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BACKGROUND: In Santiago, Chile, where typhoid had been hyperendemic (1977-1991), we investigated whether residual chronic carriers could be detected among household contacts of non-travel-related typhoid cases occurring during 2017-2019. METHODS: Culture-confirmed cases were classified as autochthonous (domestically acquired) versus travel/immigration related. Household contacts of cases had stool cultures and serum Vi antibody measurements to detect chronic Salmonella Typhi carriers. Whole genome sequences of acute cases and their epidemiologically linked chronic carrier isolates were compared. RESULTS: Five of 16 autochthonous typhoid cases (31.3%) were linked to 4 chronic carriers in case households; 2 cases (onsets 23 months apart) were linked to the same carrier. Carriers were women aged 69-79 years with gallbladder dysfunction and Typhi fecal excretion; 3 had highly elevated serum anti-Vi titers. Genomic analyses revealed close identity (≤11 core genome single-nucleotide polymorphism [SNP] differences) between case and epidemiologically linked carrier isolates; all were genotypes prevalent in 1980s Santiago. A cluster of 4 additional autochthonous cases unlinked to a carrier was identified based on genomic identity (0-1 SNPs). Travel/immigration isolate genotypes were typical for the countries of travel/immigration. CONCLUSIONS: Although autochthonous typhoid cases in Santiago are currently rare, 5 of 16 such cases (31.3%) were linked to elderly chronic carriers identified among household contacts of cases.
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Portador Sadio , Salmonella typhi , Febre Tifoide , Humanos , Chile/epidemiologia , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologia , Salmonella typhi/genética , Salmonella typhi/isolamento & purificação , Feminino , Idoso , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Masculino , Pessoa de Meia-Idade , Adulto , Fezes/microbiologia , Genótipo , Sequenciamento Completo do Genoma , Viagem , Criança , Polimorfismo de Nucleotídeo Único , Pré-Escolar , Adulto Jovem , Idoso de 80 Anos ou mais , AdolescenteRESUMO
Antimicrobial treatment in livestock can contribute to the emergence and spread of antimicrobial-resistant (AMR) microorganisms. Despite substantial surveillance of AMR bacteria in the continental United States, the prevalence of these AMR organisms in U.S. territories, such as Puerto Rico, remains understudied. The goals of this research included obtaining baseline data on the antimicrobial profile of E. coli isolates from Puerto Rico dairy farms with different husbandry practices. Seventy-nine fecal samples were collected from two types of conventional dairy farms: those that fed calves with tank milk and those that fed calves with waste milk. These samples were collected from the animals' rectums, culture, and subsequently confirmed through biochemical tests. Out of these samples, 32 isolates were analyzed phenotypically and genotypically to elucidate their AMR profiles. The results underscore a discrepancy in the occurrence of antimicrobial resistance genes between calves and adult cattle. Notably, waste milk-fed calves exhibited a significantly higher prevalence of antibiotic-resistant E. coli when compared to their tank milk-fed counterparts. These disparities emphasize the need for more comprehensive investigations to determine causative factors. These results underscore the urgency of comprehensive strategies to raise awareness about how management practices influence antimicrobial resistance, shifting the focus from treatment to prevention.
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OBJECTIVE: To test the hypothesis that healthy weight status and adherence to American Academy of Pediatrics (AAP) guidelines for diet and physical activity would extend to greater executive function (EF) at age 24 months. STUDY DESIGN: Parents of 24-month-old children from the STRONG Kids 2 cohort study (n = 352) completed the Behavioral Rating Inventory of Executive Function for Preschoolers (BRIEF-P) and reported physical activities, diet, and screen time. Toddlers met AAP guidelines if they consumed at least 5 servings of fruits and vegetables, were physically active, refrained from sugar-sweetened beverages, and limited daily screen time to <60 minutes. Relationships between EF, 24-month weight status, and meeting AAP guidelines were tested independent of child sex, ethnicity, socioeconomic status, weight status at birth, and maternal pregnancy weight status. RESULTS: Weight-for-length z-score had no effect on EF. Toddlers meeting the screen time guideline had greater EF (ß, -0.125; 95% CI, 0.234 to -0.008), inhibitory self-control (ß, -0.142; 95% CI, -0.248 to -0.029), and emergent metacognition (ß, -0.111; 95% CI, -0.221 to 0.002), indicated by lower BRIEF-P scores. Those with more minutes of screen time had poorer overall EF (ß, 0.257; 95% CI, 0.118-0.384), inhibitory self-control (ß, 0.231; 95% CI, 0.099-0.354), cognitive flexibility (ß, 0.217; 95% CI, 0.082-0.342), and emergent metacognition (ß, 0.257; 95% CI, 0.120-0.381). Daily physical activity was associated with greater emergent metacognition (ß, -0.116; 95% CI, -0.225 to -0.005). CONCLUSIONS: Meeting AAP guidelines for physical activity and screen time was related to greater EF in a demographically homogenous sample of toddlers. Future randomized control trials and more diverse samples are needed to confirm the directionality of this relationship. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03341858.
