Search

Infants with genital development considered atypical for assigned female sex may undergo feminizing genitoplasty (clitoroplasty and/or vaginoplasty) in early life. We sought to identify factors associated with parent/caregiver decisions regarding genitoplasty for their children with genital virilization.Longitudinal, observational study SETTING: Twelve pediatric centers in the United States with multidisciplinary differences/disorders of sex development clinics, 2015-2020 PARTICIPANTS: Children under 2 years old with genital appearance atypical for female sex of rearing and their parents/caregivers INTERVENTIONS/OUTCOME MEASURES: Data on the child's diagnosis and anatomic characteristics before surgery were extracted from the medical record. Parents/caregivers completed questionnaires on psychosocial distress, experience of uncertainty, cosmetic appearance of their child's genitalia, and demographic characteristics. Urologists rated cosmetic appearance. For 58 patients from the study cohort with genital virilization being raised as girls or gender-neutral, we compared these data across 3 groups based on the child's subsequent surgical intervention: (i) no surgery (n = 5), (ii) vaginoplasty without clitoroplasty (V-only) (n = 15), and (iii) vaginoplasty and clitoroplasty (V+C) (n = 38).Fathers' and urologists' ratings of genital appearance were more favorable in the no-surgery group than in the V-only and V+C groups. Clitorophallic length was greater in the V+C group compared with the V-only group, with substantial overlap between groups. Mothers' depressive and anxious symptoms were lower in the no-surgery group compared with the V-only and V+C groups.Surgical decisions were associated with fathers' and urologists' ratings of genital appearance, the child's anatomic characteristics, and mothers' depressive and anxious symptoms. Further research on surgical decision-making is needed to inform counseling practices.

Large-scale microalgae cultivation for biodiesel production is expected to be performed utilizing open air growth infrastructure that will inherently introduce ash into the system. High ash biomass represents a significant challenge for the production of biofuel as it increases processing capital and operational costs. This study assesses the economic viability of pretreatment to remove ash from biomass grown with an algal turf scrubber (ATS). An engineering process model of biofuel production was developed based on an ATS growth system followed by an ash removal process and conversion of the biomass to fuels through hydrothermal liquefaction. The model was validated with literature data for the growth and conversion processes and with experimental data for 14 de-ashing processes using water washing or alkaline extraction. The engineering process model was integrated with techno-economic modeling to investigate the impact of ash on biomass and fuel selling prices. Capital costs associated with biofuel conversion doubled as ash content increased from 0% to 70%, increasing fuel selling price by 21%. Integrating ash removal resulted in reduced conversion capital costs (14–42%) based on the reduction of total mass processed. However, only water washes scenarios at 25 °C and 50 °C were found to reduce overall fuel selling price, with alkaline extraction scenarios showing a significant increase. Operational expenses associated with alkaline extraction de-ashing including wastewater treatment, chemical costs, and heating the microalgae slurry were found to significantly increase the overall fuel selling price of the microalgae biofuel by 17–92% depending on the operational scenario.

Efforts to develop algae as a sustainable feedstock for the bioenergy economy have largely focused on cultivating microalgae for optimized lipid production. Because of this, filamentous algae are often overlooked in the algae biomass field because of their relatively low lipid content, although they do contain high levels convertible carbohydrates and proteins. Systems designed to produce filamentous biomass, such as algal turf scrubbers (ATS), have advantages over planktonic algae produced in raceway systems. Unlike raceway algae production, ATS systems do not require inoculum, nutrients, or CO2 inputs as these are readily obtained from the atmosphere or the natural waters feeding them. ATS systems are exceptional at removing nutrients from affected waterways. However, as a consequence of the growth environment (sand, silt and other suspended solids), and the composition of ATS biomass (diatoms), the periphytic biomass obtained from ATS can have very high ash, which represents non-convertible material that can complicate downstream conversion processes. We explored both physical and chemical approaches to remove ash with the goal of improving overall preprocessing costs and conversion yields while minimizing the loss of organic material. The simplest method for removing ash involved repeatedly rinsing the biomass with water at 25 °C, which removed 34.5 ± 3.4 wt% of the ash with no appreciable loss in biomass. When treated with 2.0 wt% NaOH at 80 °C, up to 87.8 ± 1.4 wt% of ash was removed. These severe conditions, however, also resulted in organic material losses of 29.9 ± 3.2 wt%. Ultimately, these results will inform future tests, both chemical and mechanical, and will provide input for models that identify energy bottlenecks and potential savings.

Balkan endemic nephropathy (BEN) is an irreversible, lethal kidney disease that occurs in regions of the Balkans where residents drink untreated well water. A key factor contributing to the development of BEN may be consumption of dissolved organic matter leached from low-rank coal called lignite. This hypothesis—known as lignite-water hypothesis—was first posed for areas of the Balkans. It is possible that a BEN-like condition exists in the United States (US) Gulf Coast region in parts of the Mississippi Embayment and the Texas Coastal Uplands aquifers —Arkansas, Louisiana, and Texas, for instance—that rely heavily on groundwater from aquifers that contain lignite. This study utilizes a geographic information system (GIS) to map the distributions of end-stage renal disease (ESRD) in relation to water from lignite-containing aquifers in the tri-state region. Regional patterns emerged from geospatial analysis, suggesting that counties that relied on lignite-containing aquifers for their main water source had higher rates of ESRD in comparison to other populations in the region that rely on other water sources, including surface water and groundwater from aquifers not associated with lignite seams. Statewide rates of ESRD and diabetes associated ESRD (ESRD-DM) showed strong correlations to the percent of families at or below poverty level and the percentage of African Americans. These confounding factors somewhat mitigate the association seen between ESRD and lignite-containing regions at the state level. However, at the larger tri-state view, there is a significant (p = 0.002) increase in incidence rates where groundwater is connected to lignite-containing aquifers when considering both race and poverty. Additionally, no relationship was observed between the rate of public water supply withdrawal from lignite-bearing aquifers and rates of ESRD or ESRD-DM at the state or tri-state regions, supporting the observation that the risk associated with water from lignite-containing aquifers is limited to water from untreated domestic supply.

To assess the outcomes of "watering can" ureterocele puncture (WCP), a technique previously associated with decreased incidence of de novo vesicoureteral reflux (VUR), as a durable option for management of ureteroceles and to determine the need for subsequent surgery for VUR following watering can puncture.We retrospectively reviewed records of 55 consecutive endoscopic ureterocele procedures performed at our institution from 1999 to 2015. The WCP was performed using a holmium laser fiber to make 10-20 puncture holes through the ureterocele. Follow-up data were collected on infection, de novo VUR in the affected renal moiety and the need for further treatment and surgery.Of 55 patients who underwent endoscopic ureterocele management, 34 underwent WCP and 21 patients underwent either incision or puncture. Median follow-up was 3.4 and 2.8 years in the incision and puncture groups, respectively. Both groups had similar rates of ureterocele decompression (88% vs 90%; P .05) and improvement in hydronephrosis (82% vs 81%; P .05). The WCP group had a significantly decreased rate of de novo VUR (32% vs 67%; P .05) and of subsequent surgery due to de novo VUR (38% vs 71%; P .05). The average grade of de novo VUR was lower in the WCP group (1.4 vs 2.8; P .05).Our study shows that the endoscopic WCP successfully decompresses the obstructing ureterocele and results in a decreased incidence of de novo VUR and ultimately in fewer invasive procedures for the patient. This update demonstrates the durable outcomes of this novel technique.

