Alterations in the microbiome correlate with improved metabolism in patients following bariatric surgery. While fecal microbiota transplantation (FMT) from obese patients into germ-free (GF) mice has suggested a significant role of the gut microbiome in metabolic improvements following bariatric surgery, causality remains to be confirmed. Here, we perform paired FMT from the same obese patients (BMI > 40; four patients), pre- and 1 or 6 months post-Roux-en-Y gastric bypass (RYGB) surgery, into Western diet-fed GF mice. Mice colonized by FMT from patients' post-surgery stool exhibit significant changes in microbiota composition and metabolomic profiles and, most importantly, improved insulin sensitivity compared with pre-RYGB FMT mice. Mechanistically, mice harboring the post-RYGB microbiome show increased brown fat mass and activity and exhibit increased energy expenditure. Moreover, improvements in immune homeostasis within the white adipose tissue are also observed. Altogether, these findings point to a direct role for the gut microbiome in mediating improved metabolic health post-RYGB surgery.

Background: While the number of women entering medicine has steadily increased since the 1970s in Canada, the gender composition along each stage of the medical training pathway has not been comprehensively reported. We therefore sought to systematically examine the gender composition of students, residents, and practicing physicians over the past 30 years in Canada. Results: In this cross-sectional analysis of Canadian medical trainees including MD applicants (137,096 male, 169,099 female), MD students (126,422 male, 152, 967 female), MD graduates (29,413 male, 34,173 female), residents by the decade (24,425 male, 28,506 female) and practicing surgeons (total 7,457 male, 3,457 female), we find that increased female representation in medicine is not matched by representation in surgery, with the key being the specialty choice process. The likelihood of female applicants matriculating to medical school was less than male applicants in the 90s (OR 0.92, 95% CI 0.92–0.93), greater in the early 2000s (OR 1.03, 95% CI 1.03–1.04), and has since balanced out (OR 1.00, 95% CI 1.00-1.01), with medical school classes being nearly 60% female for the past two decades. Despite this, females have remained underrepresented in most surgical residency programs, with odds of female medical students entering surgical residency other than Ob/Gyn being about half that of male students (OR 0.56, 95% CI 0.44–0.71), resulting in a slow increase in practicing female surgeons of less than 0.5% per year in many surgical disciplines and projected parity decades or centuries in the future. Conclusions: While undergraduate medical education has been majority female in Canada for nearly three decades, females remain greatly underrepresented in the physician workforce within surgical specialties. To build a representative medical workforce equipped to care for diverse patient populations, factors influencing the specialty choices of early career physicians will need to be examined and addressed.

BACKGROUND: Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial. METHODS: We determined cardiomyocyte renewal in 52 patients with advanced heart failure, 28 of whom received left ventricular assist device support. We measured the concentration of nuclear bomb test–derived ¹⁴ C in cardiomyocyte genomic DNA and performed mathematical modeling to establish cardiomyocyte renewal in heart failure with and without LVAD unloading. RESULTS: We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18 to 50× lower compared with the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart. CONCLUSIONS: Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.

Multiple alterations of cellular metabolism have been documented in experimental studies of autosomal dominant polycystic kidney disease (ADPKD) and are thought to contribute to its pathogenesis. To elucidate the molecular pathways and transcriptional regulators associated with the metabolic changes of renal cysts in ADPKD, we compared global gene expression data from human PKD1 renal cysts, minimally cystic tissues (MCT) from the same patients, and healthy human kidney cortical tissue samples. We found gene expression profiles of PKD1 renal cysts were consistent with the Warburg effect with gene pathway changes favoring increased cellular glucose uptake and lactate production, instead of pyruvate oxidation. Additionally, mitochondrial energy metabolism was globally depressed, associated with downregulation of gene pathways related to fatty acid oxidation (FAO), branched-chain amino acid (BCAA) degradation, the Krebs cycle, and oxidative phosphorylation (OXPHOS) in renal cysts. Activation of mTORC1 and its two target proto-oncogenes, HIF-1α and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3, HK1/HK2, ALDOA, ENO2, PKM, LDHA/LDHB, MCT4, PDHA1, PDK1/3, MPC1/2, CPT2, BCAT1, NAMPT); indeed, their predicted expression patterns were confirmed by our data. Conversely, we found AMPK inhibition was predicted in renal cysts. AMPK inhibition was associated with decreased expression of PGC-1α, a transcriptional coactivator for transcription factors PPARα, ERRα, and ERRγ, all of which play a critical role in regulating oxidative metabolism and mitochondrial biogenesis. These data provide a comprehensive map of metabolic pathway reprogramming in ADPKD and highlight nodes of regulation that may serve as targets for therapeutic intervention.

The circadian clock regulates metabolism in anticipation of regular changes in the environment. It is found throughout the body, including in key metabolic organs such as the liver, adipose tissues, and intestine, where the timing of the clock is set largely by nutrient signaling. However, the circadian clocks of these tissues during the fasted state have not been completely characterized. Moreover, the sufficiency of a functioning host clock to produce diurnal rhythms in the composition of the microbiome in fasted animals has not been explored. To this end, mice were fasted 24 h prior to collection of key metabolic tissues and fecal samples for the analysis of circadian clock gene expression and microbiome composition. Rhythm characteristics were determined using CircaCompare software. We identify tissue‐specific changes to circadian clock rhythms upon fasting, particularly in the brown adipose tissue, and for the first time demonstrate the rhythmicity of the microbiome in fasted animals.

Glaucoma refers to a spectrum of progressive optic neuropathies and remains the leading cause of irreversible blindness worldwide. Its insidious onset poses serious challenges to conventional diagnostic methods and clinicians striving to detect early-stage disease for timely and effective intervention. Artificial intelligence (AI) has demonstrated its ability to process and analyze large datasets which can help identify subtle changes in early glaucomatous clinical presentation. This study reviews the current state of AI utilization in glaucoma and elucidates the strengths and limitations of existing approaches. We dissect the role of AI in various domains: enhancing early detection and diagnosis, monitoring disease progression, and refining treatment strategies to optimize patient outcomes. Furthermore, we address the ethical, legal, and social implications, alongside the inherent limitations of AI in the clinical setting. Despite these challenges, AI holds transformative potential for glaucoma management. Future directions emphasize the need for interdisciplinary collaboration, advanced and explainable algorithm development, and equitable healthcare access to fully realize the promise of AI in combating this vision-threatening condition.