Future Surgical Leaders: Resident Perception Of Longitudinal Leadership And Non-Technical Skills Curriculum.

OBJECTIVE: A paucity of formal leadership training programs exists for residents, and outcomes of those are limited in reporting. Based on a robust needs assessment, our program created a longitudinal cohort curriculum, Future Surgical Leaders, for residents and fellows of all levels to provide training in nontechnical skills. Our objective was to evaluate surgical resident short-term outcomes and satisfaction with the Future Surgical Leaders (FSL) curriculum. DESIGN: Participants were sent a brief survey after each session of the curriculum from October 2020 to February 2022. The data was compiled after seventeen months of delivery. Likert Scale responses and text comments were analyzed with a 2-sample t-test and 2-way analysis of variance. SETTING: Academic tertiary institution. PARTICIPANTS: General surgery residents. RESULTS: Survey response rate from 54 sessions among all postgraduate year levels was 73%. Overall, 96% of residents/fellows either "agreed" or "strongly agreed" that the topics of the FSL curriculum were important to learn during surgical training. Only 24% of learners knew "a lot" or "a great deal" about the topics prior to the session which rose to 73% afterwards (p < 0.01). Each postgraduate year class showed statistically significant increase in knowledge. About 80% of learners wanted to investigate these topics further. Open comment questions identified themes requesting delivery of specific sessions earlier in residency training and positive overall attitudes toward the FSL curriculum. CONCLUSIONS: FSL is a satisfactory means of teaching leadership skills to surgical residents. Residents recognize the need to develop leadership skills prior to entering practice and want to learn more. The FSL curriculum may be considered for application at other surgical training programs.

Defining Pathologic Upstaging in cT1b Esophageal Cancer: Should We Consider Neoadjuvant Therapy?

INTRODUCTION: Neoadjuvant chemoradiation therapy (NCRT) for cT1b esophageal cancer is not recommended despite the risk of pathologic upstaging with increased depth of penetration. We aimed to (1) define the rate of and factors associated with pathologic upstaging, (2) describe current trends in treatments, and (3) compare overall survival (OS) with and without NCRT for surgically resected cT1b lesions. METHODS: We used the 2020 National Cancer Database to identify patients with cT1b N0 esophageal cancer with or without pathologic upstaging who underwent removal of their tumor. We built multivariable logistic regression models to assess factors associated with pathologic upstaging. Survival was compared using log-rank analysis and modeled using multivariable Cox proportional hazards regressions. RESULTS: Out of 1106 patients with cT1b esophageal cancer, 17.3% (N = 191) had pathologic upstaging. A higher tumor grade (P = 0.002), greater tumor size (P < 0.001), and presence of lympho-vascular invasion (P < 0.001) were associated with pathologic upstaging. 8.0% (N = 114) of patients were treated with NCRT. Five-y OS was 49.4% for patients who received NCRT compared to 67.2% for upfront esophagectomy (P < 0.05). Pathologic upstaging was associated with decreased OS (pathologic upstaging 43.7% versus no pathologic upstaging 67.7%) (hazard ratio 2.12 [95% confidence interval, 1.70-2.65; P < 0.001]). Compared to esophagectomy, endoscopic local tumor excision was associated with a decreased OS (hazard ratio 1.50 [95% confidence interval, 1.19-1.89; P = 0.001]). CONCLUSIONS: Pathologic upstaging of cT1b lesions is associated with decreased OS. Esophagectomy is associated with a survival benefit over endoscopic local tumor excision for these lesions. NCRT is not associated with an increase in OS in cT1b lesions compared to upfront esophagectomy.

Spatial distributions in disaster risk vulnerability for people with disabilities in the U.S.

