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Objectives: We aimed to estimate the prevalences of diabetes and impaired fasting glucose (IFG) in a national sample in Peru and assess the relationships with selected sociodemographic variables., Methods: We estimated prevalence in PERUDIAB study participants, a nationwide, stratified urban and suburban population selected by random cluster sampling. Between 2010 and 2012, questionnaires were completed and blood tests obtained from 1677 adults ≥25 years of age. Known diabetes was defined as participants having been told so by a doctor or nurse and/or receiving insulin or oral antidiabetic agents. Newly diagnosed diabetes was defined as fasting plasma glucose ≥126 mg/dL determined during the study and without a previous diabetes diagnosis. IFG was defined as fasting plasma glucose of 100-125 mg/dL., Results: The estimated national prevalence of diabetes was 7.0% (95% CI 5.3% to 8.7%) and it was 8.4% (95% CI 5.6% to 11.3%) in metropolitan Lima. No gender differences were detected. Known and newly diagnosed diabetes prevalences were estimated as 4.2% and 2.8%, respectively. A logistic regression response surface model showed a complex trend for an increased prevalence of diabetes in middle-aged individuals and in those with no formal education. Diabetes prevalence was higher in coastal (8.2%) than in highlands (4.5%; p=0.03), and jungle (3.5%; p<0.02) regions. The estimated national prevalence of IFG was 22.4%, higher in males than in females (28.3% vs 19.1%; p<0.001), and higher in coastal (26.4%) than in highlands (17.4%; p=0.03), but not jungle regions (14.9%; p=0.07)., Conclusions: This study confirms diabetes as an important public health problem, especially for middle-aged individuals and those with no formal education. 40% of the affected individuals were undiagnosed. The elevated prevalence of IFG shows that nearly a quarter of the adult population of Peru has an increased risk of diabetes.

The conversion of natural habitats to farmland is a major driver of the global extinction crisis. Two strategies are promoted to mitigate the impacts of agricultural expansion on biodiversity: land sharing integrates wildlife-friendly habitats within farmland landscapes, and land sparing intensifies farming to allow the offset of natural reserves. A key question is which strategy would protect the most phylogenetic diversity--the total evolutionary history shared across all species within a community. Conserving phylogenetic diversity decreases the chance of losing unique phenotypic and ecological traits and provides benefits for ecosystem function and stability. Focusing on birds in the threatened Chocó-Andes hotspot of endemism, we tested the relative benefits of each strategy for retaining phylogenetic diversity in tropical cloud forest landscapes threatened by cattle pastures. Using landscape simulations, we find that land sharing would protect lower community-level phylogenetic diversity than land sparing and that with increasing distance from forest (from 500 to >1,500 m), land sharing is increasingly inferior to land sparing. Isolation from forest also leads to the loss of more evolutionarily distinct species from communities within land-sharing landscapes, which can be avoided with effective land sparing. Land-sharing policies that promote the integration of small-scale wildlife-friendly habitats might be of limited benefit without the simultaneous protection of larger blocks of natural habitat, which is most likely to be achieved via land-sparing measures., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To report the cytologic characteristics of uveal melanoma., Design: This is a prospective, single-center study of consecutive patients., Subjects: All patients with a clinical diagnosis of uveal melanoma from May 2009 to July 2013 who underwent prognostication fine-needle aspiration biopsy (FNAB) were included., Methods: The cytologic characteristics of uveal melanoma were analyzed for 150 consecutive patients with a clinical diagnosis of uveal melanoma who were treated at the Cleveland Clinic Cole Eye Institute between May 2009 and August 2012., Main Outcome Measures: Cellular features of all cases were analyzed for cell type, presence of melanin, nuclear grade, tumor-infiltrating lymphocytes, and necrosis. Cytology was then correlated with histopathology in enucleated eyes., Results: A total of 150 patients were included. Seven samples of tumor resections were excluded from the study because they were studied by impression smears. A total of 143 FNAB samples of 143 patients formed the basis for analysis. Fifty-three percent of the patients were male, and the average age for all patients was 60 years. Transcorneal (n = 8), transscleral (n = 71), and transvitreal (n = 64) approaches were used. Of 143 samples, 131 were adequate. Among these, spindle cells were observed in 98% (63% mixed and 35% spindle only), whereas only epithelioid cells were observed in 2 samples. Melanin granules were observed in 80% of samples. Tumor nuclear grade (atypia) increased with tumor height and by tumor location (least atypia with iris tumors)., Conclusions: Cytologic features such as spindle cells and melanin granules, present in 98% and 80% of samples, respectively, are important cytologic diagnostic features. Tumor nuclear grade (atypia) increased with tumor height. Iris melanoma has bland features compared with ciliary and choroidal melanoma., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to describe a case of iris melanoma diagnosed by fine-needle aspiration biopsy (FNAB) with review of the literature., Design: This study presents a case report and review of the literature., Methods: A 76-year-old white man presented with iris melanoma arising from preexisting iris nevus that was confirmed cytologically by a transcorneal FNAB., Results: A pigmented lesion on the left iris extending from 3 to 8:30 o'clock, from the iris root to the pupillary margin without ectropion uveae, was biopsied through 1-mm clear corneal incision. A short 25-gauge needle was inserted into the tumor while applying aspiration, and 10-0 suture was used to close the wound. Cytopathology confirmed the presence of spindle-shaped cells with conspicuous cytoplasmic melanin and nuclear atypia consistent with the diagnosis of melanoma. There were no intraoperative or postoperative complications. The patient was subsequently treated with radiation plaque brachytherapy., Conclusions: Although indicated only in minority of cases, it is important to consider FNAB for the diagnosis and management of iris lesions.

Citrobacter freundii is an opportunistic pathogen responsible for many urinary tract infections acquired in hospitals and is thus a concern for public health. C. freundii phage Stevie might prove beneficial as a treatment against these infections. The complete genome of Stevie and its key features are described here., (Copyright © 2015 Shaw et al.)

