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1.
BMC Vet Res ; 20(1): 113, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519893

RESUMO

BACKGROUND: Millions of working equids provide socio-economic support for many low-income communities worldwide. With the prevalence of harness-related wounds reported as higher than 60%, this study aims to describe the equipment used by working equids in three locations of the Ethiopian national regional state of Oromia (Fiche, Bishoftu and Shashamene), and the attitudes and practices of equid owners, users and harness makers regarding work equipment. This mixed-methods study consists of cross-sectional surveying of working equids used for taxi or transport of goods or water, as well as cart-driver questionnaires and focus groups (FG) with working equid stakeholders. Activities conducted with FG included participatory ranking of equipment attributes and equipment drawing exercises. Indicators of equipment design and assembly, as well as cart-driver attitudes and practices were described quantitatively. Associations between equipment characteristics and species, work-type and cart-driver indicators were investigated through univariable logistic regression models, whereas focus group discussions were transcribed and analysed thematically. RESULTS: In total, 368 working equid surveys and cart-driver questionnaires were completed and 87 participants took part in nine FG. Equipment composition and characteristics differed considerably from ideal animal draught and harnessing principles described in the literature, with none of the observed harnesses adhering to all principles and thus not considered fully adequate. Various harness compositions were used, with only saddles and breast collars present in all. Donkey equipment had fewer components than that of horses, such as swingle trees (OR 0.02; 95% CI 0.01-0.06; p < 0.001) or girths (OR 0.09; 95%CI 0.02-0.4; p = 0.002). Horse equipment was more likely to have functional elements such as breeching (OR 7.8; 95% CI 2.9-20.9; p < 0.001). Of all equipment attributes, FG participants ranked cost, design and impact on animal wellbeing as having the highest importance. Thematic analysis identified motivations and priorities regarding equipment; awareness and knowledge of design and function; barriers to using ideal equipment; and consequences of equipment design and practices as key themes. CONCLUSIONS: Various weaknesses of design, assembly and use of equid work equipment were identified. Promoting behavioural change through awareness and training could lead to a sustainable improvement of work equipment quality, access, and prevention of equipment-related problems.


Assuntos
Criação de Animais Domésticos , Animais , Cidades , Criação de Animais Domésticos/métodos , Etiópia/epidemiologia , Estudos Transversais , Inquéritos e Questionários
2.
medRxiv ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38352390

RESUMO

Malaria remains a major health priority in Nigeria. Among children with fever who seek care, less than a quarter gets tested for malaria, leading to inappropriate use of the recommended treatment for malaria; Artemether Combination Therapies (ACT). Here we test an innovative strategy to target ACT subsidies to clients seeking care in Nigeria's private retail health sector who have a confirmed malaria diagnosis. We supported point-of-care malaria testing (mRDTs) in 48 Private Medicine Retailers (PMRs) in the city of Lagos, Nigeria and randomized them to two study arms; a control arm offering subsidized mRDT testing for USD $0.66, and an intervention arm where, in addition to access to subsidized testing as in the control arm, clients who received a positive mRDT at the PMR were eligible for a free (fully subsidized) first-line ACT and PMRs received USD $0.2 for every mRDT performed. Our primary outcome was the proportion of ACTs dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients who were tested at the PMR and adherence to diagnostic test results. Overall, 23% of clients chose to test at the PMR. Test results seemed to inform treatment decisions and resulted in enhanced targeting of ACTs to confirmed malaria cases with only 26% of test-negative clients purchasing an ACT compared to 58% of untested clients. However, the intervention did not offer further improvements, compared to the control arm, in testing rates or dispensing of ACTs to test-positive clients. We found that ACT subsidies were not passed on to clients testing positive in the intervention arm. We conclude that RDTs could reduce ACT overconsumption in Nigeria's private retail health sector, but PMR-oriented incentive structures are difficult to implement and may need to be complemented with interventions targeting clients of PMRs to increase test uptake and adherence. Clinical Trials Registration Number: NCT04428307.

