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Objective: To analyze the prevalence and incidence of Human Papillomavirus (HPV) infection and its possible association with type 2 diabetes mellitus. Materials and Methods: A retrospective cohort study was conducted. Exposure was HPV-infection. Results: 13234 females were analyzed [median of age=46], 1215 cases of diabetes (median of age=53) and 12019 cases without diabetes (median of age=45). There were 1495 (11.3%; 95%CI 10.8–11.8) new cases of HPV infection by any genotype, 234 (1.8%; 95%CI 1.5–2.0) by genotype-16, 102 (0.8%; 95%CI 0.8–0.8) by genotype-18, and 1279 (9.7%; 95%CI 9.2–10.1) by high risk (HR) genotypes. The global crude-prevalence by any genotype, and HR-genotypes was significantly lower (p=0.008) in subjects with diabetes compared with their counterparts without diabetes. The mean duration of follow-up was 1.1 years. The global crude-incidence rate of HPV-infection per 1000 person-years by any genotype, and genotypes-16, - 18, and -HR was 99.36, 15.55, 6.78, and 85.01, respectively. The crude hazard ratio of infection by HPV-18 genotype was higher in women with diabetes and age between 20-24y (HR=36.611; 95%CI 4.009-334.303, p=0.001), and 40-44y (HR=3.947; 95%CI 1.124-13.857, p=0.032) compared with their counterparts without diabetes. Conclusion: Type 2 diabetes mellitus increases the risk of infection by HPV-genotype-18 in young adult woman.

Mammalian respiratory rhythm-generating circuits in the brainstem are subject to neuromodulation by multiple peptidergic afferent inputs controlling circuit behavior and outputs. Although functionally important, actions of neuropeptide modulators have not been fully characterized. We analyzed at cellular and circuit levels two inspiratory patterns intrinsically generated by the preBötzinger complex (preBötC) and their modulation by the neuropeptides bombesin and substance P (SP) in neonatal rat medullary slices in vitro. We found that, in recordings of hypoglossal nerve and preBötC neuron inspiratory activity, some inspiratory bursts occurring spontaneously under basal conditions have a biphasic shape with longer duration than normal inspiratory bursts and occur at a lower frequency. This biphasic burst pattern has been proposed to represent inspiratory activity underling periodic sighs. Bath-applied bombesin or SP decreased the period and increased the duration of both normal inspiratory and biphasic bursts and their underlying synaptic drives. The ratio of the biphasic long-duration burst period to the normal inspiratory burst period and the ratio of their burst durations remained the same before and after peptidergic modulation. Bombesin increased the frequency of the inspiratory rhythm in a Ca

PDF file - 315K, Immunostaining of ASS1, TS, and DHFR in representative urothelial carcinomas.

PDF file - 408K, Pyrosequencing data of bladder cancer cell lines and primary bladder cancer samples.

PDF file - 177K, Kaplan-Meier plot and log-rank test for disease-specific and metastasis-free survival.

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PDF file - 198K, Table S1 Correlation between ASS1 expression and various clinicopathological factors. Table S2 Univariate log-rank analysis for disease-specific survival and metastasis-free survival. Table S3 Correlation between ASS1 IHC and pyrosequencing of primary bladder cases. Table S4 Combination index (CI) analysis.

Prostate cancer is significantly more common in Western men than in Asian men, but the basis for this difference remains unknown. Because genomic studies of Asian prostate cancer are very limited, we used a genome-wide approach to reveal the genomic alterations in Chinese prostate cancers. We found a significant reduction in the frequency of certain somatic genomic changes that are commonly found in Western prostate cancers, including the 21q22.2-22.3 deletion, which involves the TMPRSS2:ERG fusion gene, and 10q deletion, which causes PTEN inactivation. Array results were confirmed by PCR-based molecular copy-number counting in selected samples. The different frequencies of these genomic changes were further evaluated by fluorescent in situ hybridization and immunohistochemistry analyses of tissue microarray samples. These alterations might be key genetic changes underlying the regional/ethnic difference in clinical incidence and might be induced by specific environmental and/or genetic risk factors that Western men are exposed to. Our findings suggest that tumors arise in Western and Chinese populations by alternative pathogenetic mechanisms. Cancer Res; 70(13); 5207–12. ©2010 AACR.

