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1.
PLoS One ; 18(2): e0282095, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36812257

RESUMO

BACKGROUND: Cross-border use of health services is an important aspect of life in border regions. Little is known about the cross-border use of health services in neighboring low- and middle-income countries. Understanding use of health services in contexts of high cross-border mobility, such as at the Mexico-Guatemala border, is crucial for national health systems planning. This article aims to describe the characteristics of the cross-border use of health care services by transborder populations at the Mexico-Guatemala border, as well as the sociodemographic and health-related variables associated with use. METHODS: Between September-November 2021, we conducted a cross-sectional survey using a probability (time-venue) sampling design at the Mexico-Guatemala border. We conducted a descriptive analysis of cross-border use of health services and assessed the association of use with sociodemographic and mobility characteristics by means of logistic regressions. RESULTS: A total of 6,991 participants were included in this analysis; 82.9% were Guatemalans living in Guatemala, 9.2% were Guatemalans living in Mexico, 7.8% were Mexicans living in Mexico, and 0.16% were Mexicans living in Guatemala. 2.6% of all participants reported having a health problem in the past two weeks, of whom 58.1% received care. Guatemalans living in Guatemala were the only group reporting cross-border use of health services. In multivariate analyses, Guatemalans living in Guatemala working in Mexico (compared to not working in Mexico) (OR 3.45; 95% CI 1.02,11.65), and working in agriculture/cattle, industry, or construction while in Mexico (compared to working in other sectors) (OR 26.67; 95% CI 1.97,360.85), were associated with cross-border use. CONCLUSIONS: Cross-border use of health services in this region is related to transborder work (i.e., circumstantial use of cross-border health services). This points to the importance of considering the health needs of migrant workers in Mexican health policies and developing strategies to facilitate and increase their access to health services.


Assuntos
Serviços de Saúde , Migrantes , Animais , Bovinos , Humanos , México , Guatemala , Estudos Transversais , Acesso aos Serviços de Saúde
2.
Front Public Health ; 10: 921417, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910916

RESUMO

Background: Migrants in Mexico are entitled to care at all levels, independently of their migration status. However, previous studies show that access to care is difficult for this population. As the movement of in-transit migrants and asylum seekers has been interrupted at the Mexico-United States border by migration policies such as the "Remain in Mexico" program, and by border closures due to the COVID-19 pandemic, the Mexican health system has the challenge of providing them with health care. Levesque et al.'s framework, according to which access occurs at the interface of health system characteristics and potential users' abilities to interact with it, is a useful theoretical tool to analyze the barriers faced by migrants. Objective: The objective of this article is to analyze the barriers to access the public Mexican health system, encountered by migrants in cities in Mexican states at the Mexico-United States border during the COVID-19 pandemic. Methods: Data came from a multiple case study of the response of migrant shelters to health care needs during the COVID-19 pandemic. The study consisted of a non-probability survey of migrants with a recent health need, and interviews with persons working in civil society organizations providing services to migrants, governmental actors involved in the response to migration, and academics with expertise in the subject. We analyzed the quantitative and qualitative results according to Levesque et al.'s framework. Results: 36/189 migrants surveyed had sought health care in a public service. The main limitations to access were in the availability and accommodation dimension (administrative barriers decreasing migrants' ability to reach the system), and the affordability dimension (out-of-pocket costs limiting migrants' ability to pay). Civil society organizations were a major source of social support, helping migrants overcome some of the barriers identified. Conclusions: While Mexico's health regulations are inclusive of migrants, in practice there are major barriers to access public health services, which might inhibit migrants from seeking those services. In order to comply with its commitment to guarantee the right to health of all persons, the Mexican health authorities should address the implementation gap between an inclusive policy, and the barriers to access that still remain.