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Função Executiva , Tempo de Tela , Pré-Escolar , Feminino , Humanos , Estudos de Coortes , Dieta/psicologia , Exercício Físico , MasculinoRESUMO
Sixteen Escherichia coli isolates were obtained from fecal matter from a beef farm in Puerto Rico. Isolates were whole-genome sequenced for in silico characterization, including pathotype characterization, virulence, and plasmid identification. The results of the draft genomes identified potential pathogenic E. coli strains from beef cattle in Puerto Rico.
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BACKGROUND: Sociolegal barriers to cancer care are defined as health-related social needs like affordable healthy housing, stable utility service, and food security that may be remedied by public policy, law, regulation, or programming. Legal support has not been studied in cancer care. METHODS: The authors conducted a randomized controlled trial of patients who had newly diagnosed cancer at a safety-net medical center in Boston from 2014 through 2017, comparing standard patient navigation versus enhanced navigation partnered with legal advocates to identify and address sociolegal barriers. English-speaking, Spanish-speaking, or Haitian Creole-speaking patients with breast and lung cancer were eligible within 30 days of diagnosis. The primary outcome was timely treatment within 90 days of diagnosis. Secondary outcomes included patient-reported outcomes (distress, cancer-related needs, and satisfaction with navigation) at baseline and at 6 months. RESULTS: In total, 201 patients with breast cancer and 19 with lung cancer enrolled (response rate, 78%). The mean patient age was 55 years, 51% of patients were Black and 22% were Hispanic, 20% spoke Spanish and 8% spoke Haitian Creole, 73% had public health insurance, 77% reported 1 or more perceived sociolegal barrier, and the most common were barriers to housing and employment. Ninety-six percent of participants with breast cancer and 73% of those with lung cancer initiated treatment within 90 days. No significant effect of enhanced navigation was observed on the receipt of timely treatment among participants with breast cancer (odds ratio, 0.88; 95% CI, 0.17-4.52) or among those with lung cancer (odds ratio, 4.00; 95% CI, 0.35-45.4). No differences in patient-reported outcomes were observed between treatment groups. CONCLUSIONS: Navigation enhanced by access to legal consultation and support had no impact on timely treatment, patient distress, or patient needs. Although most patients reported sociolegal barriers, few required intensive legal services that could not be addressed by navigators. LAY SUMMARY: In patients with cancer, the experience of sociolegal barriers to care, such as unstable housing, utility services, or food insecurity, is discussed. Addressing these barriers through legal information and assistance may improve care. This study compares standard patient navigation versus enhanced navigation partnered with legal advocates for patients with breast and lung cancers. Almost all patients in both navigation groups received timely care and also reported the same levels of distress, needs, and satisfaction with navigation. Although 75% of patients in the study had at least 1 sociolegal barrier identified, few required legal advocacy beyond what a navigator who received legal information and coaching could provide.