Treatment of glaucoma by intraocular pressure (IOP) reduction is typically accomplished through the administration of eye drops, the difficult and frequent nature of which contributes to extremely low adherence rates. Poor adherence to topical treatment regimens in glaucoma patients can lead to irreversible vision loss and increased treatment costs. Currently there are no approved treatments for glaucoma that address the inherent inefficiencies in drug delivery and patient adherence. Brimonidine tartrate (BT), a common glaucoma medication, requires dosing every 8-12 h, with up to 97% of patients not taking it as prescribed. This study provides proof-of-principle testing of a controlled release BT formulation. BT was encapsulated in poly(lactic-co-glycolic) acid microspheres and drug release was quantified using UV-Vis spectroscopy. For in vivo studies, rabbits were randomized to receive a single subconjunctival injection of blank (no drug) or BT-loaded microspheres or twice daily topical 0.2% BT drops. The microspheres released an average of 2.1 ± 0.37 μg BT/mg microspheres/day in vitro. In vivo, the percent decrease in IOP from baseline was significantly greater in the treated eye for both topical drug and drug-loaded microspheres versus blank microspheres throughout the 4-week study, with no evidence of migration or foreign body response. IOP measurements in the contralateral, untreated eyes also suggested a highly localized effect from the experimental treatment. A treatment designed using the release systems described in this study would represent a vast improvement over the current clinical standard of 56-84 topical doses over 28 days., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Optical coherence tomography (OCT) has become pivotal in the practice of ophthalmology. Similar to other ophthalmic subspecialties, ophthalmic oncology has also incorporated OCT into practice. Anterior segment OCT (AS-OCT), ultra-high resolution OCT (UHR-OCT), spectral domain OCT (SD-OCT) and enhanced depth imaging OCT (EDI-OCT), have all been described to be helpful in the diagnosis, treatment planning and monitoring response of ocular and periocular tumours. Herein we discuss the role of OCT including the advantages and limitations of its use in the setting of common intraocular and adnexal tumours., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Molecular typing of pathogen populations is an important tool for the development of effective strategies for disease control. Diverse molecular markers have been used to characterize populations of Xanthomonas axonopodis pv. manihotis (Xam), the main bacterial pathogen of cassava. Recently, diversity and population dynamics of Xam in the Colombian Caribbean coast were estimated using AFLPs, where populations were found to be dynamic, diverse and with haplotypes unstable across time. Aiming to examine the current state of pathogen populations located in the Colombian Eastern Plains, we also used AFLP markers and we evaluated the usefulness of Variable Number Tandem Repeats (VNTRs) as new molecular markers for the study of Xam populations., Results: The population analyses showed that AFLP and VNTR provide a detailed and congruent description of Xam populations from the Colombian Eastern Plains. These two typing strategies clearly separated strains from the Colombian Eastern Plains into distinct populations probably because of geographical distance. Although the majority of analyses were congruent between typing markers, fewer VNTRs were needed to detect a higher number of genetic populations of the pathogen as well as a higher genetic flow among sampled locations than those detected by AFLPs., Conclusions: This study shows the advantages of VNTRs over AFLPs in the surveillance of pathogen populations and suggests the implementation of VNTRs in studies that involve large numbers of Xam isolates in order to obtain a more detailed overview of the pathogen to improve the strategies for disease control.

A 66-year-old woman presented with a blind, painful, hypertensive, and proptotic left eye. Computed tomographic imaging revealed a well-circumscribed mass involving the left orbit and globe. Metastatic work-up failed to reveal extraorbital lesions and the tumor was removed in toto via an evisceration approach orbitotomy. Histopathology and immunohistochemistry were most consistent with mammary-type myofibroblastoma with fascicles of bland, uniform spindle cells that stained positive for desmin and CD34. We are not aware of previous reports of orbital or ocular myofibroblastoma. This neoplasm has not been shown to recur, undergo malignant transformation, or metastasize. Familiarity with its clinical, histopathologic, and immunohistochemical features may improve diagnostic accuracy and treatment decisions for patients presenting with similar findings.

Background: Hamartoma is a slow-growing, rare mixed benign tumor. In general, it does not produce symptoms, so it is more commonly found as an incidentaloma during autopsies or laparotomies. Incidence of splenic hamartomas is low, representing 0.001% of the general population., Clinical Case: We report the case of a 39 year-old male without relevant antecedents. The evolution of his condition began 2 months prior with pyrosis and occasional pain in the upper hemi-abdomen. Abdominal ultrasound demonstrated a pseudocystic tumor in the spleen. Magnetic resonance showed four lesions in the spleen, predominating a large, bilobulated lesion in the inferior pole of 12 × 10 × 9 cm. A splenectomy was done without complications and the patient was discharged to home at third postoperative day. Pathological report showed a splenic hamartoma., Conclusions: Hamartomas of the spleen as in other localizations are benign lesions found as incidentalomas because only few produce symptoms. The final diagnosis is made histopathologically. Definitive treatment is splenectomy and treatment of choice is complete laparoscopic transabdominal splenectomy. Although there are few incidences in Mexico, it is of vital importance that the physician considers it among the differential diagnoses when evaluating a tumor.

Objectives: To assess the neurotoxic effect of the aqueous extract of boldo (Peumus boldus) in an experimental model., Materials and Methods: 20 male Holtzman rats of 250 ± 15 g were randomized into four groups: the negative control received saline solution (SS) orally (PO), the positive control received 6-hydroxydopamine intracranially (IC) and SS by PO. Experimental group 1 received aqueous extract of boldo (AEB) by PO, and experimental group 2 received 6-hydroxydopamine intracranially and AEB by PO. The experiment lasted 21 days. A neurological assessment was performed which had three components: a) clinical, evaluated with the rotarod test, b) biochemical, by measuring serum levels of uric acid, and c) histopathology, by immunohistochemistry for substantia nigra dopaminergic neurons. The Kruskal Wallis test and the Dunn test were used to assess differences between groups., Results: A significant decrease was found in the latency time of the rotarod test between the negative and positive control group (p<0.01), negative control and experimental 1 (p=0.09), negative control and experimental 2 (p<0.01), positive control and experimental 1 (p=0.04), and experimental 1 and 2 (p=0.09). There was no significant intergroup difference in the identification of uric acid. There was a depletion of the total dopaminergic neurons in the neuronal count, without intergroup difference., Conclusions: A neurotoxic effect of aqueous extract of boldo was recognized at a clinical level in Holtzman male rats.

