Urinary Incontinence and Health-Seeking Behavior Among White, Black, and Latina Women

Fewer than half of women with urinary incontinence (UI) seek care for their condition. Our objective was to qualitatively assess themes surrounding treatment seeking behaviors

Regulation of SOX11 expression through CCND1 and STAT3 in mantle cell lymphoma

The neural transcription factor SOX11 is usually highly expressed in typical mantle cell lymphoma (MCL), but it is absent in the more indolent form of MCL. Despite being an important diagnostic marker for this hard-to-treat malignancy, the mechanisms of aberrant SOX11 expression are largely unknown. Herein, we describe 2 modes of SOX11 regulation by the cell-cycle regulator cyclin D1 (CCND1) and the signal transducer and activator of transcription 3 (STAT3). We found that ectopic expression of CCND1 in multiple human MCL cell lines resulted in increased SOX11 transcription, which correlated with increased acetylated histones H3K9 and H3K14 (H3K9/14Ac). Increased H3K9/14Ac and SOX11 expression was also observed after histone deacetylase 1 (HDAC1) or HDAC2 was depleted by RNA interference or inhibited by the HDAC inhibitor vorinostat. Mechanistically, we showed that CCND1 interacted with and sequestered HDAC1 and HDAC2 from the SOX11 locus, leading to SOX11 upregulation. Interestingly, our data revealed a potential inverse relationship between phosphorylated Y705 STAT3 and SOX11 expression in MCL cell lines, primary tumors, and patient-derived xenografts. Functionally, inactivation of STAT3 by inhibiting the upstream Janus kinase (JAK) 1 or JAK2 or by STAT3 knockdown was found to increase SOX11 expression, whereas interleukin-21 (IL-21)–induced STAT3 activation or overexpression of the constitutively active form of STAT3 decreased SOX11 expression. In addition, targeting SOX11 directly by RNA interference or indirectly by IL-21 treatment induced toxicity in SOX11^+ MCL cells. Collectively, we demonstrate the involvement of CCND1 and STAT3 in the regulation of SOX11 expression, providing new insights and therapeutic implications in MCL

Isolation, characterization, and immunomodulatory activity evaluation of probiotic strains from colostrum and canine milk

BackgroundThis study aimed to characterize potential probiotic strains for use in dogs to prevent infectious enteropathies. Lactic acid bacteria (LAB) isolated from canine milk and colostrum were characterized according to their functional properties, including their resistance to gastrointestinal conditions, inhibitory effect against pathogens, and intestinal adhesion.MethodsThe immunomodulatory effects of the strains were also analyzed in in vitro and in vivo studies. Among the strains evaluated, two LAB strains (TUCO-16 and TUCO-17) showed remarkable resistance to pH 3.0, bile salts, and pancreatin, as well as inhibitory effects against pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens.ResultsThe TUCO-16 and TUCO-17 strains induced a significant increase in the expression of TNF-α, IL-8, and TLR2 in canine macrophages. The oral administration of TUCO-16 and TUCO-17 strains to mice significantly augmented their resistance to pathogenic E. coli or Salmonella intestinal infections. Both canine strains reduced intestinal damage and pathogen counts in the liver and spleen and avoided their dissemination into the bloodstream. These protective effects were related to the ability of TUCO-16 and TUCO-17 strains to differentially modulate the production of IFN-γ, IFN-β, TNF-α, IL-6, KC, MCP-1, and IL-10 in the intestinal mucosa.ConclusionBoth strains, TUCO-16 and TUCO-17, are potential probiotic candidates for improving intestinal health in dogs, particularly for their ability to inhibit the growth of Gram-negative pathogens common in gastrointestinal infections and modulate the animal's immune response. Further studies are required to effectively demonstrate the beneficial effects of TUCO-16 and TUCO-17 strains in dogs

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Regulation of SOX11 expression through CCND1 and STAT3 in mantle cell lymphoma

