Louis M, Punjabi NM. Effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers. J Appl Physiol 106: 1538 -1544, 2009. First published March 5, 2009 doi:10.1152/japplphysiol.91523.2008.-Accumulating evidence suggests that obstructive sleep apnea is associated with alterations in glucose metabolism. Although the pathophysiology of metabolic dysfunction in obstructive sleep apnea is not well understood, studies of murine models indicate that intermittent hypoxemia has an important contribution. However, corroborating data on the metabolic effects of intermittent hypoxia on glucose metabolism in humans are not available. Thus the primary aim of this study was to characterize the acute effects of intermittent hypoxia on glucose metabolism. Thirteen healthy volunteers were subjected to 5 h of intermittent hypoxia or normoxia during wakefulness in a randomized order on two separate days. The intravenous glucose tolerance test (IVGTT) was used to assess insulin-dependent and insulin-independent measures of glucose disposal. The IVGTT data were analyzed using the minimal model to determine insulin sensitivity (SI) and glucose effectiveness (SG). Drops in oxyhemoglobin saturation were induced during wakefulness at an average rate of 24.3 events/h. Compared with the normoxia condition, intermittent hypoxia was associated with a decrease in SI [4.1 vs. 3.4 (mU/l) Ϫ1 ⅐ min Ϫ1 ; P ϭ 0.0179] and SG (1.9 vs. 1.3 min Ϫ1 ϫ10 Ϫ2 , P ϭ 0.0065). Despite worsening insulin sensitivity with intermittent hypoxia, pancreatic insulin secretion was comparable between the two conditions. Heart rate variability analysis showed the intermittent hypoxia was associated with a shift in sympathovagal balance toward an increase in sympathetic nervous system activity. The average R-R interval on the electrocardiogram was 919.0 ms during the normoxia condition and 874.4 ms during the intermittent hypoxia condition (P Ͻ 0.04). Serum cortisol levels after intermittent hypoxia and normoxia were similar. Hypoxic stress in obstructive sleep apnea may increase the predisposition for metabolic dysfunction by impairing insulin sensitivity, glucose effectiveness, and insulin secretion. sleep apnea; diabetes; insulin resistance; glucose intolerance THE GLOBAL PREVALENCE of Type 2 diabetes mellitus is increasing in epidemic proportions. It is estimated that Type 2 diabetes affects ϳ150 million people worldwide and that its prevalence is likely to almost double by the year 2025 (19). Over the last decade, considerable progress has been made in our understanding of the factors that increase the propensity for Type 2 diabetes. It is now abundantly clear that insulin resistance and pancreatic ␤-cell dysfunction are common by the time hyperglycemia develops (34). Risk factors for Type 2 diabetes include age, race, family history, obesity, and sedentary lifestyle (1). In recent years, there has been increasing recognition that obstructive sleep apnea may also be an independent risk factor for altered glucose metabolism. Indeed, a num...

First developed for coverage of burn wounds, Integra (Integra LifeSciences) is a synthetic acellular dermal regeneration template that provides a base for revascularization and neodermal formation. The use of Integra has slowly grown and has now become an important consideration along the reconstructive ladder. This article reviews the basic science of Integra and provides an overview of the many expanding applications based on anatomic location.

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Since the pioneering use of autologous rib cartilage for the reconstruction of microtia, there have been significant advances in surgical technique that have helped to ameliorate the psychological burden of microtia. To date, the use of rib cartilage for auricular reconstruction is one of the most enduring and ubiquitous techniques for microtia reconstruction as it provides excellent aesthetic results with lasting durability. In this review, the authors outline the most common methods of microtia reconstruction with a comparison of each technique and illustrative case examples.

There is an increased association between women with higher ESS and planned Cesarean delivery. Severe EDS was associated with gestational diabetes in pregnant women in a small sample size. Future studies in larger samples need to confirm the association of severe EDS and gestational diabetes and elucidate potential mechanisms of the links with adverse outcomes.