Purpose: To test the therapeutic efficacy of azithromycin (AZM), a macrolide antibiotic for prolonging murine "high-risk" corneal allograft survival., Methods: Fully major histocompatibility complex-mismatched corneas were transplanted from C57BL/6 donors to BALB/c recipients with suture-induced vascularized high-risk corneal beds. Recipient mice were either not treated or treated with topical AZM, oral AZM, or both. Evaluation of graft vascularization and clarity was performed in a masked fashion. Lymph nodes were excised and analyzed for CD4, FoxP3, and CD44 by flow cytometry, and for T-cell priming by proliferation and cytokine production in mixed lymphocyte cultures. Corneal whole mounts were evaluated by confocal microscopy., Results: The incidence of graft rejection in the control group (81.8%) was significantly reduced by AZM treatment (18.2% topical, 21.7% oral, 33.3% topical + oral), although corneal vascularization was not affected by the treatment. The frequency of corneas that retained complete clarity after transplantation was higher in the AZM-treated groups. Reduced graft rejection in the AZM-treated groups was not associated with a reduced allospecific T-cell response or increased frequency of regulatory T cells., Conclusions: AZM is effective in prolonging survival of high-risk corneal allografts by an as yet undefined mechanism that does not seem to involve modulation of corneal neovascularization or allospecific T-cell priming.

Objectives: This study aimed to measure the effects of peroxisome proliferator-activated receptor-δ (PPARδ) agonist GW501516 (GW) and zinc sulfate (ZS) on ovariectomized rats' vaginal histomorphology and collagen expression., Methods: Two weeks after ovariectomy, rats received daily treatment with vaginal suppositories containing placebo, ZS, GW, ZS with GW, or estradiol for 2 weeks. Macroscopic measurements were taken and the midsection of the vagina was used for histology. Immunofluorescence was performed with antibodies against collagen I, III, and anti-actin or collagen I and V and anti-actin. Gene expression analysis of 3 collagen genes was performed by qRT-PCR., Results: Macroscopic measurements revealed that the genital hiatus was narrower in the ZS and ZS with GW groups, and the vagina was significantly longer in the animals treated with GW, ZS with GW, and estradiol compared to the placebo group. Microscopic measurements of the vaginal layers showed that the lamina propria and the vaginal muscularis were significantly thicker in the ZS and ZS with GW group compared to the placebo.The ratio of vaginal Col1a1/Col3a1 mRNA expression was significantly up-regulated by ZS with GW compared to placebo, whereas the ratio of vaginal Col1a1/Col5a1 expression was significantly up-regulated by ZS, GW, and ZS with GW. The ratio of vaginal collagen I/III protein expression was significantly up-regulated by ZS and ZS with GW, whereas the ratio of vaginal collagen I/V expression was significantly up-regulated by estradiol, ZS, and ZS with GW compared to control., Conclusions: Vaginal suppositories containing zinc and PPARδ agonist significantly altered the vagina of ovariectomized rats.

The goal of radiotherapy is to produce maximal damage to the tumor yet at the same time produce minimal damage to the surrounding tissues. Here we discuss anterior chamber complications of radiotherapy. These can vary from ocular surface irritation to blindness and can be subdivided into acute (<4 weeks) and chronic (>4 weeks). Prevention and management is also discussed and subdivided by affected tissue., (Copyright © 2013 S. Karger AG, Basel.)

Age-related macular degeneration (AMD) is the leading cause of severe irreversible vision loss in patients over the age of 50 years in the developed world. Neovascular AMD (NVAMD) is responsible for 90% of the cases with severe visual loss. In the last decade, the treatment paradigm for NVAMD has been transformed by the advent of anti-vascular endothelial growth factor therapy. Despite the excellent results of anti-vascular endothelial growth factor therapy, frequent injections remain a necessity for most patients. The burden of these frequent visits as well as the cumulative risks of indefinite intravitreal injections demand continued pursuit of more enduring therapy that provides similar functional results. Radiotherapy has been studied for two decades as a potential therapy for NVAMD. Because of its antiangiogenic properties, radiation therapy remains a promising potential adjunctive resource for the treatment of choroidal neovascularization secondary to NVAMD. This review considers the past, present and future of radiation as a treatment or combination treatment of NVAMD., (Copyright © 2013 S. Karger AG, Basel.)

The external and internal male genitalia of 327 species of 11 tribes of the subfamily Scarabaeinae, including species of Deltochilini, Scarabaeini, Gymnopleurini, Ateuchini, and Coprini, among others, were examined. Descriptions of the variations in the genital segment, the aedeagus, the internal sac, and its sclerites and raspules are presented. An exhaustive comparison of structures, names, and terminology used in literature for Scarabaeinae male genitalia are discussed. The internal sac of the aedeagus is divided in areas for an easer comparison of its internal structures; basal, submedial, medial, and apical areas are described in detail and compared. The variation of apical and medial sclerites, as well as the raspules of the submedial area, are described and compared in detail among all the taxa studied.

Introduction and Hypothesis: The aim of this study was to quantify the effects of estrogen on vaginal smooth muscle cell (SMC) tropoelastin and transforming growth factor (TGF)-β1 production., Methods: Primary SMC were incubated with estradiol, and cell proliferation was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay at 48 h. Supernatants were collected and tropoelastin and TGF-β1 levels measured., Results: SMC proliferation was significantly increased by estradiol [relative cell number, mean ± standard error (SE), estradiol 0.1 μM 116 ± 19 % of control (P = NS), 1 μM 127 ± 13 % of control (P < 0.05), 10 μM 153 ± 26 % of control, (P < 0.05)]. Tropoelastin production was significantly decreased by estrogen [mean ± SE, estradiol 0.1 μM 78 ± 2 % of control (P < 0.05), 1 μM 76 ± 4 % of control (P < 0.05), 10 μM 67 ± 3 % of control, (P < 0.05)]. In addition, TGF-β1 production was significantly decreased [mean ± SE, estradiol 0.1 μM 96 ± 4 % of control (P = NS), 1 μM 84 ± 6 % of control (P < 0.05), 10 μM 70 ± 6 % of control, (P < 0.05)]., Conclusion: Estrogen increases vaginal SMC proliferation and inhibits tropoelastin and TGF-β1 production.