PDF file - 802K, Metabolomics of ADI-PEG20 in a corroborative cell line panel (mesothelioma).

Supplementary Figures 1-2, Tables 1-8 from Distinct Genomic Alterations in Prostate Cancers in Chinese and Western Populations Suggest Alternative Pathways of Prostate Carcinogenesis

Mallines are Patagonian wetlands characterized by permanent waterlogging on its soils, sustaining small shallow lakes that hosts a vast biodiversity. In these ecosystems, aquatic plants (i.e. macrophytes) develop different life forms adapted to humid conditions, allowing them to regulate the physical and chemical conditions of the mallin. A distinctive characteristic of Patagonia is the exponential west-east decrease in rainfall, which generates three biozones: forest, ecotone and steppe. These biozones have been typified using landform plants, but whether macrophytes assemblages are related to each biozone or not has not been evaluated yet. The aim of this work is to compare the attributes of the macrophyte and wetlands landform plants community in each biozone. During the 2013-2014 austral Summer, 20 shallow lakes were sampled in the west province of Chubut, assessing macrophyte richness and physical and chemical water variables. Macrophytes were classified according to their life forms, origin, and its diversity was calculated. A total of 62 taxa were determined, most of them corresponding to the Cyperaceae, Poaceae and Ranunculaceae families. The steppe exhibited alkaline pH values, and higher conductivity and soluble reactive phosphorus (SRP) than the ecotone and the forest. High SRP values favored the abundance of macrophytes and macroalgae. However, three sites were eutrophic, exhibiting high chlorophyll a and total phosphorus values. Those sites showed higher abundances of macroalgae and emerging macrophytes. The sampled shallow lakes would act as reservoirs of macrophyte diversity at both local and regional scales. Thus, understanding the relationships among macrophytes and environmental variables could be useful for the mallines biodiversity conservation plans.

Fil: Williams Subiza, Emilio Adolfo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Norte. Centro de Investigacion Esquel de Montana y Estepa Patagonica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigacion Esquel de Montana y Estepa Patagonica; Argentina

Given the multiple stressors affecting freshwater ecosystems and the limited resources devoted to their management, effective conservation of freshwater biodiversity requires regional prioritization. Patagonian wetlands are essential for regional biodiversity and the economy, but they are still far from reaching global conservation targets and many of them could disappear due to climate change. Our study aimed at prioritizing wetlands based on aquatic and terrestrial biodiversity, their conservation status and vulnerability to climate change. First, we identified 43 priority wetlands containing all aquatic biodiversity collected in 82 Patagonian wetlands located over a 1500 km north–south gradient, by using the software Marxan. Then, we ranked within priority wetlands according to their conservation status (low priority if they were already protected; medium priority if not), importance for terrestrial biodiversity conservation (high priority) and vulnerability to climate change. Highly ranked priority wetlands in National Parks (low priority), contained diverse wetlands (57% aquatic taxon richness), including a large proportion of rare species (33%). High priority wetlands are oases of water in an arid and semiarid steppe, containing not only a large proportion of the aquatic biodiversity, but also acting as a refuge for terrestrial flora and fauna. Different management actions are proposed according to wetland priority level (e.g. fencing, creation of artificial ponds), and since 20% of medium priority and 36% of high priority wetlands are expected to disappear by 2050, their inclusion in conservation or restoration plans needs to be carefully evaluated.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease characterized by progressive ataxia and retinal degeneration. Previous cross-sectional studies show a significant decrease in the gray matter of the cerebral cortex, cerebellum, and brainstem. However, there are no longitudinal studies in SCA7 analyzing whole-brain degeneration and its relation to clinical decline. To perform a 2-year longitudinal characterization of the whole-brain degeneration and clinical decline in SCA7, twenty patients underwent MRI and clinical evaluations at baseline. Fourteen completed the 2-year follow-up study. A healthy-matched control group was also included. Imaging analyses included volumetric and cortical thickness evaluation. We measured the cognitive deterioration in SCA7 patients using MoCA test and the motor deterioration using the SARA score. We found statistically significant differences in the follow-up compared to baseline. Imaging analyses showed that SCA7 patients had severe cerebellar and pontine degeneration compared with the control group. Longitudinal follow-up imaging analyses of SCA7 patients showed the largest atrophy in the medial temporal lobe without signs of a progression of cerebellar and pontine atrophy. Effect size analyses showed that MRI longitudinal analysis has the largest effect size followed by the SARA scale and MoCA test. Here, we report that it is possible to detect significant brain atrophy and motor and cognitive clinical decline in a 2-year follow-up study of SCA7 patients. Our results support the hypothesis that longitudinal analysis of structural MRI and MOCA tests are plausible clinical markers to study the natural history of the disease and to design treatment trials in ecologically valid contexts.