Lignocellulosic biomass is a sustainable energy source that can help meet the demand for biofuels in the United States. However, the quality and availability of such feedstocks greatly affect their suitability for downstream conversion. This work reports the effects of dilute-acid leaching at various aqueous loadings, temperatures and catalyst loadings (sulfuric acid) on the quality of a traditional biochemical feedstock, corn stover, as a potential feedstock for thermochemical conversions. At 95 wt% aqueous, dilute-acid leaching was observed to effectively remove 97.3% of the alkali metals and alkaline earth metals that can negatively affect degradation pathways during pyrolysis and result in greater yield of non-condensable gases. In addition, up to 98.4% of the chlorine and 88.8% of the phosphorus, which can cause equipment corrosion and foul upgrading catalysts, respectively, were removed. At 25 °C in the absence of the acid catalyst, only 6.8% of the alkali metals and alkaline earth metals were removed; however, 88.0% of chloride was still removed. The ratio of alkaline/acidic ash species has been suggested to proportionately relate to slagging in combustion applications. The initial alkali/acid ratio of the ash species present in the untreated corn stover was 0.38 (significant slagging risk). At 95 wt% aqueous, this ratio was decreased to 0.18 (moderate slagging risk). At 0 wt% catalyst and 90 °C, the ratio was decreased to 0.07, 0.08 and 0.06 at 0.5 wt% catalyst at 25 °C, 50 °C and 90 °C, respectively (low slagging risk). Increasing the catalyst loading to 1.0% slightly decreased the measured alkali/acid ratio of remaining ash. The results presented here show that a water wash or a dilute-acid preprocessing step can improve corn stover quality for pyrolysis, hydrothermal liquefaction and combustion.

The production of biofuels from lignocellulosic feedstock is attracting considerable attention in the United States and globally as a strategy to diversify energy resources, spur regional economic development and reduce greenhouse gas emissions. Because of the wide variation in feedstock types, compositions and content of convertible organics, there is a growing need to better understand correlations among feedstock quality attributes and conversion performance. Knowledge of the feedstock impact on conversion is essential to supply quality controlled, uniform and on-spec feedstocks to biorefineries. This review paper informs the development of meaningful feedstock quality specifications for different conversion processes. Discussions are focused on how compositional properties of feedstocks affect various unit operations in biochemical conversion processes, fast pyrolysis and hydrothermal liquefaction. In addition, future perspectives are discussed that focus on the challenges and prospects of addressing compositionally intrinsic inhibitors through feedstock preprocessing at regionally distributed depots. Such preprocessing depots may allow for the commoditization of lignocellulosic feedstock and realization of stable, cost-effective and quality controlled biomass supply systems.

Biomass such as agricultural residues, energy crops and yard waste has significant potential to be used as renewable feedstocks for production of fuels, chemicals and energy. However, in a given location, biomass availability, cost and quality can vary markedly. Strategies to manage these traits must be identified and implemented so that consistent low-cost and high-quality feedstocks can be delivered to biorefineries year round. In this study, we examine air classification as a method to mitigate high ash concentrations in corn stover, switchgrass, and grass clippings. Formulation techniques were then used to produce blends that met ash quality and biomass quantity specifications at the lowest possible cost for biopower and biochemical conversion applications. It was found that air classification can separate the biomass into light fractions which contain concentrated amounts of elemental ash components introduced through soil contamination such as sodium, alumina, silica, iron and titania; and heavy fractions that are depleted in these components and have relatively lower total ash content. Light fractions of corn stover and grass clippings were found to be suitable for combustion applications since they had less propensity to slag than the whole biomass material. The remaining heavy fractions of corn stover or grass clippings could then be blended with switchgrass to produce blends that met the 5% total ash specifications suggested for biochemical conversions. However, ternary blends of the three feedstocks were not possible due to the high ash content of grass clippings. It was determined that air classification by itself was not suitable to prepare these feedstocks for pyrolysis due to high ash content.

Objective To assess the effect of contrast height during the voiding cystourethrogram (VCUG). The VCUG is the gold standard diagnostic test for vesicoureteral reflux (VUR). Variation in parameters may affect detection and grade of reflux. Materials and Methods In a multicenter, prospective, nonrandomized, observational study, patients undergoing VCUG were selected. VCUG was performed per study protocol except for a change in contrast height. The initial fill was performed at 50 cm and the second at 100 cm. Data collected included presence and grade of VUR and volume filled. The actual bladder volume filled was normalized to the estimated bladder capacity (EBC) as a percentage. A Cohen's kappa coefficient of agreement was used to test for difference in the incidence of reflux and grade between contrast heights. A Wilcoxon signed-rank test was used for differences in the percent EBC filled between heights. Results From May 2012 to November 2013, 184 patients were enrolled. Seventy-one patients (39%) exhibited VUR at 50 cm and 80 patients (43%) at 100 cm. The kappa coefficient of agreement between 50 cm and 100 cm showed substantial agreement, with no significant difference in VUR grade. The percent of EBC filled at each height was significantly different: %EBC filled at 50 cm: 101 ± 46 (range 9.2-228.3), and %EBC filled at 100 cm: 130 ± 56 (range 37.8-280.6) ( P Conclusion No significant difference was noted in the detection of VUR with different contrast heights. A significantly larger bladder volume was instilled at 100 cm.

Inorganic content in biomass decreases the efficiency of conversion processes, especially thermochemical conversions. The combined concentrations of specific ash forming elements are the primary attributes that cause pine residues to be considered a degraded energy conversion feedstock, as compared to clean pine. Air classification is a potentially effective and economical tool to isolate high inorganic content biomass fractions away from primary feedstock sources to reduce their ash content. In this work, loblolly pine forest residues were air classified into 10 fractions whose ash content and composition were measured. Ash concentrations were highest in the lightest fractions (5.8–8.5 wt%), and in a heavy fraction of the fines (8.9–15.1 wt%). The removal of fractions with high inorganic content resulted in a substantial reduction in the ash content of the remaining biomass in forest thinnings (1.69–1.07 wt%) and logging residues (1.09–0.68 wt%). These high inorganic content fractions from both forest residue types represented less than 7.0 wt% of the total biomass, yet they contained greater than 40% of the ash content by mass. Elemental analysis of the air classified fractions revealed the lightest fractions were comprised of high concentrations of soil elements (silicon, aluminum, iron, sodium, and titanium). However, the elements of biological origin including calcium, potassium, magnesium, sulfur, manganese, and phosphorous were evenly distributed throughout all air classified fractions, making them more difficult to isolate into fractions with high mineral concentrations. Under the conditions reported in this study, an economic analysis revealed air classification could be used for ash removal for as little as $2.23 per ton of product biomass. This study suggests air classification is a potentially attractive technology for the removal of introduced soil minerals from pine forest residues.