3.
medRxiv ; 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37745516

RESUMO

ACTs are responsible for a substantial proportion of the global reduction in malaria mortality over the last ten years. These reductions would not have been possible without publicly-funded subsidies making these drugs accessible and affordable in the private sector. However, inexpensive ACTs available in retail outlets have contributed substantially to their overconsumption. We test an innovative, scalable, and sustainable strategy to target ACT subsidies to clients with a confirmatory diagnosis. We supported point-of-care malaria testing (mRDTs) in 39 retail medicine outlets in western Kenya and randomized them to three study arms; control arm offering subsidized RDT testing for 0.4USD, client-directed intervention where all clients who received a positive RDT at the outlet were eligible for a free (fully subsidized) first-line ACT, and a combined client and provider directed intervention where clients with a positive RDT were eligible for free ACT and outlets received 0.1USD for every RDT performed. Our primary outcome was the proportion of ACT dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients tested at the outlet and adherence to diagnostic test results. 43% of clients chose to test at the outlet. Test results informed treatment decisions and resulted in targeting of ACTs to confirmed malaria cases - 25.3% of test-negative clients purchased an ACT compared to 75% of untested clients. Client-directed and client+provider-directed interventions did not offer further improvements, compared to the control arm, in testing rates (RD=0.09, 95%CI:-0.08,0.26) or dispensing of ACTs to test-positive clients (RD=0.01,95% CI: -0.14, 0.16). Clients were often unaware of the price they paid for the ACT leading to uncertainty in whether the ACT subsidy was passed on to the client. We conclude that mRDTs could reduce ACT overconsumption in the private retail sector, but incentive structures are difficult to scale and their value to private providers is uncertain.

4.
Nature ; 611(7937): 677-681, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36418451

RESUMO

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization-the only range available until now-probe extended regions of the jet containing particles that left the acceleration site days to years earlier1-3, and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree ΠX of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock.

5.
Vision Res ; 201: 108119, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36108416

RESUMO

The current study examined the relationships among temporal processing speed, spatial visual span and Chinese character reading speed in normal central and peripheral vision. Maximum reading speed (MRS) and critical print size (CPS) of 26 native Chinese readers (13 young and 13 older adults) were determined at three visual field locations: central vision, 10° left and 10° below fixation using a rapid serial visual presentation (RSVP) task. Temporal processing speed was measured using trigrams of randomly selected Chinese characters presented at a range of exposure durations, while spatial visual span was measured using trigrams presented at different spatial positions. It was found that shorter temporal processing speed and larger spatial visual span were associated with faster MRS at the central and inferior visual field locations, but not at the left of fixation location. As expected, reading and visual span metrics were better in central vision compared to both peripheral locations. In addition, reading, temporal processing, and spatial visual span metrics were better in the young than older subjects (except for similar temporal processing speed at two peripheral locations). The results for central and inferior presentation locations support the hypothesis that temporal processing speed and spatial visual span were associated with Chinese character reading speed. Surprisingly, no correlation was observed for the 10° left of the fixation location, suggesting that the factors affecting reading speed might differ for inferior and lateral peripheral viewing locations.


Assuntos
Leitura , Testes de Campo Visual , Humanos , Idoso , Psicofísica , Visão Ocular , China
6.
J Adv Res ; 38: 55-75, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35572402