Assuntos
COVID-19 , Migrantes , COVID-19/epidemiologia , Acesso aos Serviços de Saúde , Humanos , México , Pandemias , Política Pública , Estados Unidos
3.
Artigo em Inglês | MEDLINE | ID: mdl-35682502

RESUMO

Assessing COVID-19 vaccination uptake of transborder populations is critical for informing public health policies. We conducted a probability (time-venue) survey of adults crossing from Mexico into Guatemala from September to November 2021, with the objective of describing COVID-19 vaccination status, willingness to get vaccinated, and associated factors. The main outcomes were receipt of ≥1 dose of a COVID-19 vaccine, being fully vaccinated, and willingness to get vaccinated. We assessed the association of outcomes with sociodemographic characteristics using logistic regressions. Of 6518 participants, 50.6% (95%CI 48.3,53.0) were vaccinated (at least one dose); 23.3% (95%CI 21.4,25.2) were unvaccinated but willing to get vaccinated, and 26.1% (95%CI 24.1,28.3) were unvaccinated and unwilling to get vaccinated. Those living in Mexico, independent of country of birth, had the highest proportion vaccinated. The main reason for unwillingness was fear of side effects of COVID-19 vaccines (47.7%, 95%CI 43.6,51.9). Education level was positively associated with the odds of partial and full vaccination as well as willingness to get vaccinated. People identified as Catholic had higher odds of getting vaccinated and being fully vaccinated than members of other religious groups or the non-religious. Further studies should explore barriers to vaccination among those willing to get vaccinated and the motives of the unwilling.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , COVID-19/prevenção & controle , Estudos Transversais , Guatemala , Conhecimentos, Atitudes e Prática em Saúde , Humanos , México , Vacinação
4.
J Migr Health ; 6: 100110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35540795

RESUMO

Introduction: In the context of a health contingency such as the current COVID-19 pandemic, some groups may remain invisible, so that their health needs go unnoticed. These groups include migrants, asylum seekers, and refugees (MAR). In Mexico there is a network of migrant shelters (casas del migrante-CM) that provide humanitarian assistance, including access to heath care. Given the major role of the CM in caring for migrants, it was important to identify the main elements of their internal capacities, and of the external resources in the cities in which they are located, that contributed to their role in protecting MRA`s health during the COVID-19 pandemic. Methods: we use a comparative case study approach to understand, explain, and compare how internal capacities and external resources available to four CM in the north of Mexico, influenced the development and implementation of COVID-19 related strategies to protect MRA. The project took place during 2021 in Saltillo and Piedras Negras in Coahuila; Ciudad Juarez, Chihuahua, and in Monterrey, Nuevo Leon. A total of 18 in-depth interviews were performed with key actors from the CM, academia, health care services and international agencies. Results: We found a range from a total closure of one CM, to the continuation of operation of three of them, with differences in the strategies developed to provide services and avoid infections within the facilities. MARs' still face multiple barriers to exercise their right to health, and the response of local governments towards migration and health impacts the response that CM were able to implement. Conclusion: There is a need to strengthening the preparedness and response capacities and coordination mechanisms of local, state and federal authorities to attain their responsibilities in the provision of services directed to MAR, including access to health care.

6.
Nat Commun ; 10(1): 5021, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685819

RESUMO

The world's first superconducting megahertz repetition rate hard X-ray free-electron laser (XFEL), the European XFEL, began operation in 2017, featuring a unique pulse train structure with 886 ns between pulses. With its rapid pulse rate, the European XFEL may alleviate some of the increasing demand for XFEL beamtime, particularly for membrane protein serial femtosecond crystallography (SFX), leveraging orders-of-magnitude faster data collection. Here, we report the first membrane protein megahertz SFX experiment, where we determined a 2.9 Å-resolution SFX structure of the large membrane protein complex, Photosystem I, a > 1 MDa complex containing 36 protein subunits and 381 cofactors. We address challenges to megahertz SFX for membrane protein complexes, including growth of large quantities of crystals and the large molecular and unit cell size that influence data collection and analysis. The results imply that megahertz crystallography could have an important impact on structure determination of large protein complexes with XFELs.


