Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth-restricted fetal sheep.

KEY POINTS: Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes. We demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight-specific basis. Net hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was significantly lower in IUGR fetal sheep. Among all fetuses, blood O2 saturation and plasma glucose, insulin and insulin-like growth factor-1 were positively associated and norepinephrine was negatively associated with hindlimb weight. These results further our understanding of the metabolic and hormonal adaptations to reduced oxygen and nutrient supply with placental insufficiency that develop to slow hindlimb growth and muscle protein accretion. ABSTRACT: Reduced skeletal muscle mass in the fetus with intrauterine growth restriction (IUGR) persists into adulthood and may contribute to increased metabolic disease risk. To determine how placental insufficiency with reduced oxygen and nutrient supply to the fetus affects hindlimb blood flow, substrate uptake and protein accretion rates in skeletal muscle, late gestation control (CON) (n = 8) and IUGR (n = 13) fetal sheep were catheterized with aortic and femoral catheters and a flow transducer around the external iliac artery. Muscle protein kinetic rates were measured using isotopic tracers. Hindlimb weight, linear growth rate, muscle protein accretion rate and fractional synthetic rate were lower in IUGR compared to CON (P < 0.05). Absolute hindlimb blood flow was reduced in IUGR (IUGR: 32.9 ± 5.6 ml min-1 ; CON: 60.9 ± 6.5 ml min-1 ; P < 0.005), although flow normalized to hindlimb weight was similar between groups. Hindlimb oxygen consumption rate was lower in IUGR (IUGR: 10.4 ± 1.4 µmol min-1  100 g-1 ; CON: 14.7 ± 1.3 µmol min-1  100 g-1 ; P < 0.05). Hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was lower in IUGR (IUGR: 1.3 ± 0.5 µmol min-1  100 g-1 ; CON: 2.9 ± 0.2 µmol min-1  100 g-1 ; P < 0.05). Blood O2 saturation (r2  = 0.80, P < 0.0001) and plasma glucose (r2  = 0.68, P < 0.0001), insulin (r2  = 0.40, P < 0.005) and insulin-like growth factor (IGF)-1 (r2  = 0.80, P < 0.0001) were positively associated and norepinephrine (r2  = 0.59, P < 0.0001) was negatively associated with hindlimb weight. Slower hindlimb linear growth and muscle protein synthesis rates match reduced hindlimb blood flow and oxygen consumption rates in the IUGR fetus. Metabolic adaptations to slow hindlimb growth are probably hormonally-mediated by mechanisms that include increased fetal norepinephrine and reduced IGF-1 and insulin.

Positive Impact of Transition From Noon Conference to Academic Half Day in a Pediatric Residency Program.

OBJECTIVE: To evaluate the impact of transitioning from noon conference (NC) to academic half day (AHD) on conference attendance, interruptions, and perceived protected educational time and to describe pediatric resident experiences with AHD. METHODS: In this mixed-methods study, data before and after AHD implementation were collected. Quantitative data were analyzed with a 2-variable t test or chi-square test. Five focus groups and 5 individual interviews of pediatric residents were conducted. Data were analyzed using constant comparative methods, and were collected until reaching saturation. In accordance with grounded theory methodology, we developed codes using an iterative approach and identified major themes. RESULTS: After AHD implementation, resident attendance increased from 55% (of residents expected at NC) to 94% (of residents scheduled for AHD) (P < .001); interruptions decreased from 0.25 to 0.01 per resident per hour (P < .001). Positive responses regarding perceived protected educational time improved from 50% to 95% (2015 class) and from 19% to 50% (2016 class) (P < .001). Thirty-two residents participated in focus groups and interviews. Analysis yielded 5 themes: aids and barriers to AHD attendance; teaching; curricular content; learning and engagement; and resident well-being. Residents felt aided attending AHD when clinical supervisors supported their educational time. Compared to NC, residents noted better topic selection but fewer covered topics. Residents valued protected educational time without clinical responsibilities and thought that small-group discussions at AHD facilitated learning. Although cross-covering was stressful, AHD positively contributed to resident well-being. CONCLUSIONS: AHD improves resident attendance, interruptions, and perceived learning, and it contributes to resident wellness. More work is needed to mitigate the workload of cross-covering residents.