RESUMO

Background: In recent years, nanotechnology has been playing an important role in designing smart fabrics. Nanomaterials have been employed to introduce in a sustainable manner, antimicrobial, ultraviolet resistant, electrically conductive, optical, hydrophobic and flame-retardant properties into textiles and garments. Nanomaterial based smart devices are now also being integrated with the textiles so as to perform various functions such as energy harvesting and storage, sensing, drug release and optics. These advancements have found wide applications in the fashion industry and are being developed for wider use in defence, healthcare and on-body energy harnessing applications. Aim of review: The objective of this work is to provide an insight into the current trends of using nanotechnology in the modern textile industries and to inspire and anticipate further research in this field. This review provides an overview of the most current advances concerning on-body electronics research and the wonders which could be realized by nanomaterials in modern textiles in terms of total energy reliance on our clothes. Key scientific concepts of review: The work underlines the various methods and techniques for the functionalization of nanomaterials and their integration into textiles with an emphasis on cost-effectiveness, comfort, wearability, energy conversion efficiency and eco-sustainability. The most recent trends of developing various nanogenerators, supercapacitors and photoelectronic devices on the fabric are highlighted, with special emphasis on the efficiency and wearability of the textile. The potential nanotoxicity associated with the processed textiles due to the tendency of these nanomaterials to leach into the environment along with possible remediation measures are also discussed. Finally, the future outlook regarding progress in the integration of smart nano-devices on textile fabrics is provided.


Assuntos
Indústria Têxtil , Dispositivos Eletrônicos Vestíveis , Eletrônica , Nanotecnologia , Têxteis
7.
Afr J Lab Med ; 10(1): 1229, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917494

RESUMO

BACKGROUND: Globally, tuberculosis remains a major cause of mortality, with an estimated 1.3 million deaths per annum. The Xpert MTB/RIF assay is used as the initial diagnostic test in the tuberculosis diagnostic algorithm. To extend the national tuberculosis testing programme in South Africa, mobile units fitted with the GeneXpert equipment were introduced to high-burden peri-mining communities. OBJECTIVE: This study sought to assess the cost of mobile testing compared to traditional laboratory-based testing in a peri-mining community setting. METHODS: Actual cost data for mobile and laboratory-based Xpert MTB/RIF testing from 2018 were analysed using a bottom-up ingredients-based approach to establish the annual equivalent cost and the cost per result. Historical cost data were obtained from supplier quotations and the local enterprise resource planning system. Costs were obtained in rand and reported in United States dollars (USD). RESULTS: The mobile units performed 4866 tests with an overall cost per result of $49.16. Staffing accounted for 30.7% of this cost, while reagents and laboratory equipment accounted for 20.7% and 20.8%. The cost per result of traditional laboratory-based testing was $15.44 US dollars (USD). The cost for identifying a tuberculosis-positive result using mobile testing was $439.58 USD per case, compared to $164.95 USD with laboratory-based testing. CONCLUSION: Mobile testing is substantially more expensive than traditional laboratory services but offers benefits for rapid tuberculosis case detection and same-day antiretroviral therapy initiation. Mobile tuberculosis testing should however be reserved for high-burden communities with limited access to laboratory testing where immediate intervention can benefit patient outcomes.

9.
PLoS Pathog ; 16(12): e1009107, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33338061

RESUMO

Mycolactone, a lipid-like toxin, is the major virulence factor of Mycobacterium ulcerans, the etiological agent of Buruli ulcer. Its involvement in lesion development has been widely described in early stages of the disease, through its cytotoxic and immunosuppressive activities, but less is known about later stages. Here, we revisit the role of mycolactone in disease outcome and provide the first demonstration of the pro-inflammatory potential of this toxin. We found that the mycolactone-containing mycobacterial extracellular vesicles produced by M. ulcerans induced the production of IL-1ß, a potent pro-inflammatory cytokine, in a TLR2-dependent manner, targeting NLRP3/1 inflammasomes. We show our data to be relevant in a physiological context. The in vivo injection of these mycolactone-containing vesicles induced a strong local inflammatory response and tissue damage, which were prevented by corticosteroids. Finally, several soluble pro-inflammatory factors, including IL-1ß, were detected in infected tissues from mice and Buruli ulcer patients. Our results revisit Buruli ulcer pathophysiology by providing new insight, thus paving the way for the development of new therapeutic strategies taking the pro-inflammatory potential of mycolactone into account.


