Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.

Aged hematopoietic stem cells (HSCs) display diminished self-renewal and a myeloid differentiation bias. However, the drivers and mechanisms that underpin this fundamental switch are not understood. HSCs produce genotoxic formaldehyde that requires protection by the detoxification enzymes ALDH2 and ADH5 and the Fanconi anemia (FA) DNA repair pathway. We find that the HSCs in young Aldh2-/-Fancd2-/- mice harbor a transcriptomic signature equivalent to aged wild-type HSCs, along with increased epigenetic age, telomere attrition, and myeloid-biased differentiation quantified by single HSC transplantation. In addition, the p53 response is vigorously activated in Aldh2-/-Fancd2-/- HSCs, while p53 deletion rescued this aged HSC phenotype. To further define the origins of the myeloid differentiation bias, we use a GFP genetic reporter to find a striking enrichment of Vwf+ myeloid and megakaryocyte-lineage-biased HSCs. These results indicate that metabolism-derived formaldehyde-DNA damage stimulates the p53 response in HSCs to drive accelerated aging.

Is It Time to Say Goodbye to BMI? A Commentary.

The linkage between weight and health is complicated and our current body of evidence is inconsistent. We cannot have a discussion about weight without understanding the larger context of our antifat society and the influence of the diet industrial complex. Weight bias and a focus on weight in health care produce known harms. Additionally, clinicians often recommend losing weight without a nuanced discussion of the evidence showing that most people are unlikely to be successful with sustained weight loss. In this piece, I argue that using our precious time with patients and health care dollars to focus on health behaviors with indisputable evidence such as increasing physical activity and promoting smoking cessation is a more effective use of resources and more closely aligns with our ethical obligation to "do no harm."

Responding to an Emerging Need: Implementing Telehealth in Acute Hospital Rehabilitation.

This article outlines a multidisciplinary approach to implementing a telehealth program in the acute care hospital setting during the coronavirus disease 2019 (COVID-19) pandemic. Telehealth has been used in many practice areas, although it can be a particular challenge to establish in an acute care hospital given the fast-paced environment. However, the COVID-19 pandemic presented a unique situation. In-person treatment interactions became increasingly high risk for both patient and provider, and there was an emerging need to conserve personal protective equipment and limit exposure. In response to these developments, physical therapists, occupational therapists, and speech language pathologists treating an adult population turned to telehealth to supplement in-person treatment. This article outlines the clinical reasoning and practical application to implementing a telehealth program in an acute care hospital and includes regulations, identified successful strategies, barriers, considerations, decision-making algorithms, and discipline-specific interventions.

Hormone receptor expression and outcomes in low-grade serous ovarian carcinoma.

OBJECTIVE: Low-grade serous ovarian carcinomas (LGSC) are frequently ER/PR positive, though the mechanisms by which ER/PR regulate prognosis or anti-estrogen treatment efficacy are poorly understood. We studied ER/PR expression in LGSC tumors and cell lines to evaluate patient outcomes and cellular treatment responses. METHODS: LGSC tumors and patient-derived cell lines were studied from patients with advanced-stage (III/IV) disease. Tumor samples and clinical data were obtained from the Canadian Ovarian Experimental Unified Resource (COEUR-tissue microarray) and the Ovarian Cancer Research (OvCaRe) tissue bank. ER/PR expression was assessed by both Western blot and immunohistochemistry (IHC). Two different IHC scoring systems (simple and Allred) were used. Cox regression was used to identify factors (age, disease residuum, ER/PR status, etc.) associated with progression-free (PFS) and overall survival (OS). Estradiol and tamoxifen proliferation and viability experiments were performed in LGSC cell lines. RESULTS: In 55 LGSC cases studied, median follow-up was 56 months (range 1-227). Fifty-three (96%) cases strongly expressed ER whereas 37 (67%) expressed PR. Cox-regression analysis showed that residuum (p < 0.001) was significantly associated with PFS, whereas both ER Allred score (p = 0.005) and residuum (p = 0.004) were significant for OS. None of the LGSC cell lines expressed PR. Loss of PR and ER expression over time was detected in LGSC tumors and cell lines respectively. Estrogen and tamoxifen treatment did not alter LGSC cell proliferation or viability in-vitro. CONCLUSIONS: In patients with advanced LGSC, higher ER Allred scores were significantly associated with better overall survival. ER/PR expression changed over time in both LGSC tumors and cell lines. Better translational research models are needed to elucidate the molecular mechanisms of ER/PR signalling in LGSC.