Objective To determine factors that influence sperm recovery after testosterone-associated infertility. Design Clinical retrospective study. Setting Academic male-infertility urology clinic. Patient(s) Sixty-six men who presented with infertility after testosterone use. Intervention(s) Testosterone (T) cessation and combination high-dose human chorionic gonadotropin (hCG) and selective estrogen modulator (SERM) therapy. Main Outcome Measure(s) Whether patients successfully achieved or failed to achieve a total motile count (TMC) of greater than 5 million sperm within 12 months of T cessation and initiation of therapy. Result(s) A TMC of greater than 5 million sperm was achieved by 46 men (70%). Both increased age and duration of testosterone use directly correlated with time to sperm recovery at both 6 and 12 months of hCG/SERM therapy. Age more consistently limited sperm recovery, while duration of testosterone use had less influence at 12 months than at 6 months. Only 64.8% of azoospermic men achieved a TMC greater than 5 million sperm at 12 months, compared with 91.7% of cryptozoospermic men, yet this did not predict a failure of sperm recovery. Conclusion(s) Increasing age and duration of testosterone use significantly reduce the likelihood of recovery of sperm in the ejaculate, based on a criterion of a TMC of 5 million sperm, at 6 and 12 months. Physicians should be cautious in pursuing long-term testosterone therapy, particularly in men who still desire fertility. Using these findings, physicians can counsel men regarding the likelihood of recovery of sperm at 6 and 12 months.

The global medical and psychological burden of cleft lip and palate is large, especially in low- and middle-income countries. For decades, medical missions have sought to alleviate this burden; however, there are significant barriers to providing sustainable, high-quality cleft care using the mission model. Smile Train, an international children's charity founded in 1999, has developed a scalable model which provides support to local partner hospitals and surgeons around the world. Smile Train partners with hospitals to support cleft care treatment across the developing world. Partner hospitals are held to strict safety and quality standards. Local or regional providers are primarily used to train medical personnel. A quality assurance process developed by the Smile Train's Medical Advisory Board is used to assess cleft surgery cases and suggest additional review and training as needed. Surgical candidates are systematically evaluated and must meet specific medical criteria to ensure safety. Experienced anesthetists adhere to Smile Train's safety and quality protocols including anesthesia guidelines. Smile Train and its partners have provided more than 1.2 million safe, high-quality cleft surgical treatments since 1999. Smile Train has sponsored more than 3,000 hands-on training opportunities, 30,000 opportunities to participate in cleft conferences, and 40,000 virtual cleft training opportunities. Through rigorous self-governance and its sustainable, scalable model, this organization has elevated the standard of cleft care in the developing world.

Summary: Wound healing problems are a major cause of morbidity for gender-affirming surgery (GAS) patients. Prior studies have shown sex differences in wound healing may exist. We hypothesized exogenous testosterone supplementation may impair post-GAS wound healing and developed a model to investigate this phenomenon. Mice were randomized by hormone regimen and gonadectomy (OVX). Gonadectomy or sham occurred on day 0 and mice were assigned to no testosterone (-T), mono- or bi-weekly (T/2T) testosterone groups. Dorsal splinted wounding occurred on day 14 and harvest on day 21. Serum testosterone levels were quantified with mass spectrometry. Tissue underwent analysis with planimetry, qPCR, ELISA, and immunofluorescence. Mean testosterone trough levels for bi-weekly regimen were higher compared to mono-weekly (397 versus 272 ng/dL; P = 0.027). At POD5, 2T injections led to 24.9% and 24.7% increases in mean wound size relative to SHAM and OVX/-T, respectively (P = 0.004; 0.001). Wounds in OVX/+2T mice demonstrated increased gene expression for inflammatory cytokines and macrophage marker F4/80 (P < 0.05). ELISA confirmed elevated wound TNFα levels (P < 0.05). Quantitative multiplex immunofluorescence with F4/80/NOS2/ARG1 showed significant increases in macrophage prevalence in OVX/+2T (P < 0.05). We developed a novel model of GAS hormonal milieu to study effects of exogenous testosterone on wound healing. Optimized twice-weekly dosing yielded serum levels comparable to clinical therapy. We showed exogenous testosterone administered to XX/OVX mice significantly impairs wound healing. A hyperinflammatory wound environment results in increased macrophage proliferation and elevated cytokines. Future efforts are directed toward mechanistic investigation and clinical validation.