Introduction and Hypothesis: The objective was to measure the effects of peroxisome proliferator-activated receptor delta (PPAR-delta) agonist and zinc sulfate (ZS) on vaginal smooth muscle cell (SMC) proliferation, tropoelastin production, and collagen production., Methods: SMC cultures were performed from vaginal wall biopsies and were incubated with ZS and PPAR-delta agonist GW501516 (GW). Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Supernatants and cell lysates were collected. Tropoelastin production was measured by Fastin Elastin Assay and collagen was measured with Sircol Collagen Assay., Results: SMC proliferation was similar with 20 μM ZS or 10 nM GW compared to control. Tropoelastin production was significantly increased by 20 μM ZS and by 10 nM GW. Cell culture surface deposited elastin production was significantly increased by 20 μM ZS and by the combination of 20 μM ZS with 10 nM GW, and collagen production was significantly increased by 10 nM GW and by the combination of 20 μM ZS with 10 nM GW., Conclusions: PPAR-delta agonist and ZS increases vaginal SMC tropoelastin and collagen production.

The aim of the study was to determine the effects of 3 feeding dose programs of the β-adrenergic agonists (β-AA) ractopamine hydrochloride (RH) or zilpaterol hydrochloride (ZH) for the final 30 d before slaughter on growth performance and carcass and meat characteristics of feedlot ram lambs. Eighty-four Dorper × Katahdin ram lambs (30.0 ± 1.6 kg) were blocked by BW and randomly assigned to pens (4 lambs per pen and 3 pens per treatment). Pens within a block were assigned randomly to 1 of 7 dietary treatments: 1) control (CTL) = diet without β-AA; 2) RH constant (RHC) = 20.0 mg/kg of RH, d 1 to 30; 3) RH increasing (RHI) = 10.0 mg/kg, d 1 to 10; 20.0 mg/kg, d 11 to 20; and 30.0 mg/kg, d 21 to 30; 4) RH decreasing (RHD) = 30.0 mg/kg, d 1 to 10; 20.0 mg/kg, d 11 to 20; and 10.0 mg/kg, d 21 to 30; 5) ZH constant (ZHC) = 6.0 mg/kg of ZH, d 1 to 30; 6) ZH increasing (ZHI) = 3.0 mg/kg, d 1 to 10; 6.0 mg/kg, d 11 to 20; and 9.0 mg/kg d 21 to 30; and 7) ZH decreasing (ZHD) = 9.0 mg/kg, d 1 to 10; 6.0 mg/kg, d 11 to 20; and 3.0 mg/kg, d 21 to 30. Overall, β-AA supplementation reduced DMI (P < 0.001) compared with CTL lambs, but lambs fed RHI and ZHI programs had greater (P < 0.05) total BW gain, ADG, and G:F. Carcass weight was improved (P < 0.05) by RHI and ZHI programs, but dressing percentage was enhanced (P < 0.05) by only ZHC or ZHI treatments. Fat thickness and yield grade were reduced (P < 0.05) by ZH or RH regardless of feeding program. Most LM characteristics (pH, moisture loss, and chemical composition) were not different among treatments (P > 0.05), with the exception of fat content that was reduced (P < 0.001) in lambs fed β-AA, and diameter of muscle fibers that was increased (P < 0.05) by ZHI treatment. Constant and increasing doses of ZH reduced (P < 0.05) the a* value of LM and semitendinosus muscles, with no effects on L* or b* values. The mass of liver was reduced (P < 0.05) in ZHI-treated lambs compared with CTL lambs, and plasma urea concentration was reduced (P < 0.05) by RH or ZH administration regardless of feeding program, although there were no other differences in organ mass weight (P ≥ 0.35) or blood metabolites (P ≥ 0.16). Increasing doses of RH or ZH augmented the growth performance response without negative effects on organ mass weight or blood metabolites. Although a ZHI program improved carcass characteristics, the increased LM fiber diameter of lambs fed ZHI program could be unfavorable because of the potential negative effect on tenderness.

Introduction and Hypothesis: Our aims were to correlate transforming growth factor (TGF)-β1 and elastin mRNA expression in the vagina of women and to measure the effects of TGF-β1 on vaginal smooth muscle cell (SMC) proliferation and tropoelastin production., Methods: Vaginal walls were sampled in women (n = 20). TGF-β1 and elastin mRNA expression was assessed by RT-PCR. SMC cultures were performed from vaginal wall biopsies. SMC were incubated with TGF-β1, and cell proliferation was assessed by MTT-assay. Tropoelastin production was measured by the Fastin Elastin Assay., Results: There was a significant positive correlation between TGF-β1 and elastin mRNA (r = 0.784, P < 0.01). SMC proliferation was significantly increased by 10 ng/mL TGF-β1 [relative cell number, mean ± SD, 198% ± 32% of control (P = 0.01)]. Tropoelastin production was significantly increased by TGF-β1 [mean ± SD, 645% ± 180% of control (P = 0.01)]., Conclusions: There is a positive correlation between TGF-β1 and elastin mRNA expression in the vaginal wall. In vitro, TGF-β1 increases vaginal tropoelastin production in vaginal SMC.

A new genus of cynipid oak gallwasp, Zapatella Pujade-Villar & Melika, gen. n. (Hymenoptera: Cynipidae: Cynipini), with two new species, Zapatella grahami Pujade-Villar & Melika, sp. n. and Zapatella nievesaldreyi Melika & Pujade-Villar, sp. n., is described from the Neotropics. Zapatella grahami,known only from the sexual generation,induces galls in acorns of Quercus costaricensis and is currently known only from Costa Rica. Zapatella nievesaldreyi, known only from the asexual generation, induces inconspicuous galls in twigs of Quercus humboldtii, and is known only from Colombia. Diagnostic characters for both new species are given in detail. Five Nearctic species are transferred from Callirhytis to Zapatella: Zapatella cryptica (Weld), comb. n., Zapatella herberti (Weld), comb. n., Zapatella oblata (Weld), comb. n., Zapatella quercusmedullae (Ashmead), comb. n.,Zapatella quercusphellos (Osten Sacken), comb. n. (= Zapatella quercussimilis (Bassett), syn. n.). A key based on adults for the species belonging to Zapatella is also given. Generic limits and morphological characteristics of Zapatella and closely related genera are discussed.

