Development and Evaluation of a Direct Care Hospitalist Service Internal Medicine Sub-internship Rotation.

BACKGROUND: Direct Care Hospitalist Services (DCHS) can increase internal medicine (IM) sub-internship rotation availability while providing hospitalists additional teaching opportunities. AIM: Implement and evaluate a DCHS sub-internship. SETTING: Urban Academic Medical School. PARTICIPANTS: IM sub-interns, hospitalists. PROGRAM DESCRIPTION: One to two sub-interns were paired with three hospitalists on 3 weeks of day service and five nights in an apprenticeship model. Sub-interns admitted and followed patients on days and cross-covered and admitted on nights. PROGRAM EVALUATION: DCHS sub-intern rotation satisfaction and skills preparedness were surveyed over 2 years. Sub-interns rotating on resident-covered service (RCS) were surveyed in year 2, and results compared to DCHS. Hospitalists were surveyed year 1 to rate satisfaction. Year 2 DCHS cross-cover paging data was tabulated to evaluate clinical content. DCHS and RCS sub-interns rated satisfaction and preparedness similarly. DCHS sub-interns rated time management (3.86 vs 4.33, p = 0.19) and calling consults (4.4 vs 4.8, p = 0.56) lower, but cross-cover higher (4.14 to 3.67, p = 0.34) than RCS. DCHS sub-interns averaged 39.4 (SD 4.1) nightly cross-cover pages with most related to acute symptoms (46%). Hospitalists were highly satisfied with their rotation experience. DISCUSSION: Sub-interns were highly satisfied with DCHS sub-internship. Future work will target gaps in preparedness for urgent patient care issues.

Metabolomic profiles and pathogenesis of nephrolithiasis.

PURPOSE OF REVIEW: Kidney stone disease is caused by supersaturation of urine with certain metabolites and minerals. The urine composition of stone formers has been measured to prevent stone recurrence, specifically calcium, uric acid, oxalate, ammonia, citrate. However, these minerals and metabolites have proven to be unreliable in predicting stone recurrence. Metabolomics using high throughput technologies in well defined patient cohorts can identify metabolites that may provide insight into the pathogenesis of stones as well as offer possibilities in therapeutics. RECENT FINDINGS: Techniques including 1H-NMR, and liquid chromatography paired with tandem mass spectroscopy have identified multiple possible metabolites involved in stone formation. Compared to formers of calcium oxalate stones, healthy controls had higher levels of hippuric acid as well as metabolites involved in caffeine metabolism. Both the gut and urine microbiome may contribute to the altered metabolome of stone formers. SUMMARY: Although metabolomics has offered several potential metabolites that may be protective against or promote stone formation, the mechanisms behind these metabolomic profiles and their clinical significance requires further investigation.

Cystinuria: Review of a Life-long and Frustrating Disease.

Cystinuria, accounting for about 1-2% of kidney stones in adults, carries significant morbidity beginning at a young age [1]. Cystine stone formers have more stone events compared to other stone formers, as well as more surgical interventions, potentially contributing to faster progression to chronic kidney disease (CKD), and end-stage kidney disease (ESKD) [2]. Successful medical therapy for cystine stone formers may be limited by adherence to the extensive lifestyle changes and the adverse side effect profiles of some interventions, leading to decreased quality of life for these patients relative to other stone formers.

Selective Survival of Sim1/MC4R Neurons in Diet-Induced Obesity.

In the melanocortin pathway, melanocortin-4 receptor (MC4R) functions to control energy homeostasis. MC4R is expressed in a sub-population of Sim1 neurons (Sim1/MC4R neurons) and functions in hypothalamic paraventricular nuclei (PVN) to control food intake. Mapping sites of hypothalamic injury in obesity is essential to counteract the disease. In the PVN of male and female mice with diet-induced obesity (DIO) there is neuronal loss. However, the existing subpopulation of PVN Sim1/MC4R neurons is unchanged, but has a loss of mitochondria and MC4R protein. In mice of both sexes with DIO, dietary intervention to re-establish normal weight restores abundance of MC4R protein in Sim1/MC4R neurons and neurogenesis in the PVN. However, the number of non-Sim1/MC4R neurons in the PVN continues to remain decreased. Selective survival and recovery of Sim1/MC4R neurons after DIO suggests these neurons as preferential target to restore energy homeostasis and of therapy against obesity.

Lipid stress inhibits endocytosis of melanocortin-4 receptor from modified clathrin-enriched sites and impairs receptor desensitization.

Melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor expressed in the brain's hypothalamus where it regulates energy homeostasis. MC4R agonists function to lower food intake and weight. In this respect, although obesity promotes hyperlipidemia and hypothalamic injury, MC4R agonists are nevertheless more effective to reduce food intake within hours of administration in overweight, rather than lean, mice. MC4R undergoes constitutive internalization and recycling to the plasma membrane with agonist binding inducing receptor retention along the intracellular route and, under prolonged exposure, desensitization. Here, we found that, in neuronal cells, lipid stress by exposure to elevated palmitate leaves unchanged the rate by which MC4R and transferrin receptor are constitutively excluded from the cell surface. However, lipid stress disrupted later steps of MC4R and transferrin receptor internalization to endosomes as well as traffic of agonist-occupied MC4R to lysosomes and MC4R desensitization. In the lipid-stressed cells, MC4R and clathrin were redistributed to the plasma membrane where they colocalized to sites that appeared by super-resolution microscopy to be modified and to have higher clathrin content than those of cells not exposed to elevated palmitate. The data suggest that lipid stress disrupts steps of endocytosis following MC4R localization to clathrin-coated sites and exclusion of the receptor from the extracellular medium. We conclude that increased effectiveness of MC4R agonists in obesity may be an unexpected outcome of neuronal injury with disrupted clathrin-dependent endocytosis and impaired receptor desensitization.