Background: The spread of Coronavirus Disease 2019 (COVID-19) in the United States has centered the role of natural hazards such as pandemics into the public health sphere. The impacts of these hazards disproportionately affect people with disabilities, who are frequently in situations of social, political, or economic disadvantage. Because of these disadvantages, people with disabilities may have less access to necessary resources and services, putting them at risk due to unmet health needs. These disparities in access also highlight important regional, state, and county-level differences with regards to vulnerability and preparedness for natural hazards. Objective: The objective of this paper is to examine the relationship between disability and disaster risk in the United States. We examine the geographic variation in the relationship between risk from natural disasters and the percentage of people with disabilities living in a community. Because emergency management functions in the U.S. are directed and enacted at the county level, we also explore how these relationships change across U.S. counties. In addition to the overall prevalence of people with disabilities, we disaggregate the population of people with disabilities by gender, race, ethnicity, age, and disability impairment type. Methods: To measure risk of natural hazards, we use Expected Annual Loss index, a component of the 2020 National Risk Index, developed by Federal Emergency Management Agency, which identifies communities most at risk to18 natural hazards. We measure the percent of people with disabilities per county using the American Community Survey. We estimate the nationwide relationship between the proportion of people with disabilities and risk of natural hazards using ordinary least squares regression. To explore geographic differences in these relationships across the United States, we use a geographically weighted regression model to estimate local relationships for each county in the contiguous United States. We use mapping techniques to display regional differences across different disability demographic groups. Results: Counties with higher percentages of people with disabilities have a lower risk of natural disasters. Across the United States, a one percent increase in prevalence of people with disabilities in a county is associated with two percent decrease in the natural hazard risk score. Small but statistically significant regional differences exist as well. County-specific estimates range from a five percent decrease to a one percent increase. Stronger associations between risk and the prevalence of people with disabilities are observed in the Midwest and parts of the Southwest and West, whereas the relationship across racial groups is more scattered across the United States. Conclusion: In this study, nationwide results suggest that people with disabilities are more likely to live in communities with lower risk of natural hazards, but this relationship differs across U.S. counties and by demographic subgroups. These findings represent a contribution in further understanding the health and well-being of people with disabilities in the United States and the geographic variation therein.

Bridging the Gap: How to Get Osteopathic Residents Into Fellowships.

Introduction The fellowship match process is convoluted, with each specialty having its match on its timeline- with some programs having a Post Graduate Year (PGY) 4th-year or 5th-year match. This study aims to identify tangible recommendations for osteopathic surgery residents to use to improve their applications and, ultimately, the success rate for matching into post-graduate fellowship training. Methods In October 2021, as a part of the American College of Osteopathic Surgeons (ACOS) Strategic Planning efforts, the ACOS Resident Student Section sent a questionnaire to the listed email contact for each surgical fellowship program. Fellowship coordinators and program directors were included in the survey. The programs that were included in the study were vascular, thoracic (which included cardiothoracic), surgical critical care, endocrine, hepatobiliary, transplant, pediatric, surgical oncology, breast, minimally invasive, and colorectal surgery. Results Of the 108 programs that answered the survey, 36% of them reported they currently had an osteopathic fellow, and another 29% said they had an osteopathic fellow in the past. 35% of the programs listed that they had never had an osteopathic fellow in their program. In regards to how residents can improve their application for fellowship matches the most common answer was research in the field, they were trying to match into. They wanted to see high scores on the United States Medical Licensing Examination (USMLE) and American Board of Surgery In-Training Examination (ABSITE) exams. They also noted that they wanted candidates from more well know residency programs, where they knew the residents would have gotten good training. Conclusion We recommend that any potential fellowship applicant focus on the following three areas increase competitiveness for matching into fellowship training: publication in the desired field, increased overall scholarly activity, and increased ABSITE scores.

Rare Case of Tracheal Fibromyxoma in Obstructive Tracheal Mass.

A 77-year-old male with a history of chronic obstructive pulmonary disease (COPD) who presented with cough, congestion, and stridor and was found to have a near obstructing tracheal mass. He subsequently underwent excision of the mass. On pathologic examination, it was diagnosed as fibromyxoma of the trachea. Primary tumors of the trachea are rare, and fibromyxoma of the trachea is extremely rare. This is the third report of a fibromyxoma on the tracheal wall. In this report the clinical manifestations, and surgical management were compared with the other two reported cases.