Purpose: To assess cell proliferation in pelvic organ prolapse (POP)., Methods: Tissue samples of the anterior vaginal wall and uterosacral ligaments (USLs) were obtained from eight women with combined anterior vaginal wall and uterine prolapse and from eight women without POP in a standardized fashion. Immunohistochemistry against Ki-67 was used to assess cell proliferation in vaginal and USL biopsies., Results: There were no significant differences in age, parity, menopausal status or hormone replacement therapy between the two groups. The POP-Q stage of uterine and anterior vaginal wall prolapse was significantly higher in the group of women with prolapse compared to the group without prolapse [median (range) 3 (3-4) vs. 0 (0), <0.01]. There was no significant difference between Ki-67 expressions in women with or without prolapse., Conclusion: There were no significant differences in cell proliferation between samples from women with or without POP.

A thorough insight into the female genital anatomy is crucial for understanding and performing pelvic reconstructive procedures. The intimate relationship between the genitalia and the muscles, ligaments, and fascia that provide support is complex, but critical to restore during surgery for correction of prolapse or aesthetic reasons. The external female genitalia include the mons pubis, labia majora and minora, clitoris, vestibule with glands, perineal body, and the muscles and fascia surrounding these structures. Through the perineal membrane and the perineal body, these superficial vulvar structures are structurally related to the deep pelvic muscle levator ani with its fascia. The levator ani forms the pelvic floor with the coccygeus muscle and provides vital support to all the pelvic organs and stability to the perineum. The internal female genital organs include the vagina, cervix, uterus, tubes, and ovaries with their visceral fascia. The visceral fascia also called the endopelvic fascia, surrounds the pelvic organs and connects them to the pelvic walls. It is continuous with the paraurethral and paravaginal fascia, which is attached to the perineal membrane. Thus, the internal and external genitalia are closely related to the muscles and fascia, and work as one functioning unit.

Aims: To compare the effects of polypropylene mesh or porcine dermal acellular collagen matrix mesh with and without estradiol supplementation on vaginal smooth muscle cells (VaSMC) proliferation., Results: Under in vitro culture conditions, VaSMC proliferation was significantly higher in the porcine dermal acellular collagen matrix mesh exposed cells compared to the type I polypropylene mesh exposed cells (relative cell number, mean ± SD, 0.27 ± 0.03 vs. 0.21 ± 0.01, P = 0.03). Under estradiol supplementation cell proliferation in the porcine mesh exposed cells remained significantly higher compared to the polypropylene mesh exposed cells (relative cell number, mean ± SD, 0.27 ± 0.04 vs. 0.15 ± 0.03, P < 0.01)., Conclusion: The decreased rate of erosion found with the utilization of biological absorbable mesh in vaginal reconstructive surgery may partially be explained by the significantly increased VaSMC proliferation with porcine dermal acellular collagen mesh compared to polypropylene mesh., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: To measure the effects of levormeloxifene on vaginal smooth muscle cell (SMC) proliferation, tropoelastin and transforming growth factor (TGF)-β1 production., Methods: Primary SMC cultures were performed from vaginal wall biopsies. SMC were incubated with levormeloxifene (0.1 µM, 1 µM), in 96-well plates and cell proliferation was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide (MTT) assay at 24 hours. Tropoelastin production was measured by the Fastin Assay kit and TGF-β1 levels were assessed by ELISA., Results: SMC proliferation was significantly increased by levormeloxifene [relative cell number, mean ± SE, levormeloxifene 0.1 µM 130 ± 13% of control (P=NS), 1 µM 151 ± 19% of control (P<0.05)]. Tropoelastin production was significantly decreased by levormeloxifene [mean ± SE, levormeloxifene 0.1 µM 75 ± 4% of control (P=NS), 1 µM 64 ± 2% of control (P<0.05)]. In addition, TGF-β1 production was significantly decreased [mean ± SE, levormeloxifene 0.1 µM 79 ± 11% of control (P=NS), 1 µM 72 ± 14% of control (P<0.05)]., Conclusions: Levormeloxifene increases vaginal SMC proliferation, inhibits tropoelastin and TGF- β1 production.

Purpose: To compare fibulin-3 (FIB-3) and fibulin-5 (FIB-5) expressions in uterosacral ligaments (USL) of women with and without uterine prolapse., Study Design: USL were sampled in a standardized fashion from women with (n = 8) or without (n = 8) uterine prolapse. Quantitative Real-Time PCR was performed to measure mRNA and immunohistochemistry to assess protein expression., Results: FIB-3 mRNA expression and FIB-3 staining intensity was similar in the USL of women with and without uterine prolapse {[(FIB-3 mean +/- SD mRNA relative units) 0.45 +/- 0.41 vs. 0.46 +/- 0.82, NS] and [Intensity score, median (range), 1(0-1) vs. 1(0-1), NS]}. Both FIB-5 mRNA expression and FIB-5 staining intensity was significantly decreased in USL from women with uterine prolapse compared to women without prolapse {[(FIB-5 mean +/- SD mRNA relative units) 0.07 +/- 0.02 vs. 0.26 +/- 0.20, P = 0.02] and [Intensity score, median (range), 0(0-2) vs. 3(2-3), P = 0.002]}., Conclusion: FIB-5 expression is decreased in USL of women with uterine prolapse.

