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Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin Slitin jakob Neef Shashank S.Chepurwar Regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona j.lia.preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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Assessment of the Indirect Cost of Drug Resistant Tuberculosis Treatment to Patients in a High Burden, Low Income Setting in Mozambique

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journal of Tuberculosis Research 2024年第2期12卷 91-104页

作者： júlia Malache António Domingas Pacala Isabelle Munyangaju Isaías Benzana Claudia Mutaquiha Dulce Osório Benedita josé Edy Nacarapa Pereira Zindoga Faculdade de Cincias de Sade Universidade Catlica de Moambique Beira Moambique Programa Nacional de Controlo da Tuberculose Ministrio da Sade de Moambique Maputo Moambique ISGlobal Hospital Clnic Universitat de Barcelona Barcelona Spain Tinpswalo Association Vincentian Association to Fight AIDS and TB Chokwe Mozambique Centro de Estudos e Apoio Psicolgico (CEAP) Universidade Eduardo Mondlane Maputo Moambique

Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from january 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psy

关键词： Economic Costs Drug Resistance Tuberculosis Catastrophic Costs

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An Analysis of the Accounting Costs Associated with 20-Month DR TB Regimens in Maputo City, Mozambique

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journal of Tuberculosis Research 2024年第2期12卷 73-90页

作者： júlia Malache António Isaías Benzana Isabelle Munyangaju Benedita josé Dulce Osório Edy Nacarapa Claudia Mutaquiha Simeão Nhabinde Pereira Zindoga Universidade Catlica de Moambique Beira Moambique Centro de Estudos e Apoio Psicolgico (CEAP) Universidade Eduardo Mondlane Maputo Moambique ISGlobal Hospital Clnic Universitat de Barcelona Barcelona Spain Tinpswalo Association Vincentian Association to Fight AIDS and TB Chokwe Mozambique Programa Nacional de Controlo da Tuberculose Ministrio da Sade de Moambique Maputo Mozambique Faculdade de Economia Universidade Eduardo Mondlane Maputo Moambique

Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among the 30 countries with the highest TB burden. Objective: The study aimed to estimate the average direct medical cost of treating drug-resistant tuberculosis in 19 health centers in Maputo City, Mozambique. Methods: A retrospective analysis of direct medical costs was conducted on patients aged 18 and older who completed 20-month drug-resistant tuberculosis treatment regimens in Maputo City in 2019. Results: This analysis covered 140 patients who completed a 20-month treatment regimen, with 64.3% (78) being male and 35.7% (62) female. Approximately 50% of the participants were aged between 29 and 47. The average direct medical cost of DRTB treatment was $4789.43, reaching up to $6568.00, with a standard deviation of $753.26, including clinical interventions and treatment. Conclusion: The direct medical costs for a basic treatment package for a patient with drug-resistant TB in Mozambique equal 36 minimum wages. Developing alternative and innovative funding mechanisms and identifying ways to mitigate costs through the use of generic medicines would be beneficial.

关键词： Antitubercular Agents Multidrug-Resistant Healthcare Costs Tuberculosis Mozambique

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Risk Stratification in Obstetrics: An Integrated Approach to Maternal Health

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Open journal of Obstetrics and Gynecology 2024年第6期14卷 903-910页

作者： Taina Crespo Mendonca Bianca Beatriz Soares dos Reis júlia Cruz Coelho Antônio de Oliveira Battistini Pestana Vitória Carolina Barreto Negri Alvaro Augusto Trigo Department of Medicine University of Franca Franca Brazil

Introduction: Prenatal care is crucial for maternal and fetal health, highlighting the importance of obstetric risk stratification. This enables personalized care, avoiding unnecessary interventions and reducing costs. Conditions such as first trimester bleeding, spontaneous abortion, gestational trophoblastic disease, and ectopic pregnancy require specific approaches. Early identification of these complications is vital, especially in urgent and emergency obstetric cases, which demand immediate hospital attention. Objective: Comprehensive review of first trimester pathologies and gestational hypertension, focusing on obstetric risks and personalized prenatal management. Methods: Literature review on bleeding and gestational hypertension. Results: The study provides a detailed analysis of pathologies associated with first trimester uterine bleeding and hypertensive disorders, focusing on obstetric risk stratification. The main causes of maternal and fetal mortality are hypertensive disorders, hemorrhages, infections, childbirth complications, and abortion. Spontaneous abortion is common, with different classifications, ranging from threatened to missed abortion. Infected abortion is a severe complication. Brazil has restrictive abortion laws, but many unsafe abortions occur, resulting in high public health costs. Pharmacological treatment with misoprostol is a safe option. Other pathologies include gestational trophoblastic disease, ectopic pregnancy, and placenta previa. Preeclampsia and eclampsia are severe conditions requiring immediate treatment to avoid complications. Conclusion: Early identification and management of obstetric risk factors, such as uterine bleeding, are essential for positive maternal and fetal outcomes. A multidisciplinary approach is fundamental.