Background: Dietary cocoa is an important source of flavonoids and is associated with favorable cardiovascular disease effects, such as improvements in vascular function and lipid profiles, in nondiabetic adults. Type 2 diabetes (T2D) is associated with adverse effects on postprandial serum glucose, lipids, inflammation, and vascular function. Objective: We examined the hypothesis that cocoa reduces metabolic stress in obese T2D adults after a high-fat fast-food–style meal. Methods: Adults with T2D [n = 18; age (mean ± SE): 56 ± 3 y; BMI (in kg/m2): 35.3 ± 2.0; 14 women; 4 men] were randomly assigned to receive cocoa beverage (960 mg total polyphenols; 480 mg flavanols) or flavanol-free placebo (110 mg total polyphenols

OBJECTIVE: Obesity and type 2 diabetes mellitus (T2DM) are associated with oxidative stress. Oxidative damage of high-density lipoprotein (oxHDL) leads to a dysfunctional molecule, potentially a mediator and/or marker of cardiometabolic disease. We tested the hypothesis that circulating concentration of oxHDL is higher in obese (Ob) or T2DM adolescents compared to normal-weight (NW) peers. METHODS: In 37 NW, 38 Ob, and 42 T2DM adolescents, ages 11–18 y, fasting concentrations of HDL and LDL cholesterol, oxHDL, oxidized low-density lipoprotein (oxLDL), and myeloperoxidase (MPO) were measured. RESULTS: Compared to the NW group, oxHDL in the Ob group was not different, but was 65% higher (p < 0.01) in the T2DM group. Within the T2DM group oxHDL was higher in boys than in girls but this sex difference was not evident in NW or Ob groups. OxLDL was 23% higher in Ob (p =0.02), and 56% higher in T2DM (p < 0.01) versus NW and did not differ between boys and girls. MPO was not different between NW and Ob but was 88% (p < 0.02) higher in T2DM compared to NW. Contrary to our hypothesis MPO and insulin resistance (HOMA-IR) were not correlated with oxHDL. OxHDL was positively associated with oxLDL and lean body mass while oxLDL was positively associated with apolipoprotein B, triglycerides, HOMA-IR and trunk fat. CONCLUSIONS: The higher concentrations of oxHDL and oxLDL, along with higher MPO in children with T2DM reflect higher oxidative stress compared with obesity alone and potentially increased cardiovascular disease risk in youth with T2DM.

Both otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs) are sexually dimorphic, and both are believed to be influenced by prenatal androgen exposure. OAEs and AEPs were collected from people affected by 1 of 3 categories of disorders of sex development (DSD) – (1) women with complete androgen insensitivity syndrome (CAIS); (2) women with congenital adrenal hyperplasia (CAH); and (3) individuals with 46, XY DSD including prenatal androgen exposure who developed a male gender despite initial rearing as females (men with DSD). Gender identity (GI) and role (GR) were measured both retrospectively and at the time of study participation, using standardized questionnaires. The main objective of this study was to determine if patterns of OAEs and AEPs correlate with gender in people affected by DSD and in controls. A second objective was to assess if OAE and AEP patterns differed according to degrees of prenatal androgen exposure across groups. Control males, men with DSD, and women with CAH produced fewer spontaneous OAEs (SOAEs) – the male-typical pattern – than control females and women with CAIS. Additionally, the number of SOAEs produced correlated with gender development across all groups tested. Although some sex differences in AEPs were observed between control males and females, AEP measures did not correlate with gender development, nor did they vary according to degrees of prenatal androgen exposure, among people with DSD. Thus, OAEs, but not AEPs, may prove useful as bioassays for assessing early brain exposure to androgens and predicting gender development in people with DSD.

Wound healing, angiogenesis, and hair follicle maintenance are often impaired in the skin of diabetic patients, but the pathogenesis has not been well understood. Here, we report that circulation levels of kallistatin, a member of the serine proteinase inhibitor (SERPIN) superfamily with antiangiogenic activities, were elevated in type 2 diabetic patients with diabetic vascular complications. To test the hypothesis that elevated kallistatin levels could contribute to a wound-healing deficiency via the inhibition of Wnt/β-catenin signaling, we generated kallistatin-transgenic (KS-TG) mice. KS-TG mice had reduced cutaneous hair-follicle density, microvascular density, and panniculus adiposus layer thickness, as well as altered skin microvascular hemodynamics and delayed cutaneous wound healing. Using Wnt reporter mice, our results showed that Wnt/β-catenin signaling is suppressed in the dermal endothelium and hair follicles in KS-TG mice. Lithium, a known activator of β-catenin via inhibition of glycogen synthase kinase-3β, reversed the inhibition of Wnt/β-catenin signaling by kallistatin and rescued the wound-healing deficiency in KS-TG mice. These observations suggest that elevated circulating antiangiogenic serpins in diabetic patients may contribute to impaired wound healing through inhibition of Wnt/β-catenin signaling. Activation of Wnt/β-catenin signaling, at a level downstream of Wnt receptors, may ameliorate the wound-healing deficiency in diabetic patients.

Summary. Background: Superficial thrombophlebitis can produce pain and result in a deep vein thrombosis (DVT) if not treated. Conservative therapies including prescription of non-steroidal anti-inflammatory drugs (NSAID) and heat have been standard care. Recently, studies have been published reporting efficacy and safety of low-molecular-weight heparin for the treatment of superficial thrombophlebitis. However, there are few comparative trials to conservative therapy. We studied the effectiveness and safety of treatment with dalteparin compared with ibuprofen in patients with confirmed superficial thrombophlebitis. Methods: Consecutive patients were randomized to receive daily dalteparin vs. ibuprofen three times daily for up to 14 days. The primary outcome measure was the incidence of extension of thrombus or new symptomatic venous thromboembolism during the 14-day and 3-month follow-up period. The secondary outcome was a reduction in pain. The outcome measure of safety was the incidence of major and minor bleeding. Results: Of 302 consecutive patients screened, 72 were enrolled. Four patients receiving ibuprofen compared with no patients receiving dalteparin had thrombus extension at 14 days (P = 0.05), however, there was no difference in thrombus extension at 3 months. Both treatments significantly reduced pain. There were no episodes of major or minor bleeding during the treatment period. Conclusions: Dalteparin is superior to the NSAID ibuprofen in preventing extension of superficial thrombophlebitis during the 14-day treatment period with similar relief of pain and no increase in bleeding. However, questions concerning the optimal treatment duration should be explored in future trials.