Using a group medical visit model to promote healthy behaviour change with an underserved population.

BACKGROUND: Models of care are needed to address physical activity, nutrition promotion and weight loss in primary care settings, especially with underserved populations who are disproportionately affected by chronic illness. Group medical visits (GMVs) are one approach that can help overcome some of the barriers to behaviour change in underserved populations, including the amount of time required to care for these patients due to socio-economic stressors and psychosocial complexities (1). GMVs have been shown to improve care in coronary artery disease and diabetes, but more evidence is needed in underserved settings. OBJECTIVE: This project sought to evaluate a GMV incorporating a physical activity component in an underserved patient population, measuring biometric and motivation outcome measures. METHODS: This project used a pre-post intervention study design through patient surveys at baseline and 12 weeks. We included validated motivational measures along with self-reported demographic information. A GMV intervention promoting physical activity and nutrition to promote weight loss was delivered by an interdisciplinary primary care team and community partners in a Federally Qualified Health Center in Rochester, NY. The intervention consisted of six, 2-hour sessions that occurred every other week at the clinic site. RESULTS: Participants lost a significant amount of weight and maintained the weight loss at 6 months. In addition, there was a significant improvement in motivation measures. CONCLUSION: This study provides preliminary evidence that our GMV model can improve weight loss and autonomous motivation in an underserved population. This project has potential for scalability and sustainability.

What Now for Rehabilitation Specialists? Coronavirus Disease 2019 Questions and Answers.

Recognizing a need for more guidance on the coronavirus disease 2019 (COVID-19) pandemic, members of the Archives of Physical Medicine and Rehabilitation Editorial Board invited several clinicians with early experience managing the disease to collaborate on a document to help guide rehabilitation clinicians in the community. This consensus document is written in a "question and answer" format and contains information on the following items: common manifestations of the disease; rehabilitation recommendations in the acute hospital setting, recommendations for inpatient rehabilitation and special considerations. These suggestions are intended for use by rehabilitation clinicians in the inpatient setting caring for patients with confirmed or suspected COVID-19. The text represents the authors' best judgment at the time it was written. However, our knowledge of COVID-19 is growing rapidly. The reader should take advantage of the most up-to-date information when making clinical decisions.

Gastroenteritis in Children.

Acute gastroenteritis is defined as a diarrheal disease of rapid onset, with or without nausea, vomiting, fever, or abdominal pain. In the United States, acute gastroenteritis accounts for 1.5 million office visits, 200,000 hospitalizations, and 300 deaths in children each year. Evaluation of a child with acute gastroenteritis should include a recent history of fluid intake and output. Significant dehydration is unlikely if parents report no decrease in oral intake or urine output and no vomiting. The physical examination is the best way to evaluate hydration status. The four-item Clinical Dehydration Scale can be used to determine severity of dehydration based on physical examination findings. In children with mild illness, stool microbiological tests are not routinely needed when viral gastroenteritis is the likely diagnosis. Mild gastroenteritis in children can be managed at home. Oral rehydration therapy, such as providing half-strength apple juice followed by the child's preferred liquids, is the mainstay of treatment for mild dehydration and is as effective as intravenous rehydration for preventing hospitalization and return to the emergency department. Oral rehydration solutions are recommended for moderate dehydration. Ondansetron may be prescribed if needed to prevent vomiting and improve tolerance of oral rehydration solutions. Hospitalization and intravenous fluids are recommended for children who do not respond to oral rehydration therapy plus an antiemetic and patients with severe dehydration (i.e., signs of shock or more than 10% dehydration). Handwashing, breastfeeding, and rotavirus vaccination reduce the incidence of acute gastroenteritis in young children.

Mobile-Web app to self-manage low back pain: randomized controlled trial.