The neural transcription factor SOX11 is usually highly expressed in typical mantle cell lymphoma (MCL), but it is absent in the more indolent form of MCL. Despite being an important diagnostic marker for this hard-to-treat malignancy, the mechanisms of aberrant SOX11 expression are largely unknown. Herein, we describe 2 modes of SOX11 regulation by the cell-cycle regulator cyclin D1 (CCND1) and the signal transducer and activator of transcription 3 (STAT3). We found that ectopic expression of CCND1 in multiple human MCL cell lines resulted in increased SOX11 transcription, which correlated with increased acetylated histones H3K9 and H3K14 (H3K9/14Ac). Increased H3K9/14Ac and SOX11 expression was also observed after histone deacetylase 1 (HDAC1) or HDAC2 was depleted by RNA interference or inhibited by the HDAC inhibitor vorinostat. Mechanistically, we showed that CCND1 interacted with and sequestered HDAC1 and HDAC2 from the SOX11 locus, leading to SOX11 upregulation. Interestingly, our data revealed a potential inverse relationship between phosphorylated Y705 STAT3 and SOX11 expression in MCL cell lines, primary tumors, and patient-derived xenografts. Functionally, inactivation of STAT3 by inhibiting the upstream Janus kinase (JAK) 1 or JAK2 or by STAT3 knockdown was found to increase SOX11 expression, whereas interleukin-21 (IL-21)–induced STAT3 activation or overexpression of the constitutively active form of STAT3 decreased SOX11 expression. In addition, targeting SOX11 directly by RNA interference or indirectly by IL-21 treatment induced toxicity in SOX11^+ MCL cells. Collectively, we demonstrate the involvement of CCND1 and STAT3 in the regulation of SOX11 expression, providing new insights and therapeutic implications in MCL

Ancient mitogenomes from Pre-Pottery Neolithic Central Anatolia and the effects of a Late Neolithic bottleneck in sheep (Ovis aries)

Occupied between ~10,300 and 9300 years ago, the Pre-Pottery Neolithic site of Aşıklı Höyük in Central Anatolia went through early phases of sheep domestication. Analysis of 629 mitochondrial genomes from this and numerous sites in Anatolia, southwest Asia, Europe, and Africa produced a phylogenetic tree with excessive coalescences (nodes) around the Neolithic, a potential signature of a domestication bottleneck. This is consistent with archeological evidence of sheep management at Aşıklı Höyük which transitioned from residential stabling to open pasturing over a millennium of site occupation. However, unexpectedly, we detected high genetic diversity throughout Aşıklı Höyük’s occupation rather than a bottleneck. Instead, we detected a tenfold demographic bottleneck later in the Neolithic, which caused the fixation of mitochondrial haplogroup B in southwestern Anatolia. The mitochondrial genetic makeup that emerged was carried from the core region of early Neolithic sheep management into Europe and dominates the matrilineal diversity of both its ancient and the billion-strong modern sheep populations

Experience of the strategy implemented by the rapid response and clinical follow-up teams to reduce COVID-19 lethality, Lambayeque-Peru 2020