Objective: To compare smooth muscle regulatory protein expression in the uterosacral ligament (USL) of women with and without uterine prolapse., Study Design: USLs ligament were sampled in women with (n = 9) or without (n = 9) uterine prolapse. Caldesmon, smooth muscle actin (SMA), myosin heavy chain, and zinc finger protein messenger RNA expression was assessed by quantitative real-time polymerase chain reaction. Immunohistochemistry and digital image analysis were used to determine protein expression., Results: Caldesmon messenger RNA expression and the ratio of caldesmon-SMA messenger RNA expression was significantly increased in the USL from women with uterine prolapse compared with women without prolapse (caldesmon mean +/- standard deviation messenger RNA, 0.81 +/- 0.46 vs 0.39 +/- 0.16; P = .01 and caldesmon-SMA messenger RNA ratio, mean +/- standard deviation, 0.11 +/- 0.04 vs 0.07 +/- 0.02; P = .01). In addition, the ratio of caldesmon-SMA staining was significantly increased in women with uterine prolapse compared with women without prolapse (mean +/- standard deviation, 0.44 +/- 0.28 vs 0.28 +/- 0.16; P = .03)., Conclusion: Uterine prolapse is associated with an increased ratio of caldesmon-SMA actin expression., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objective: To measure the effects of estrogen, progesterone and polypropylene mesh on vaginal smooth muscle cell proliferation., Methods: Primary smooth muscle cell (SMC) cultures were performed from vaginal biopsies which were then incubated with estradiol (0.1 microM, 1 microM, 10 microM), progesterone (5 nM, 50 nM, 0.5 microM), or polypropylene mesh to assess cell proliferation., Results: In vitro vaginal SMC proliferation was significantly increased by estradiol but not by progesterone or by polypropylene mesh (relative cell number, mean +/- SD, control vs. estrogen 0.24 +/- 0.02 vs. 0.28 +/- 0.02, P=0.01; control vs. progesterone 0.24 +/- 0.02 vs. 0.23 +/- 0.02, P=NS and control vs. mesh, 0.24 +/- 0.02 vs. 0.24 +/- 0.01, P=NS). In addition, estradiol increased cell proliferation in a dose responsive fashion (estradiol dose: 0.1 microM, 1 microM, 10 microM) compared to control (P=0.01)., Conclusion: Vaginal SMC proliferation is significantly increased by estrogen.

Introduction and Hypothesis: The purpose of this study is to compare vaginal caldesmon expression in women with and without anterior vaginal wall prolapse., Methods: Vaginal tissues were sampled in women with (n = 11) or without (n = 11) vaginal wall prolapse. Caldesmon messenger RNA (mRNA) expression was assessed by quantitative real-time polymerase chain reaction. Immunohistochemistry and digital image analysis were used to determine caldesmon protein expression in the histologic sections., Results: There were no significant differences in demographic data between the two groups. Caldesmon mRNA expression was significantly decreased in the vaginal tissue from women with anterior vaginal wall prolapse compared to women without prolapse [(caldesmon mean +/- SD mRNA expression in relative units) 0.03 +/- 0.03 vs 0.17 +/- 0.17, P = 0.02]. The fractional area of nonvascular caldesmon staining in the vagina of women with anterior vaginal wall prolapse was significantly decreased compared to women without prolapse [mean +/- SD (0.09 +/- 0.04 vs 0.16 +/- 0.09, P = 0.03)]., Conclusions: Vaginal caldesmon expression is significantly decreased in women with anterior vaginal wall prolapse compared to normal subjects.

Purpose: The purpose of this study was to compare the smooth muscle content and apoptosis of the uterosacral ligament in women with and without uterine prolapse., Study Design: Uterosacral ligaments were sampled in women with (n = 9) or without (n = 9) uterine prolapse undergoing hysterectomy. Smooth muscle of the uterosacral ligament was identified by immunohistochemistry. Digital image analysis was used to determine the fractional area of smooth muscle in the histologic cross sections. Apoptosis was assessed by terminal deoxynucelotidyl-transferase-mediated dUTP nick-end-labeling method., Results: The fractional area of nonvascular smooth muscle in the uterosacral ligament of women with uterine prolapse was significantly decreased compared to women without prolapse (0.32 +/- 0.12 vs. 0.42 +/- 0.03, P = .02) and the apoptotic index was significantly higher compared to women without prolapse (0.20 +/- 0.06 vs. 0.08 +/- 0.04, P < .01)., Conclusion: The fraction of smooth muscle in the uterosacral ligaments is significantly decreased, and the rate of apoptosis is higher in women with uterine prolapse compared to women without prolapse.

The aim of this study was to compare fibulin-5 expression in women with and without anterior vaginal wall prolapse. Vaginal tissues were sampled in a standardized fashion from women with (n = 12) or without (n = 10) anterior vaginal wall prolapse. Quantitative real-time polymerase chain reaction was performed to measure mRNA levels of fibulin-5 (FIB-5). FIB-5 protein expression was assessed by immunohistochemistry. There were no significant differences in demographic data between the two groups. FIB-5 mRNA expression was significantly decreased in women with anterior vaginal wall prolapse compared to women without prolapse [(FIB-5 mean +/- SD mRNA expression in relative units) 0.01 +/- 0.01 vs. 0.09 +/- 0.14, P = 0.04]. Fibulin-5 staining intensity was diminished in women with prolapse compared to women without prolapse [intensity score, median (range), 1 (1-2) vs. 3 (2-3), P = 0.04]. Fibulin-5 expression is decreased in vaginal biopsies from women with prolapse. Changes in fibulin expression may play a role in the development of pelvic organ prolapse.

To compare the smooth muscle content and apoptosis of the vagina in women with and without anterior vaginal wall prolapse. Vaginal tissues were sampled in women with (n = 6) or without (n = 6) anterior vaginal wall prolapse undergoing hysterectomy. Smooth muscle of the vagina was studied by immunohistochemistry. Digital image analysis was used to determine the fractional area of smooth muscle in the histologic cross-sections. Apoptosis was assessed by TUNEL assay. The fractional area of non-vascular smooth muscle in the vagina of women with anterior vaginal wall prolapse was significantly decreased compared to women without prolapse (0.36 +/- 0.12 vs. 0.16 +/- 0.12 P = 0.021) and the apoptotic index was significantly higher compared to women without prolapse (0.04 +/- 0.01 vs. 0.02 +/- 0.03, P = 0.041). The fraction of smooth muscle in the vagina is significantly decreased and the rate of apoptosis is higher in women with anterior vaginal wall prolapse compared to women without prolapse.

Objective: To determine if a wide genital hiatus is a risk factor for recurrence of anterior vaginal wall prolapse following anterior vaginal repair., Methods: A retrospective cohort study was performed on patients who had undergone an anterior vaginal wall repair. Patients were placed into 1 of 2 groups: wide genital hiatus (> or =5 cm) or normal genital hiatus (<5 cm). The wide genital hiatus group (n=35) was compared with the normal genital hiatus group (n=30) for surgical failure., Results: There were no significant differences between the 2 groups in demographic data, additional operative procedures, or apical suspensions. The rate of postoperative anterior vaginal wall prolapse was greater in patients with a wide genital hiatus compared with those with a normal genital hiatus (34.3% vs 10% respectively; odds ratio 4.7 [95% confidence interval, 1.0-24.1]; P=0.02)., Conclusion: The rate of recurrent anterior vaginal wall prolapse is higher in patients with a wide genital hiatus.