BACKGROUND: Nonspecific low back pain (NLBP) is the diagnosis for individuals with back pain that has no underlying medical cause (eg, tumor, infection, fracture, herniated disc, spinal stenosis). The American College of Physicians (ACP) and American Pain Society (APS) recommend multidisciplinary treatments for NLBP that lasts more than 4 weeks. This approach, however, is impractical for many physicians to implement, and relatively few providers offer NLBP treatment that meets the joint ACP-APS guidelines. OBJECTIVE: This study evaluated the efficacy of a mobile-Web intervention called "FitBack" to help users implement self-tailored strategies to manage and prevent NLBP occurrences. METHODS: A total of 597 adults were recruited, screened, consented, and assessed online at baseline, at 2 months (T2), and at 4 months (T3). After baseline assessments, participants were randomized into three groups: FitBack intervention, alternative care group that received 8 emails urging participants to link to six Internet resources for NLBP, and control group. The FitBack group also received weekly email reminder prompts for 8 weeks plus emails to do assessments. The control group was only contacted to do assessments. RESULTS: Users of the FitBack program showed greater improvement compared to the control group in every comparison of the critical physical, behavioral, and worksite outcome measures at 4-month follow-up. In addition, users of the FitBack program performed better than the alternative care group on current back pain, behavioral, and worksite outcomes at 4-month follow-up. For example, subjects in the control group were 1.7 times more likely to report current back pain than subjects in the FitBack group; subjects in the alternative care group were 1.6 times more likely to report current back pain at 4-month follow-up. Further, the users of the FitBack program showed greater improvement compared to both the control and alternative care groups at 4-month follow-up on patient activation, constructs of the Theory of Planned Behavior, and attitudes toward pain. CONCLUSIONS: This research demonstrated that a theoretically based stand-alone mobile-Web intervention that tailors content to users' preferences and interests can be an effective tool in self-management of low back pain. When viewed from the RE-AIM perspective (ie, reach, efficacy/effectiveness, adoption, implementation fidelity, and maintenance), this study supports the notion that there is considerable value in this type of intervention as a potentially cost-effective tool that can reach large numbers of people. The results are promising considering that the FitBack intervention was neither supported by professional caregivers nor integrated within a health promotion campaign, which might have provided additional support for participants. Still, more research is needed on how self-guided mobile-Web interventions will be used over time and to understand factors associated with continuing user engagement. TRIAL REGISTRATION: Clinicaltrials.gov NCT01950091; http://clinicaltrials.gov/ct2/show/NCT01950091 (Archived by WebCite at http://www.webcitation.org/6TwZucX77).

Novel role of sorting nexin 5 in renal D(1) dopamine receptor trafficking and function: implications for hypertension.

The D1 dopamine receptor (D1R) is widely expressed in the kidney and plays a crucial role in blood pressure regulation. Although much is known about D1R desensitization, especially through G-protein-coupled receptor kinase 4 (GRK4), comparatively little is known about other aspects of D1R trafficking and the proteins involved in the process. We now report the discovery of a dynamic interaction between sorting nexin 5 (SNX5), a component of the mammalian retromer, and D1R in human renal epithelial cells. We show that internalization of agonist-activated D1R is regulated by both SNX5 and GRK4, and that SNX5 is critical to the recycling of the receptor to the plasma membrane. SNX5 depletion increases agonist-activated D1R phosphorylation (>50% at basal condition), prevents D1R internalization and cAMP response, and delays receptor recycling compared to mock siRNA-transfected controls. Moreover, renal restricted subcapsular infusion of Snx5-specific siRNA (vs. mock siRNA) decreases sodium excretion (Δ=-0.2±0.005 mEq/mg creatinine) and further elevates the systolic blood pressure (Δ=48±5 mm Hg) in spontaneously hypertensive rats, indicating that SNX5 depletion impairs renal D1R function. These studies demonstrate an essential role for SNX5 in regulating D1R function, which may have important diagnostic, prognostic, and therapeutic implications in the management of essential hypertension.

'You need a support. When you don't have that . . . chocolate looks real good'. Barriers to and facilitators of behavioural changes among participants of a Healthy Living Program.

BACKGROUND: Health behavioural change is complex, especially for underserved patients who have higher rates of obesity and physical inactivity. Behavioural change interventions that show high efficacy in clinical trials may be difficult to disseminate and may not be effective in the office. OBJECTIVE: We sought to identify factors that facilitate or hinder behavioural change among past participants of a healthy lifestyle intervention in an urban underserved health centre. METHODS: Between March and October 2011, we conducted five focus group sessions with a total of 23 past participants. The focus group transcripts were analysed with a framework approach using the Social Ecological Model as a coding structure. RESULTS: We found four interconnected levels of social contexts: individual, interpersonal, programmatic and community levels. Themes of social support and the importance of relationships for making and maintaining behavioural changes were found at all levels. CONCLUSION: Social support and relatedness were key facilitators of healthy lifestyle changes and influenced individual motivation and perseverance. Harnessing the power of social support and motivation may be a way for future behavioural change interventions to bridge the gap between efficacy and effectiveness.

Motivations Behind Lifestyle Changes.