Aims of this study This descriptive ethnobiological research is the first documentation of the materials utilized in the pharmacopeia of a novel group of herbalists, Rasta bush doctors, found in the botanically diverse Western Cape of South Africa. This article suggests that medicinal plants used by bush doctors unite the disparate ethnomedicines found in South Africa. Materials and methods Ethnospecies name and parts used were recorded during detailed inventories of 39 bush doctors. Collection of voucher specimens for botanical identification occurred in 15 locations. Herbal remedies were classified into use categories and were compared to historical ethnobotanical literature to ascertain previous cultural affiliations. Results There were 205 ethnospecies found in the Rastafari ethnobiology, 181 were used medicinally. Ethnospecies belong to 71 plant families and 71% belonged to six plant families: Rutaceae (13), Asteraceae (13), Apiaceae (9), Lamiaceae (8), Fabaceae (8), and Euphorbiaceae (7). The majority of remedies (49%) were foliage. Medicinal plants treated over 30 ailments including: gastrointestinal symptoms (11%), urogential complaints (11%), skin ailments (9%), and cardiovascular diseases (8%). Bush doctors appropriated remedies traditionally important to Zulu, KhoiSan, European and Xhosa healing traditions. Novel plants and plant utilization were noted for 22 plant species. Conclusions Use of previously undocumented plant materials as medicinals denote distinct local knowledge including novel Rastafarian utilization of herbs for spiritual and ritual purposes. The range of the largely herbaceous pharmacopeia is narrow compared to the region's highly biodiverse materials and historical records of medicinal use. Bush doctors’ experimentation with known herbal remedies illustrates a striking level of cross-cultural adaptation. This syncretic pharmacopeia reflects the cultural diversity of Southern Africa, drawing upon recent invasive species, European influence and traditional herbs used by the KhoiSan, Zulu and Xhosa peoples.

Objective Green tea ( Camellia sinensis ) has shown to exert cardioprotective benefits in observational studies. The objective of this clinical trial was to assess the effects of green tea on features of metabolic syndrome and inflammation in obese subjects. Methods We conducted a randomized controlled trial in obese subjects with metabolic syndrome. Thirty-five subjects [(mean ± SE) age 42.5 ± 1.7 y, body mass index 36.1 ± 1.3 kg/m 2 ] completed the 8-wk study and were randomly assigned to receive green tea (4 cups/d), green tea extract (2 capsules and 4 cups water/d), or no treatment (4 cups water/d). Both the beverage and extract groups had similar dosing of epigallocatechin-3-gallate, the active green tea polyphenol. Fasting blood samples were collected at screening, 4 and 8 wk of the study. Results Green tea beverage or extract supplementation did not significantly alter features of metabolic syndrome or biomarkers of inflammation including adiponectin, C-reactive protein, interleukin-6, interleukin-1β, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, leptin, or leptin:adiponectin ratio. However, both green tea beverage and extracts significantly reduced plasma serum amyloid alpha versus no treatment ( P Conclusion This study suggests that the daily consumption of green tea beverage or extracts for 8 wk was well tolerated but did not affect the features of metabolic syndrome. However, green tea significantly reduced plasma serum amyloid alpha, an independent cardiovascular disease risk factor, in obese subjects with metabolic syndrome.

Among all fruits, berries have shown substantial cardio-protective benefits due to their high polyphenol content. However, investigation of their efficacy in improving features of metabolic syndrome and related cardiovascular risk factors in obesity is limited. We examined the effects of blueberry supplementation on features of metabolic syndrome, lipid peroxidation, and inflammation in obese men and women. Forty-eight participants with metabolic syndrome [4 males and 44 females; BMI: 37.8 ± 2.3 kg/m2; age: 50.0 ± 3.0 y (mean ± SE)] consumed freeze-dried blueberry beverage (50 g freeze-dried blueberries, #126 350 g fresh blueberries) or equivalent amounts of fluids (controls, 960 mL water) daily for 8 wk in a randomized controlled trial. Anthropometric and blood pressure measurements, assessment of dietary intakes, and fasting blood draws were conducted at screening and at wk 4 and 8 of the study. The decreases in systolic and diastolic blood pressures were greater in the blueberry-supplemented group (− 6 and − 4%, respectively) than in controls (− 1.5 and − 1.2%) (P lt 0.05), whereas the serum glucose concentration and lipid profiles were not affected. The decreases in plasma oxidized LDL and serum malondialdehyde and hydroxynonenal concentrations were greater in the blueberry group (− 28 and − 17%, respectively) than in the control group (− 9 and − 9%) (P lt 0.01). Our study shows blueberries may improve selected features of metabolic syndrome and related cardiovascular risk factors at dietary achievable doses.

Introduction Patients with heart failure face enormous challenges with disease burden. Socioeconomic and lifestyle patterns and disease insights have been sparsely reported in the past. The current study aims to go in-depth into understanding these characteristics in patients with heart failure. Methods 110 patients with heart failure with reduced ejection fraction (HFrEF) were enrolled in the study. During clinic/hospital visit, patients filled out a questionnaire survey identifying various socioeconomic and lifestyle characteristics. Data were expressed as %. Gender comparisons were made using Pearson chi-squared tests. Results Of the 110 patients. 56% were male. Mean age was 63± 14 yrs. 49% of patients were >65 yrs. Major self-reported co-morbidities were heart attack (35%), erectile dysfunction (55%), rhythm issues (60%), diabetes (44%) and arthritis (49%). Depression was common at 44%. 70% of the subjects had Medicare and 9% were uninsured. 81% had NYHA class 2 or more symptoms. Vision (79%) and hearing issues (33%) were common and 8% had trouble with combined vision, hearing and reading. 22% had trouble reading pill bottles. 39% of patients lived alone. Only 42% of the patients knew the names of their HF medications and 84% set their own pill schedules. 35% of patients reported forgetfulness as the main reason for missing pills. A summary of author reported significant characteristics are listed in the table with gender-based differences. While no key gender-based differences exist, females fared better in being able to recollect the names of their HF medications. Conclusion The current analysis highlights the significant limitations HFrEF. patients face on a day to day basis. While certain variables are non-modifiable; patients, caregivers and healthcare systems need to continue to evolve and adapt to these limitations/barriers to make a meaningful improvement in the morbidity and mortality associated with HFrEF.