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Neoplasias da Mama , Neoplasias Pulmonares , Navegação de Pacientes , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Feminino , Haiti , Humanos , Seguro Saúde , Pessoa de Meia-IdadeRESUMO
Typhoid fever epidemiology was investigated rigorously in Santiago, Chile during the 1980s, when Salmonella enterica serovar Typhi (S. Typhi) caused seasonal, hyperendemic disease. Targeted interventions reduced the annual typhoid incidence rates from 128-220 cases/105 population occurring between 1977-1984 to <8 cases/105 from 1992 onwards. As such, Santiago represents a contemporary example of the epidemiologic transition of an industrialized city from amplified hyperendemic typhoid fever to a period when typhoid is no longer endemic. We used whole genome sequencing (WGS) and phylogenetic analysis to compare the genotypes of S. Typhi cultured from acute cases of typhoid fever occurring in Santiago during the hyperendemic period of the 1980s (n = 74) versus the nonendemic 2010s (n = 80) when typhoid fever was rare. The genotype distribution between "historical" (1980s) isolates and "modern" (2011-2016) isolates was similar, with genotypes 3.5 and 2 comprising the majority of isolations, and 73/80 (91.3%) of modern isolates matching a genotype detected in the 1980s. Additionally, phylogenomically 'ancient' genotypes 1.1 and 1.2.1, uncommon in the global collections, were also detected in both eras, with a notable rise amongst the modern isolates. Thus, genotypes of S. Typhi causing acute illness in the modern nonendemic era match the genotypes circulating during the hyperendemic 1980s. The persistence of historical genotypes may be explained by chronic typhoid carriers originally infected during or before the 1980s.
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Salmonella typhi , Febre Tifoide , Chile/epidemiologia , Humanos , Filogenia , Salmonella typhi/genética , Febre Tifoide/epidemiologia , Sequenciamento Completo do GenomaRESUMO
The Deepwater Horizon (DWH) oil spill profoundly impacted the health of bottlenose dolphins (Tursiops truncatus) in Barataria Bay, LA (BB). To comprehensively assess the cardiac health of dolphins living within the DWH oil spill footprint, techniques for in-water cardiac evaluation were refined with dolphins cared for by the U.S. Navy Marine Mammal Program in 2018 and applied to free-ranging bottlenose dolphins in BB (n = 34) and Sarasota Bay, Florida (SB) (n = 19), a non-oiled reference population. Cardiac auscultation detected systolic murmurs in the majority of dolphins from both sites (88% BB, 89% SB) and echocardiography showed most of the murmurs were innocent flow murmurs attributed to elevated blood flow velocity [1]. Telemetric six-lead electrocardiography detected arrhythmias in BB dolphins (43%) and SB dolphins (31%), all of which were considered low to moderate risk for adverse cardiac events. Echocardiography showed BB dolphins had thinner left ventricular walls, with significant differences in intraventricular septum thickness at the end of diastole (p = 0.002), and left ventricular posterior wall thickness at the end of diastole (p = 0.033). BB dolphins also had smaller left atrial size (p = 0.004), higher prevalence of tricuspid valve prolapse (p = 0.003), higher prevalence of tricuspid valve thickening (p = 0.033), and higher prevalence of aortic valve thickening (p = 0.008). Two dolphins in BB were diagnosed with pulmonary arterial hypertension based on Doppler echocardiography-derived estimates and supporting echocardiographic findings. Histopathology of dolphins who stranded within the DWH oil spill footprint showed a significantly higher prevalence of myocardial fibrosis (p = 0.003), regardless of age, compared to dolphins outside the oil spill footprint. In conclusion, there were substantial cardiac abnormalities identified in BB dolphins which may be related to DWH oil exposure, however, future work is needed to rule out other hypotheses and further elucidate the connection between oil exposure, pulmonary disease, and the observed cardiac abnormalities.