Lifestyle modification has been demonstrated as a powerful tool in combating the morbidity and mortality of disease. Due to lack of training or education not enough physicians are discussing lifestyle changes with patients. The objective of this study was to determine what influenced participants to make lifestyle changes, and if it was a physician, what was said or done to motivate that decision. Inclusion criterion was participants were enrolled in a program dedicated to dietary modifications. One hundred participants were surveyed. Eighty-eight percent were over the age of 50; 78% were female; 92% were White; and 70% had a bachelor's degree or higher. Sixty-eight percent felt they had not been educated by their health care provider about nutrition; 41% of participants felt information provided was the most impactful statement; 60% of participants noted that their medical diagnosis had a moderate to significant impact on their decision to make a lifestyle change. This study emphasizes that dietary modifications are not being discussed enough to alter the health decisions of patients in the clinical setting. Furthermore, it is paramount physicians take into account patient motivations when discussing lifestyle changes, as well as the role that proper patient education plays in motivating patients to make a change.

Addressing COVID-19 vaccine hesitancy in rural communities: A case study in engaging trusted messengers to pivot and plan.

The pandemic declaration of COVID-19 in 2020 presented unique challenges, lessons, and opportunities for public health practice in the United States. Despite clear evidence of COVID-19 vaccine effectiveness, vaccine uptake and vaccine confidence remained low in many regions. Vaccine holdouts, or those who are vaccine hesitant, have been an increasingly difficult population to reach. Several factors influence vaccine hesitancy and behavior in rural areas, including health care access challenges, misinformation, political loyalties, and concerns regarding the perceived lack of trustworthy evidence and knowledge of long-term effects. In March 2021, the Finger Lakes Rural Immunization Initiative (FLRII) engaged stakeholders to address vaccine hesitancy in a nine-county region of rural New York known as the Finger Lakes. Driven by data collected from community partners, physicians, and local health departments regarding their biggest barriers and greatest needs, the FLRII team created an interactive program for trusted messengers (TMs) including a stakeholder panel, called the Trusted Messenger Forum (TMF). The TMF met every 2 weeks from August 2021- August 2022 to engage local TMs and disseminate up-to-date knowledge in real time. During forum sessions, TMs shared detailed accounts of their experiences combating vaccine hesitancy in their communities and supported one another in their efforts through positive interaction and reaffirming conversations. Collaborations between community stakeholders can form a scaffolding to support a rapid response to a variety of public health problems and result in impactful change. For researchers implementing community-based research projects, modeling stakeholder panels after trusted messenger forums can be effective for diversifying the scope of the project and reacting to emergent problems in real-time.

Addressing Sexual Harassment and Gender Bias: Mandatory Modules Are Not Enough.

BACKGROUND AND OBJECTIVES: Despite decades of new policy guidelines and mandatory training modules, sexual harassment (SH) and gender bias (GB) continue in academic medicine. The hierarchical structure of medical training makes it challenging to act when one experiences or witnesses SH or GB. Most trainings designed to address SH and GB are driven by external mandates and do not utilize current educational techniques. Our goal was to design training that is in-person, active, and directed toward skills development. METHODS: Our academic family medicine (FM) department began by surveying our faculty and residents about their lived experiences of SH and GB. We used these data, incorporating principles of adult learning, to deliver voluntary, experiential, interactive workshops throughout 2019. The workshops took place during faculty development meetings and an annual retreat. We used interactive techniques that included case-based and Theater of the Oppressed formats. OUTCOMES: Eighty percent of faculty and residents participated in at least one of our voluntary training sessions. In April of 2020, we administered a retrospective, pre/postsurvey on confidence in recognizing, responding to, and reporting SH and GB. We found significant improvements in all domains surveyed; many participants reported using the skills in the 6 months prior to completing the surveys. CONCLUSION: We demonstrated that voluntary, interactive training sessions using the recommendations of the National Academies of Science Engineering and Medicine Report on the Sexual Harassment of Women improve participants' reported confidence in recognizing, responding to, and reporting SH and GB in one academic FM department. This training intervention is practical and can be disseminated and implemented in many settings.

Implementation of a self-determination based clinical program to reduce cardiovascular disease risk.

Health behaviors are the cornerstone of cardiovascular risk reduction but change is challenging and maintenance is uncommon. The use of Self-Determination Theory (SDT) can promote long-term change however the pathway is uncertain related to cardiovascular risk reduction. A multi-disciplinary clinical team trained in SDT counseled 294 individuals with high cardiovascular risk. Our participants had a significant decrease in cholesterol as well as a significant increase healthy diet and motivation measures. Autonomous motivation was a critical element in the pathways. We demonstrated that a SDT team-based clinical intervention can promote cardiovascular risk reduction through autonomous motivation.

