Gonadotropin-releasing hormone induces classical meiotic maturation in subpopulations of atretic preantral follicles

GnRH has been shown to induce premature meiotic maturation in preantral follicles of the immature estrogen-primed hypophysectomized rat. As these animals are free of circulating gonadotropins and contain large numbers of full-grown oocytes in preantral follicles, we have investigated this model to determine its usefulness in studying meiotic maturation. We show that a maximum dose of the agonist D-Trp6,Pro9,Net-LRF (GnRH-a) induces approximately 25% of full grown oocytes to resume meiosis within a 12-h period. This response is dose dependent (ED50 = 0.24 microgram/rat) and specific for GnRH-a. GnRH-a stimulates germinal vesicle breakdown and first polar body formation within 2 and 8 h, respectively. More than 75% of those oocytes that initiate meiotic maturation reach metaphase II by 15 h. This effect of GnRH parallels the time course of physiological meiotic maturation triggered by LH as well as that of oocytes maturing spontaneously in vitro. Oocytes in primordial and primary follicles do not respond to GnRH. The majority of affected follicles are small tertiary follicles (200-400 micron in diameter) and show signs of atresia. This atresia is not caused by GnRH-a and does not, in itself, result in meiotic maturation, but appears to confer susceptibility to GnRH-a-induced meiotic maturation. Our studies indicate that this animal model will be useful to elucidate further the mechanisms and requirements for meiotic maturation. It will also facilitate investigation of the role of atresia in the GnRH response of tertiary follicles and the issue of follicle heterogeneity within these animals.     

A specific FSH receptor in rat granulosa cells: properties of binding in vitro.

The specific binding of [125I]iodoFSH to granulosa cells collected from immature, hypophysectomized, DES-treated rats, was studied in vitro. Specific binding occurred after 5 min and reached maximum after 3 h of incubation at 37 C. Non specific binding was very low (less than 10% of the total binding). The [25I]iodoFSH remained tightly associated with the receptor at pH 7.5, but was rapidly dissociated at pH 5. Unlabeled hFSH competitively inhibited [125I]iodoFSH binding. Kinetic analyses of equilibrium binding experiments gave an apparent association constant (Ka) of 1.34 (+/- 0.31) x 10(10)M-1 [mean (+/- SE)] and a number of binding sites per cell of (NB) 1, 130 +/- 70 (mean +/- SE). Rat prolactin, wheat germ agglutinin, and concanavalin-A did not compete with [125I]iodoFSH, but hLH, hCG, and rTSH competed at doses 300- to 900-fold higher than those of hFSH. Granulosa cells isolated from adult DES-treated rats, as well as cells collected from medium and preovulatory follicles of proestrous rats, gave Ka and NB values similar to those described above. A comparative study of rabbit granulosa cells indicated a much lower binding affinity compared with those from the rat.     

Automated Algorithm for GI Spike Burst Detection and Demonstration of Efficacy in Ischemic Small Intestine

We present a novel, fully-automated gastrointestinal spike burst detection algorithm. Following pre-processing with SALPA (Wagenaar and Potter, J. Neurosci. Methods 120:113–120, 2002) and a Savitzky–Golay filter to remove unwanted low and high frequency components, candidate spike waveforms are detected utilizing the non-linear energy operator. Candidate waveforms are classified as spikes or artifact by a support vector machine. The new method achieves highly satisfactory performance with >90% sensitivity and positive prediction value. We also demonstrate an application of the new method to detect changes in spike rate and spatial propagation patterns upon induction of mesenteric ischemia in the small intestine. Spike rates were observed to transiently increase 10–20 fold for a duration of ≈600 s, relative to baseline conditions. In ischemic conditions, spike activity propagation patterns included retrograde-longitudinal wavefronts with occasional spontaneous conduction blocks, as well as self-terminating concentric-circumferential wavefronts. Longitudinal and circumferential velocities were 6.8–8.0 cm/s and 18.7 cm/s, respectively.     

Perinatal depression screening practices in a large health system: identifying current state and assessing opportunities to provide more equitable care

The purpose of this study was to assess the prevalence of prenatal and postpartum depression screening in a large health system and to identify covariates for screening, with a specific focus in understanding disparities in practice. A retrospective cohort of women with deliveries in 2016 was created using electronic health records. Primary outcomes were depression screening during pregnancy and the first 3 months postpartum. Generalized linear mixed models with women nested within clinic were used to determine the effect of maternal and clinical characteristics on depression screening. The sample included 7548 women who received prenatal care at 35 clinics and delivered at 10 hospitals. The postpartum sample included 7059 women who returned within 3 months for a postpartum visit. Of those, 65.1% were screened for depression during pregnancy, and 64.4% were screened postpartum. Clinic site was the strongest predictor of screening, accounting for 23–30% of the variability in screening prevalence. There were no disparities identified with regard to prenatal screening. However, several disparities were identified for postpartum screening. After adjusting for clinic, women who were African American, Asian, and otherwise non-white (Native American, multi-racial) were less likely to be screened postpartum than white women (AOR (CI)’s 0.81 (0.65, 1.01), 0.64 (0.53, 0.77), and 0.44 (0.21, 0.96), respectively). Women insured by Medicaid/Medicare, a proxy for low-income, were less likely to be screened postpartum than women who were privately insured (AOR (CI) 0.78 (0.68, 0.89)). National guidelines support universal depression screening of pregnant and postpartum women. The current study found opportunities for improvement in order to achieve universal screening and to deliver equitable care.

     

Long Term Effect of Intensive Lifestyle Intervention on Cerebral Blood Flow

Objectives

To determine whether long‐term behavioral intervention targeting weight loss through increased physical activity and reduced caloric intake would alter cerebral blood flow (CBF ) in individuals with type 2 diabetes mellitus.

Design

Postrandomization assessment of CBF.

Setting

Action for Health in Diabetes multicenter randomized controlled clinical trial.

Participants

Individuals with type 2 diabetes mellitus who were overweight or obese and aged 45 to 76 (N = 310).

Interventions

A multidomain intensive lifestyle intervention (ILI ) to induce weight loss and increase physical activity for 8 to 11 years or diabetes support and education (DSE ), a control condition.

Measurements

Participants underwent cognitive assessment and standardized brain magnetic resonance imaging (MRI ) (3.0 Tesla) to assess CBF an average of 10.4 years after randomization.

Results

Weight changes from baseline to time of MRI averaged ?6.2% for ILI and ?2.8% for DSE (P < .001), and increases in self‐reported moderate or intense physical activity averaged 444.3 kcal/wk for ILI and 114.8 kcal/wk for DSE (P = .03). Overall mean CBF was 6% greater for ILI than DSE (P = .04), with the largest mean differences between ILI and DSE in the limbic region (3.39 mL /100 g per minute, 95% confidence interval (CI ) = 0.07–6.70 mL /100 g per minute) and occipital lobes (3.52 mL /100 g per minute, 95% CI = 0.20–6.84 mL /100 g per minute). In ILI , greater CBF was associated with greater decreases in weight and greater increases in physical activity. The relationship between CBF and scores on a composite measure of cognitive function varied between intervention groups (P = .02).

Conclusions

Long‐term weight loss intervention in overweight and obese adults with type 2 diabetes mellitus is associated with greater CBF .