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Golfinho Nariz-de-Garrafa , Traumatismos Cardíacos/veterinária , Poluição por Petróleo/efeitos adversos , Animais , Golfinho Nariz-de-Garrafa/anormalidades , Golfinho Nariz-de-Garrafa/fisiologia , Ecocardiografia/veterinária , Eletrocardiografia/veterinária , Fibrose/diagnóstico por imagem , Fibrose/veterinária , Coração/diagnóstico por imagem , Coração/fisiologia , Traumatismos Cardíacos/diagnóstico por imagem , Hipertensão/veterináriaRESUMO
SARS-CoV-2 mortality has been extensively studied in relation to host susceptibility. How sequence variations in the SARS-CoV-2 genome affect pathogenicity is poorly understood. Starting in October 2020, using the methodology of genome-wide association studies (GWAS), we looked at the association between whole-genome sequencing (WGS) data of the virus and COVID-19 mortality as a potential method of early identification of highly pathogenic strains to target for containment. Although continuously updating our analysis, in December 2020, we analyzed 7548 single-stranded SARS-CoV-2 genomes of COVID-19 patients in the GISAID database and associated variants with mortality using a logistic regression. In total, evaluating 29,891 sequenced loci of the viral genome for association with patient/host mortality, two loci, at 12,053 and 25,088 bp, achieved genome-wide significance (p values of 4.09e-09 and 4.41e-23, respectively), though only 25,088 bp remained significant in follow-up analyses. Our association findings were exclusively driven by the samples that were submitted from Brazil (p value of 4.90e-13 for 25,088 bp). The mutation frequency of 25,088 bp in the Brazilian samples on GISAID has rapidly increased from about 0.4 in October/December 2020 to 0.77 in March 2021. Although GWAS methodology is suitable for samples in which mutation frequencies varies between geographical regions, it cannot account for mutation frequencies that change rapidly overtime, rendering a GWAS follow-up analysis of the GISAID samples that have been submitted after December 2020 as invalid. The locus at 25,088 bp is located in the P.1 strain, which later (April 2021) became one of the distinguishing loci (precisely, substitution V1176F) of the Brazilian strain as defined by the Centers for Disease Control. Specifically, the mutations at 25,088 bp occur in the S2 subunit of the SARS-CoV-2 spike protein, which plays a key role in viral entry of target host cells. Since the mutations alter amino acid coding sequences, they potentially imposing structural changes that could enhance viral infectivity and symptom severity. Our analysis suggests that GWAS methodology can provide suitable analysis tools for the real-time detection of new more transmissible and pathogenic viral strains in databases such as GISAID, though new approaches are needed to accommodate rapidly changing mutation frequencies over time, in the presence of simultaneously changing case/control ratios. Improvements of the associated metadata/patient information in terms of quality and availability will also be important to fully utilize the potential of GWAS methodology in this field.
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COVID-19 , Glicoproteína da Espícula de Coronavírus , Brasil , Estudo de Associação Genômica Ampla , Humanos , Mutação , Filogenia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Rotavirus vaccines have been adopted in African countries since 2009, including Mozambique (2015). Disease burden data are needed to evaluate the impact of rotavirus vaccine. We report the burden of rotavirus-associated diarrhea in Mozambique from the Global Enteric Multicenter Study (GEMS) before vaccine introduction. Methods: A case-control study (GEMS), was conducted in Manhiça district, recruiting children aged 0-59 months with moderate-to-severe diarrhea (MSD) and less-severe-diarrhea (LSD) between December 2007 and November 2012; including 1-3 matched (age, sex and neighborhood) healthy community controls. Clinical and epidemiological data and stool samples (for laboratory investigation) were collected. Association of rotavirus with MSD or LSD was determined by conditional logistic regression and adjusted attributable fractions (AF) calculated, and risk factors for rotavirus diarrhea assessed. Results: Overall 915 cases and 1,977 controls for MSD, and 431 cases and 430 controls for LSD were enrolled. Rotavirus positivity was 44% (217/495) for cases and 15% (160/1046) of controls, with AF = 34.9% (95% CI: 32.85-37.06) and adjusted Odds Ratio (aOR) of 6.4 p< 0.0001 in infants with MSD compared to 30% (46/155) in cases and 14% (22/154) in controls yielding AF = 18.7%, (95% CI: 12.02-25.39) and aOR = 2.8, p = 0.0011 in infants with LSD. The proportion of children with rotavirus was 32% (21/66) among HIV-positive children and 23% (128/566) among HIV-negative ones for MSD. Presence of animals in the compound (OR = 1.9; p = 0.0151) and giving stored water to the child (OR = 2.0, p = 0.0483) were risk factors for MSD; while animals in the compound (OR = 2.37, p = 0.007); not having routine access to water on a daily basis (OR = 1.53, p = 0.015) and washing hands before cooking (OR = 1.76, p = 0.0197) were risk factors for LSD. Conclusion: The implementation of vaccination against rotavirus may likely result in a significant reduction of rotavirus-associated diarrhea, suggesting the need for monitoring of vaccine impact.