关键词： Obstetrics Emergencies Hypertension Pregnancy-Induced Uterine Hemorrhage Pregnancy Trimester First

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Understanding plant drought resistance in a Mediterranean coastal sand dune ecosystem:differences between native and exotic invasive species

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journal of Plant Ecology 2018年第1期11卷 26-38页

作者： Cristina Antunes Ana júlia Pereira Patrícia Fernandes Margarida Ramos lia Ascensão Otília Correia Cristina Máguas Centre for Ecology Evolution and Environmental ChangesFaculdade de CiênciasUniversidade de LisboaCampo Grande1749-016 LisboaPortugal PPG-Ecologia Instituto de BiologiaCP 6109Universidade Estadual de Campinas-UNICAMP13083-970 CampinasSão PauloBrazil SPBotânica-Botanical Society of Portugal Travessa do Jardim 3A-dos-Potes2615-018 Alverca do RibatejoPortugal CESAM-Centre for Environmental and Marine Studies Faculdade de Ciências-CBVUniversidade de Lisboa1749-016 LisboaPortugal

Aims Mediterranean coastal dunes are habitats of great conservation interest,with a distinctive and rich *** the last century,Acacia spp.,native from Australia,have been introduced in Portugal,with the objective of stabilizing sand dunes,and since have become dominant in numerous sand dune *** invasion process led to the reduction of native plant species richness,changed soil characteristics and modified habitat’s microclimatic *** aim of this research was to typify and compare,in Mediterranean sand dune ecosystems,the ecophysiological responses to drought of Helichrysum italicum and Corema album,two native species,and Acacia longifolia,an exotic invasive *** addressed the following specific objectives:(i)to com-pare water relations and water use efficiencies,(ii)to evaluate water stress,(iii)to assess water use strategies and water sources used by plants and(iv)to evaluate the morphological adaptations at leaf and phyllode *** In order to obtain an integrative view of ecophysiological patterns,water relations and performance measuring methods have been applied:predawn(ψPD)and midday(ψMD)water potential,chloro-phyll a fluorescence,oxygen isotopic composition of xylem,rain and groundwater(δ18O)and leaf carbon isotopic discrimination(Δ13C).The leaf characteristics of the three species,as well as the histochemistry of non-glandular trichome cell walls,were also studied to identify morpho-traits related to drought *** Findings The results support our initial hypothesis:although *** clearly possesses a degree of resistance to water stress,such ability is provided by a different water strategy,when compared to native *** relied on morphological adaptations to restrict water loss,whereas the invasive species adjusted the water uptake as a way to balance their limited ability of restricting water *** corroborate that woody native species(i)have a conservative water-saving strategy an

关键词： ecophysiology water use strategy leaf morphology Acacia longifolia Corema album Helichrysum italicum

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Effects of the availability of floral resources and neighboring plants on nectar robbery in a specialized pollination system

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Current Zoology 2022年第5期68卷 541-548页

作者： júlia Mendonça Almeida Caio César Corrêa Missagia Maria Alice Santos Alves Graduação Instituto de BiociênciasUniversidade Federal do Estado do Rio de Janeiro(UNIRIO)CEPAvenida Pasteur458Rio de Janeiro 22290-240Brazil Departamento de Ecologia Programa de Pós-Graduação em Ecologia e EvoluçãoInstituto de Biologia Roberto Alcantara Gomes(IBRAG)Laboratório de Ecologia de Aves e ComportamentoUniversidade do Estado do Rio de Janeiro(UERJ)Rua São Francisco Xavier524 Rio de JaneiroRJCEPRio de Janeiro 20550-011Brazil Departamento de Ecologia IBRAGLaboratório de Ecologia de Aves UERJ.Rua São Francisco Xavier524 Rio de JaneiroRJCEPRio de Janeiro 20550-011Brazil