Objectives The aim of this study was to compare the procedural and clinical outcomes of femoral arterial access with ultrasound (US) guidance with standard fluoroscopic guidance. Background Real-time US guidance reduces time to access, number of attempts, and complications in central venous access but has not been adequately assessed in femoral artery cannulation. Methods Patients (n = 1,004) undergoing retrograde femoral arterial access were randomized 1:1 to either fluoroscopic or US guidance. The primary end point was successful common femoral artery (CFA) cannulation by femoral angiography. Secondary end points included time to sheath insertion, number of forward needle advancements, first pass success, accidental venipunctures, and vascular access complications at 30 days. Results Compared with fluoroscopic guidance, US guidance produced no difference in CFA cannulation rates (86.4% vs. 83.3%, p = 0.17), except in the subgroup of patients with CFA bifurcations occurring over the femoral head (82.6% vs. 69.8%, p Conclusions In this multicenter randomized controlled trial, routine real-time US guidance improved CFA cannulation only in patients with high CFA bifurcations but reduced the number of attempts, time to access, risk of venipunctures, and vascular complications in femoral arterial access. (Femoral Arterial Access With Ultrasound Trial [FAUST]; NCT00667381 )

We have examined the association of 14 tagging single nucleotide polymorphisms (tagSNPs) in peroxisome proliferator activated receptor-gamma transcripts 1 and 2 (PPARG1 and 2) and 5 tagSNPs in adiponectin (ADIPOQ) genes for their effect on type 2 diabetes mellitus (T2D) risk in Asian Indian Sikhs. A total of 554 T2D cases and 527 normoglycemic controls were examined for association with T2D and other subphenotypes of T2D. With the exception of a strong association of PPARG2/Pro12Ala with T2D (odds ratio, 0.13; 95% confidence interval, 0.03-0.56; P = .0007), no other tagSNP in the PPARG locus revealed any significant association with T2D in this population. Similarly, none of the tagSNPs in the ADIPOQ gene was associated with T2D susceptibility in single-site analysis. However, haplotype analysis provided strong evidence of association of these loci with T2D. Three-site haplotype analysis in the PPARG locus using the 2 marginally associated SNPs (P/rs11715073 and P/rs3892175) in combination with Pro12 Ala (P/rs1801282) revealed a strong association of 1 "risk" (CGC) (P = .003, permutation P = .015) and 1 "protective" (CAC) (P = .001, permutation P = .005) haplotype associated with T2D. However, the major effect still appears to be driven by Pro12Ala, as the association of these haplotypes did not remain significant when analyzed conditional upon Pro12Ala (P = .262). In addition, 2-site haplotype analysis in the ADIPOQ locus using only 2 marginally associated SNPs (AD/rs182052 and AD/rs7649121) revealed a significant protective association of the GA haplotype with T2D (P = .009, permutation P = .026). Multiple linear regression analysis also revealed significant association of an ADIPOQ variant (AD/rs12495941) with total body weight (P = .010), waist (P = .024), and hip (P = .021), although these associations were not significant after adjusting for multiple testing. Our new findings strongly suggest that the genetic variation in PPARG and ADIPOQ loci could contribute to the risk for the development of T2D in Indian Sikhs. Identification of causal SNPs in these important biological and positional candidate genes would help determine the true physiologic significance of these loci in T2D and obesity.

In yeast Saccharomyces cerevisiae the G protein betagamma subunits (Ste4/Ste18) have long been known to transmit the signal required for mating. Here we demonstrate that GTPase-deficient mutants of Galpha (Gpa1) directly activate the mating response pathway. We also show that signaling by activated Gpa1 requires direct coupling to an RNA binding protein Scp160. These findings suggest an additional role for Gpa1 and reveal Scp160 as a component of the mating response pathway in yeast.

Objective To test the hypothesis that lower sex hormone–binding globulin (SHBG) concentrations are associated with heterozygosity for the G972R variant of the IRS-1 gene among adolescent girls with a history of precocious pubarche (PP) and hyperinsulinemic ovarian hyperandrogenism. Design Association study. Setting Academic research environment. Patient(s) Adolescent girls with a history of PP and healthy adolescent female control subjects. Intervention(s) Determine body mass index; measure serum androgen, insulin-like growth factor (IGF)–binding protein 1, lipids, IGF-1, and SHBG concentrations; perform glucose tolerance tests; and assay for G972R variant of the IRS-1 gene. Main outcome measure(s) Serum androgen, IGFBP-1, and SHBG concentrations; IRS-1 genotypes. Result(s) Twenty-five of 54 (45%) girls with a history of PP developed hyperinsulinemic ovarian hyperandrogenism at adolescence. Frequency of heterozygosity for G972 was 31% among girls with a history of PP, 40% among girls with hyperinsulinemic ovarian hyperandrogenism, and 19% among healthy control subjects. Sex hormone–binding globulin concentrations were lower among girls heterozygous for G972R variant. Predictors of progression from PP to hyperinsulinemic ovarian hyperandrogenism included chronological age, insulin, low-density lipoprotein cholesterol, and IGFBP-1 concentrations. Conclusion(s) The low mean SHBG concentration found among G972R carriers suggests that this variant may be a minor locus associated with development of hyperinsulinemic insulin resistance and ovarian androgen excess in girls with a history of PP.

Objective: To ascertain the extent of phenotypic heterogeneity for premature pubarche and polycystic ovary syndrome between and within families. Design: Association study. Setting: Academic research environment. Patient(s): Three families in which the propositus had presented with either premature pubic hair or adolescent hyperandrogenism. Intervention(s): Detailed medical histories, hormone determinations, and genotype analyses. Main Outcome Measure(s): Clinical phenotype. Genotypes for CYP21, HSD3B2 , G972R variant of IRS-1 , N363S variant of GRL , W64R variant of ADRB3 , CAG repeat in exon 1 of AR , Msp AI polymorphism in CYP17 , and R264C variant of CYP19 . Result(s): Significant phenotypic and genetic heterogeneity was observed both within and between families. In one family, CYP21 and IRS-1 variants were observed to co-segregate with symptoms of androgen excess and obesity. No genetic markers were consistently noted to associate with clinical features of hyperandrogenism in the other two families. Conclusion(s): The difficulties in classifying female family members as clearly affected or unaffected and lack of definitive male phenotype complicate the use of linkage analysis to identify the polycystic ovary syndrome genes. Each family is best considered on an individual basis to identify genetic markers that segregate with the clinical features of androgen excess.

Objective: To identify genetic markers associated with premature pubarche in children and hyperandrogenism in adolescent girls. Design: Association study. Setting: Academic research environment. Patient(s): Forty children with premature pubarche (PP), 29 adolescent girls with hyperandrogenism (HA), and 15 healthy control women. Intervention(s): None. Main Outcome Measure(s): Genetic variations at five loci selected because of known associations with hyperandrogenism, insulin resistance, hyperinsulinemia, or obesity. Result(s): Heterozygosity for CYP21 mutations was identified in 14 of 40 (35%) PP, 8 of 29 (28%) HA, and 1 of 30 (3%) controls. Heterozygosity for HSD3B2 variants was identified in 3 of 40 (7.5%) PP, 5 of 29 (17%) HA, and 0/15 controls. Among the PP, 11 of 80 (14%), 5 of 80 (6%), and 7 of 80 (9%) alleles showed the IRS-1 , GRL , and ADRB3 variants, respectively. Among the HA, 5 of 58 (8.6%), 3 of 58 (5%), and 6 of 58 (10%) alleles showed the IRS-1 , GRL , and ADRB3 variants, respectively. Among the control participants, variant allele frequency was 1 of 30 (3.3%) for IRS-1 , 2 of 30 (6.6%) for GRL , and 2 of 30 (6.6%) for ADRB3 . Conclusion(s): Our findings suggest that the development of PP and HA can be associated with the occurrence of multiple sequence variants at five susceptibility loci, especially steroidogenic enzyme genes. This approach offers a novel paradigm to investigate and identify the genetic factors relevant to polycystic ovary syndrome.