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Humanos , Masculino , Feminino , Criança , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/epidemiologia , Rotavirus/imunologia , Vacinas contra Rotavirus/imunologia , Moçambique , Modelos LogísticosRESUMO
OBJECTIVE: To test the hypothesis that fermentable fiber prevents Salmonella typhimurium infection-associated symptoms by enhancing innate and adaptive immune system in neonatal pigs. METHODS: Two-d-old piglets (n=120) were randomized to receive either a nutritionally complete sow milk replacer formula (CON), or supplemented with methylcellulose (MCEL-non-fermentable), soy polysaccharides (SPS-moderately fermentable), or fructooligosaccharides (FOS-highly fermentable). On d7, piglets received an oral gavage of S. typhimurium-798, and continued receiving the same diets up to 48h post-infection. Ileal mucosal samples were obtained for further analyses. RESULTS: A reduction in chloride secretion was observed in FOS when compared to other diets (p<0.0003). The number of ileal sulfo-acidomucins was higher (p<0.05) in FOS before infection compared with other diets. NFkB was inhibited in FOS following infection (p<0.05), when compared with CON. IL-1ß expression was increased at 4h post-infection (p<0.05) in CON; however, this response was attenuated in the fiber groups. IL-6 expression was higher (p<0.05) in CON post- infection, higher in SPS at 24h (p<0.05), but unchanged in MCEL and FOS when compared to pre-infection values. FOS had a higher expression of neutrophil-chemoattractant IL-8 before infection (p<0.05) compared to other groups. CONCLUSION: The reduction in chloride secretion, proinflammatory cytokines expression and NFkB activation, and increased number of sulfo-acidomucins, and IL-8 expression in the fiber groups, indicates that the degree of fermentability impacts the innate and adaptive immune system, and could be the mechanisms by which dietary fibers reduce S. typhimurium infection-associated-symptoms in neonatal pigs and apply these results to infants.
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Fibras na Dieta/administração & dosagem , Fermentação , Oligossacarídeos/administração & dosagem , Infecções por Salmonella/prevenção & controle , Imunidade Adaptativa/imunologia , Animais , Animais Recém-Nascidos , Citocinas/imunologia , Fibras na Dieta/farmacologia , Imunidade Inata/imunologia , Metilcelulose/administração & dosagem , Metilcelulose/farmacologia , Oligossacarídeos/farmacologia , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Distribuição Aleatória , Infecções por Salmonella/imunologia , Salmonella typhimurium/isolamento & purificação , Glycine max/química , SuínosRESUMO
Salmonella enterica serovar Typhi H58, an antimicrobial-resistant lineage, is globally disseminated but has not been reported in Latin America. Genomic analysis revealed 3 independent introductions of Salmonella Typhi H58 with reduced fluoroquinolone susceptibility into Chile. Our findings highlight the utility of enhanced genomic surveillance for typhoid fever in this region.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Fluoroquinolonas/farmacologia , Salmonella typhi , Febre Tifoide , Chile/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/genética , Febre Tifoide/epidemiologia , Febre Tifoide/microbiologiaRESUMO
Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10-6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10-10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.
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Indígena Americano ou Nativo do Alasca/genética , Aquaporina 4/genética , Predisposição Genética para Doença , Antígenos HLA/genética , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Masculino , México/epidemiologiaRESUMO
Most studies on autism spectrum disorder (ASD) risk factors have been conducted in developed countries where ethnicity and environment are different than in developing countries. We compared nutritional status, immune response and microbiota composition in mestizo children with ASD with matched controls in Ecuador. Twenty-five cases and 35 controls were matched by age, sex and school location. The prevalence of under- and overweight was higher in children with ASD. Nutritional differences were accompanied by abnormal food habits and more frequent gastrointestinal symptoms in children with ASD. Also, greater serum concentrations of TGF-ß1 were observed in children with ASD. Finally, there was greater alpha diversity and abundance of Bacteroides (2 OTUs), Akkermansia, Coprococcus and different species of Ruminococcus in ASD children.