Many plants pollinated by nectar-foraging animals have to maintain a balance between legitimate visitor attraction strategies and mechanisms that minimize illegitimate *** study investigated how floral display and neighboring species composition influences nectar robbing by hummingbirds in the tropical ornithophilous herb Heliconia *** tested the role of inflorescence display,flower abundance,and neighboring species in the reduction of nectar robbing in *** results indicate that nectar robbing hummingbird activity was higher in moderately large inflorescence displays and that the frequency of nectar robbing in *** decreases with increased flower abundance and the presence of neighboring plant *** non-ornithophilous plants decreased the frequency of nectar robbing in *** flowers to a greater extent than ornithophilous *** results suggest that nectar robbing hummingbirds are attracted to similar conditions that attract legitimate visitors and that spatial aggregation and mixed-species displays may represent a mechanism to dilute nectar robbing effects at an individual level.

关键词： Brazilian Atlantic forest density floral antagonists Heliconiaceae

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Elevated nitric oxide and 3',5' cyclic guanosine monophosphate levels in patients with alcoholic cirrhosis

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World journal of Gastroenterology 2008年第2期14卷 236-242页

作者： Cíntia Siqueira Miguel Carneiro de Moura Ana júlia Pedro Paula Rocha Center of Gastroenterology Institute of Molecular Medicine School of Medicine University of Lisbon Portugal Department of Medicine Ⅱ University Hospital of Santa MariaLisbonPortugal

AIM: To evaluate whether serum levels of nitric oxide (NO ·) and plasma levels of cyclic guanosine monophosphate (cGMP) and total glutathione (GSH) are altered in patients with alcoholic cirrhosis and to examine their correlation with the severity of liver ***: Twenty-six patients with alcoholic liver cirrhosis were studied. Serum levels of NO · and plasma levels of cGMP and GSH were measured in 7 patients with compensated alcoholic cirrhosis (Child-Pugh A) and 19 patients with advanced cirrhosis (Child-Pugh B and C). The model for end-stage liver disease (MELD) score was evaluated. Sixteen healthy volunteers served as controls. Liver enzymes and creatinine levels were also ***: NO · and cGMP levels were higher in patients with Child-Pugh B and C cirrhosis than in Child-Pugh A cirrhosis or controls (NO ·: 21.70 ± 8.07 vs 11.70 ± 2.74; 21.70 ± 8.07 vs 7.26 ± 2.47 μmol/L, respectively; P < 0.001) and (cGMP: 20.12 ± 6.62 vs 10.14 ± 2.78; 20.12 ± 6.62 vs 4.95 ± 1.21 pmol/L, respectively; P < 0.001). Total glutathione levels were lower in patients with Child-Pugh B and C cirrhosis than in patients with Child-Pugh A cirrhosis or controls (16.04 ± 6.06 vs 23.01 ± 4.38 or 16.04 ± 6.06 vs 66.57 ± 26.23 μmol/L, respectively; P < 0.001). There was a significant correlation between NO · and cGMP levels in all patients with alcoholic cirrhosis. A significant negative correlation between reduced glutathione/glutathione disulfide and the MELD score was found in all cirrhotic ***: Our results suggest a role for oxidative stress in alcoholic liver cirrhosis, which is more significant in decompensated patients with higher levels of NO ·and cGMP and lower GSH levels than in compensated and control patients. Altered mediator levels in decompensated patients may influence the hemodynamic changes in and progression of liver disease.

关键词： Oxidative stress Nitric oxide Alcoholic cirrhosis Fibrosis Model for end-stage liver disease

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Distribution, habitat and adaptability of the genus Tapirus

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Integrative Zoology 2012年第4期7卷 346-355页

作者： Manolo j.GARCÍA Emília Patrícia MEDICI, Eduardo j.NARANjO Wilson NOVARINO Raquel S.LEONARDO Conservationist Research Center San Carlos UniversityGuatemala CityGuatemala Institute for Ecological Research Campo GrandeBrazil El Colegio de la Frontera Sur ChiapasMexico Biology Department Andalas UniversityWest SumatraIndonesia Defensores de la Naturaleza Foundation Guatemala CityGuatemala

In this manuscript,as a starting point,the ancient and current distribution of the genus Tapirus are summarized,from its origins,apparently in Europe,to current ***,original and current tapir habitats are de-scribed,as well as changes in ancient *** the manuscript goes on,we examine the ways in which tapir species interact with their habitats and the main aspects of habitat use,spatial ecology and *** reviewed the historic and current distribution of tapirs,as well as their use and selection of habitats,we intro-duce the concept of adaptability,considering that some of the tapir physiological characteristics and behavior-al strategies can reduce the negative impact of habitat alteration and climate ***,we provide rec-ommendations for future research *** conservation community is still missing important pieces of information for the effective conservation of tapirs and their remaining habitats in Central and South America and Southeast *** how tapir species reached their current distribution ranges,interpreting how they interact with their habitats and gathering information regarding the strategies they use to cope with habitat changes will increase our understanding about these animals and contribute to the development of conservation strategies.