Gripopterygidae is a diverse family of stoneflies, Plecoptera, distributed in the Southern Hemisphere. It has been traditionally divided into five subfamilies, but the monophyly of most of these is not supported by molecular the more comprehensive molecular analysis of the order. To test the monophyly of Antarctoperlinae, and to establish the phylogenetic position of a new Gripopterygidae species, we performed a morphological cladistic analysis including 38 morphological characters and 27 terminal taxa, with representatives of the four subfamilies present in South America and three Austroperlidae. Based on published information, we rooted the tree with Penturoperla barbata, Austroperlidae. As a result, Antarctoperlinae was recovered as polyphyletic, with Vesicaperla kuscheli and Plegoperla punctata, two members of the subfamily, placed outside the clade that includes the nine remaining genera of Antarctoperlinae. Vesicaperla also falls outside the family in previous molecular analysis. Based on this evidence, it should not be placed in Antarctoperlinae. Plegoperla punctata, known only from the type series, possesses many missing entries in our data matrix. Based on this, it seems convenient to maintain its subfamilial placement. In the tree obtained, the potential new species nests together with Pehuenioperla llaima. We thus accept it as a member of Pehuenioperla and describe it as P. microptera sp. nov Fil: Pessacq, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: Duarte Tacio. Universidade de Sao Paulo; Brasil Fil: Epele, Luis Beltran. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina

In 2016, the World Health Organization classification system of testicular tumors included the new entity prepubertal-type teratoma based on its morphological and molecular profile, and the realization that these tumors may occur in postpubertal men. For treatment and prognostic purposes, it is important to distinguish prepubertal-type teratoma from the usual postpubertal-type teratoma, because the former is benign unlike the latter. The distinction may be challenging. In this study, we investigated clinical, morphological, and molecular criteria for distinguishing prepubertal-type teratoma from postpubertal-type teratoma in a prospective series of pure testicular teratomas. All cases of pure teratoma in postpubertal men assessed at Barts Health NHS Trust or in consultation since the introduction of routine investigation of chromosome 12p status in 2010 were reviewed. Morphological features suggestive of prepubertal-type teratoma were observed in 14 out of 35 cases. All underwent molecular testing and none displayed 12p amplification. Mean tumor size was 16 mm (range 7–28 mm). None had associated germ cell neoplasia in situ or significant atrophy. Four incorporated a well-differentiated neuroendocrine tumor, 1–2 mm in size. Of the ten patients with follow-up information, none have recurred or metastasized. Twenty-one of the 35 cases were diagnosed as postpubertal-type teratoma, mean tumor size 40 mm (range 6–90 mm). One case underwent molecular testing: a tumor of pure skeletal muscle differentiation and possessed 12p amplification. Three cases presented with clinical metastases. Eight cases contained immature areas, ten cases had associated germ cell neoplasia in situ, and 17 cases had severe atrophy of the parenchyma. One case with neither germ cell neoplasia in situ nor atrophy showed necrosis. We conclude that both morphological and molecular features are of help in differentiating prepubertal-type teratoma from postpubertal-type teratoma. In nearly all postpubertal-type teratomas, molecular testing was unnecessary, and merely confirmed the morphological impression in the prepubertal-type teratomas. Our study confirmed the high incidence of well-differentiated neuroendocrine tumors in the prepubertal-type.

