Neuropeptide Y enhances the release of luteinizing hormone (LH) induced by LH-releasing hormone

Depending upon the steroid hormonal milieu, centrally administered neuropeptide Y (NPY) exerts differential effects on the release of LH. Ovarian hormones also effect the concentrations of NPY in hypothalamic nuclei, and some of the changes are similar to those caused by LHRH. The present studies tested whether NPY acts directly on the pituitary gland, either alone or in combination with LHRH, to modify LH secretion. Hemipituitary fragments obtained from ovariectomized rats were incubated in medium 199, and the in vitro effects on LH release of LHRH, NPY, or the two peptides together were assessed. As expected, LHRH (10(-9)-10(-7) M) produced a dose-dependent release of LH, whereas NPY alone had a lesser stimulatory effect at concentrations of 10(-7) or 10(-6) M. On the other hand, 10(-6) M NPY significantly enhanced LH release in response to 10(-9) M LHRH. A potentiation by NPY of the LHRH-induced LH response was observed in an anterior pituitary cell culture system. Cells from the pituitaries of ovariectomized rats were dispersed and cultured for 3 days in medium 199 with BSA, gentamicin, horse serum, and fetal calf serum. During a 3-h incubation, NPY alone (10(-9)-10(-7) M) failed to affect LH release, but significantly potentiated the release induced by 10(-9) or 10(-8) M LHRH. These findings are in accord with the hypothesis that hypothalamic NPY neurons may participate in the regulation of LH secretion in the rat and indicate that one of the mechanisms of its action may be to increase the pituitary LH response to LHRH.     

Two-year trends in physical performance following supervised exercise among community-dwelling older veterans

The extent to which exercise can delay the normal decline in physical performance associated with aging is unknown. We examined the impact of 2 years of supervised exercise on cardiovascular fitness, flexibility, and strength in a group of elderly (age 65-74) veterans. Seventy-five patients exercised 3 days/week for 90-minute sessions emphasizing aerobic, flexibility, and strength development. Thirty-six (47%) completed 2 years of a voluntary supervised exercise program (n = 16-25 with complete data). Over a 2-year follow-up period, cardiovascular outcome variables improved significantly: metabolic equivalents increased 20% (7.4 +/- 2.2 to 9.0 +/- 2.4, P less than 0.001) and submaximal heart rate decreased 7% (131.4 +/- 14.8 to 121.0 +/- 18.5 beats/minute, P = 0.06). Resting heart rate decreased 8% (68.5 +/- 8.0 to 63.6 +/- 8.4 beats/minute, P = 0.02) but this difference did not reach statistical significance. Flexibility, measured by hamstring length, improved 11% (57.5 +/- 15.1 to 64.0 +/- 11.1 degrees, P = 0.02). Strength variables did not improve. The study indicates that improvements in cardiovascular function and flexibility achieved by the elderly in the early stages of an exercise program can be maintained for at least 2 years.     

X-linked adrenal hypoplasia congenita: a mutation in DAX1 expands the phenotypic spectrum in males and females

