Aims We previously reported that sodium-dependent glucose cotransporter 1 (SGLT1) is highly expressed in cardiomyocytes and is further up-regulated in ischaemia. This study aimed to determine the mechanisms by which SGLT1 contributes to ischaemia/reperfusion (I/R) injury. Methods and results Mice with cardiomyocyte-specific knockdown of SGLT1 (TGSGLT1-DOWN) and wild-type controls were studied. In vivo, the left anterior descending coronary artery was ligated for 30 min and reperfused for 48 h. Ex vivo, isolated perfused hearts were exposed to 20 min no-flow and up to 2 h reperfusion. In vitro, HL-1 cells and isolated adult murine ventricular cardiomyocytes were exposed to 1 h hypoxia and 24 h reoxygenation (H/R). We found that TGSGLT1-DOWN hearts were protected from I/R injury in vivo and ex vivo, with decreased infarct size, necrosis, dysfunction, and oxidative stress. 5’-AMP-activated protein kinase (AMPK) activation increased SGLT1 expression, which was abolished by extracellular signal-related kinase (ERK) inhibition. Co-immunoprecipitation studies showed that ERK, but not AMPK, interacts directly with SGLT1. AMPK activation increased binding of the hepatocyte nuclear factor 1 and specificity protein 1 transcription factors to the SGLT1 gene, and HuR to SGLT1 mRNA. In cells, up-regulation of SGLT1 during H/R was abrogated by AMPK inhibition. Co-immunoprecipitation studies showed that SGLT1 interacts with epidermal growth factor receptor (EGFR), and EGFR interacts with protein kinase C (PKC). SGLT1 overexpression activated PKC and NADPH oxidase 2 (Nox2), which was attenuated by PKC inhibition, EGFR inhibition, and/or disruption of the interaction between EGFR and SGLT1. Conclusion During ischaemia, AMPK up-regulates SGLT1 through ERK, and SGLT1 interacts with EGFR, which in turn increases PKC and Nox2 activity and oxidative stress. SGLT1 may represent a novel therapeutic target for mitigating I/R injury.

Objective: To determine if weight or body mass index (BMI) affects the serum progesterone level at the time of the pregnancy test in cryopreserved blastocyst transfer cycles and to determine if those serum progesterone levels affect live births. Design: Retrospective cohort study. Setting: US academic medical center. Patient(s): Six hundred thirty-three patients undergoing their first cryopreserved embryo transfer cycle. Intervention(s): None. Main Outcome Measure(s): The primary outcome was the serum progesterone level on the day of the pregnancy test by patient weight and BMI. Our secondary analysis assessed the serum progesterone effect on live birth rate (LBR) in a clinic where progesterone supplementation was increased if the progesterone level was <15 ng/mL on the day of the pregnancy test. Results(s): There was a strong negative correlation between serum progesterone level and both BMI and weight, with BMI accounting for 27% and weight accounting for 29% of the variance in progesterone level. Serum progesterone level on the day of the pregnancy test was <15 ng/mL in 3% of women weighing <68 kg compared with 29% of women weighing R90.7 kg. Among women weighing R90.7 kg, live birth occurred in 47% whose serum progesterone level was <15 ng/mL on the day of the pregnancy test compared with 49% in those with serum progesterone level of 15-19 ng/mL and 44% in those with serum progesterone level of R20 ng/mL. Conclusion(s): Body weight was a significant factor in serum progesterone level at the time of the pregnancy test, with nearly 30% of patients weighing R90.7 kg having serum progesterone level of <15 ng/mL, a value associated with lower LBRs in prior studies. However, we found no effect of low progesterone levels on LBR after cryopreserved embryo transfer cycles in a clinic where progesterone dosing was increased if serum progesterone levels were <15 ng/mL. (Fertil Steril Rep Ò 2021;2:195-200. Ó2021 by American Society for Reproductive Medicine.

Background Transitioning from preclinical to clinical medical education is a significant milestone in medical training; however, it is associated with anxiety and uncertainty about adapting to a new work and learning environment. These feelings may be additionally heightened when students are also transitioning to a branch or regional campus for their clerkship training. A guided, near-peer mentorship program was designed at a regional medical campus in hopes of reducing anxiety associated with transitioning into clinical rotations, as well as teach clinical medical students how to effectively mentor a fellow student. Methods This curricular improvement program was developed and implemented at a regional campus of a US Midwestern medical school. A list of 14 topics for discussion was created from responses to reflection questions completed by students participating in the program. These topics were sorted into meeting guides that mentors could reference during three individual meetings with their mentee. Mentors attended a workshop prior to the start of the program to learn more about effective mentorship in medicine. Participants from the first two years of this program were asked to complete feedback surveys evaluating their experience in the program. Results Forty-one of 48 potential second-year students agreed to participate as mentees and 40 of 48 potential third-year students agreed to participate as mentors. Ninety-two percent of mentees agreed that participating in the program decreased their stress and anxiety about transitioning into clerkships and 96% reported they would recommend the program to other students. Among the mentors, 93% reported they would recommend the program to other students and 78% agreed that the mentorship skills they practiced during the program are useful in their professional and academic development. Discussion With the introduction of this guided, near-peer mentorship program, mentees reported feeling supported in their transition into clinical clerkships and mentors reported feeling prepared to effectively mentor a fellow student. Though such one-on-one programs can be somewhat time-intensive to establish and execute, the skills gained by mentors can serve them for the rest of their careers and the individualized advice given to mentees markedly decreases anxiety in a high-stress transition.