Assuntos
Elétrons , Lasers , Proteínas de Membrana/química , Cristalografia , Cianobactérias/metabolismo , Modelos Moleculares , Complexo de Proteína do Fotossistema I/química , Complexo de Proteína do Fotossistema I/isolamento & purificação , Eletricidade Estática , Síncrotrons , Thermosynechococcus , Raios X
7.
Arch Esp Urol ; 68(7): 627-32, 2015 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-26331400

RESUMO

OBJECTIVE: To report two cases of emphysematous cystitis, a rare, potentially serious disease. METHODS: Analysis of two different cases treated in our center and review of the existing literature. RESULTS: One patient underwent emergency surgery (radical cystectomy) due to the advanced stage of the disease. The second patient, whose was in an initial stage, benefited from a new treatment, consisting of hyperbaric oxygen and wide spectrum antibiotics. CONCLUSIONS: Early diagnosis is the cornerstone of the conservative management of the disease. Hyperbaric oxygen therapy may be beneficial due to the improvement in oxygenation of the tissues affected by the disease.


Assuntos
Cistite/complicações , Enfisema/complicações , Idoso , Idoso de 80 Anos ou mais , Cistite/diagnóstico , Cistite/terapia , Enfisema/diagnóstico , Enfisema/terapia , Feminino , Humanos , Masculino , Resultado do Tratamento
8.
Arch. esp. urol. (Ed. impr.) ; 68(7): 627-632, sept. 2015. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-144575

RESUMO

OBJETIVO: Reportar dos nuevos casos de cistitis enfisematosa, una patología poco frecuente pero potencialmente grave. MÉTODO: Análisis de dos casos tratados en nuestro centro de diferente forma y revisión de la literatura. RESULTADO: El primer paciente dado lo avanzado del caso tuvo que ser sometido a una cistectomía radical urgente; el segundo, se benefició de un tratamiento conservador y novedoso, al ser sometido a dos sesiones de oxigenoterapia hiperbárica. CONCLUSIONES: Es importante un diagnóstico precoz de esta patología. La oxigenoterapia hiperbárica puede ser beneficiosa debido a la mejora en la oxigenación de los tejidos afectos por la enfermedad


OBJECTIVE: To report two cases of emphysematous cystitis, a rare, potentially serious disease. METHODS: Analysis of two different cases treated in our center and review of the existing literature. RESULTS: One patient underwent emergency surgery (radical cystectomy) due to the advanced stage of the disease. The second patient, whose was in an initial stage, benefited from a new treatment, consisting of hyperbaric oxygen and wide spectrum antibiotics. CONCLUSIONS: Early diagnosis is the cornerstone of the conservative management of the disease. Hyperbaric oxygen therapy may be beneficial due to the improvement in oxygenation of the tissues affected by the disease


Assuntos
Feminino , Humanos , Masculino , Colecistite Enfisematosa/patologia , Colecistite Enfisematosa/urina , Sistema Urinário/anormalidades , Sistema Urinário/lesões , Pielite/urina , Diabetes Mellitus/diagnóstico , Hematúria/sangue , Cistectomia/métodos , Cistectomia/normas , Colecistite Enfisematosa/complicações , Colecistite Enfisematosa/metabolismo , Sistema Urinário/metabolismo , Sistema Urinário/patologia , Diabetes Mellitus/patologia , Hematúria/urina , Cistectomia/instrumentação , Cistectomia , Literatura de Revisão como Assunto
9.
Pediatr Infect Dis J ; 33(10): 1004-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25361185

RESUMO

BACKGROUND: Studies examining the etiology-specific effects of diarrheal disease on growth are limited and variable in their analytic methods, making comparisons difficult and priority setting based on these findings challenging. A study by Black et al (Black RE, Brown KH, Becker S. Effects of diarrhea associated with specific enteropathogens on the growth of children in rural Bangladesh. Pediatrics. 1984;33:1004-1009.) examined the association between Shigella and enterotoxigenic Escherichia coli-related disease and weight gain and linear growth in Bangladeshi children aged 0-5 years. We estimated similar associations in a 2002 cohort of 0- to 6-year-old children in the Peruvian Amazon. METHODS: Diarrheal surveillence was conducted using household visits 3 times per week. Anthropometry was collected monthly. Mixed-effect models were used to estimate the association between Shigella, ETEC and Campylobacter diarrhea and weight gain in a 2-month period and linear growth over a 9-month period. Diarrheal disease burdens and growth intervals were quantified so as to be as comparable as possible to the original report. RESULTS: Shigella- and ETEC-associated diarrhea were not associated with diminished weight gain, although the association between ETEC diarrhea and weight gain (-4.5 g/percent of days spent with ETEC, P = 0.098) was twice that of other etiologic agents, as well as similar in magnitude to the original report. Shigella-associated diarrhea was associated with decreased linear growth (0.055 cm less growth/percent days, P = 0.008), also similar to the original study. CONCLUSIONS: Our findings suggest that associations between enteropathogen-specific diarrheal episodes and growth, particularly Shigella, are comparable across geographic and epidemiological contexts.