Contains fulltext : 286841.pdf (Publisher’s version ) (Closed access) BACKGROUND: Resistant hypertension is associated with increased cardiovascular risk. The endothelin pathway has been implicated in the pathogenesis of hypertension, but it is currently not targeted therapeutically, thereby leaving this relevant pathophysiological pathway unopposed with currently available drugs. The aim of the study was to assess the blood pressure lowering efficacy of the dual endothelin antagonist aprocitentan in patients with resistant hypertension. METHODS: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 study, which was done in hospitals or research centres in Europe, North America, Asia, and Australia. Patients were eligible for randomisation if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardised background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: part 1 was the 4-week double-blind, randomised, and placebo-controlled part, in which patients received aprocitentan 12·5 mg, aprocitentan 25 mg, or placebo in a 1:1:1 ratio; part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg; and part 3 was a 12-week double-blind, randomised, and placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes. The study is registered on ClinicalTrials.gov, NCT03541174. FINDINGS: The PRECISION study was done from June 18, 2018, to April 25, 2022. 1965 individuals were screened and 730 were randomly assigned. Of these 730 patients, 704 (96%) completed part 1 of the study; of these, 613 (87%) completed part 2 and, of these, 577 (94%) completed part 3 of the study. The least square mean (SE) change in office systolic blood pressure at 4 weeks was -15·3 (SE 0·9) mm Hg for aprocitentan 12·5 mg, -15·2 (0·9) mm Hg for aprocitentan 25 mg, and -11·5 (0·9) mm Hg for placebo, for a difference versus placebo of -3·8 (1·3) mm Hg (97·5% CI -6·8 to -0·8, p=0·0042) and -3·7 (1·3) mm Hg (-6·7 to -0·8; p=0·0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was -4·2 mm Hg (95% CI -6·2 to -2·1) and -5·9 mm Hg (-7·9 to -3·8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5·8 mm Hg, 95% CI 3·7 to 7·9, p

Pesticides are important contributors to the global freshwater biodiversity crisis. Among pesticides, neonicotinoids are the best-selling class of agricultural insecticides and are suspected to represent significant risks to freshwater and terrestrial ecosystems worldwide. Despite growing recognition that neonicotinoid impacts may be modified by the presence of additional stressors, there is limited information about their interactions with other agricultural stressors in freshwater ecosystems. We conducted an outdoor pond-mesocosm experiment to investigate the individual and interactive effects of nutrients, fine sediment, and imidacloprid (a neonicotinoid insecticide) inputs on freshwater community structure (density, diversity, and composition of zooplankton and benthic invertebrates) and ecosystem functioning (ecosystem metabolism, primary production, and organic matter decomposition). We hypothesized antagonistic nutrient-imidacloprid, and synergistic sediment-imidacloprid interactions, affecting aquatic invertebrate communities. The three stressors had significant individual and interactive effects on pond ecosystems. The insecticide neutralized the positive effects of nutrient additions on benthic invertebrate richness and mitigated the negative effects of sediment on zooplankton communities (antagonistic interactions). Moreover, we observed compensatory responses of tolerant benthic invertebrates, which resulted in reversal interactions between sediment and imidacloprid. Furthermore, our observations suggest that imidacloprid has the potential to increase net ecosystem production at environmentally relevant concentrations. Our findings support the hypothesis that the impacts of imidacloprid may be modified by other agricultural stressors. This has important implications on a global scale, given the widespread use of these pesticides in intensive agricultural landscapes and the growing body of literature suggesting that traditional pesticide assessment frameworks, based on laboratory toxicity tests alone, may be insufficient to adequately predict effects to complex freshwater ecosystems.

Status epilepticus (SE) promotes neuronal proliferation and differentiation in the adult and developing rodent hippocampus. However, the effect of SE on other neurogenic brain regions such as the cerebellum has been less explored. To determine whether SE induced by pentylentetrazole (PTZ-SE) and lithium-pilocarpine (Li-Pilo-SE) increases cell proliferation and neurogenesis in the developing rat cerebellum. SE was induced in 14-day-old (P14) Wistar rat pups (both sexes). One hour after SE and the following day rats were injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdU, 50 mg/kg). Seven days after SE, immunohistochemistry was performed to detect BrdU-positive (BrdU+) cells or BrdU/NeuN+ cells in the cerebellar vermis. SE induced by PTZ or Li-Pilo statistically significant increased the number of cerebellar BrdU+ cells when compared with the control group (58% and 40%, respectively); maximal cell proliferation occurred in lobules II, III, VIb, VIc, VIII, IXa, and IXb of PTZ-SE group and II, V, VIc, VII, and X of Li-Pilo-SE group. An increased number of BrdU/NeuN+ cells was detected in lobules V (17 ± 1.9), VIc (25.8 ± 2.7), and VII (26.2 ± 3.4) after Li-Pilo-SE compared to their control group (9.8 ± 1.7, 12.8 ± 2.8, and 11 ± 1.7, respectively), while the number of BrdU/NeuN+ cells remained the same after PTZ-induced SE or control conditions. SE induced in the developing rat by different experimental models increases cell proliferation in the granular layer of the cerebellar vermis, but only SE of limbic seizures increases neurogenesis in specific cerebellar lobes.

