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1.
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.

2.
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
3.
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
4.
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
5.
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
6.
Gut ; 64(10): 1605-15, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25214320

RESUMO

OBJECTIVE: The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. DESIGN: We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥ 0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥ 20 g/day for ≥ 5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR. RESULTS: Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. CONCLUSIONS: Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.


Assuntos
Hepacivirus/genética , Hepatite C Crônica/complicações , Cirrose Hepática/etiologia , Polimorfismo de Nucleotídeo Único , RNA Viral/análise , Medição de Risco/métodos , Biópsia , Progressão da Doença , Feminino , Estudo de Associação Genômica Ampla , Hepatite C Crônica/virologia , Humanos , Incidência , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Suíça/epidemiologia , Fatores de Tempo
7.
J Neurosci ; 34(46): 15223-33, 2014 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-25392491

RESUMO

The development of the nervous system is critically dependent on the production of functionally diverse neuronal cell types at their correct locations. In the embryonic neural tube, dorsoventral signaling has emerged as a fundamental mechanism for generating neuronal diversity. In contrast, far less is known about how different neuronal cell types are organized along the rostrocaudal axis. In the developing mouse and chick neural tube, hindbrain serotonergic neurons and spinal glutamatergic V3 interneurons are produced from ventral p3 progenitors, which possess a common transcriptional identity but are confined to distinct anterior-posterior territories. In this study, we show that the expression of the transcription factor Neurogenin3 (Neurog3) in the spinal cord controls the correct specification of p3-derived neurons. Gain- and loss-of-function manipulations in the chick and mouse embryo show that Neurog3 switches ventral progenitors from a serotonergic to V3 differentiation program by repressing Ascl1 in spinal p3 progenitors through a mechanism dependent on Hes proteins. In this way, Neurog3 establishes the posterior boundary of the serotonergic system by actively suppressing serotonergic specification in the spinal cord. These results explain how equivalent p3 progenitors within the hindbrain and the spinal cord produce functionally distinct neuron cell types.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Diferenciação Celular , Proteínas do Tecido Nervoso/fisiologia , Rombencéfalo/citologia , Neurônios Serotoninérgicos/citologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Embrião de Galinha , Regulação da Expressão Gênica no Desenvolvimento , Interneurônios/fisiologia , Camundongos , Proteínas do Tecido Nervoso/biossíntese , Proteínas Repressoras/biossíntese , Proteínas Repressoras/fisiologia , Rombencéfalo/metabolismo , Medula Espinal/metabolismo , Medula Espinal/fisiologia , Células-Tronco/metabolismo , Células-Tronco/fisiologia
8.
J Acoust Soc Am ; 138(4): 2537-47, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26520336

RESUMO

Scattering from a cavity in a soft elastic medium, such as silicone rubber, resembles scattering from an underwater bubble in that low-frequency monopole resonance is obtainable in both cases. Arrays of cavities can therefore be used to reduce underwater sound transmission using thin layers and low void fractions. This article examines the role of cavity shape by microfabricating arrays of disk-shaped air cavities into single and multiple layers of polydimethylsiloxane. Comparison is made with the case of equivalent volume cylinders which approximate spheres. Measurements of ultrasonic underwater sound transmission are compared with finite element modeling predictions. The disks provide a deeper transmission minimum at a lower frequency owing to the drum-type breathing resonance. The resonance of a single disk cavity in an unbounded medium is also calculated and compared with a derived estimate of the natural frequency of the drum mode. Variation of transmission is determined as a function of disk tilt angle, lattice constant, and layer thickness. A modeled transmission loss of 18 dB can be obtained at a wavelength about 20 times the three-layer thickness, and thinner results (wavelength/thickness ∼ 240) are possible for the same loss with a single layer depending on allowable hydrostatic pressure.

