Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial.

People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans.

Immunomodulatory Role of the Stem Cell Circadian Clock in Muscle Repair.

The circadian clock orchestrates vital physiological processes such as metabolism, immune function, and tissue regeneration, aligning them with the optimal time of day. This study identifies an intricate interplay between the circadian clock within muscle stem cells (SCs) and their capacity to modulate the immune microenvironment during muscle regeneration. We uncover that the SC clock provokes time of day-dependent induction of inflammatory response genes following injury, particularly those related to neutrophil activity and chemotaxis.

Harmonizing the Tripartite Mission in Academic Family Medicine: A Longitudinal Case Example.

Academic practices and departments are defined by a tripartite mission of care, education, and research, conceived as being mutually reinforcing. But in practice, academic faculty have often experienced these 3 missions as competing rather than complementary priorities. This siloed approach has interfered with innovation as a learning health system in which the tripartite missions reinforce each other in practical ways.

Mitochondria regulate proliferation in adult cardiac myocytes.

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice.

Circadian timing of satellite cell function and muscle regeneration.

Recent research has highlighted an important role for the molecular circadian machinery in the regulation of tissue-specific function and stress responses. Indeed, disruption of circadian function, which is pervasive in modern society, is linked to accelerated aging, obesity, and type 2 diabetes. Furthermore, evidence supporting the importance of the circadian clock within both the mature muscle tissue and satellite cells to regulate the maintenance of muscle mass and repair capacity in response injury has recently emerged.

Departmental Metrics to Guide Equity, Diversity, and Inclusion for Academic Family Medicine Departments.

Problem: Equity, diversity, and inclusion (EDI) efforts have accelerated over the past several years, without a traditional guidebook that other missions often have. To evaluate progress over time, departments of family medicine are seeking ways to measure their current EDI state. Across the specialty, unity regarding which EDI metrics are meaningful is absent, and discordance even exists about what should be measured.

Tight regulation of a nuclear HAPSTR1-HUWE1 pathway essential for mammalian life.

The recently discovered HAPSTR1 protein broadly oversees cellular stress responses. This function requires HUWE1, a ubiquitin ligase that paradoxically marks HAPSTR1 for degradation, but much about this pathway remains unclear. Here, leveraging multiplexed proteomics, we find that HAPSTR1 enables nuclear localization of HUWE1 with implications for nuclear protein quality control.

Negotiating a new chair package: context and considerations.

Negotiating a resource package as a potential new department chair is common practice in academic medicine. The foundations for this negotiation include the historical presence of the department in relation to the broader institution, projections for future growth, accounting for mission/vision, resource needs (space, personnel, finances, etc), faculty and staff development, and external partnerships within and outside the institution. Despite similarities in this process across departments, many nuances influence the development of a specific new chair package, such as, department size; desires, perspectives and talents of the incoming chair, the department faculty, the medical school and dean; prevailing agendas and mission imperatives; and the overall priorities of the institution.

Loss of alters trabecular bone loss during osteomyelitis in a cell-specific manner.

Osteomyelitis, or bone infection, is a major complication of accidental trauma or surgical procedures involving the musculoskeletal system. is the most frequently isolated pathogen in osteomyelitis and triggers significant bone loss. Hypoxia-inducible factor (HIF) signaling has been implicated in antibacterial immune responses as well as bone development and repair.

The Anglo-Saxon migration and the formation of the early English gene pool.

The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans-including 278 individuals from England-alongside archaeological data, to infer contemporary population dynamics.

Intestinal Inflammation Promotes MDL-1 Osteoclast Precursor Expansion to Trigger Osteoclastogenesis and Bone Loss.

Background & Aims: Inflammatory bowel disease (IBD) is characterized by severe gastrointestinal inflammation, but many patients experience extra-intestinal disease. Bone loss is one common extra-intestinal manifestation of IBD that occurs through dysregulated interactions between osteoclasts and osteoblasts. Systemic inflammation has been postulated to contribute to bone loss, but the specific pathologic mechanisms have not yet been fully elucidated.

Impact of circadian time of dosing on cardiomyocyte-autonomous effects of glucocorticoids.