International audience; Standard clinical parameters fail to accurately differentiate indolent from aggressive prostate cancer. Our previous studies showed that immunohistochemical testing for Ki-67 improved prediction of prostate cancer death in a previous cohort of conservatively treated clinically localized prostate cancer. However there is a need for validation of usage with whole biopsy sections rather than tissue micro-arrays for use in routine diagnostics. Prostate cancer biopsy cases were identified in the UK, between 1990 and 2003, treated conservatively. Tumor extent and prostate-specific antigen (PSA) serum measurements were available. Biopsy cases were centrally reviewed by three uropathologists and Gleason conformed to contemporary ISUP 2014 criteria. Follow-up was through cancer registries up until 2012. Deaths were divided into those from prostate cancer and those from other causes. The percentage of Ki-67 in tumor cells was evaluated by immunohistochemistry on whole biopsy sections and was available for 756 patients. This percentage was used in analysis of cancer specific survival using a Cox proportional hazards model. In univariate analysis, the interquartile hazard ratio (HR) (95% confidence intervals) for continuous Ki-67 was 1.68 (1.49, 1.89), χ 1 2 = 47.975, P < 0.001. In grade groups 1 and 2, continuous Ki-67 was a statistically significant predictor of time to death from prostate cancer, HR (95% CI) = 1.97 (1.34, 2.88), χ 1 2 = 9.017, p = 0.003. In multivariate analysis, continuous Ki-67 added significant predictive information to that provided by grade groups, extent of disease and serum PSA, HR (95% CI) = 1.34 (1.16, 1.54), Δχ 1 2 = 13.703, P < 0.001. We now advocate the introduction of Ki-67 as a viable and practicable prognostic biomarker in clinical practice. The association of Ki-67 with mortality was highest in grade groups 1 and 2, showing that Ki-67 can be used as a routine biomarker in patients being considered for active surveillance.

Introduction In mammals, the preBotzinger complex (preBotC) is a bilateral and symmetrical neural network located in the brainstem which is essential for the generation and modulation of respiratory rhythm. Few human studies have addressed the preBotC and its relationship with neurological diseases has not been described. However, the possibility that the preBotC is important in neural control of breathing, and potentially involved in neurological diseases in humans, has been suggested based on pharmacological manipulation and lesion of the preBotC in animal models, both in vivo and in vitro. Method In this review, we describe the effects of certain drugs on the inspiratory activity in vitro in a transverse slice that contains the preBotC, as well as some in vivo experiments. Drugs were classified according to their effects on the main neurotransmitter systems and their importance as stimulators or inhibitors of preBotC activity and therefore for the generation of the respiratory rhythm. Conclusion Clinical neurologists will find this information relevant to understanding how the central nervous system generates the respiratory rhythm and may also relate this information to the findings made in daily practice.