X-linked adrenal hypoplasia congenita (AHC) is a disorder associated with primary adrenal insufficiency and hypogonadotropic hypogonadism (HH). The gene responsible for X-linked AHC, DAX1, encodes a member of the nuclear hormone receptor superfamily. We studied an extended kindred with AHC and HH in which two males (the proband and his nephew) were affected with a nucleotide deletion (501delA). The proband's mother, sister, and niece were heterozygous for this frameshift mutation. At age 27 yr, after 7 yr of low dose hCG therapy, the proband underwent a testicular biopsy revealing rare spermatogonia and Leydig cell hyperplasia. Despite steadily progressive doses of hCG and Pergonal administered over a 3-yr period, the proband remained azoospermic. The proband's mother, sister (obligate carrier), and niece all had a history of delayed puberty, with menarche occurring at ages 17-18 yr. Baseline patterns of pulsatile gonadotropin secretion and gonadotropin responsiveness to exogenous pulsatile GnRH were examined in the affected males. LH, FSH, and free alpha-subunit were determined during 12.5-24 h of frequent blood sampling (every 10 min). Both patients then received pulsatile GnRH (25 ng/kg) sc every 2 h for 6-7 days. Gonadotropin responses to a single GnRH pulse iv were monitored daily to assess the pituitary responsiveness to exogenous GnRH. In the proband, FSH and LH levels demonstrated a subtle, but significant, response to GnRH over the week of pulsatile GnRH therapy. Free alpha-subunit levels demonstrated an erratic pattern of secretion at baseline and no significant response to pulsatile GnRH. We conclude that 1) affected males with AHC/HH may have an intrinsic defect in spermatogenesis that is not responsive to gonadotropin therapy; 2) female carriers of DAX1 mutations may express the phenotype of delayed puberty; and 3) although affected individuals display minimal responses to pulsatile GnRH, as observed in other AHC kindreds, subtle differences in gonadotropin patterns may nevertheless exist between affected individuals within a kindred.     

Research Priorities for Economic Analyses of Prevention: Current Issues and Future Directions

In response to growing interest in economic analyses of prevention efforts, a diverse group of prevention researchers, economists, and policy analysts convened a scientific panel, on “Research Priorities in Economic Analysis of Prevention” at the 19th annual conference of the Society for Prevention Research. The panel articulated four priorities that, if followed in future research, would make economic analyses of prevention efforts easier to compare and more relevant to policymakers and community stakeholders. These priorities are: (1) increased standardization of evaluation methods, (2) improved economic valuation of common prevention outcomes, (3) expanded efforts to maximize evaluation generalizability and impact as well as (4) enhanced transparency and communicability of economic evaluations. In this paper, we define three types of economic analyses in prevention, provide context and rationale for these four priorities as well as related sub-priorities, and discuss the challenges inherent in meeting them.     

Nonpharmacologic Treatments for Depression Related to Reproductive Events

With the rapid and ubiquitous acceptance of new technologies, algorithms will be used to estimate new measures of mental state and behavior based on digital data. The algorithms will analyze data collected from sensors in smartphones and wearable technology, and data collected from Internet and smartphone usage and activities. In the future, new medical measures that assist with the screening, diagnosis, and monitoring of psychiatric disorders will be available despite unresolved reliability, usability, and privacy issues. At the same time, similar non-medical commercial measures of mental state are being developed primarily for targeted advertising. There are societal and ethical implications related to the use of these measures of mental state and behavior for both medical and non-medical purposes.     

Nordic OCD & Related Disorders Consortium: Rationale,design, and methods

Obsessive‐compulsive disorder (OCD) is a debilitating psychiatric disorder, yet its etiology is unknown and treatment outcomes could be improved if biological targets could be identified. Unfortunately, genetic findings for OCD are lagging behind other psychiatric disorders. Thus, there is a pressing need to understand the causal mechanisms implicated in OCD in order to improve clinical outcomes and to reduce morbidity and societal costs. Specifically, there is a need for a large‐scale, etiologically informative genetic study integrating genetic and environmental factors that presumably interact to cause the condition. The Nordic countries provide fertile ground for such a study, given their detailed population registers, national healthcare systems and active specialist clinics for OCD. We thus formed the Nordic OCD and Related Disorders Consortium (NORDiC, www.crowleylab.org/nordic ), and with the support of NIMH and the Swedish Research Council, have begun to collect a large, richly phenotyped and genotyped sample of OCD cases. Our specific aims are geared toward answering a number of key questions regarding the biology, etiology, and treatment of OCD. This article describes and discusses the rationale, design, and methodology of NORDiC, including details on clinical measures and planned genomic analyses.     

Social Vulnerability Factors and Reported Post-Disaster Needs in the Aftermath of Hurricane Florence

This research examines the relationship between social vulnerability factors and reported needs following Hurricane Florence.Weighted least squares regression m...