Correction to: Benefit Duration and Return to Work Outcomes in Short Term Disability Insurance Programs: Evidence from Rhode Island's Temporary Disability Insurance Program.

The original version of this article unfortunately contained a mistake in the article title. The text "Rhode Island's" inadvertently omitted in the original publication.

Benefit Duration and Return to Work Outcomes in Short Term Disability Insurance Programs: Evidence from Temporary Disability Insurance Program.

Purpose The Workforce Innovation and Opportunity Act strengthens the vocational rehabilitation program's focus on providing early intervention services to keep workers with disabilities in the workforce. At the same time, some have suggested that short-term disability insurance (STDI) programs may hold promise as an early intervention service, helping people with disabilities stay in the labor force and avoid needing longer-term benefits. Rhode Island is one of five states with a mandatory STDI program. We examine the extent to which Rhode Island STDI claimant characteristics are correlated with partial return-to-work (PRTW) benefit receipt and certain STDI benefit receipt duration measures.Methods Our study used administrative data from 2011 to 2014 to explore Rhode Island's STDI program-called the Temporary Disability Insurance program-and regression analysis to estimate the correlations of interest. Results Regression adjusted estimates revealed that claimants opting to receive PRTW benefits earned more and received benefits for fewer weeks than claimants opting to not receive PRTW benefits. We also observed significant correlations between duration of benefit receipt and claimant characteristics such as diagnosis and treating healthcare provider specialty. Conclusions Findings suggest that STDI claimants with certain characteristics are more likely to receive benefits for a long duration or not receive PRTW benefits, signaling that they might benefit from early Vocational Rehabilitation supports and services that would allow them to remain productive members of the workforce and avoid long term benefit receipt.

Understanding the Disability Dynamics of Youth: Health Condition and Limitation Changes for Youth and Their Influence on Longitudinal Survey Attrition.

Disability status-experiencing a functional limitation caused by a health condition-is dynamic throughout the life cycle, even during adolescence and young adulthood. We use data from the 1997 cohort of the National Longitudinal Survey of Youth to better understand these dynamics, examining how health condition and limitation statuses evolve during adolescence and young adulthood as well as how changes in these characteristics are related to survey nonresponse and attrition. Health condition and limitation dynamics are evident in our data: the proportion of sample members who reported having a limitation in their activities for any interview increased from approximately 12 % during the initial interview (when sample members were 12 to 17 years old) to almost 25 % 13 years later. Multivariate analyses revealed that women are more likely than men to report changes in health condition or limitation status. Those with mild limitations were relatively less likely than those without limitations or with severe limitations to experience changes in limitation status. Somewhat surprisingly, a survival analysis of survey participation outcomes found limited correlation among health conditions, limitations, and either missing a survey interview for the first time or permanently leaving the survey sample.

The role and potential sites of action of thyroid hormone in timing the onset of puberty in male primates.

Puberty in primates is first delayed by a neurobiological switch that arrests pulsatile GnRH release during infancy and then triggered, after a protracted period of juvenile development, by resurgence in intermittent release of this hypothalamic peptide. The purpose of this chapter is to review recent studies conducted in our laboratories to begin to examine the role of thyroid hormone (TH) in governing this postnatal development of pulsatile GnRH release in primates and therefore the timing of puberty in these species. The male rhesus monkey was used as the experimental model and TH activity was manipulated by surgical and chemical thyroidectomy on the one hand, and by thyroxine (T(4)) and triiodothyronine (T(3)) replacement on the other. Our results indicate that the resurgence in pulsatile GnRH release at the termination of the juvenile phase of development is dependent on a permissive action of TH. Whether this action of TH is mediated directly on hypothalamic centers regulating the pulsatile release of GnRH, or indirectly by circulating signals reflecting TH action on somatic development remains to be determined.

Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer.

INTRODUCTION: We have shown previously that treatment with pegylated leptin peptide receptor antagonist 2 (PEG-LPrA2) reduced the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor type 2 (VEGFR2) and growth of 4T1-breast cancer (BC) in syngeneic mice. In this investigation, PEG-LPrA2 was used to evaluate whether the inhibition of leptin signaling has differential impact on the expression of pro-angiogenic and pro-proliferative molecules and growth of human estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) BC xenografts hosted by immunodeficient mice. METHODS: To test the contribution of leptin signaling to BC growth and expression of leptin-targeted molecules, PEG-LPrA2 treatment was applied to severe immunodeficient mice hosting established ER+ (MCF-7 cells; ovariectomized/supplemented with estradiol) and ER- (MDA-MB231 cells) BC xenografts. To further assess leptin and PEG-LPrA2 effects on ER+ and ER- BC, the expression of VEGF and VEGFR2 (protein and mRNA) was investigated in cell cultures. RESULTS: PEG-LPrA2 more effectively reduced the growth of ER+ (>40-fold) than ER- BC (twofold) and expression of pro-angiogenic (VEGF/VEGFR2, leptin/leptin receptor OB-R, and IL-1 receptor type I) and pro-proliferative molecules (proliferating cell nuclear antigen and cyclin D1) in ER+ than in ER- BC. Mouse tumor stroma in ER+ BC expressed high levels of VEGF and leptin that was induced by leptin signaling. Leptin upregulated the transcriptional expression of VEGF/VEGFR2 in MCF-7 and MDA-MB231 cells. CONCLUSIONS: These results suggest that leptin signaling plays an important role in the growth of both ER+ and ER- BC that is associated with the leptin regulation of pro-angiogenic and pro-proliferative molecules. These data provide support for the potential use of leptin-signaling inhibition as a novel treatment for ER+ and ER- BC.

Regulation of circulating leptin and its soluble receptor during pubertal development in the male rhesus monkey (Macaca mulatta).

In humans, circulating leptin levels are low in early childhood and rise until puberty, whereas the reverse occurs for the soluble leptin receptor (sOB-R). In women, leptin remains high and sOB-R remains low, but in men leptin declines after adolescence and sOB-R increases. These observations suggest that leptin may regulate the production of sOB-R, and that the increased testosterone in adolescent boys may be responsible for the gender differences in leptin and sOB-R. To test this hypothesis, leptin was administered continuously to agonadal juvenile male monkeys for 16 days. No change in sOB-R was observed. Intact juvenile male monkeys were given pulsatile doses of gonadotropins for a period of 7 weeks to induce precocious puberty and assess the effect on plasma testosterone, leptin, and sOB-R. By 4 weeks testosterone had reached adult levels. No changes were observed in leptin, but by week 4, sOB-R was higher than pretreatment values and remained higher at week 7. These data suggest that leptin may not play a significant role in regulating the production of sOB-R and that gender differences in sOB-R in humans may be driven by the increased production of testosterone at puberty in males.

Influence of a leptin deficiency on testicular morphology, germ cell apoptosis, and expression levels of apoptosis-related genes in the mouse.