Human apolipoprotein C-IV (apoC-IV, protein; APOC4, gene) is a new member of the APO E/C1/C2 gene cluster. In transgenic mice, human apoC-IV is predominantly associated with very low-density lipoprotein (VLDL) and thus may play an important role in lipid metabolism. To our knowledge, the extent and nature of APOC4 genetic variation and its role in lipid metabolism are unknown. In this study we have assessed the presence of genetic variation in all three exons of APOC4 and their flanking intronic sequence by SSCP and DNA sequencing. A total of five point mutations were observed, including two in the non-coding part of exon 1 (A609G and G620A), two in exon 2 (codons 36 and 52) and one in exon 3 (codon 96). The three mutations in exons 2 and 3 predict amino acid substitutions, Leu36Pro, Gly52Asp, and Leu96Arg. The frequencies of the variant alleles were: 0.010 for 609G, 0.039 for 620A, 0.502 for Pro36, 0.003 for Asp52 and 0.357 for Arg96. Significant pairwise linkage disequilibrium was observed between five of the ten APOC4 pairs, including nt. 620/codon 36, nt. 620/codon 96, codon 36/codon 52, codon 36/codon 96 and codon 52/codon 96. A general linear model analysis reveled a significant association of the Leu36Pro and the Leu96Arg polymorphisms with triglyceride levels in women. This is consistent with the proposed role of apoC-IV in triglyceride metabolism. The characterization of APOC4 genetic variation may lead to the identification of a specific role of apoC-IV in lipid metabolism or in other physiologic pathways.

Families are being increasingly recognized as carrying an inherited susceptibility for pancreatic cancer, apparently unrelated to any currently recognized syndrome. The authors provide a review of the current evidence for familial susceptibility to pancreatic cancer. A formal segregation analysis of the pattern of inheritance of pancreatic cancer in 70 families from the National Registry for Familial Pancreatic Cancer is described. This analysis suggests a single major gene with an autosomal dominant mode of inheritance controlling susceptibility for pancreatic cancer in these families.

Elevated levels of lipoprotein(a) [Lp(a)] are associated with increased risk for coronary heart disease (CHD). However, racial differences in both Lp(a) levels and their associated CHD risk are observed, with African Americans having, on average, higher Lp(a) levels than US whites but not the expected increase in CHD risk. We determined Lp(a) levels and their correlates in a large cohort (n = 2379) of black and white girls, ages 9 to 10 years, at the baseline visit of a longitudinal study of obesity development, the National Heart, Lung, and Blood Institute Growth and Health Study. Lp(a) levels were available for 1269 girls. The median Lp(a) level in black girls was over 3-fold higher than that in white girls. Associations were examined between Lp(a) levels and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, adiposity, pubertal maturation stage, body fat patterning (triceps/truncal skinfold ratio), and dietary fat (Keys’ score). In black girls multiple regression analysis identified LDL-C ( P P = .08) as predictors of Lp(a) levels. In white girls only LDL-C ( P = .02) was associated with Lp(a). In conclusion, the level of Lp(a) was significantly higher in black girls. Our study also revealed a racial difference in correlates of Lp(a), such as LDL-C and adiposity. Whether this racial difference is due to an underlying biologic difference or is merely a reflection of a greater statistical power to detect a relationship with the level, which was 2.5-fold higher in black girls than in white girls, needs further investigation. (J Pediatr 1999;135:169-76)

Serum PEDF levels (mean (S.D.)) were increased in 96 Type 2 diabetic vs. 54 non-diabetic subjects; 5.3 (2.8) vs. 3.2 (2.0)mug/ml, p

Summary Genetic epidemiological studies have shown that genetic factors are important in the pathogenesis of the idiopathic inflammatory bowel diseases (IBD), Crohn disease (CD), and ulcerative colitis (UC). A genome screen in the United Kingdom found linkage of IBD to a 41-cM region of chromosome 12, surrounding D12S83. We aimed to replicate this linkage and to narrow the region of interest. Nonparametric linkage analyses at microsatellites surrounding D12S83 were performed in 122 North American Caucasian families containing 208 genotyped IBD-affected relative pairs. Transmission/disequilibrium tests (TDTs) were also performed. We confirmed that IBD is linked to chromosome 12 (peak GENEHUNTER-PLUS LOD* score 2.76 [ P = .00016] between D12S1724 and D12S90). The evidence for linkage is contributed by both the group of CD-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.79 [ P = .0021] between D12S1724 and D12S90) and the group of UC-affected relative pairs (peak GENEHUNTER-PLUS LOD* score 1.82 [ P = .0019] at D12S335). The TDT is positive at the D12S83 locus (global χ 2 = 16.41, 6 df, P = .012). In conclusion, we have independently confirmed linkage of IBD to the chromosome 12 region that we investigated. A positive TDT at D12S83 suggests that we have greatly narrowed the chromosome 12 region that contains an IBD locus.

A common polymorphism at codon 192 in the human paraoxonase (PON) 1 gene has been shown to be associated with increased risk for coronary heart disease (CHD) in Caucasian populations. However, these findings have not been reported consistently in all Caucasian and non-Caucasian populations, suggesting that this is not a functional mutation but may mark a functional mutation present in either PON1 or a nearby gene. Recently, two other PON-like genes, designated "PON2" and "PON3," have been identified, and they are linked with the known PON1 gene on chromosome 7. Identification of additional polymorphisms in the PON-gene cluster may help to locate the functional polymorphism. In this report, we describe the existence of a common polymorphism at codon 311 (Cys-->Ser; PON2*S) in the PON2 gene, as well as its association with CHD alone and in combination with the PON1 codon 192 polymorphism in Asian Indians. The frequency of the PON2*S allele was significantly higher in cases than in controls (.71 vs. .61; P=.016). The age- and sex-adjusted odds ratio (OR) was 2.5 (95% confidence interval &sqbl0;95% CI&sqbr0;=1.8-3.1; P=.0090) for the PON2*S allele carriers. Further stratification of the PON2*S association, on the basis of the presence or absence of the PON1*B allele, showed that the CHD risk associated with the PON2*S allele was confined to PON1*B-allele carriers. Likewise, the PON1*B-allele risk was present only among PON2*S carriers. Age- and sex-adjusted ORs for the PON2*S and PON1*B were 3.6 (95% CI=2.6-4.6; P=.011) and 2.9 (95% CI=2.4-3.5; P=.0002) among the PON1*B and PON2*S carriers, respectively. Our data indicate that both polymorphisms synergistically contribute to the CHD risk in this sample and that this genetic risk is independent of the conventional plasma lipid profile.

