating multiparametric (mp) magnetic resonance imaging (MRI) scans into risk stratification, active surveillance, and treatment paradigms for prostate cancer. The purpose of our study was to determine whether demographic disparities exist in staging MRI utilization for prostate cancer patients. Methods and materials: An institutional database of 705 nonmetastatic prostate cancer patients treated with radiation therapy from 2005 through 2013 was used to identify patients undergoing versus not undergoing pretreatment diagnostic prostate mpMRI. Uni- and multivariable logistic regression evaluated the relationship of clinical and demographic characteristics with MRI utilization. Results: All demographic variables assessed, except the other race category, were significantly associated with MRI utilization (all P < .05), including age (odds ratio [OR], 0.92), black race (OR, 0.51), poverty (OR, 0.53), closer distance to radiation facility (OR, 1.79), and nonprivate primary insurance (OR, 0.57) on univariable analysis, while clinical stage T3 (OR, 3.37) was the only clinical characteristic. On multivariable analysis stratified by D'Amico risk group, age remained significant across all risk groups, whereas the black versus white racial (OR, 0.21; 95% confidence interval, 0.08-0.55) and nonprivate versus private insurance type (OR, 0.37; 95% confidence interval, 0.16-0.86) disparities persisted in the low-risk group. Clinical stage T3 remained associated in the high-risk group. For race specifically, the percentages of whites, blacks, and others undergoing MRI in the overall cohort and by risk group were, respectively: overall, 80% (343/427), 68% (156/231), and 85% (40/47); low risk, 86%, 56%, and 63%; intermediate risk, 79%, 72%, and 95%; and high risk, 72%, 72%, and 100%. Conclusions: In this urban, academic center cohort, older patients across all risk groups and black or nonprivate insurance patients in the low risk group were less likely to undergo staging prostate MRI scans. Further research should investigate these differences to ensure equitable utilization across all demographic groups considering the burden of prostate cancer disparities.

The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

Background: Our community-based clinic decided to implement routine screening for anorectal Gonorrhea (GC) and Chlamydia (CT) for patients undergoing HRA for anal cancer prevention, due to high risk for asymptomatic GC and CT among our patient population (predominantly HIV+ MSM in NYC) and the impact undiagnosed GC/CT infection may have on recovery after biopsy or ablation of HPV-related lesions. In 2016, the CDC reported a prevalence of anorectal GC and CT of 0.146% and 0.497% in the general population nationally, and 12.1% and 12.7% in MSM in NYC clinics in the STD Surveillance Network. Methods: Retrospective chart review for all HRA completed in 2017 using associated CPT and testing codes. Results: 839 HRA procedures were done in 2017. Of the anorectal NAATs performed, 6.6% were positive for either GC and/or CT (4% for GC and 3% for CT). Conclusions: Implementing routine screening for anorectal GC/CT at every HRA for HPV-related disease revealed a prevalence of concurrent anorectal GC and/or CT infection well above national prevalence for the general population, though at a lower rate than anorectal GC/CT among MSM seeking screening or treatment in NYC DOH clinics. We were unable to make conclusions about how treating these incidental infections impacted recovery after the procedure, as this was outside the scope of this limited chart review. But the prevalence of GC/CT infection discovered in this analysis supports the importance of adding routine GC/CT screening for all patients undergoing HRA for the diagnosis or treatment of HPV-related anal neoplasia.

Cullin-RING ubiquitin ligases (CRLs) catalyze the ubiquitylation of substrates many of which are degraded by the 26S proteasome. Their modular architecture enables recognition of numerous substrates via exchangeable substrate receptors that competitively bind to a cullin scaffold with high affinity. Due to the plasticity of these interactions there is ongoing uncertainty how cells maintain a flexible CRL repertoire in view of changing substrate loads. Based on a series of in vivo and in vitro studies, different groups proposed that the exchange of substrate receptors is mediated by a protein exchange factor named Cand1. Here, we have performed mathematical modeling to provide a quantitative underpinning of this hypothesis. First we show that the exchange activity of Cand1 necessarily leads to a trade-off between high ligase activity and fast receptor exchange. Supported by measurements we argue that this trade-off yields an optimal Cand1 concentration in cells where the time scale for substrate degradation becomes minimal. In a second step we show through simulations that (i) substrates bias the CRL repertoire leading to preferential assembly of ligases for which substrates are available and (ii) differences in binding affinities or substrate receptor abundances create a temporal hierarchy for the degradation of substrates. Finally, we compare the Cand1-mediated exchange cycle with an alternative architecture lacking Cand1 which indicates superiority of a system with exchange factor if substrate receptors bind substrates and the cullin scaffold in a random order. Together, our results provide general constraints for the operating regimes of molecular exchange systems and suggest that Cand1 endows the CRL network with the properties of an "on demand" system allowing cells to dynamically adjust their CRL repertoire to fluctuating substrate abundances.