How to overcome hesitancy for COVID-19 and other vaccines.

These evidence-based strategies (and list of do's and don'ts) can help you to increase the likelihood of vaccine uptake in hesitant patients.

The family physician's role in long COVID management.

A paucity of both data and therapeutics presents obstacles to care and makes your role in symptom management, psychological support, and referral-all described here-essential.

Sexual Harassment and Gender Bias in Family Medicine: Divergent Experiences of Men and Women.

BACKGROUND AND OBJECTIVES: Awareness of sexual harassment (SH), gender bias (GB), and gender discrimination (GD) has spread throughout popular culture and has been highlighted at universities across the United States. More nuanced data is needed to inform policies that address these issues. However, there are currently limited qualitative studies examining the nature of SH, GB, and GD in academic medicine, particularly family medicine. METHODS: In 2018, we conducted a series of gender-specific focus groups with faculty and residents in a department of family medicine (DFM) to understand their experiences with and responses to SH, GB, and GD. The focus groups were transcribed verbatim. We used immersion-crystallization and an adapted SH Experiences model to review the transcripts and identify patterns or themes during the immersion process. RESULTS: Participants identified the potential for patients, colleagues, faculty, and themselves as perpetrators and victims of SH, GB, and GD. Results suggested that GB was often implicit. SH was experienced verbally and physically. Women participants, especially, reported that both SH and GB occurred frequently and had lasting psychological effects. Gender, age, and position (faculty vs trainee) moderated SH and GB experiences. The effects seemed to be mediated by moral distress. CONCLUSIONS: This study emphasizes the importance of recognizing differences in experiences across gender, age, and position of SH, GB, and GD in academic family medicine. Our findings can be leveraged to develop antiharassment policies and set cultural expectations.

Attending a Biopsychosocially Focused Buprenorphine Training Improves Clinician Attitudes.

Objective: Substance use disorders remain highly stigmatized. Access to medications for opioid use disorder is poor. There are many barriers to expanding access including stigma and lack of medical education about substance use disorders. We enriched the existing, federally required, training for clinicians to prescribe buprenorphine with a biopsychosocial focus in order to decrease stigma and expand access to medications for opioid use disorder. Methods: We trained a family medicine team to deliver an enriched version of the existing buprenorphine waiver curriculum. The waiver training was integrated into the curriculum for all University of Rochester physician and nurse practitioner family medicine residents and also offered to University of Rochester residents and faculty in other disciplines and regionally. We used the Brief Substance Abuse Attitudes Survey to collect baseline and post-training data. Outcomes: 140 training participants completed attitude surveys. The overall attitude score increased significantly from pre to post-training. Additionally, significant changes were observed in non-moralism from pre-training (M = 20.07) to post-training (M = 20.98, p < 0.001); treatment optimism from pre-training (M = 21.56) to post-training (M = 22.33, p < 0.001); and treatment interventions from pre-training (M = 31.03) to post-training (M = 32.10, p < 0.001). Conclusion: Increasing medical education around Opioid Use Disorder using a Family Medicine trained team with a biopsychosocial focus can improve provider attitudes around substance use disorders. Enriching training with cases may improve treatment optimism and may help overcome the documented barriers to prescribing medications for opioid use disorder and increase access for patients to lifesaving treatments.

Increasing Access to Medications for Opioid Use Disorder in Primary Care: Removing the Training Requirement May Not Be Enough.

BACKGROUND: Substance use disorders, including opioid use disorder (OUD), are understood as chronic diseases with a relapsing and remitting course and no known cure. Medications for OUD (MOUD) are well established with decades of evidence supporting their safety and efficacy; however, treatment access remains poor and inequitable. Buprenorphine is an MOUD that can be prescribed in a primary care outpatient setting, although regulatory and administrative challenges are a barrier to prescribing it. Recent regulatory changes offer an opportunity to expand the number of family doctors who treat OUD. METHODS: We offered free, easily accessible buprenorphine "x-waiver training" led by a team of primary care clinicians. In addition, we provided wrap-around support for MOUD clinical questions and administrative needs with experienced family medicine mentors. RESULTS: More than 400 clinicians attended our trainings, including medical students, residents, and attending physicians. Of the 101 attending physicians who completed our trainings, only 30 went on to apply for an x-wavier, and of those only 7 were currently prescribing when contacted 12 months later. CONCLUSION: Our experience indicates that removing the training requirement is a necessary first step but is unlikely to result in major changes to rates of prescribing without other significant cultural changes.