关键词： adaptability climate change distribution habitat Tapirus

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Qualitative analysis of compassion fatigue and coping strategies among nurses

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International journal of Nursing Sciences 2022年第4期9卷 467-480页

作者： Natália Ondrejková júlia Halamová Institute of Applied Psychology Faculty of Social and Economic SciencesComenius University in BratislavaMlynske Luhy 482105BratislavaSlovakia

Objectives:Nurses are considered to be at risk of experiencing compassion fatigue,which can affect their personal and professional *** aim of this study was to investigate stressful factors contributing to the development of compassion fatigue in nurses,their experiences of compassion fatigue,and the coping strategies they used to cope with compassion ***:The convenience sample of 86 nurses fromCentral Europewas recruited via social networking sites during the pandemic of *** collection was conducted via an online battery of questionnaires which included open-ended questions on the stressful factors,experiences,and coping strategies for compassion *** data were analysed using a theoretical thematic analysis based on Figley’s descriptions of compassion *** initial datawas read several times to identify recurring *** statement was then categorized into the emerging domains,subdomains,categories,and ***:The results of our study show that stressful factors,experiences,and coping strategies for compassion fatigue in nurses in Central Europe could be related to cognitive,emotional,behavioural,somatic,personal relations,spiritual,and work-related symptoms of compassion fatigue as identified by Figley and that these may resemble experiences of nurses in North America,japan,and ***:This study provides a detailed overview of the stressful factors,experiences,and coping strategies for compassion fatigue,which could be used to develop an early screening tool and interventions for alleviating compassion fatigue and for preventive adaptation of the health care system.

关键词： Compassion fatigue Coping Self-care Nurses Qualitative research Psychological adaptation

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Soil ecosystem changes by vegetation on old-field sites over five decades in the Brazilian Atlantic forest

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journal of Forestry Research 2022年第2期33卷 667-677页

作者： Danielle Cristina Ortiz Tancredo Augusto Feitosa de Souza Tatiani Maria Pech Marie Luise Carolina Bartz Dilmar Baretta Alexandre Siminski júlia Carina Niemeyer Federal University of Santa Catarina Ulysses Gaboardikm 3CuritibanosSC 89520-000Brazil Postgraduate Programme in Agricultural and Natural Ecosystems(PPGEAN) Federal University of Santa CatarinaUlysses Gaboardikm 3CuritibanosSC 89520-000Brazil Centre for Functional Ecology Department of Life SciencesUniversity of Coimbra3000-456 CoimbraPortugal Department of Animal Science UDESC OesteSanta Catarina State UniversityChapecóSC 89815-630Brazil

Vegetation types alter soil ecosystems by changing soil fauna community activities and soil physi-cal-chemical ***,it is unclear how tree species(natural forest,native and exotic tree plantations)promote changes in the soil ecosystem,and if these changes alter functional groups of soil fauna and ecosystem *** determine the effects of five decades of old-field veg-etation on soil ecosystems in the Brazilian Atlantic Forest,field sampling of three ecosystems(exotic tree species Pinus elliottii ***,endangered tree species Arau-caria angustifolia(Bertol.)Kuntze plantation,and a natural ecosystem)were carried out,as well using bait-lamina tests and bioassays with collembolans,earthworms and seeds of Lactuca sativa *** sampling evaluated the soil fauna community and soil physical-chemical *** bait-lamina test in situ was carried out for 14-days to deter-mine fauna feeding activity,and the bioassays evaluated the reproduction of Folsomia candida,the avoidance of Eisenia andrei,and germination of *** in the soil from each *** results are:(1)vegetation type altered the soil fauna community composition;(2)soil fauna feeding was reduced in the plantations compared to the natural eco-system;(3)a physical barrier was created by recalcitrant litter that compromised fauna community structure and seed bank germination in situ;and,(4)changes in soil physical-chemical properties promoted decomposers.

关键词： Endangered tree species Exotic tree species Forest ecosystem Soil fauna functional groups Soil invertebrates

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