Resumen: Introducción: En los mamíferos, el complejo pre-Bötzinger (preBötC) es una red neuronal bilateral y simétrica localizada en el tallo cerebral, la cual es indispensable para la generación y modulación del ritmo respiratorio. En humanos existen pocos estudios acerca del preBötC y su relación con enfermedades neurológicas no ha sido descrita. Sin embargo, la importancia del preBötC en el control neural del ritmo respiratorio y su posible participación en enfermedades neurológicas en humanos ha sido mostrada gracias a la manipulación farmacológica y de lesiones del preBötC realizadas en modelos animales in vivo e in vitro. Método: En esta revisión describimos los efectos de algunos fármacos sobre la actividad inspiratoria in vitro en el modelo de rebanada transversal del tallo cerebral que contiene el preBötC, y algunos experimentos in vivo. La farmacología fue clasificada de acuerdo con los principales sistemas de neurotransmisión y con la importancia de los fármacos como estimuladores o inhibidores de la actividad del preBötC y, por tanto, de la generación del ritmo respiratorio. Conclusiones: El neurólogo clínico encontrará esta información relevante para entender cómo el sistema nervioso central genera el ritmo respiratorio y, además, podrá relacionarla con las observaciones hechas durante su práctica. Abstract: Introduction: In mammals, the preBötzinger complex (preBötC) is a bilateral and symmetrical neural network located in the brainstem which is essential for the generation and modulation of respiratory rhythm. There are few human studies about the preBötC and, its relationship with neurological diseases has not been described. However, the importance of the preBötC in neural control of breathing and its potential participation in neurological diseases in humans, has been suggested based on pharmacological manipulation and lesion of the preBötC in animal models, both in vivo and in vitro. Method: In this review, we describe the effects of some drugs on the inspiratory activity in vitro in a transverse slice that contains the preBötC, as well as some in vivo experiments. Drugs were classified according to their effects on the main neurotransmitter systems and their importance as stimulators or inhibitors of preBötC activity and therefore for the generation of the respiratory rhythm. Conclusion: Clinical neurologists will find this information relevant to understanding how the central nervous system generates the respiratory rhythm and may also relate this information to the findings made in daily practice. Palabras clave: Generación del ritmo respiratorio, Respiración, Complejo pre-Bötzinger, Control neural de la respiración, NK1R, In vitro, Keywords: Respiratory rhythm generation, Breathing, preBötzinger complex, Neural control of breathing, NK1R, In vitro

AIMS It has been recommended that the percentage of high-grade (HG) Gleason patterns 4 and 5 should be quantified in prostate cancer. However, this has not been assessed in a cohort using prostate cancer death as an outcome, and there is debate as to whether the biopsy with the 'worst' percentage of HG disease or an 'overall' percentage of HG disease should be reported. Such data may assist in active surveillance decisions. METHODS AND RESULTS Men with clinically localised prostate cancer diagnosed by needle biopsy from 1990 to 2003 were included. The endpoint was prostate cancer death. Clinical variables included Gleason score (GS), prostate-specific antigen level, age, clinical stage, and disease extent. Deaths were divided into those from prostate cancer and those from other causes, according to World Health Organization criteria. Nine hundred and eighty-eight biopsy cases were centrally reviewed according to criteria agreed at the Chicago International Society of Urological Pathology conference in 2014. Cores were given individual GSs and Grade Groups (GGs), and a percentage of each grade was given for each core. Both the worst percentage of HG disease seen in a biopsy series and overall percentage of HG disease were calculated. The overall percentage of HG disease was highly significant, with a hazard ratio of 4.45 for the interquartile range (95% confidence interval 3.30-6.01, P

Knowledge of immature habitats is an important focus for investigations of mosquito community ecology, and may improve our understanding of how environmental variables increase risk of mosquito-borne diseases by influencing the distributions and abundances of species. In Patagonia region, where climatic and ecological factors could be only borderline suitable for mosquito development, relatively little is known about larval ecology. The present study focuses on associations of environmental conditions in natural aquatic habitats with abundances of mosquito species that have colonized such habitats in Patagonia. We described the mosquito community composition within 26 natural temporary pools, and assessed the general relationships between environmental variables (pH, water temperature, conductivity, salinity, dissolved oxygen, aquatic plant cover and main nutrients) and larval abundances using redundancy analysis (RDA). Additionally, we compiled monthly climate data and vegetation indices for each larval habitat, and estimated the probability of presence for two of the most abundant species, describing through generalized linear models (GLM) the environmental, climatic and landscape variables-probability of occurrence relationships. Seven species belonging to the genera Culex and Aedes were identified, with Culex apicinus, Cx. acharistus and Aedes albifasciatus being the most abundant. Mean larval densities were low (6.8 ± 2.8 larvae/dip), and the highestspecies richness and larval densities were recorded in northern and central areas. Aedes albifasciatus, a species of sanitary importance, was widely distributed, being the only one collected south of the 45th parallel of S latitude. RDA indicated that aquatic conductivity, pH, water depth, dissolved oxygen, ammonia and soluble reactive phosphorous accounted for the main part of the variation in the species composition. According to GLMs, wind speed was thevariable that best described the presence of Ae. albifasciatus, and the probability of finding this species was positively associated with high wind speed values. On the other hand, the EVI vegetation index was the only variable included in the Cx. apicinus model, whereby there was a great probability of presence in arid areas with lower EVI values. Our results enhance our knowledge of larval habitat ecology under the extreme environmental conditions of Patagonia and will guide future efforts to understand how multiple effects can affect mosquito ecology and public health at higher latitudes. Fil: Grech, Marta Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: Manzo, Luz Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: Epele, Luis Beltran. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: Laurito, Magdalena. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Investigaciones Entomológicas de Córdoba; Argentina Fil: Claverie, Alfredo Ñancuche. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina Fil: Ludueña Almeida, Francisco. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Investigaciones Entomológicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina Fil: Miserendino, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: Almiron, Walter Ricardo. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Investigaciones Entomológicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina

There are few studies into the rate and causes of histopathological false-positive diagnosis of prostate cancer. Only two of these, including a previous one from our group, incorporate survival data. In addition, in none of the previous studies had immunohistochemistry been originally requested on any of the misdiagnosed cases. Diagnostic biopsies (n=1080) and trans-urethral resection of prostate specimens (n=314) from 1394 men with clinically localised prostate cancer diagnosed in the UK but treated conservatively between 1990 and 2003 were reviewed by a panel of 3 genitourinary pathologists. Thirty five cases were excluded for being potentially incomplete. Of the remaining 1359, 30 (2.2%) were re-assigned to a non-malignant category (26 benign and 4 suspicious for malignancy). Immunohistochemistry had been originally performed on 7 of these. The reasons for the errors were recorded on each case: adenosis (19), partial atrophy (3), PIN (2), seminal vesicle epithelium (1) and hyperplasia (1). Follow-up of these men revealed only one prostate cancer related death, possibly due to un-sampled tumour. In conclusion, a relatively small number of prostate cancer mimics were responsible for a large proportion of the false-positive prostate cancer diagnoses and the use of immunohistochemistry did not prevent the overcall of benign entities as cancer in approximately a quarter of these cases. Targeting these mimics at educational events and raising awareness of the pitfalls in the interpretation of immunohistochemistry in prostate cancer diagnosis, emphasising that glands within a suspicious focus should be treated as a whole rather than individually, may be beneficial in lowering the rate of false-positive diagnosis.

Ecological regions are areas of similar nature in terms of environmental features. Examination of the correspondence between organismal assemblage structure and function at different levels of spatial scale is crucial regarding pond conservation, especially in unexplored areas as continental austral Patagonia, where the extensive sheep breeding has been the historical land use. We assessed relationships between invertebrate assemblages and environmental characteristics at local (hydrogeomorphology and genesis) and landscape scale (phytogeographical and biozones) on 20 isolated wetland ponds (Southern Patagonia, Argentina). Additionally, we recognized best environmental predictors of invertebrate community attributes using generalized linear models (GLM). Most ponds displayed low anthropogenic stress since most of them were far from urban and rural settlements. Even though a few sites showed strong oxygen depletion (n = 3), most were well oxygenated (>85%, >11 mg/l). Also, ponds had low ammonia and soluble reactive phosphorus contents (>60%, 25 µg/l). A total of 80 invertebrate taxa were found, with Insecta and Oligochaeta displaying the highest richness. Cyanallagma interruptum (Anisoptera), Parapsectrocladius sp. and Parachironomus sp. (Chironomidae) were the most abundant taxa. Redundancy Analysis (RDA) showed that local environmental factors greatly explained the abundance patterns of invertebrates. In addition, variance partitioning analyses displayed that taxa responded more strongly to pond genesis (7% of variation) than to the other levels of spatial scale analyzed. Structural and functional attributes of communities (metrics) also showed that genesis (local scale) resulted a reliable predictor. Thus, the community composition changed according to fluvial, glacigenic, mass removal or anthropogenic origin of the ponds. Our results suggest that ponds across the austral continental Patagonia area appeared as crucial reservoirs of invertebrate biodiversity sustaining several endemic taxa. However, the expansion of new agricultural and land use practices in surrounding areas could impact negatively on pond integrity. Conservation programs should include major constrains at both, local and landscape scale, in which part of the physical complexity is driving by pond origin. Fil: Manzo, Luz Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: Epele, Luis Beltran. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: Grech, Marta Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: Kandus, Patricia. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; Argentina Fil: Miserendino, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina

A good number of search and optimization problems, computationally speaking, fall within the "intractable problems" and their complexity is of the exponential order.In this type of problem, genetic algorithms are an excellent alternative to find solutions close to the optimum. One of the phases of the genetic algorithms requires a fitness function, which will allow to select the individuals of the next generation. This aptitude function is generally implemented based on mathematical expressions or functions.However, some of the problems that can be solved with genetic algorithms present the difficulty of requiring subjective information to define the fitness function; above all, when the individual selection process requires an assessment conditioned by sensory aspects or experience. In these cases, defining the fitness function mathematically presents a lot of complexity or becomes unfeasible.The present work aims to find computer solutions to this type of problem, embedding the support vector machines in the implementation of the fitness functions of the genetic algorithms.

The efficiency of biodiversity assessments and biomonitoring studies is commonly challenged by limitations in taxonomic identification and quantification approaches. In this study, we assessed the effects of different taxonomic and numerical resolutions on a range of community structure metrics in invertebrate compositional data sets from six regions distributed across North and South America. We specifically assessed the degree of similarity in the metrics (richness, equitability, beta diversity, heterogeneity in community composition and congruence) for data sets identified to a coarse resolution (usually family level) and the finest taxonomic resolution practical (usually genus level, sometimes species or morphospecies) and by presence-absence and relative abundance numerical resolutions. Spearman correlations showed highly significant and positive associations between univariate metrics (richness and equitability) calculated for coarse- and finest-resolution datasets. Procrustes analysis detected significant congruence between composition datasets. Higher correlation coefficients were found for datasets with the same numerical resolutions regardless of the taxonomic level (about 90%), while the correlations for comparisons across numerical resolutions were consistently lower. Our findings indicate that family-level resolution can be used as a surrogate of finer taxonomic resolutions to calculate a range of biodiversity metrics commonly used to describe invertebrate community structure patterns in New World freshwater wetlands without significant loss of information. However, conclusions on biodiversity patterns derived from datasets with different numerical resolutions should be critically considered in studies on wetland invertebrates. Fil: Marques Pires, Mateus. Universidad de Vale do Rio dos Sinos; Brasil Fil: Grech, Marta Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: Stenert, Cristina. Universidad de Vale do Rio dos Sinos; Brasil Fil: Maltchik, Leonardo. Universidad de Vale do Rio dos Sinos; Brasil Fil: Epele, Luis Beltran. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina Fil: McLean, Kyle I.. United States Geological Survey; Estados Unidos Fil: Kneitel, Jamie M.. California State University; Estados Unidos Fil: Bell, Douglas A.. East Bay Regional Park District; Estados Unidos Fil: Greig, Hamish S.. The University Of Maine (the University Of Maine); Fil: Gagne, Chase R.. The University Of Maine (the University Of Maine); Fil: Batzer, Darold P.. University of Georgia; Estados Unidos

Introduction The growth hormone (GH) has been reported as a crucial neuronal survival factor in the hippocampus against insults of diverse nature. Status epilepticus (SE) is a prolonged seizure that produces extensive neuronal cell death. The goal of this study was to evaluate the effect of intracerebroventricular administration of GH on seizure severity and SE-induced hippocampal neurodegeneration. Methodology Adult male rats were implanted with a guide cannula in the left ventricle and different amounts of GH (70, 120 or 220 ng/3 μl) were microinjected for 5 days; artificial cerebrospinal fluid was used as the vehicle. Seizures were induced by the lithium–pilocarpine model (3 mEq/kg LiCl and 30 mg/kg pilocarpine hydrochloride) one day after the last GH administration. Neuronal injury was assessed by Fluoro-Jade B (F-JB) staining. Results Rats injected with 120 ng of GH did not had SE after 30 mg/kg pilocarpine, they required a higher number of pilocarpine injections to develop SE than the rats pretreated with the vehicle, 70 ng or 220 ng GH. Prefrontal and parietal cortex EEG recordings confirmed that latency to generalized seizures and SE was also significantly higher in the 120 ng group when compared with all the experimental groups. FJ-B positive cells were detected in the hippocampus after SE in all rats, and no significant differences in the number of F-JB cells in the CA1 area and the hilus was observed between experimental groups. Conclusion Our results indicate that, although GH has an anticonvulsive effect in the lithium–pilocarpine model of SE, it does not exert hippocampal neuroprotection after SE.