Objective: Mitochondrial capacity is critical to adapt the high energy demand of the heart to circadian oscillations and diseased states. Glucocorticoids regulate the circadian cycle of energy metabolism, but little is known about how circadian timing of exogenous glucocorticoid dosing directly regulates heart metabolism through cardiomyocyte-autonomous mechanisms. While chronic once-daily intake of glucocorticoids promotes metabolic stress and heart failure, we recently discovered that intermittent once-weekly dosing of exogenous glucocorticoids promoted muscle metabolism in normal and obese skeletal muscle.

Dissociating executive function and ADHD influences on reading ability in children with dyslexia.

Developmental dyslexia (DD) and attention-deficit/hyperactivity disorder (ADHD) are two of the most common neurodevelopmental disorders among school-age children. These disorders frequently co-occur, with up to 40-50% of children with one diagnosis meeting criteria for the other, and similar percentages of children with either DD or ADHD exhibiting impaired executive functions (EF). Although both ADHD and EF deficits are common in dyslexia, there is little evidence about how ADHD and EF deficits specifically influence the brain basis of reading difficulty in dyslexia, and whether the influences of ADHD and EF on dyslexia can be disentangled.

Muscle mitochondrial remodeling by intermittent glucocorticoid drugs requires an intact circadian clock and muscle PGC1α.

Exogenous glucocorticoids interact with the circadian clock, but little attention is paid to the timing of intake. We recently found that intermittent once-weekly prednisone improved nutrient oxidation in dystrophic muscle. Here, we investigated whether dosage time affected prednisone effects on muscle bioenergetics.

BMAL1 drives muscle repair through control of hypoxic NAD regeneration in satellite cells.

The process of tissue regeneration occurs in a developmentally timed manner, yet the role of circadian timing is not understood. Here, we identify a role for the adult muscle stem cell (MuSC)-autonomous clock in the control of muscle regeneration following acute ischemic injury. We observed greater muscle repair capacity following injury during the active/wake period as compared with the inactive/rest period in mice, and loss of within MuSCs leads to impaired muscle regeneration.

NADH inhibition of SIRT1 links energy state to transcription during time-restricted feeding.

In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD, a cosubstrate of the class III histone deacetylase sirtuin 1 (SIRT1) that associates with clock transcription factors. Although NAD also participates in redox reactions, the extent to which NAD(H) couples nutrient state with circadian transcriptional cycles remains unknown. Here we show that nocturnal animals subjected to time-restricted feeding of a calorie-restricted diet (TRF-CR) only during night-time display reduced body temperature and elevated hepatic NADH during daytime.

Shared Language for Shared Work in Population Health.

People working on behalf of population health, community health, or public health often experience confusion or ambiguity in the meaning of these and other common terms-the similarities and differences and how they bear on the tasks and division of labor for care delivery and public health. Shared language must be clear enough to help, not hinder people working together as they ultimately come to mutual understanding of roles, responsibilities, and actions in their joint work. Based on an iterative lexicon development process, the authors developed and propose a definitional framework as an aid to navigating among related population and community health terms.

Expanding Family Medicine Scholarship to All Faculty: The Minnesota Model for Harmonizing Clinical Care, Education, and Research Missions.

Background: The Department of Family Medicine and Community Health at the University of Minnesota engaged in a 5-year transformation to expand research and scholarship opportunities to all faculty. A harmonization framework was used to integrate the 3 missions of clinical care, education, and research to ensure that research and scholarship were an ongoing focus of the department.

Methods: The key elements of our transformation included as follows: (1) a general culture of inquiry, (2) harmonized leadership, (3) training and mentoring, and (4) infrastructure and resources.

Coming Together in Action for Equity, Diversity, and Inclusion.

Family medicine departments see elevating equity, diversity, and inclusion (EDI)* as socially necessary and as powerful in achieving core missions. The importance and timeliness of this longstanding issue in medicine are magnified by the COVID-19 pandemic with its disproportionate effect on communities of color and by civil unrest focused on racial justice. EDI plays out in three pillars: (1) care delivery and health, (2) workforce recruitment and retention, and (3) learner recruitment and training.