Leptin-deficient (ob/ob) male mice are morbidly obese and exhibit impaired reproductive function. The objective of this study was to assess the effect of a leptin deficiency on testicular morphology, germ cell development, apoptotic activity within germ cells, and expression levels of apoptosis-related genes in the testis. Sixteen week-old ob/ob male mice (n = 8) and controls (n = 8) were killed, and their reproductive organs were weighed. Testes were processed for either histomorphological analysis (hematoxylin and eosin [H&E] staining), germ cell apoptosis assessment (deoxy-UTP-digoxigenin nick end labeling [TUNEL] method), or apoptosis-related gene expression analysis (microarray). Cross sections of the testes of leptin-deficient animals showed reduced seminiferous tubule area, fewer pachytene spermatocytes, and fewer tubules exhibiting elongated spermatids/mature spermatozoa. Condensation of germ cell nuclei and Sertoli cell vacuolization were evident in the testes of some ob/ob animals. Overall there was an elevation of apoptotic activity in the germ cells of ob/ob mice, particularly within the pachytene spermatocytes. With microarray technology, we identified 9 proapoptosis-related genes that were expressed at a significantly higher level in the testes of ob/ob mice than in the testes of the controls. Among these were members of the tumor necrosis factor receptor super family 1A and 5 (TNFR1 and 5) and peptidoglycan recognition proteins (associated with the extrinsic apoptotic pathway), and granzymes A and B, growth arrest and DNA damage inducible 45 gamma, sphingosine phosphate lyase 1, and caspase 9 (associated with the intrinsic apoptotic pathway). The results of the current study show that a leptin deficiency in mice is associated with impaired spermatogenesis, increased germ cell apoptosis, and up-regulated expression of proapoptotic genes within the testes.

Impact of gonadotropin administration on folliculogenesis in prepubertal ob/ob mice.

Female leptin deficient (ob/ob) mice exhibit abnormal ovarian folliculogenesis resulting in an impaired ability to reproduce. This effect may be related to the hypogonadotropic state of these animals, or leptin may directly modulate ovarian follicle development. In the present study we assessed whether exogenous gonadotropin administration would normalize folliculogenesis and induce ovulation in immature ob/ob animals. Eight 26-day-old ob/ob and eight control mice were injected sc with pregnant mare serum gonadotropin followed 48 h later with a sc injection of human chorionic gonadotropin. Animals were killed 24 h later. Gonadotropin (GTH) administration increased both ovarian and uterine weights in control mice, but this effect was attenuated in leptin deficient animals. The number of preantral follicles was greater in ob/ob mice than controls, but in GTH-treated animals the number of antral follicles was subnormal in the ovaries of leptin deficient animals. Ob/ob animals also failed to ovulate in response to GTH, and the protective actions of GTH against granulosa cell apoptosis and follicular atresia were attenuated in these animals. Interestingly, however, serum levels of estradiol and progesterone were higher in ob/ob mice than controls, regardless of whether or not the animals received GTH treatment. We conclude that the ovarian responsiveness to GTH is subnormal in leptin deficient animals suggesting that leptin may modulate the process of folliculogenesis by directly altering the sensitivity of the ovary to GTH.

Relationship between serum concentrations of leptin, soluble leptin receptor, testosterone and IGF-I, and growth during the first year of postnatal life in the male rhesus monkey, Macaca mulatta.

OBJECTIVES: Subnormal leptin levels in low birth weight infants may allow for catch-up growth during infancy. Scant data are available that relate growth with circulating leptin during normal infancy in primates. The current study objective was to examine the association between serum leptin, its soluble receptor (sOB-R), testosterone and IGF-I concentrations, and body weight during infancy in male rhesus monkeys. DESIGN: Hormone levels were assessed longitudinally in animals (n = 7) from birth until 1 year of age. RESULTS: Body weight increased during the first 6 months of life and was strongly correlated with rising IGF-I levels and, as IGF-I plateaued and then declined during the second half of the year, body weight gain decelerated. In contrast, leptin levels declined gradually with age during the first year of life in conjunction with increasing body weight. There was no association between body weight gain and serum leptin levels or between serum testosterone and leptin values. Since sOB-R levels also declined with leptin values, it does not appear that levels of bioavailable leptin changed during infancy. CONCLUSIONS: The data do not support the contention that leptin regulates growth during infancy, but the close association between IGF-I levels and body weight suggested that this hormone may regulate growth in infant male monkeys. The failure to observe an association between serum testosterone and leptin concentrations suggested that leptin is not involved in the activation of the hypothalamic-pituitary -testicular axis during this developmental period.

Folliculogenesis is impaired and granulosa cell apoptosis is increased in leptin-deficient mice.