Assuntos
Infecções por Campylobacter/patologia , Desenvolvimento Infantil , Diarreia/patologia , Disenteria Bacilar/patologia , Infecções por Escherichia coli/patologia , Campylobacter/isolamento & purificação , Infecções por Campylobacter/epidemiologia , Criança , Pré-Escolar , Diarreia/epidemiologia , Disenteria Bacilar/epidemiologia , Escherichia coli Enterotoxigênica/isolamento & purificação , Estudos Epidemiológicos , Infecções por Escherichia coli/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Peru/epidemiologia , Estudos Prospectivos , Shigella/isolamento & purificação
10.
Clin Infect Dis ; 59 Suppl 4: S310-6, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25305303

RESUMO

The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study communities in Peru are located in Loreto province, in a rural area 15 km from the city of Iquitos. This riverine population of approximately 5000 individuals is fairly representative of Loreto. The province lags behind the rest of the country in access to water and sanitation, per capita income, and key health indicators including infant mortality (43.0 vs 16.0 per 1000 nationwide) and under-5 mortality (60.6 vs 21.0 per 1000). Total fertility rates are higher than elsewhere in the country (4.3 vs 2.6). Nationwide, the prevalence of human immunodeficiency virus is estimated at 0.45%, the prevalence of tuberculosis is 117 per 100 000, and the incidence of malaria is 258 per 100 000. Stunting in this community is high, whereas acute undernutrition is relatively uncommon. The population suffers from high rates of diarrheal disease. Prevalent enteric pathogens include Ascaris, Giardia, enterotoxigenic Escherichia coli, Shigella, and Campylobacter.


Assuntos
Transtornos da Nutrição Infantil/epidemiologia , Projetos de Pesquisa Epidemiológica , Estudos Longitudinais , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doenças Transmissíveis/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Peru/epidemiologia , Adulto Jovem
11.
Dalton Trans ; 42(33): 11992-2004, 2013 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-23824245

RESUMO

New 1,2-disubstituted ferrocenes [5(b-j), in which R = -SMe, -SPh, -SiPr, -SiMe3, -SePh, -SnBu3, -B(OH)2, -Me, -I] with a thiazoline ring in the ferrocene backbone using as key intermediate a ferrocenyl Fischer carbene complex were synthesized. The capability of the 2-thiazoline moiety as an ortho-directed metalation group was demonstrated by subsequent quenching of lithium intermediate with several electrophiles, proving to be an excellent method for synthesizing bidentate ligands. The catalytic scope of the [N,S] ligand 5b as the corresponding palladium complex 5b-PdCl(2) in a microwave-promoted Heck reaction was also tested. Results obtained showed better catalytic activity of 5b-PdCl(2) compared to other catalytic systems based on a [N,S] ferrocenyl ligand.


Assuntos
Compostos Ferrosos/síntese química , Compostos Organometálicos/síntese química , Compostos Ferrosos/química , Ligantes , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/química , Paládio/química
12.
Malar J ; 12: 178, 2013 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-23724869