Abstract Introduction This resource is a part of a six-module curriculum that uses TBL approaches to teach medical students clinical applications of general pediatric topics. This case is one of six used for third-year medical students during their pediatric clerkship at the University of Michigan during a weekly 2-hour time slot. The six pediatric modules cover topics of asthma, nutrition, fever, abdominal pain, anemia, and pneumonia. Methods This module is on pediatric asthma. Included are questions, answer keys, citations for reference articles, and descriptions of how to facilitate and evaluate a TBL exercise. A prior version of this module was previously published in MedEdPORTAL in 2010, but it has been revised in 2015 to reflect updated readings as well as to address student concerns that there were too many readiness questions and too few application questions. Results After implementation of TBL in our clerkship, National Board of Medical Examiners Pediatric Shelf examination scores improved by 3.04 points (from 79.46 to 82.50; p

Abstract This resource is a part of a six-module curriculum that uses TBL approaches to teach medical students clinical applications of general pediatric topics. This case is one of six used for third-year medical students during their pediatric clerkship at the University of Michigan during a weekly 2-hour time slot. The six pediatric modules cover topics of asthma, nutrition, fever, abdominal pain and mass, anemia, and pneumonia. This module is on pediatric abdominal pain and mass. Included are questions, answer keys, citations for reference articles, and descriptions of how to facilitate and evaluate a TBL exercise. A prior version of this module was previously published in MedEdPORTAL in 2010, but it has been revised in 2015 to reflect updated readings as well as to address student concerns that there were too many readiness questions and too few application questions. After implementation of TBL in our clerkship, National Board of Medical Examiners Pediatric Shelf examination scores improved as did students' scores on a pediatric asthma observed clinical skills examination and a pediatric fever question on their emergency medicine examination administered the subsequent year.

Abstract This resource is a part of a six-module curriculum that uses TBL approaches to teach medical students clinical applications of general pediatric topics. This case is one of six used for third-year medical students during their pediatric clerkship at the University of Michigan during a weekly 2-hour time slot. The six pediatric modules cover topics of asthma, nutrition, fever, abdominal pain, anemia, and pneumonia. This module is on pediatric fever. Included are questions, answer keys, citations for reference articles, and descriptions of how to facilitate and evaluate the TBL exercise. A prior version of this module was previously published in MedEdPORTAL in 2010, but it has been revised in 2015 to reflect updated readings as well as to address student concerns that there were too many readiness questions and too few application questions. After implementation of TBL in our clerkship, National Board of Medical Examiners Pediatric Shelf examination scores improved as did students' scores on an emergency medicine rotation exam question on pediatric fever taken the subsequent academic year.

The transcription factor ATF2 has been shown to attenuate melanoma susceptibility to apoptosis and to promote its ability to form tumors in xenograft models. To directly assess ATF2's role in melanoma development, we crossed a mouse melanoma model (Nras(Q61K)::Ink4a⁻/⁻) with mice expressing a transcriptionally inactive form of ATF2 in melanocytes. In contrast to 7/21 of the Nras(Q61K)::Ink4a⁻/⁻ mice, only 1/21 mice expressing mutant ATF2 in melanocytes developed melanoma. Gene expression profiling identified higher MITF expression in primary melanocytes expressing transcriptionally inactive ATF2. MITF downregulation by ATF2 was confirmed in the skin of Atf2⁻/⁻ mice, in primary human melanocytes, and in 50% of human melanoma cell lines. Inhibition of MITF transcription by MITF was shown to be mediated by ATF2-JunB-dependent suppression of SOX10 transcription. Remarkably, oncogenic BRAF (V600E)-dependent focus formation of melanocytes on soft agar was inhibited by ATF2 knockdown and partially rescued upon shMITF co-expression. On melanoma tissue microarrays, a high nuclear ATF2 to MITF ratio in primary specimens was associated with metastatic disease and poor prognosis. Our findings establish the importance of transcriptionally active ATF2 in melanoma development through fine-tuning of MITF expression.