9.
Ecotoxicol Environ Saf ; 109: 48-55, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25164202

RESUMO

In aquatic ecosystems several stressors may act together and affect the life traits of organisms. Pesticide runoffs are usually associated with high inputs of organic matter and depletion of oxygen in aquatic systems. This study aimed at combining anthropogenic stress (chemicals) and natural stress (food availability) and evaluates their joint effect to the life traits of Daphnia magna. The neonicotinoid insecticide imidacloprid and the heavy metal nickel chloride were used and a 21 d chronic test was carried out to obtain reproduction and growth data. The conceptual model Independent action, usually used for assessing response patterns in chemical mixtures, was used for data interpretation. Results showed an increase in the reproduction and growth pattern of D. magna as food levels increased. Both chemicals significantly impaired the reproduction as well as the somatic growth of the organism while the same happened with food concentrations lower than 3×10(5) cells/mL. It was also observed that food availability did not change the toxicity of imidacloprid and nickel chloride when food levels were higher than 3×10(5) cells/mL. When combined with low food levels, imidacloprid showed a slight increase in toxicity, showing that daphnids become more sensitive with reduced food availability, however in a non-significant way. However, toxicity of nickel appeared to be independent of the food level. Both chemicals induced mortality to the organisms exposed in the absence of food only at the end of the test.


Assuntos
Daphnia/efeitos dos fármacos , Dieta , Poluentes Químicos da Água/toxicidade , Animais , Tamanho Corporal/efeitos dos fármacos , Daphnia/crescimento & desenvolvimento , Imidazóis/toxicidade , Inseticidas/toxicidade , Neonicotinoides , Níquel/toxicidade , Nitrocompostos/toxicidade , Reprodução/efeitos dos fármacos , Testes de Toxicidade
10.
Acta Gastroenterol Latinoam ; 44(3): 257-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26742300

RESUMO

Barrett's esophagus (BE), consequence of chronic gastroesophageal reflux disease (GERD), is a premalignant condition, capable of turning into adenocarcinoma (ACa). However, the presence ofsquamous cell carcinoma (SCa) coexisting with Barrett's metaplasia is reported in some papers. The aim of this paper is to present 17 patients involving synchronous BE and SCa.


Assuntos
Esôfago de Barrett/complicações , Carcinoma de Células Escamosas/complicações , Neoplasias Esofágicas/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
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.

12.
Pathol Biol (Paris) ; 61(1): 11-6, 2013 Jan.
Artigo em Francês | MEDLINE | ID: mdl-23399414

RESUMO

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major public health problem worldwide, resulting in 8.7 million new cases and 1.4 million deaths each year. One third of the world's population is exposed to M. tuberculosis and, after exposure, most, but not all, individuals become infected. Among infected subjects, only a minority (∼10%) will eventually develop clinical disease, which is typically either a primary, often extra-pulmonary, TB in children, or a reactivation, pulmonary TB in adults. Considerable genetic epidemiological evidence has accumulated to support a major role for human genetic factors in the development of TB. Numerous association studies with various candidate genes have been conducted in pulmonary TB, with very few consistent results. Recent genome-wide association studies revealed only a modest role for two inter-genic polymorphisms. However, a first major locus for pulmonary TB was mapped to chromosome 8q12-q13 in a Moroccan population after a genome-wide linkage screen. Using a similar strategy, two other major loci controlling TB infection were recently identified. While the precise identification of these major genes is ongoing, the other fascinating observation of these last years was the demonstration that TB can also reflect a Mendelian predisposition. Following the findings obtained in the syndrome of Mendelian susceptibility to mycobacterial diseases, several children with complete IL-12Rß1 deficiency, were found to have severe TB as their sole phenotype. Overall, these recent findings provide the proof of concept that the human genetics of TB involves a continuous spectrum from Mendelian to complex predisposition with intermediate major gene involvement. The understanding of the molecular genetic basis of TB will have fundamental immunological and medical implications, in particular for the development of new vaccines and treatments.


Assuntos
Predisposição Genética para Doença , Tuberculose/genética , Adulto , Idade de Início , Criança , Estudo de Associação Genômica Ampla , Humanos , Índice de Gravidade de Doença , Tuberculose/epidemiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/genética
13.
Nat Genet ; 14(2): 181-4, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8841190

RESUMO

Three hundred million individuals are at risk of infection by schistosomes and around 200,000 die each year of this disease. Severe clinical disease in schistosomiasis is often the consequence of heavy infection which, in several endemic areas, are determined largely by the susceptibility/resistance of individuals. Previously, we reported evidence, based on a segregation analysis in Brazilian pedigrees, that intensity of infection by Schistosoma mansoni was influenced by a major gene, indicating that host genetic factors are probably critical in controlling schistosome infection and disease development. To localize this gene, referred to as SM1, we performed a genome-wide study on 142 Brazilian subjects belonging to 11 informative families Our results show a linkage to only one region, on chromosome 5q31-q33, with maximum two-point lod scores of +4.74 and +4.52 for D5S636 and the colony stimulating factor-1 receptor marker (CSF1R), respectively. This was corroborated by multipoint analysis, indicating a close proximity to CSF1R as the most likely location of SM1. This region contains several candidate genes encoding immunological molecules that were shown to play important roles in human protection against schistosomes.