RESUMO

BACKGROUND: Plasmodium vivax and Plasmodium falciparum cause a significant illness burden in Peru. Anopheline indices for populated communities in the peri-Iquitos region of Loreto have been reported to be remarkably low, with entomological inoculation rates (EIR) estimated at one to 30 infective bites per year based on a few studies in close proximity to the urban centre of Iquitos and surrounding deforested areas. Local reports suggest that a large number of the reported cases are contracted outside of populated communities in undeveloped riverine areas frequented by loggers and fishermen. METHODS: To better understand vectorial capacity in suspected high malaria transmission zones in a rural district near Iquitos, Peru, mosquito collections were conducted at different points in the seasonality of malaria transmission in 21 sites frequented by occupational labourers. Prevalence of Plasmodium spp in vectors was determined by circumsporozoite protein ELISA on individual mosquitoes. Slide surveillance was performed for humans encountered in the zone. RESULTS: In total, of 8,365 adult female mosquitoes examined, 98.5% were identified as Anopheles darlingi and 117 (1.4%) tested positive for sporozoites (P. falciparum, P. vivax VK210 or P. vivax VK247). Measured human biting rates at these sites ranged from 0.102 to 41.13 bites per person per hour, with EIR values as high as 5.3 infective bites per person per night. Six percent of the 284 blood films were positive for P. vivax or P. falciparum; however, 88% of the individuals found to be positive were asymptomatic at the time of sampling. CONCLUSIONS: The results of this study provide key missing indices of prominent spatial and temporal heterogeneity of vectorial capacity in the Amazon Basin of Peru. The identification of a target human subpopulation as a principal reservoir and dispersion source of Plasmodium species has important implications for vaccine development and the delivery of effective targeted malaria control strategies.


Assuntos
Culicidae/parasitologia , Doenças Endêmicas , Malária Falciparum/transmissão , Malária Vivax/transmissão , Exposição Ocupacional , Viagem , Animais , Culicidae/classificação , Feminino , Geografia , Humanos , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Peru/epidemiologia , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação
13.
PLoS Negl Trop Dis ; 7(1): e2036, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23383356

RESUMO

BACKGROUND: Although diarrheal illnesses are recognized as both a cause and effect of undernutrition, evidence for the effect of specific enteropathogens on early childhood growth remains limited. We estimated the effects of undernutrition as a risk factor for campylobacteriosis, as well as associations between symptomatic and asymptomatic Campylobacter infections and growth. METHODOLOGY/PRINCIPAL FINDINGS: Using data from a prospective cohort of 442 children aged 0-72 months, the effect of nutritional status on the incidence of Campylobacter infection was estimated using uni- and multivariate Poisson models. Multivariate regression models were developed to evaluate the effect of Campylobacter infection on weight gain and linear growth. Overall, 8.3% of diarrheal episodes were associated with Campylobacter (crude incidence rate = 0.37 episodes/year) and 4.9% of quarterly asymptomatic samples were Campylobacter positive. In univariate models, the incidence of Campylobacter infection was marginally higher in stunted than non-stunted children (IRR 1.270, 95% CI (0.960, 1.681)(p = 0.095). When recent diarrheal burdens were included in the analysis, there was no difference in risk between stunted and unstunted children. Asymptomatic and symptomatic Campylobacter infections were associated with reduced weight gain over a three-month period (65.5 g (95% CI: -128.0, -3.0)(p = 0.040) and 43.9 g (95% CI:-87.6, -1.0)(p = 0.049) less weight gain, respectively). Symptomatic Campylobacter infections were only marginally associated with reduced linear growth over a nine month period (-0.059 cm per episode, 95% CI: -0.118, 0.001)(p = 0.054), however relatively severe episodes were associated with reduced linear growth (-0.169 cm/episode, 95% CI -0.310, -0.028)(p = 0.019). CONCLUSIONS/SIGNIFICANCE: Our findings suggest that Campylobacter is not as benign as commonly assumed, and that there is evidence to support expanding the indications for antibiotic therapy in campylobacteriosis in children.


Assuntos
Infecções por Campylobacter/epidemiologia , Infecções por Campylobacter/etiologia , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Doenças Assintomáticas/epidemiologia , Campylobacter/isolamento & purificação , Infecções por Campylobacter/complicações , Criança , Pré-Escolar , Feminino , Transtornos do Crescimento/complicações , Humanos , Lactente , Recém-Nascido , Masculino , Peru , Estudos Prospectivos
14.
Am J Trop Med Hyg ; 86(6): 1018-25, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22665611