Leptin purportedly plays an important role in pubertal development in a number of mammalian species. Adult leptin-deficient (ob/ob) female mice are infertile, but the mechanisms responsible for the reproductive failure have not been fully elucidated. The major objective of the current study was to assess the effects of a leptin deficiency on ovarian folliculogenesis and apoptosis. Beginning at 4 wk of age, control (n = 8) and ob/ob (n = 7) mice were weighed and examined daily for vaginal opening. After 3 wk the mice were killed, and the reproductive organs were weighed. Ovaries were paraffin-embedded for hematoxylin and eosin histology, TUNEL assay, and immunohistochemistry for Fas, Fas ligand (FasL), and proliferating cell nuclear antigen (PCNA). Vaginal opening was delayed, uteri were smaller, and the number of primordial follicles and total number of ovarian follicles were subnormal in ob/ob animals. Leptin-deficient animals also had a higher number of atretic follicles than controls. Granulosa cells (predominantly in preantral and early antral follicles) of ob/ob mice exhibited increased apoptotic activity as documented by TUNEL assay and elevated expression of the apoptotic markers Fas and FasL, compared with that in control animals. Ovarian expression of PCNA, a marker of DNA replication, repair, or both, did not differ between ob/ob and control mice. The data suggest that a leptin deficiency in mice is associated with impaired folliculogenesis, which results in increased follicular atresia. This impairment may be one of the causative components of infertility in leptin-deficient animals.

Changes in circulating leptin, leptin receptor, and gonadal hormones from infancy until advanced age in humans.

We determined developmental changes in circulating levels of the soluble leptin receptor (sOB-R), leptin, and gonadal hormones in human subjects. In both sexes the rise in leptin with age was associated with a decline in sOB-R, and age-related changes in both parameters preceded the pubertal rise in gonadal hormones. Leptin levels above 10 ng/ml were a strong predictor of sOB-R concentrations, but this predictive value decreased as leptin declined. In young subjects there were no gender differences in serum leptin, but boys had higher sOB-R levels. In adults neither leptin nor sOB-R changed with age, but serum leptin was higher and sOB-R was lower in women than men. There was a significant negative correlation between sOB-R and leptin in women, but not men. The data suggest that bioavailable leptin in the circulation may be increasing more rapidly during development than indicated by total leptin levels, and that these changes may serve as one of the signals to the central nervous system that metabolic conditions are adequate to support pubertal development. Furthermore, the study provides suggestive evidence that leptin regulates the secretion of its own binding protein, but it also appears that an additional gender-specific, leptin-independent, regulatory mechanism is functional before puberty.

Does leptin mediate the effect of photoperiod on immune function in mice?

Seasonal fluctuations in immune status have been documented for avian and mammalian populations. During the late summer and early fall, immune function is bolstered to help animals cope with the more physiologically demanding winter. The environmental cue for these seasonal changes is apparently decreasing photoperiod. In the present study, we determined the potential role of leptin in mediating the effect of photoperiod on cell-mediated immune responses in male mice. Leptin-deficient (ob/ob) and littermate control mice were housed for 10 wk in either a short (8L:16D) or a long (16L:8D) photoperiod beginning at 6 wk of age. After the mice were killed, immune and reproductive organs were weighed and splenocytes isolated. The proliferative and cytokine responses (interleukin [IL]-2 and IL-4) of splenocytes to the T-cell mitogen, concanavalin A (Con A; 0-40 microg/ml), were determined. Body weights were elevated and both testes and seminal vesicle weights subnormal in ob/ob mice (by ANOVA, main effect of leptin deficiency), but thymuses and spleens were of normal size. Serum leptin levels were at minimum detection limits in ob/ob mice, but leptin levels in control mice housed at 8L:16D were higher than in control mice housed at 16L:8D. The proliferative response of splenocytes from ob/ob mice to Con A was subnormal (by ANOVA, main effect of leptin deficiency), but photoperiod had no effect on this response. Production of IL-2 in splenocytes of ob/ob mice was subnormal (by ANOVA, main effect of leptin deficiency) irrespective of photoperiod, but cells from mice housed at 8L:16D (by ANOVA, main effect of photoperiod) produced more IL-2 than cells from animals housed at 16L:8D. In contrast, a leptin deficiency did not alter IL-4 production, but cells from animals (ob/ob and controls) housed at 16L:8D produced less IL-4 than cells from animals housed at 8L:16D (by ANOVA, main effect of photoperiod). The present study suggests that both photoperiod and leptin have mutually independent effects on the proliferation of lymphocytes and cytokine production profiles. The data do not provide definitive support for the hypothesis that photoperiod-induced changes in leptin secretion mediate the effects of season on immune status.