Assuntos
Cromossomos Humanos Par 5/genética , Ligação Genética , Esquistossomose mansoni/genética , Brasil , Mapeamento Cromossômico , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Repetições de Microssatélites , Linhagem , Receptor de Fator Estimulador de Colônias de Macrófagos/genética
14.
Nat Genet ; 4(4): 346-50, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8401580

RESUMO

Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5,000 newborns) of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut. Taking advantage of a proximal deletion of chromosome 10q (del 10q11.2-q21.2) in a patient with total colonic aganglionosis, and of a high-density genetic map of microsatellite DNA markers, we performed genetic linkage analysis in 15 non-syndromic long-segment and short-segment HSCR families. Multipoint linkage analysis indicated that the most likely location for a HSCR locus is between loci D10S208 and D10S196, suggesting that a dominant gene for HSCR maps to 10q11.2, a region to which other neural crest defects have been mapped.


Assuntos
Cromossomos Humanos Par 10 , Doença de Hirschsprung/genética , Sequência de Bases , Mapeamento Cromossômico , DNA Satélite/genética , Família , Feminino , Ligação Genética , Genótipo , Humanos , Recém-Nascido , Masculino , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Linhagem , Reação em Cadeia da Polimerase/métodos
15.
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.

16.
Trop Med Int Health ; 17(11): 1369-75, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22974459

RESUMO

OBJECTIVE: To evaluate demographic variation in the prevalence of overweight (OW) and obesity (OB) among 3240 children and adolescents (girls: n = 1714; boys: n = 1526) aged 9-16 years attending primary and secondary schools in Benue State of Nigeria. METHODS: Participants' anthropometric characteristics (body weight, stature, body mass index: BMI and lean body mass: LBM) were determined using standard protocols. OW and OB were estimated using International Obesity task Force diagnostic criteria. Data were analysed with one-way anova and binary logistic regression method. RESULTS: Overall, 88.5%, 9.7% and 1.8% of the adolescents had normal BMI and were OW and obese, respectively. Prevalence of OW was higher among girls (20.3%) than boys (16.2%), whereas a relatively higher incidence of OB was noted among the boys (3.5%). Girls in urban areas had a significantly higher BMI (t524 = 3.61, P = 0.002) than their rural peers, but the rural girls were more significantly OW than their urban counterparts (BMI: t1186 = 2.506). Logistic regression models assessing the influence of age, gender and location on OW/OB in children (α(2) (3, N = 1014) = 6.185, P = 0.103) and adolescents (α(2) (3, N = 2226) = 1.435, P = 0.697) did not turn up significant results. In the gender-specific analysis, the younger boys' model was also not significant (α(2) (2, N = 488) = 1.295, P = 0.523) in contrast to the girls' (α(2) (2, N = 526) = 15.637, P = 0.0005), thus discriminating between OW and healthy weight among the children. Overall, the model explained 2.9-4.4% of the variance in weight status and correctly classified 76.8% of the cases. Age wise, the model yielded a significant odds ratio of 1.49, suggesting that the likelihood of being OW increases by a factor of 1.5 with a unit increase in age. Also, the likelihood of an urban girl becoming OW or obese was 0.57 times that of a rural girl. CONCLUSIONS: In general, girls in urban areas had higher prevalence of OW and OB than girls in rural settings. Among the boys, similar but less marked trends were found, except that the rural boys tended to be more OW on average than their peers in urban areas. In view of its public health significance, it is important to periodically evaluate the prevalence of weight disorders in children and adolescents so that appropriate preventative strategies can be instituted.