Assuntos
Úlcera de Buruli/imunologia , Inflamação/imunologia , Interleucina-1beta/imunologia , Macrolídeos/imunologia , Animais , Úlcera de Buruli/metabolismo , Úlcera de Buruli/patologia , Vesículas Extracelulares/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/microbiologia , Interleucina-1beta/metabolismo , Macrolídeos/metabolismo , Macrolídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium ulcerans
10.
J Clin Exp Hepatol ; 10(6): 555-562, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33311892

RESUMO

AIMS: Telemedicine between health care providers could be useful for improving the access to hepatology consultations, which is challenging in some regions. The primary objective of this study was to estimate the proportion of consultations that were resolved through a telemedicine program. Additionally, we evaluated patient satisfaction with this strategy. METHODS: Consecutive telemedicine consultations made by non-hepatologist health care providers from different regions of Argentina to a specialty hepatology team were included. Participants and hepatologists used e-mail, teleconference systems, WhatsApp, or telephone to interact, depending on their preferences. Consultations were considered to be resolved through telemedicine when a diagnosis and an adequate follow-up were achieved without the need to refer the patient to a hepatologist or other specialist. Patient satisfaction with telemedicine was evaluated using the Patient Satisfaction Questionnaire Short Form and Telemedicine Satisfaction Questionnaire. RESULTS: A total of 200 telemedicine consultations made by 24 physicians from 10 different provinces of Argentina were evaluated, of which 145 (73%; 95% CI: 66%-79%) were resolved through telemedicine. Practitioners specialities were as follows: family physicians, internists, gastroenterologists, infectious diseases, and obstetrics. The most frequent final diagnoses for those patients whose consultation was resolved through telemedicine were non-alcoholic fatty liver disease, viral hepatitis, and benign hepatic lesions. A high degree of patient satisfaction with telemedicine was observed in both questionnaires. CONCLUSIONS: Our results show the effectiveness of telemedicine in hepatology, with high resolution rate of consultations and rapid access to experts' assessment. Additionally, a high degree of patient satisfaction was observed using prevalidated questionnaires.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32823494

RESUMO

Purpose: This study examinedthe independent and joint association of fitness and fatness with clustered cardiovascular disease risk (CVDrs) in 11-18 year-old Nigerian adolescents. Methods: A hundred and ninety seven adolescents (100 girls and 97 boys) were evaluated forfitness, fatness and CVDrs. Fitness was evaluated with the progressive aerobic cardiovascular endurance run test while fatness was assessed using body mass index. A clustered CVDrs was computed from the standardized residuals of total cholesterol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, triglycerides, plasma glucose, systolic blood pressure, and diastolic blood pressure. Regression models controlling for waist circumference assessed the association of fitness and fatness with CVDrs. Results: Prevalence of clustered CVD risk was 7.1% (girls = 3.0%; boys = 4.1%). Based on risk factor abnormalities, 52.8% of participants had one or more CVD risk factor abnormalities with more boys (27.4%) affected. Low fitness was associated with clustered CVDrs in both girls (R2 = 9.8%, ß = -0.287, p = 0.05) and boys (R2 = 17%, ß = -0.406, p < 0.0005). Fatness was not associated with the CVDrs in both sexes. After controlling for all the variables in the model, only fitness (R2 = 10.4%) and abdominal fat (R2 = 19.5%) were associated with CVDrs respectively. Unfit girls were 3.2 (95% CI = 1.31-7.91, p = 0.011) times likely to develop CVD risk abnormality compared to their fit counterparts. The likelihood of unfit boys developing CVD risk abnormality was 3.9 (95% CI = 1.15-10.08, p = 0.005) times compared to their fit peers. Conclusions: Fitness but not fatness was a better predictor of CVDrs in Nigerian boys and girls. The result of this study suggests that any public health strategies aimed at preventing or reversing the increasing trends of CVD risk in adolescents should emphasize promotion of aerobic fitness.