Objective: To compare vaginal length after iliococcygeus fixation (ICF) and sacrospinous ligament fixation (SSLF)., Methods: A retrospective cohort study was performed on patients undergoing ICF or SSLF. Sixty-seven patients were identified and, of these, only 46 had complete data sets, leaving 23 patients in either group eligible for study., Results: There were no significant differences in demographic data between the 2 groups. Mean vaginal length measurements were not significantly different before and after the ICF procedure (7.7+/-0.9 cm vs 7.6+/-0.8 cm, respectively; P=0.68). However, the mean vaginal length was significantly shortened following SSLF (7.9+/-0.8 cm vs 7.1+/-1.1 cm, P=0.001). The mean vaginal lengths preoperatively (7.7+/-0.9 cm vs 7.9+/-0.8 cm, P=0.51) and postoperatively (7.6+/-0.8 cm vs 7.1+/-1.1 cm, P=0.07) were similar., Conclusion: Iliococcygeus fixation does not significantly shorten vaginal length at the time of vaginal vault suspension, whereas the sacrospinous ligament fixation procedure does shorten vaginal length.

Purpose: Disseminated melanoma is highly therapy resistant. The finding that 66% of melanomas harbor the activating BRAF(V600E) mutation has raised expectations for targeting the Ras/RAF/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathway in melanoma. This study addresses the anti-melanoma activity of the MEK inhibitor AZD6244 (ARRY-142886)., Experimental Design: We recently have shown that growing melanoma cells as three-dimensional collagen-implanted spheroids enhances resistance to the MEK inhibitor U0126. Here, we investigated the anti-melanoma activity of AZD6244 in two-dimensional cell culture, the three-dimensional spheroid model, and an in vivo model., Results: In two-dimensional cell culture, AZD6244 was cytostatic and reduced the growth of melanoma cells in a concentration-dependent fashion through the induction of G(1)-phase cell cycle arrest. In our three-dimensional spheroid model, the effects of AZD6244 were largely cytostatic and reversible, with drug washout leading to spheroid regrowth. Finally, 1205Lu cells were grown as tumor xenografts in severe combined immunodeficient mice. After tumor establishment, mice were dosed twice daily with 0, 10, or 30 mg/kg AZD6244 p.o. AZD6244 treatment decreased phospho-ERK in the tumors and significantly suppressed tumor growth. The original tumors remained viable, suggesting that AZD6244 monotherapy was largely cytostatic, and not proapoptotic in this model. Further studies showed that co-administration of AZD6244 (30 mg/kg) with docetaxel (15 mg/kg) led to tumor regression, indicating the potential for MEK inhibitor/chemotherapy drug combinations., Conclusions: Inhibition of MEK is cytostatic as a monotherapy in melanoma, but cytotoxic when combined with docetaxel.

The purpose of this study was to determine if the quality of the intraoperative cough test could help to predict which patient would fail the post void residual test (PVR) immediately after a tension-free vaginal tape (TVT) procedure. Patients undergoing a TVT procedure only, under spinal or local anesthesia were enrolled. Patients were divided into two groups based on the outcome of the first postoperative PVR, failure group (FG) vs successful group (SG). Before adjusting the tape, patients underwent a standardized cough test. The quality of the cough test was determined to be either good or poor based on whether every cough produced a spurt of urine or not. Variables analyzed between the FG and SG were demographic and urodynamic data. Multivariate logistic regression analysis was used to calculate the adjusted odds ratios. Twenty-six (60.5%) women passed and 17 (39.5%) failed the initial postoperative PVR evaluation. There was a 4.89-fold greater odds of failing the postoperative PVR for women 65 and older compared to younger women (OR 4.89, 95% CI [1.07-26.45]). In addition, there was an 8.63-fold greater odds of failing postoperative PVR for patients with poor quality cough test (OR 8.63, 95% CI [1.54-54.66]). However, multivariate logistic regression analysis revealed that poor quality cough test was the only significant predictor for failing a postoperative PVR (OR 6.83, 95% CI [1.39-33.49], P = 0.018). A poor quality intraoperative cough test at the time of TVT procedure is a predictor of immediate postoperative urinary retention.

Purpose: Male breast cancer has been linked extensively to mutations of BRCA2 and, to a lesser extent, BRCA1. The aim of this study was to perform a comprehensive analysis of point mutations and genomic rearrangements in the BRCA1 and BRCA2 genes in 41 men with breast cancer., Patients and Methods: Deleterious point mutations were identified in 15 men (37%): 4 (10%) and 11 (27%) in BRCA1 and BRCA2, respectively. In the remaining 26 men, we screened for large genomic rearrangements in BRCA1 and BRCA2 using multiplex ligation-dependent probe amplification., Results: We did not detect any large genomic rearrangements. Men with BRCA1 or BRCA2 mutations were more likely to have a family history of prostate cancer (P = 0.025). Three of 4 male breast tumors with BRCA1 mutations (75%) were estrogen receptor positive. Whereas some studies have reported an 8%-0 rate of large BRCA2 genomic rearrangement in familial male breast cancer cases, we did not detect any such genomic rearrangements in BRCA1 or BRCA2 for our cohort., Conclusion: Despite this negative finding, our study, to the best of our knowledge, is one of the first to comprehensively screen for mutations, including large genomic rearrangement mutations, in BRCA1 and BRCA2 in men with breast cancer in the United States.

The loss of tumour phospho-extracellular responsive kinase (pERK) positivity is the major treatment biomarker for mitogen-activated protein kinase/extracellular responsive kinase (MEK) inhibitors. Here, we demonstrate that there is a poor correlation between pERK inhibition and the anti-proliferative effects of MEK inhibitors in melanoma cells. We suggest that Ki67 is a better biomarker for future clinical studies.