Assuntos
Antropometria , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Saúde Pública/estatística & dados numéricos , Adolescente , Estatura , Índice de Massa Corporal , Peso Corporal , Criança , Feminino , Humanos , Masculino , Nigéria/epidemiologia , Prevalência , Saúde da População Rural , Fatores Sexuais , Saúde da População Urbana
17.
Mol Cell Biochem ; 366(1-2): 123-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22476863

RESUMO

Central to the maintenance of genomic integrity is the cellular DNA damage response. Depending on the type of genotoxic stress and through the activation of multiple signaling cascades, it can lead to cell cycle arrest, DNA repair, senescence, and apoptosis. p19INK4d, a member of the INK4 family of CDK inhibitors, plays a dual role in the DNA damage response, inhibiting cell proliferation and promoting DNA repair. Consistently, p19INK4d has been reported to become upregulated in response to UV irradiation and a great variety of genotoxic agents. Here, this induction is shown to result from a transcriptional stimulatory mechanism that can occur at every phase of the cell cycle except during mitosis. Moreover, evidence is presented that demonstrates that E2F1 is involved in the induction of p19INK4d following UV treatment, as it is prevented by E2F1 protein ablation and DNA-binding inhibition. Specific inhibition of this regulation using triplex-forming oligonucleotides that target the E2F response elements present in the p19INK4d promoter also block p19INK4d upregulation and sensitize cells to DNA damage. These results constitute the first description of a mechanism for the induction of p19INK4d in response to UV irradiation and demonstrate the physiological relevance of this regulation following DNA damage.


Assuntos
Inibidor de Quinase Dependente de Ciclina p19/metabolismo , Dano ao DNA , Fator de Transcrição E2F1/metabolismo , Ativação Transcricional/efeitos da radiação , Raios Ultravioleta , Animais , Ciclo Celular , Cricetinae , Inibidor de Quinase Dependente de Ciclina p19/genética , DNA/farmacologia , Reparo do DNA , Fator de Transcrição E2F1/antagonistas & inibidores , Fator de Transcrição E2F1/fisiologia , Células HEK293 , Humanos , Elementos de Resposta , Transcrição Gênica/efeitos da radiação
18.
Eur J Neurol ; 19(3): 462-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22329857

RESUMO

BACKGROUND AND PURPOSE: Niemann-Pick disease type C (NPC) is a progressive neurovisceral disorder associated with dystonia, ataxia and a characteristic gaze palsy. Neuropathological studies have demonstrated brainstem atrophy associated with neuronal inclusions and loss, and neurofibrillary tangles, although it is not known whether this pathology can be detected in vivo or how these changes relate to illness variables, particularly ocular-motor changes. Our aim was to utilize a method for brainstem atrophy, validated in progressive supranuclear palsy (PSP), in a group of adult patients with NPC, and explore its relationship to illness variables and ocular-motor functioning. METHODS: We calculated the midbrain and pontine area, and pontine-to-midbrain ratio (PMR) from midsagittal images of 10 adult patients with NPC and 27 age- and gender-matched controls. Measures were correlated with illness variables, and measures of horizontal saccadic functioning. RESULTS: Pontine-to-midbrain ratio was 14% higher in the NPC group, but this difference was not significant. However, PMR showed a significant positive correlation with duration of illness and a measure of illness severity. Furthermore, PMR was significantly negatively correlated with saccadic peak velocity and gain, and self-paced saccadic performance. CONCLUSIONS: Pontine-to-midbrain ratio was increased in adult patients with NPC compared to controls, although not to the same degree as previously described in PSP, which also presents with significant gaze palsy. These changes were driven predominantly by progressive midbrain atrophy. The strong correlation with illness and ocular-motor variables suggests that it may be a useful marker for illness progression in NPC.


Assuntos
Tronco Encefálico/patologia , Doença de Niemann-Pick Tipo C/patologia , Movimentos Sacádicos/fisiologia , Adolescente , Adulto , Tronco Encefálico/fisiopatologia , Progressão da Doença , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Niemann-Pick Tipo C/complicações , Doença de Niemann-Pick Tipo C/fisiopatologia , Adulto Jovem
19.
J Acoust Soc Am ; 132(1): EL1-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22779566

RESUMO

Axisymmetric monopole resonances of an oblate spheroidal cavity in a soft elastic medium are computed using both separation of variables and finite-element approaches. The resonances are obtained for compression wavelengths much longer than the cavity size and thus have a low-frequency character. Resonant frequencies for high-aspect-ratio oblate spheroids (either air-filled or evacuated) are found to be significantly lower than their spherical counterparts with equivalent volume. This finding contrasts with the case of an air bubble in water which features weak shape dependence. The results are relevant to the design of locally-resonant acoustic media using soft-lithography techniques with elastomers.

20.
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
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