Assuntos
Adiposidade , Índice de Massa Corporal , Doenças Cardiovasculares , Aptidão Física , Adolescente , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Nigéria/epidemiologia , Fatores de Risco
13.
Cell Rep ; 28(9): 2264-2274.e3, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461644

RESUMO

Generation of neuronal types at the right time, location, and number is essential for building a functional nervous system. Significant progress has been reached in understanding the mechanisms that govern neuronal diversity. Cerebrospinal fluid-contacting neurons (CSF-cNs), an intriguing spinal cord central canal population, are produced during advanced developmental stages, simultaneous with glial and ependymal cells. It is unknown how CSF-cNs are specified after the neurogenesis-to-gliogenesis switch. Here, we identify delayed Ascl1 expression in mouse spinal progenitors during the gliogenic phase as key in CSF-cN differentiation. With fate mappings and time-controlled deletions, we demonstrate that CSF-cNs derive from Ascl1-expressing cells and that Ascl1 triggers late neurogenesis in the amniote spinal cord. Ascl1 abrogation transforms prospective CSF-cN progenitors into ependymocytes. These results demonstrate that late spinal progenitors have the potential to produce neurons and that Ascl1 initiates CSF-cN differentiation, controlling the precise neuronal and nonneuronal composition of the spinal central canal.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Epêndima/metabolismo , Neurogênese , Neurônios/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Epêndima/citologia , Camundongos , Neurônios/citologia , Medula Espinal/citologia , Medula Espinal/embriologia , Medula Espinal/metabolismo , Peixe-Zebra
15.
Rev. Asoc. Méd. Argent ; 131(1): 4-9, mar. 2018.
Artigo em Espanhol | LILACS | ID: biblio-973092

RESUMO

Alejandro Posadas fue un destacado cirujano en la Buenos Aires del siglo XIX. Sus trabajos contribuyeron al desarrollo del conocimiento médico. El objetivo del presente artículo es describir las actividades de Alejandro Posadas desde perspectivas diferentes: cirugía, investigación, educación médica y la innovación que sus métodos aportaron al proceso de enseñanza-aprendizaje.


Alejandro Posadas was a renowned surgeon in the Buenos Aires of the XIX century. His works contributed to the development of medical knowledge. The purpose of present research article is to describe the activities of Alejandro Posadas from different perspectives: surgery research, medical education and that the innovation of his methods brought them in the teaching and learning processes.


Assuntos
Humanos , História do Século XIX , História do Século XX , Cirurgiões/história , Educação Médica/história , Cirurgia Torácica/educação , Cirurgia Torácica/história , História da Medicina , Médicos/história , Pesquisa/história , Recursos Audiovisuais/história , Filmes Cinematográficos/história , Argentina
16.
Artigo em Inglês | MEDLINE | ID: mdl-28632175

RESUMO

There is substantial evidence of rising prevalence of overweight and obesity and its co-morbidities among children in western-high income developed countries. In the European Union, the prevalence of overweight and obesity is increasing fastest among Polish children. Yet, there is paucity of evidence on the relationship of behavioral factors with body weight status of children in Poland. This study examined the association of obesity with physical fitness, physical activity, sedentary behavior and diet among Polish children. A total of 641 children (10-15 years) recruited from the Lower Silesia region of Poland participated in this cross-sectional study. Participants' anthropometrics, physical fitness, physical activity, sedentary behavior and dietary intake were assessed. Outcome variables were weight categories (according to body mass index [BMI], waist-to-hip ratio [WHR], and percentage body fat [% BF]). The strongest negative correlation was found between VO2max and %BF (r = -0.39, p <0.05). Significant negative correlation was also found between VO2max and weight categories (r = -0.15). Results of the multinomial logit analysis showed that VO2max increased in groups of overweight, normal weight and underweight children by 13%, 26% and 19%, respectively as compared to the group of obese children. VO2max and weight and obesity indices were strongly correlated in both gender and age groups. Education and intervention programs to increase physical fitness (VO2max) through aerobic training are recommended for Physical Education teachers, parents and children in order to reduce the rate of overweight and obesity among children in the Lower Silesia region of Poland.