Leptin and pubertal development.

Sexual development after birth in rodents, nonhuman primates, and humans is driven by the gonadotropin-releasing hormone (GnRH) pulse generator. During the neonatal period in primates, pulsatile GnRH discharge from the medial basal hypothalamus drives an active period of pituitary gonadotropin and gonadal hormone secretion. During the transition from the neonatal to the juvenile period, however, the activity of the GnRH pulse generator is restrained or arrested and gonadotropin and gonadal hormone secretion enters a quiescent period that continues until the onset of puberty. As puberty approaches the GnRH pulse generator is reactivated, resulting in enhanced gonadotropin secretion, accelerated growth, maturation of the gonads, and the achievement of sexual competence. Rodents do not appear to exhibit a developmental phase analogous to the quiescent juvenile period in primates when the GnRH pulse generator is held in check. Instead, progressive maturational changes in the pattern of GnRH pulsatility appear to drive sexual development in rodents. The role that leptin plays in sexual development has not been fully defined, but the balance of current evidence appears to support the idea that, in both rodents and primates, leptin plays a permissive rather than a causal role in timing this process. When body energy reserves rise above a critical level, blood leptin increases to a threshold concentration signaling to the central nervous system that the body can support sexual function. Puberty can apparently occur over a wide range of concentrations above this critical leptin threshold. Leptin does not appear to act as a trigger to time the initiation of puberty but, instead, once leptin reaches this threshold pubertal development may proceed if, and only if, other critical control mechanisms are operational.

Validation of radioimmunoassays for LH and FSH in the sooty mangabey (Cercocebus atys): Characterization of LH and the response to GnRH.

Heterologous radioimmunoassays (RIA) for macaque LH and FSH were validated for the measurement of these hormones in the sooty mangabey and mangabey pituitary LH was characterized relative to rhesus monkey LH. Dilutions of a pituitary mangabey extract and a partially purified preparation of mangabey LH ran parallel to a rhesus monkey standard (LER 1909-2) in the ovine-ovine (o-o) LH assay but showed some deviation from parallelism in the rhesus monkey FSH assay. The LH potency of the mangabey extract and standard were six and 190 times more potent, respectively, than LER 1909-2 in the LH RIA. Mangabey LH was estimated to have a molecular weight of 40,000-42,000 daltons vs 35,000-38,000 daltons for rhesus LH on Sephadex G-100 chromatography. Plasma levels of radioimmunoreactive LH, FSH, and testosterone were assayed before and after a bolus administration of 25, 50, or 100 µg synthetic go-nadotropin releasing hormone (GnRH) to adult male mangabeys. A significant increase in serum levels of LH was seen within 30 min with levels more than fourfold higher than the basal level of LH after administration of 100 µg GnRH. However, no consistent increases in plasma FSH values were detected. The integrated mean LH response above preinjection levels following 25, 50, or 100 µg GnRH was dose related. Serum levels of testosterone were also elevated after administration of GnRH, but peak concentrations of testosterone lagged behind peak levels of LH by approximately 30 min. These studies indicate that the heterologous RIAs may be used for measuring gonadotropins in the mangabey and that the male mangabey is apparently more sensitive to GnRH than the rhesus monkey.