Introducción: El Perú fue considerado la mayor tasa de letalidad por COVID-19 (9.39%); siendo Lambayeque en julio del 2020 presentó seroprevalencias más altas reportadas en el mundo para SARS-CoV-2 con 29,5%. Objetivo. Describir la experiencia de la estrategia implementada por Equipos de Respuesta Rápida y Seguimiento Clínico de Casos de COVID-19 (ERSC) para reducir la letalidad por COVID-19 durante la primera ola en el 2020. Descripción de la estrategia. Se realizó una investigación operativa en una cohorte retrospectiva. La población estudiada estuvo conformada por los casos COVID-19 sospechosos y confirmados durante el periodo abril-diciembre 2020, atendidos en la Red Asistencial de Lambayeque. La metodología se llevó a cabo bajo la Implementación y funcionamiento de los ERSC que realizaban la Vigilancia Epidemiológica, rastreo y seguimiento clínico domiciliario de los casos sospechosos y confirmados de COVID-19. El proceso de captación y tamizaje inicial de los pacientes se realizó mediante tres procesos: tamizaje diferenciado, “call center” y vigilancia de rumores. Tras el tamizaje, se categorizaba al paciente en base a la atención que requería. Los casos eran asignados a los equipos de respuesta rápida quiénes acudían al domicilio del paciente para realizar las actividades indicadas de acuerdo al tipo de brigada. Las brigadas eran cuatro: brigadas de evaluación clínica domiciliaría, de diagnóstico o laboratorio a domicilio, de seguimiento clínico y brigada topo. c. La letalidad en pacientes moderados/severos disminuyó de 60% (Semana Epidemiológica 19) a 10% (Semana Epidemiológica 50) (p<0,001). La estrategia implementada y ejecutada redujo la letalidad por COVID-19 en población atendida

Ancient mitogenomes from Pre-Pottery Neolithic Central Anatolia and the effects of a Late Neolithic bottleneck in sheep (Ovis aries)

Occupied between ~10,300 and 9300 years ago, the Pre-Pottery Neolithic site of Aşıklı Höyük in Central Anatolia went through early phases of sheep domestication. Analysis of 629 mitochondrial genomes from this and numerous sites in Anatolia, southwest Asia, Europe, and Africa produced a phylogenetic tree with excessive coalescences (nodes) around the Neolithic, a potential signature of a domestication bottleneck. This is consistent with archeological evidence of sheep management at Aşıklı Höyük which transitioned from residential stabling to open pasturing over a millennium of site occupation. However, unexpectedly, we detected high genetic diversity throughout Aşıklı Höyük's occupation rather than a bottleneck. Instead, we detected a tenfold demographic bottleneck later in the Neolithic, which caused the fixation of mitochondrial haplogroup B in southwestern Anatolia. The mitochondrial genetic makeup that emerged was carried from the core region of early Neolithic sheep management into Europe and dominates the matrilineal diversity of both its ancient and the billion-strong modern sheep populations

Rising nutrient-pulse frequency and high UVR strengthen microbial interactions

Solar radiation and nutrient pulses regulate the ecosystem’s functioning. However, little is known about how a greater frequency of pulsed nutrients under high ultraviolet radiation (UVR) levels, as expected in the near future, could alter the responses and interaction between primary producers and decomposers. In this report, we demonstrate through a mesocosm study in lake La Caldera (Spain) that a repeated (press) compared to a one-time (pulse) schedule under UVR prompted higher increases in primary (PP) than in bacterial production (BP) coupled with a replacement of photoautotrophs by mixotrophic nanoflagellates (MNFs). The mechanism underlying these amplified phytoplanktonic responses was a dual control by MNFs on bacteria through the excretion of organic carbon and an increased top-down control by bacterivory. We also show across a 6-year whole-lake study that the changes from photoautotrophs to MNFs were related mainly to the frequency of pulsed nutrients (e.g. desert dust inputs). Our results underscore how an improved understanding of the interaction between chronic and stochastic environmental factors is critical for predicting ongoing changes in ecosystem functioning and its responses to climatically driven changes.This study was supported by the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER) (CGL2011-23681 and CGL2015-67682-R to PC), Ministerio de Medio Ambiente, Rural, y Marino (PN2009/067 to PC) and Junta de Andalucía (Excelencia projects P09-RNM-5376 and P12-RNM-327 to PC and JMMS, respectively). M.J.C. was supported by the Spanish Government “Formación de Profesorado Universitario” PhD grant (FPU12/01243) and I.D.-G. by the Junta de Andalucía “Personal Investigador en Formación” PhD grant (FPI RNM-5376). This work is in partial fulfillment of the Ph. D. thesis of M.J.C