Assuntos
Dieta , Exercício Físico , Obesidade Infantil/epidemiologia , Aptidão Física , Comportamento Sedentário , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade Infantil/etiologia , Polônia/epidemiologia , Prevalência , Fatores de Risco
17.
Int J Tuberc Lung Dis ; 20(12): 1639-1646, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27931340

RESUMO

SETTING: The utility of interferon-gamma release assays (IGRAs), such as the QuantiFERON-TB Gold In-Tube (QFT-GIT) test, in diagnosing active tuberculosis (TB) in children is unclear and depends on the epidemiological setting. OBJECTIVE: To evaluate the performance of QFT-GIT for TB diagnosis in children living in Morocco, an intermediate TB incidence country with high bacille Calmette-Gurin vaccination coverage. DESIGN: We prospectively recruited 109 Moroccan children hospitalised for clinically suspected TB, all of whom were tested using QFT-GIT. RESULTS: For 81 of the 109 children, the final diagnosis was TB. The remaining 28 children did not have TB. QFT-GIT had a sensitivity of 66% (95%CI 5277) for the diagnosis of TB, and a specificity of 100% (95%CI 88100). The tuberculin skin test (TST) had lower sensitivity, at 46% (95%CI 3360), and its concordance with QFT-GIT was limited (69%). Combining QFT-GIT and TST results increased sensitivity to 83% (95%CI 6992). CONCLUSION: In epidemiological settings such as those found in Morocco, QFT-GIT is more sensitive than the TST for active TB diagnosis in children. Combining the TST and QFT-GIT would be useful for the diagnosis of active TB in children, in combination with clinical, radiological and laboratory data.


Assuntos
Testes de Liberação de Interferon-gama , Teste Tuberculínico , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Vacina BCG/administração & dosagem , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Marrocos/epidemiologia , Estudos Prospectivos , Sensibilidade e Especificidade , Tuberculose/prevenção & controle , Vacinação
18.
Sci Data ; 3: 160018, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26978244

RESUMO

There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders-representing academia, industry, funding agencies, and scholarly publishers-have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.


Assuntos
Coleta de Dados , Curadoria de Dados , Projetos de Pesquisa , Sistemas de Gerenciamento de Base de Dados , Guias como Assunto , Reprodutibilidade dos Testes
19.
Development ; 143(5): 880-91, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26839365

RESUMO

Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells.


Assuntos
Líquido Cefalorraquidiano/metabolismo , Neurônios/citologia , Medula Espinal/embriologia , Medula Espinal/fisiologia , Animais , Diferenciação Celular , Linhagem da Célula , Eletrofisiologia , Proteínas do Olho/genética , Feminino , Fatores de Transcrição Forkhead/genética , Fator de Transcrição GATA2/genética , Genótipo , Imuno-Histoquímica , Hibridização In Situ , Interneurônios/citologia , Camundongos , Neurônios Motores/citologia , Células-Tronco/citologia
20.
Hum Genet ; 135(3): 299-307, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26767831

RESUMO

Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10(-4). The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10(-6) < p < 4 × 10(-5)): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10(-6)) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB.


Assuntos
Estudo de Associação Genômica Ampla , Tuberculose Pulmonar/genética , Adolescente , Adulto , Idade de Início , Idoso , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Loci Gênicos , Técnicas de Genotipagem , Humanos , Lactente , Íntrons , Masculino , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Marrocos , Mycobacterium tuberculosis , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Reprodutibilidade dos Testes , Fatores de Risco , Tuberculose Pulmonar/microbiologia , Adulto Jovem
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