A common MspI polymorphism (G/A) in the promoter region of the APOA1 gene (-75 bp) has been shown to be associated with plasma apo A-I and HDL-C variation in several, but not all, studies. Recently another MspI polymorphic site (+/-) in the 5'region of APOA1 (+83 bp) has been identified which may also be relevant to HDL metabolism. This study was undertaken to elucidate the individual and combined effects of these two polymorphisms on plasma apo A-I and HDL-C levels in a cohort of 534 normoglycemic US Whites from the San Luis Valley, Colorado. Both polymorphisms were in strong linkage disequilibrium (P0.005); of the expected four haplotypes (G+, G-, A+, A-) the A- was not observed in this sample. Single site RFLP analysis revealed an independent and significant effect associated with each polymorphism on plasma apo A-I variation but not on HDL-C variation. Further analyses showed that the genotype effects of both polymorphisms were confined to non-smokers only. Haplotype analysis, combining both RFLPs, was more informative as this explained almost twice the amount of phenotypic variation in plasma apo A-I compared to single RFLP analysis in non-smokers. Compared to the most common haplotype (G+), the A+ and G- haplotypes were associated with increased plasma apo A-I levels by 6.7 mg/dl and 22.0 mg/dl, respectively in non-smoking men, and by 4.6 mg/dl and 15.1 mg/dl in non-smoking women, respectively. These data indicate that haplotype analysis in this region may be important to elucidate the functional significance of the APOA1 gene in HDL metabolism.

OBJECTIVE: In our general experience, about 2% of samples referred for fragile X testing showed positive results on Southern blot analysis. The aim of this project was to determine whether screening criteria could be developed to increase the proportion of positive test results without sacrificing sensitivity. STUDY DESIGN: We retrospectively analyzed nine clinical characteristics from patient records of 273 male and 62 female pediatric probands (average age, 5.7 years) referred for fragile X testing. The characteristics included mental retardation, family history of mental retardation, large or prominent ears, elongated face, attention deficit hyperactivity disorder, autistic-like behavior, simian crease, macroorchidism, and hyperextensible joints. These were scored as 2 if present, 1 if borderline present, and 0 if absent. RESULTS: Analysis of the nine characteristics identified three (simian crease, macroorchidism, and hyperextensible joints) with low frequency and statistical insignificance, which were therefore eliminated. With the use of the remaining six characteristics, if a score of 5 or more was used as the criterion for requesting fragile X testing, then close to 60% of those tests from our patient population could have been eliminated without missing any positive cases. The validity of our threshold score of 5 was subsequently confirmed among an additional six cases of fragile X syndrome. CONCLUSION: With our simplified six-item clinical checklist, 60% of testing could have been eliminated, thereby improving the cost-effectiveness of fragile X testing and increasing the proportion of cases with positive results by threefold. (J PEDIATR 1996;129:611-5)

To the Editor: Systemic lupus erythematosus (SLE) is a chronic, sometimes life threatening, systemic autoimmune disease. African Americans (AA) have a 2–4 times higher incidence of SLE, a higher rate of SLE nephritis, and a less favorable prognosis than European Americans (EA) (Petri 1998). Renal disease occurs in 40%–75% of patients with SLE, within 5 years of disease onset (Garcia et al. 1996), contributing significantly to the disease morbidity and mortality rates of these patients. Patients with focal and diffuse proliferative glomerulonephritis, as described in the World Health Organization's classification of SLE nephritis, have a clearly increased risk of developing severe renal impairment (Clark 1994). Confirmation of genetic linkage effects has become a major impediment to progress in elucidating complex genetic disorders. Explanations include false-positive reports of linkage and uncertainty that originates from the unknown complexity of the overall genetic heterogeneity in the sampled populations. In addition, when genetic effects are modest in magnitude across the sample and are dependent on variables, such as ethnicity, replication may require very large samples before confident conclusions are possible. Proposed standards for robust genetic linkages suggest that significance of the original linkage effect be atthe P

We have determined apolipoprotein E (apoE = protein, APOE = gene) polymorphism and its relationship with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels in normoglycemic Hispanics (n = 446) and non-Hispanic whites (NHWs) (n = 659) as well as in diabetic Hispanics (n = 235) and NHWs (n = 116) from the San Luis Valley, Colorado. Effects were estimated separately for each group, and within each group men and women were analyzed separately; women were further categorized into pre- and post-menopausal status. The distribution of the APOE genotype pattern was comparable between the NHW normoglycemics and diabetics but it was significantly different among Hispanic normoglycemics and diabetics (P0.005). In the normoglycemic sample the APOE allele frequencies were significantly different between the two ethnic groups: the APOE*2 (0.09 vs. 0.05; P0.01) and APOE*4 (0.15 vs. 0.09; P0.002) allele frequencies were higher while the APOE*3 (0.76 vs. 0.86; P0.0001) allele frequency was lower in NHWs than in Hispanics. Significant variability among the three common APOE genotypes (3-2, 3-3, and 4-3) was observed for TC and LDL-C in normoglycemic Hispanic women (P = 0.09 and P = 0.03) but not in Hispanic men. In normoglycemic NHWs, however, significant mean differences among APOE genotypes were observed for TC and LDL-C in both women (P0.0001 and P0.0001) and men (P = 0.009 and P = 0.01). In Hispanic females, the APOE polymorphism accounted for 5.6% and 7.6% of the phenotypic variance for TC and LDL-C, respectively. In NHW females, the APOE polymorphism explained 10.2% of the phenotypic variance for TC and LDL-C, and in NHW males these values were 6.2% and 7.5%, respectively. There was no evidence of physiologic interaction between the APOE polymorphism and menopause status in affecting TC and LDL-C in NHW women (P = 0.65 and P = 0.55) but a suggestion of interaction was observed in Hispanic women for TC and LDL-C (P = 0.11 and 0.07). After the Hispanic women were stratified into pre- and postmenopausal groups, the effect of the APOE polymorphism on TC and LDL-C was significant only in the premenopausal group. Among diabetics, no significant effect of the APOE polymorphism was seen on cholesterol levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Objectives To determine, in Type 1 diabetic (T1DM) women, if kidney injury associated with subsequent pre-eclampsia (PE) is detectable early in pregnancy, before overt proteinuria develops. Methods The prospective cohort comprised 22 T1DM women who developed PE at ∼ 37 weeks, 23 T1DM women who remained normotensive, and 17 non-diabetic women. All participants had normal urinary albumin levels at study entry. Urine samples were collected at three study visits (12.2 ± 1.9, 21.6 ± 1.5, and 31.5 ± 1.7 weeks of gestation; mean ± SD), preceding PE onset. Urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were measured by ELISA and normalized to urinary creatinine. Data were analyzed by ANOVA followed by post-hoc t tests, and by Generalized Estimating Equations. Results In T1DM PE vs. T1DM normotensive women, NGAL was significantly higher at V1 (P = 0.016), and non-significantly higher at V2 and V3, although the difference was not statistically significant when all three visits were considered together (p = 0.13). There was no difference between women with vs. without T1DM. KIM-1 showed a trend to higher values at V1 (P = 0.098) and across all three visits (P = 0.085) in T1DM PE vs. T1DM normotensive women; again, there was no difference between women with vs. without T1DM. Conclusions Subclinical kidney injury occurring in early pregnancy may predict PE. NGAL and KIM-1 have the potential to be sensitive early biomarkers, but need further evaluation. Disclosures M.B. Hookham: None. J.Y. Yu: None. A.J. Jenkins: None. K.F. Hanssen: None. C.E. Aston: None. T.J. Lyons: None.