Network analysis of sea turtle movements and connectivity: A tool for conservation prioritization

Aim: Understanding the spatial ecology of animal movements is a critical element in conserving long-lived, highly mobile marine species. Analyzing networks developed from movements of six sea turtle species reveals marine connectivity and can help prioritize conservation efforts. Location: Global. Methods: We collated telemetry data from 1235 individuals and reviewed the literature to determine our dataset's representativeness. We used the telemetry data to develop spatial networks at different scales to examine areas, connections, and their geographic arrangement. We used graph theory metrics to compare networks across regions and species and to identify the role of important areas and connections. Results: Relevant literature and citations for data used in this study had very little overlap. Network analysis showed that sampling effort influenced network structure, and the arrangement of areas and connections for most networks was complex. However, important areas and connections identified by graph theory metrics can be different than areas of high data density. For the global network, marine regions in the Mediterranean had high closeness, while links with high betweenness among marine regions in the South Atlantic were critical for maintaining connectivity. Comparisons among species-specific networks showed that functional connectivity was related to movement ecology, resulting in networks composed of different areas and links. Main conclusions: Network analysis identified the structure and functional connectivity of the sea turtles in our sample at multiple scales. These network characteristics could help guide the coordination of management strategies for wide-ranging animals throughout their geographic extent. Most networks had complex structures that can contribute to greater robustness but may be more difficult to manage changes when compared to simpler forms. Area-based conservation measures would benefit sea turtle populations when directed toward areas with high closeness dominating network function. Promoting seascape connectivity of links with high betweenness would decrease network vulnerability.Fil: Kot, Connie Y.. University of Duke; Estados UnidosFil: Åkesson, Susanne. Lund University; SueciaFil: Alfaro Shigueto, Joanna. Universidad Cientifica del Sur; Perú. University of Exeter; Reino Unido. Pro Delphinus; PerúFil: Amorocho Llanos, Diego Fernando. Research Center for Environmental Management and Development; ColombiaFil: Antonopoulou, Marina. Emirates Wildlife Society-world Wide Fund For Nature; Emiratos Arabes UnidosFil: Balazs, George H.. Noaa Fisheries Service; Estados UnidosFil: Baverstock, Warren R.. The Aquarium and Dubai Turtle Rehabilitation Project; Emiratos Arabes UnidosFil: Blumenthal, Janice M.. Cayman Islands Government; Islas CaimánFil: Broderick, Annette C.. University of Exeter; Reino UnidoFil: Bruno, Ignacio. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Canbolat, Ali Fuat. Hacettepe Üniversitesi; Turquía. Ecological Research Society; TurquíaFil: Casale, Paolo. Università degli Studi di Pisa; ItaliaFil: Cejudo, Daniel. Universidad de Las Palmas de Gran Canaria; EspañaFil: Coyne, Michael S.. Seaturtle.org; Estados UnidosFil: Curtice, Corrie. University of Duke; Estados UnidosFil: DeLand, Sarah. University of Duke; Estados UnidosFil: DiMatteo, Andrew. CheloniData; Estados UnidosFil: Dodge, Kara. New England Aquarium; Estados UnidosFil: Dunn, Daniel C.. University of Queensland; Australia. The University of Queensland; Australia. University of Duke; Estados UnidosFil: Esteban, Nicole. Swansea University; Reino UnidoFil: Formia, Angela. Wildlife Conservation Society; Estados UnidosFil: Fuentes, Mariana M. P. B.. Florida State University; Estados UnidosFil: Fujioka, Ei. University of Duke; Estados UnidosFil: Garnier, Julie. The Zoological Society of London; Reino UnidoFil: Godfrey, Matthew H.. North Carolina Wildlife Resources Commission; Estados UnidosFil: Godley, Brendan J.. University of Exeter; Reino UnidoFil: González Carman, Victoria. Instituto National de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Harrison, Autumn Lynn. Smithsonian Institution; Estados UnidosFil: Hart, Catherine E.. Grupo Tortuguero de las Californias A.C; México. Investigacion, Capacitacion y Soluciones Ambientales y Sociales A.C; MéxicoFil: Hawkes, Lucy A.. University of Exeter; Reino UnidoFil: Hays, Graeme C.. Deakin University; AustraliaFil: Hill, Nicholas. The Zoological Society of London; Reino UnidoFil: Hochscheid, Sandra. Stazione Zoologica Anton Dohrn; ItaliaFil: Kaska, Yakup. Dekamer—Sea Turtle Rescue Center; Turquía. Pamukkale Üniversitesi; TurquíaFil: Levy, Yaniv. University Of Haifa; Israel. Israel Nature And Parks Authority; IsraelFil: Ley Quiñónez, César P.. Instituto Politécnico Nacional; MéxicoFil: Lockhart, Gwen G.. Virginia Aquarium Marine Science Foundation; Estados Unidos. Naval Facilities Engineering Command; Estados UnidosFil: López-Mendilaharsu, Milagros. Projeto TAMAR; BrasilFil: Luschi, Paolo. Università degli Studi di Pisa; ItaliaFil: Mangel, Jeffrey C.. University of Exeter; Reino Unido. Pro Delphinus; PerúFil: Margaritoulis, Dimitris. Archelon; GreciaFil: Maxwell, Sara M.. University of Washington; Estados UnidosFil: McClellan, Catherine M.. University of Duke; Estados UnidosFil: Metcalfe, Kristian. University of Exeter; Reino UnidoFil: Mingozzi, Antonio. Università Della Calabria; ItaliaFil: Moncada, Felix G.. Centro de Investigaciones Pesqueras; CubaFil: Nichols, Wallace J.. California Academy Of Sciences; Estados Unidos. Center For The Blue Economy And International Environmental Policy Program; Estados UnidosFil: Parker, Denise M.. Noaa Fisheries Service; Estados UnidosFil: Patel, Samir H.. Coonamessett Farm Foundation; Estados Unidos. Drexel University; Estados UnidosFil: Pilcher, Nicolas J.. Marine Research Foundation; MalasiaFil: Poulin, Sarah. University of Duke; Estados UnidosFil: Read, Andrew J.. Duke University Marine Laboratory; Estados UnidosFil: Rees, ALan F.. University of Exeter; Reino Unido. Archelon; GreciaFil: Robinson, David P.. The Aquarium and Dubai Turtle Rehabilitation Project; Emiratos Arabes UnidosFil: Robinson, Nathan J.. Fundación Oceanogràfic; EspañaFil: Sandoval-Lugo, Alejandra G.. Instituto Politécnico Nacional; MéxicoFil: Schofield, Gail. Queen Mary University of London; Reino UnidoFil: Seminoff, Jeffrey A.. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Seney, Erin E.. University Of Central Florida; Estados UnidosFil: Snape, Robin T. E.. University of Exeter; Reino UnidoFil: Sözbilen, Dogan. Dekamer—sea Turtle Rescue Center; Turquía. Pamukkale University; TurquíaFil: Tomás, Jesús. Institut Cavanilles de Biodiversitat I Biologia Evolutiva; EspañaFil: Varo Cruz, Nuria. Universidad de Las Palmas de Gran Canaria; España. Ads Biodiversidad; España. Instituto Canario de Ciencias Marinas; EspañaFil: Wallace, Bryan P.. University of Duke; Estados Unidos. Ecolibrium, Inc.; Estados UnidosFil: Wildermann, Natalie E.. Texas A&M University; Estados UnidosFil: Witt, Matthew J.. University of Exeter; Reino UnidoFil: Zavala Norzagaray, Alan A.. Instituto politecnico nacional; MéxicoFil: Halpin, Patrick N.. University of Duke; Estados Unido