Background: Mutations in BRAF have recently been identified in a significant percentage of primary and metastatic cutaneous malignant melanomas. As ultraviolet (UV) exposure may play a role in the development of cutaneous melanoma lesions with BRAF mutations, BRAF mutation frequency in melanomas arising in sites protected from sun exposure may be lower than those from sun-exposed areas. Thus, we determined the BRAF mutation frequency in a panel of 13 mucosal melanomas and compared those data with data from all currently published series of cutaneous melanomas., Methods: BRAF exon 15 DNA from 13 archival primary mucosal melanomas (eight vulvar, four anorectal, and one laryngeal) was sequenced using intron-based primers. As archival DNA occasionally produces poor-quality template, results were confirmed with a TspRI restriction fragment length polymorphism (RFLP) that distinguishes wild-type BRAF from the common mutant form V599E. A binomial test was used to compare the mutation frequency in the mucosal melanomas with the published mutation frequency in cutaneous melanomas., Results: None of the 13 mucosal melanomas in this series had an exon 15 BRAF mutation, as compared to 54/165 (33%) primary cutaneous melanomas with BRAF mutations in a compilation of all current published studies (p = 0.006)., Discussion: These data suggest that UV exposure, plays a role in the genesis of BRAF mutations in cutaneous melanoma, despite the absence of the characteristic C>T or CC>TT mutation signature associated with UV exposure, and suggests mechanisms other than pyrimidine dimer formation are important in UV-induced mutagenesis.

To describe the relationship of blood lead levels to menopause and bone lead levels, we conducted a cross-sectional study on 232 pre- or perimenopausal (PreM) and postmenopausal (PosM) women who participated in an osteoporosis-screening program in Mexico City during the first quarter of 1995. Information regarding reproductive characteristics and known risk factors for blood lead was obtained using a standard questionnaire by direct interview. The mean age of the population was 54.7 years (SD = 9.8), with a mean blood lead level of 9.2 microg/dL (SD = 4.7/dL) and a range from 2.1 to 32.1 microg/dL. After adjusting for age and bone lead levels, the mean blood lead level was 1.98 microg/dL higher in PosM women than in PreM women (p = 0.024). The increase in mean blood lead levels peaked during the second year of amenorrhea with a level (10.35 microg/dL) that was 3.51 microg/dL higher than that of PreM women. Other important predictors of blood lead levels were use of lead-glazed ceramics, schooling, trabecular bone lead, body mass index, time of living in Mexico City, and use of hormone replacement therapy. Bone density was not associated with blood lead levels. These results support the hypothesis that release of bone lead stores increases during menopause and constitutes an internal source of exposure possibly associated with health effects in women in menopause transition.

Background: Priapism of the clitoris is a rare condition associated with prolonged erection of the clitoris causing engorgement, swelling, and pain to the clitoris and immediate adjacent area., Case: A 47-year-old woman presented complaining of vulvar and clitoral pain. Self-reported findings of a swollen and tender clitoris had been confirmed by physical examination during an episode of priapism, otherwise there were no abnormal findings on routine evaluation. The history and findings of prolonged clitoral swelling, tenderness, and pain of the clitoris and adjacent area were considered consistent with clitoral priapism, and discovered to be attributed to the use of trazodone hydrochloride, a heterocyclic antidepressant. The patient was initially treated with imipramine hydrochloride; however, it was the withdrawal of the medication instigating the condition that was the focal point in its management., Conclusion: Priapism of the clitoris is a condition that may develop during therapy with certain medications, specifically those possessing a strong alpha-adrenergic blockade. Conditions altering blood flow to the clitoris may also predispose to developing this condition. Familiarity with this condition and a high index of suspicion are paramount in establishing a diagnosis.

Objectives: To examine the prevalence and effects of diabetes mellitus in a subgroup of older Mexicans to allow comparisons to older persons of Mexican origin living in the United States., Design: Longitudinal study., Setting: High-rise retirement housing in Mexico City., Participants: Seven hundred eighty-five public servants and their family members aged 65 and older., Measurements: Geriatric survey of function; mental status and depression; a physical examination; and blood samples for glucose and cholesterol., Results: The prevalence of diabetes mellitus in this population was 15.1%, substantially lower than the prevalence reported in people of Mexican origin living in the United States. Nondiabetics were more obese than diabetics. Diabetes mellitus was more common in men than women. The mortality rate was greater in diabetics than nondiabetics (relative risk=1.73, P <.05). Diabetics had more coronary artery disease and were more likely to die from myocardial infarction and neoplasms than nondiabetics. Diabetics were more likely to be functionally impaired (P <.0001) but no more likely to fall or to have fractures. Diabetics did not differ from nondiabetics in cognitive impairment or level of dysphoria., Conclusion: These studies highlight some important similarities and differences in comparing a middle class subgroup of older diabetics in Mexico City with diabetics of Mexican origin living in the United States.

Purpose: To investigate the effect of Fas and Fas ligand (FasL) deficiency on the development of herpes stromal keratitis and on the von Szily model of herpes retinitis in C57BL/6 mice, which are ordinarily resistant to development of both of these herpetic diseases., Methods: Anterior chamber inoculation of the right eye of each mouse with various titers of HSV-1 (KOS strain) was performed. Both eyes of each mouse were enucleated on postinoculation day 15 and processed for histopathologic examination. HSV-1 was inoculated into one cornea of other mice, and the severity of stromal keratitis was scored., Results: Contralateral destructive chorioretinitis developed in susceptible Balb/cByj mice (19/23); ipsilateral chorioretinitis did not occur (0/23). Stromal keratitis developed in susceptible C.AL-20 mice (15/16). None of the C57BL/6 (0/10 for keratitis or 0/20 for retinitis) developed inflammation. Neither did B6.SMN.C3H.gld (FasL deficient; 0/12 or 0/28) or B6.MRL.lpr (Fas deficient; 0/11 or 0/34) mice (keratitis or contralateral chorioretinitis). Minimal scattering of inflammatory cells in the contralateral retina but not destructive chorioretinitis was observed in two C57BL/6, three B6.SMN.C3H.gld, and five B6.MRL.lpr mice. Few inflammatory cells were also found in the ipsilateral vitreous and vitreoretinal interface (but not destructive chorioretinitis) of all C57BL/6, two gld, and three lpr mice., Conclusions: Immune dysregulation secondary to deficiency in Fas or FasL system does not influence the resistance of the C57BL/6 mice to develop herpes simplex keratitis or destructive herpes simplex chorioretinitis.