The extent of apolipoprotein E (apo E) polymorphism and its effect on eight quantitative risk factors for coronary heart disease (total cholesterol; low density lipoprotein (LDL) cholesterol; total high density lipoprotein and its subfractions, HDL2 and HDL3; triglycerides; fasting glucose and fasting insulin) has been determined in 238 randomly selected Hispanics (120 males and 118 females) and 201 non-Hispanic whites (NHWs) (105 males and 96 females) from the San Luis Valley, Colorado. The frequencies for the E∗2, E∗3 and E∗4 alleles were 0.048, 0.853 and 0.099, respectively, in Hispanics and 0.080, 0.783 and 0.137, respectively, in NHWs. Relatively low frequency of the E∗2 and E∗4 alleles in Hispanics compared with NHWs is consistent with the genetic and anthropologic data that Hispanics have substantial Amerindian admixture. The impact of apo E polymorphism on each quantitative trait was estimated after adjusting for concomitant variables including age, cigarette smoking and body mass index in both genders and pre- or post-menopause status in females. The distribution of eight quantitative traits was analyzed among three common apo E phenotypes, 3-2, 3-3 and 4-3. In Hispanics, significant variability among apo E phenotypes was observed for total cholesterol ( P = 0.001) in females only and the apo E polymorphism accounts for 12.4% variation in total cholesterol and 15.2% variation in LDL-cholesterol. In NHWs, significant mean differences among apo E phenotypes were observed for total cholesterol in both males ( P = 0.007) and females ( P = 0.0004). In NHW males and females, the apo E polymorphism explained 9.2% and 12.4%, respectively, of the variation in total cholesterol, and 15.1% and 6.6%, respectively, of the variation in LDL-cholesterol. In NHWs, borderline significance levels were also noted for phenotype specific differences in HDL2-cholesterol in males ( P = 0.04) and females ( P = 0.05), for total HDL cholesterol in females ( P = 0.02) and HDL3-cholesterol in females ( P = 0.06). While the estimated effects of the apo E polymorphism on quantitative traits differ somewhat between Hispanics and non-Hispanic whites, this probably reflects the overall difference in frequencies of the less common alleles in the Hispanics rather than a biological difference in the effects of these alleles on lipid metabolism.

Apolipoprotein A-IV (apo A-IV) is a major component of several lipoprotein particles and may, therefore, play an important role in lipid metabolism. Genetic polymorphism of apo A-IV has been reported in humans and several other animal species. The presence of two common alleles, apo A-IV ∗ 1 and apo A-IV ∗ 2 has been documented in several human populations. In this investigation, we have determined apo A-IV polymorphism by isoelectric focusing- immunoblotting in 82 non-insulin-dependent diabetic and 204 control non-Hispanic Whites from the San Luis Valley, Colorado. We have also estimated the impact of apo A-IV polymorphism on eight quantitative traits: total cholesterol, HDL-cholesterol, HDL3 and HDL2-cholesterol, LDL-cholesterol, triglycerides, fasting glucose and fasting insulin. No statistically significant difference was seen in apo A-IV allele frequencies between the control and diabetics, and these frequencies were comparable with those reported for U.S. White and European populations. Among controls, the impact of the apo A-IV polymorphism was significant on LDL-cholesterol ( P = 0.04) in females and on fasting insulin levels ( P = 0.06) in males. In diabetics, the effect was significant on insulin ( P = 0.03) levels in males only. Furthermore, our data suggest that when making comparison of lipid profiles between the controls and diabetics the presence or absence of common apo A-IV phenotypes should be taken into account as these appear to effect these comparisons.

Summary Objective The current study evaluates whether the preoperative scrotal examination in children with non-palpable testes is sufficient in all cases or if laparoscopy is necessary to confirm the examination findings. Are the findings different amongst physicians depending on their level of experience? Materials and methods This retrospective study was done between October 2009 and May 2013. Children with non-palpable testes underwent an examination under anesthesia prior to surgery to feel for a testis or nubbin, followed by a diagnostic laparoscopy to validate the scrotal examination. The test was considered correct if the laparoscopic findings supported the scrotal examination. It was considered incorrect if laparoscopy revealed a different finding. Results A total of 74 testes were evaluated. All patients underwent examination under anesthesia by the surgeon and senior resident. The findings were recorded separately. Despite careful examination by experienced surgeons under anesthesia, the scrotal examination was incorrect in 14 patients. Four viable testes would have been missed if laparoscopy had not been performed. Conclusion Laparoscopy should be considered in case of palpable scrotal nubbins to ensure no testis is left within the abdominal cavity. Download : Download high-res image (269KB) Download : Download full-size image Figure . Algorithm for the preoperative presence or absence of a scrotal nubbin.

The Snoring, Tiredness, Observed apnea, high blood Pressure (STOP)-Body mass index (BMI), Age, Neck circumference, and Gender (BANG) questionnaire is a well validated screening tool for diagnosis of Obstructive sleep apnea (OSA) by an in- lab sleep study. However, performance of STOP-BANG as a screening tool for diagnosis of OSA in patients undergoing portable monitoring (PM) sleep study has not been well validated. We conducted a retrospective chart review of patients older than 18 years who had unattended portable monitoring sleep study done at a VA medical center between June 2012 and October 2014. STOP-BANG questionnaire and Epworth sleepiness scale (ESS) were routinely done prior to study. Sensitivity, specificity, and positive predictive value (PPV) various STOP-BANG score thresholds were calculated for diagnosis of OSA defined by Apnea Hypopnea Index (AHI) ≥5. Out of 502 unattended portable monitoring sleep studies, there were 465 males and 37 females. STOP-BANG thresholds of ≥2 and 3 have high sensitivity of 99.8 and 98.9 %, respectively, but very low specificity. Higher score thresholds of ≥7 and 8 have high specificity of 95 and 98.3 %, and PPV of 98.1 and 98.5 %, respectively, but very low sensitivity. A threshold of ≥7 in patients with BMI ≥30 was 100 % specific. The false negative rate for unattended portable monitoring sleep study compared to in-lab study was 80 %. STOP-BANG score thresholds of ≥7 and 8 are highly specific and have high PPV and therefore can potentially reduce need of diagnostic sleep studies in selected patients. Score thresholds of ≤2 or 3 are highly sensitive for AHI ≥5 by unattended portable monitoring sleep study but have high false negative rates. Therefore, in-lab sleep study should be performed to rule out OSA.