RESUMO

To evaluate the performance of enterobacterial repetitive intergenic sequence-based polymerase chain reaction (ERIC-PCR) typing versus the current standard for the typing of Shigella pulsed gel electrophoresis (PFGE), we typed 116 Shigella isolates from a village in an endemic setting over a 20-month period using both methods. PFGE identified 37 pulse types and had a discrimination index of 0.925 (95% confidence interval = 0.830-1.00), whereas ERIC-PCR identified 42 types and had a discrimination index of 0.961 (95% confidence interval = 0.886-1.00). PFGE and ERIC-PCR showed a 90.4% correlation in the designation of isolates as clonal or non-clonal in pairwise comparisons. Both systems were highly reproducible and provided highly similar and supplementary data compared with serotyping regarding the transmission dynamics of shigellosis in this community. ERIC-PCR is considerably more rapid and inexpensive than PFGE and may have a complementary role to PFGE for initial investigations of hypothesized outbreaks in resource-limited settings.


Assuntos
Técnicas de Tipagem Bacteriana/métodos , Reação em Cadeia da Polimerase/métodos , Sequências Repetitivas de Ácido Nucleico , Shigella/isolamento & purificação , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , DNA Intergênico/metabolismo , Diarreia/epidemiologia , Diarreia/microbiologia , Disenteria Bacilar/epidemiologia , Disenteria Bacilar/microbiologia , Eletroforese em Gel de Campo Pulsado/métodos , Humanos , Prevalência , Sorotipagem , Shigella/classificação , Shigella/genética
15.
J Biol Chem ; 286(8): 6733-41, 2011 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-21173145

RESUMO

ATP binding enhances the activity of ClC-5, the transporter mutated in Dent disease, a disease affecting the renal proximal tubule. Previously, the ATP binding site was revealed in x-ray crystal structures of the cytoplasmic region of this membrane protein. Disruption of this site by mutagenesis (Y617A-ClC-5) reduced the functional expression and ATP-dependent regulation of the full-length transporter in Xenopus oocytes. However, insight into the conformational changes underlying ATP-dependent regulation is lacking. Here, we show that ATP binding induces a change in protein conformation. Specifically, small angle x-ray scattering experiments indicate that ATP binding promotes a clamp-like closure of the isolated ClC-5 carboxyl-terminal region. Limited proteolysis studies show that ATP binding induces conformational compaction of the carboxyl-terminal region in the intact membrane protein as well. In the context of fibroblasts and proximal tubule epithelial cells, disruption of the ATP binding site in full-length ClC-5 (Y617A-ClC-5) led to a defect in processing and trafficking out of the endoplasmic reticulum. These latter findings account for the decrease in functional expression previously reported for this ATP-binding mutant and prompt future study of a model whereby conformational compaction caused by ATP binding promotes biosynthetic maturation.


Assuntos
Trifosfato de Adenosina/química , Proteínas Repressoras/química , Trifosfato de Adenosina/genética , Trifosfato de Adenosina/metabolismo , Substituição de Aminoácidos , Animais , Sítios de Ligação , Células CHO , Cricetinae , Cricetulus , Doença de Dent/genética , Doença de Dent/metabolismo , Retículo Endoplasmático/química , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Humanos , Mutagênese , Mutação de Sentido Incorreto , Oócitos , Mapeamento de Peptídeos , Estrutura Terciária de Proteína , Transporte Proteico/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Xenopus laevis
16.
J Biol Chem ; 286(4): 3047-56, 2011 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-21098488

RESUMO

Complex II superfamily members catalyze the kinetically difficult interconversion of succinate and fumarate. Due to the relative simplicity of complex II substrates and their similarity to other biologically abundant small molecules, substrate specificity presents a challenge in this system. In order to identify determinants for on-pathway catalysis, off-pathway catalysis, and enzyme inhibition, crystal structures of Escherichia coli menaquinol:fumarate reductase (QFR), a complex II superfamily member, were determined bound to the substrate, fumarate, and the inhibitors oxaloacetate, glutarate, and 3-nitropropionate. Optical difference spectroscopy and computational modeling support a model where QFR twists the dicarboxylate, activating it for catalysis. Orientation of the C2-C3 double bond of activated fumarate parallel to the C(4a)-N5 bond of FAD allows orbital overlap between the substrate and the cofactor, priming the substrate for nucleophilic attack. Off-pathway catalysis, such as the conversion of malate to oxaloacetate or the activation of the toxin 3-nitropropionate may occur when inhibitors bind with a similarly activated bond in the same position. Conversely, inhibitors that do not orient an activatable bond in this manner, such as glutarate and citrate, are excluded from catalysis and act as inhibitors of substrate binding. These results support a model where electronic interactions via geometric constraint and orbital steering underlie catalysis by QFR.


Assuntos
Proteínas de Escherichia coli/química , Escherichia coli/enzimologia , Modelos Químicos , Modelos Moleculares , Oxirredutases/química , Catálise , Complexo II de Transporte de Elétrons/química , Complexo II de Transporte de Elétrons/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Proteínas de Escherichia coli/metabolismo , Fumaratos/química , Fumaratos/metabolismo , Oxirredutases/metabolismo , Especificidade por Substrato/fisiologia
17.
Pediatrics ; 122(3): e541-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18710884

RESUMO

OBJECTIVE: Our goal was to estimate the impact of a Shigella vaccine in an area where shigellosis is endemic by characterizing the disease burden and antibiotic-resistance profiles of isolates and by determining the prevalence of Shigella flexneri serotypes. PATIENTS AND METHODS: We conducted a 43-month-long prospective, community-based diarrheal disease surveillance in 442 children <72 months of age in the Peruvian Amazon between October 1, 2002, and April 15, 2006. RESULTS: The incidence of diarrheal disease was 4.38 episodes per child-year. The incidence rate for shigellosis was 0.34 episodes per child-year in children <72 months of age and peaked in children between 12 and 23 months at 0.43 episodes per child-year. Maternal education at or beyond the primary grade level, piped water supply, weight-for-age z score, and improved water-storage practices were the most significant determinants of disease in this community with living conditions comparable to many rural areas in the developing world. CONCLUSIONS: Children living in this region had a 20-fold higher rate of disease incidence detected by active surveillance as those recently estimated by passive detection. Most symptomatic disease was caused by S flexneri, although the diversity of serotypes will require a multivalent vaccine to have a significant impact on the burden of disease caused by shigellosis. Several other public health disease-control interventions targeted at water source and improved storage, nutritional interventions, and improved maternal education seem to have a greater impact than a univalent S flexneri 2a vaccine.


Assuntos
Farmacorresistência Bacteriana , Disenteria Bacilar/epidemiologia , Doenças Endêmicas/estatística & dados numéricos , Shigella flexneri/isolamento & purificação , Anticorpos Antibacterianos/análise , Pré-Escolar , DNA Bacteriano/análise , Disenteria Bacilar/microbiologia , Disenteria Bacilar/prevenção & controle , Fezes/microbiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Peru/epidemiologia , Reação em Cadeia da Polimerase , Estudos Prospectivos , Fatores de Risco , População Rural , Shigella flexneri/genética , Shigella flexneri/imunologia , Fatores Socioeconômicos
20.
Am J Trop Med Hyg ; 78(3): 492-8, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18337348

RESUMO

We evaluated a PCR-RFLP of the ribosomal internal transcribed spacer 2 region (ITS2) to distinguish species of Anopheles commonly reported in the Amazon and validated this method using reared F1 offspring. The following species of Anopheles were used for molecular analysis: An. (Nys.) benarrochi, An. (Nys.) darlingi, An. (Nys.) nuneztovari, An. (Nys.) konderi, An. (Nys.) rangeli, and An. (Nys.) triannulatus sensu lato (s.l.). In addition, three species of the subgenus Anopheles, An. (Ano.) forattini, An. (Ano.) mattogrossensis, and An. (Ano.) peryassui were included for testing. Each of the nine species tested yielded diagnostic banding patterns. The PCR-RFLP method was successful in identifying all life stages including exuviae with small fractions of the sample. The assay is rapid and can be applied as an unbiased confirmatory method for identification of morphologic variants, disputed samples, imperfectly preserved specimens, and life stages from which taxonomic keys do not allow for definitive species determination.


Assuntos
Anopheles/classificação , Anopheles/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Animais , DNA Espaçador Ribossômico/genética , Especificidade da Espécie , Clima Tropical
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