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Transtorno do Espectro Autista/imunologia , Transtorno do Espectro Autista/microbiologia , Citocinas/sangue , Microbioma Gastrointestinal , Imunidade , Estado Nutricional , Estudos de Casos e Controles , Criança , Pré-Escolar , DNA Bacteriano , Equador , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Análise de Sequência , Fator de Crescimento Transformador beta1/sangueRESUMO
OBJECTIVE: Among US-born children of Latina US (USB) and Latina foreign-born mothers (FBM), to determine whether 1) household and child characteristics differ; 2) child health outcomes differ; 3) these differences diminish for children of FBM with longer duration of residence in the United States; and 4) these differences can be explained by food insecurity (FI) or by Supplemental Nutrition Assistance Program (SNAP) participation. METHODS: Cross-sectional survey of 2145 Latina mothers of publicly insured US-born children 0 to 48 months old in a Boston emergency department (ED) 2004 to 2013. Predictors were FBM versus USBM and duration of residence in the United States. Outcomes were mothers' report of child health, history of hospitalization, developmental risk, and hospital admission on the day of ED visit. Multivariable logistic regression adjusted for potential confounders and effect modification. RESULTS: FBM versus USBM households had more household (31% vs 26%) and child (19% vs 11%) FI and lower SNAP participation (44% vs 67%). Children of FBM versus USBM were more likely to be reported in fair/poor versus good/excellent health (adjusted odds ratios 1.9, 95% confidence interval [1.4, 2.6]), with highest odds for children of FBM with shortest duration of residence, and to be admitted to the hospital on the day of the ED visit (adjusted odds ratios 1.7, 95% confidence interval [1.3, 2.2]). SNAP and FI did not fully explain these outcomes. CONCLUSION: When providing care and creating public policies, clinicians and policymakers should consider higher rates of food insecurity, lower SNAP participation, and risk for poor health outcomes in Latinx children of FBM.
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Saúde da Criança , Emigrantes e Imigrantes/estatística & dados numéricos , Assistência Alimentar/estatística & dados numéricos , Insegurança Alimentar , Hispânico ou Latino/estatística & dados numéricos , Mães/estatística & dados numéricos , Adulto , Boston/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Deficiências do Desenvolvimento/epidemiologia , República Dominicana/etnologia , El Salvador/etnologia , Serviço Hospitalar de Emergência , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , América Latina/etnologia , Modelos Logísticos , Masculino , Porto Rico/etnologia , Fatores Socioeconômicos , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The Colorado Adult Joint Assessment Scale (CAJAS) is designed to assess joint health in adults with hemophilia. The CAJAS comprises nine items (swelling, muscle atrophy, axial deformity, crepitus, range of motion, contracture, instability, strength, gait) and assesses six joints. OBJECTIVE: To assess CAJAS content validity and psychometric properties. PATIENTS/METHODS: Data were obtained from the Trial to Evaluate the Effect of Secondary Prophylaxis With rFVIII Therapy in Severe Hemophilia A Adult and/or Adolescent Subjects Compared to That of Episodic Treatment (SPINART) study and a separate CAJAS validation study. CAJAS assessments in SPINART were performed by physical therapists (PTs) from the United States, Romania, Bulgaria, and Argentina. In the validation study, content validity was assessed from interviews with six PTs at three US hemophilia centers; cultural equivalence was assessed with seven non-US PTs from SPINART. Reliability data were collected from 30 subjects at four US centers. Test-retest reliability was evaluated by having the same PT perform CAJAS examinations at two visits, 7-10 days apart. Inter-rater reliability was assessed by comparing CAJAS scores of two different PTs performing separate examinations of the same patient several hours apart at the same visit. Psychometric properties were assessed using SPINART and validation study data. RESULTS: The CAJAS demonstrated good content validity. Test-retest reliability was high (intraclass correlation coefficient, 0.98), as was inter-rater reliability (intraclass correlation coefficient, 0.88). Internal consistency reliability was strong (α = .90). The CAJAS demonstrated good convergent/divergent validity, known-groups validity, and ability to detect change. CONCLUSIONS: The CAJAS is a valid and reliable measure of joint health in adults with moderate-severe hemophilia and is appropriate for use in clinical practice.
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Hemofilia A , Adulto , Argentina , Colorado , Hemofilia A/diagnóstico , Hemofilia A/terapia , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To describe the methodology of a family-focused, culturally tailored program, Abriendo Caminos, for the prevention of excess weight gain in children. DESIGN: Randomized control trial with outcome assessment at pretest, posttest, and 6 months after intervention or abbreviated-attention control group. SETTING: Community setting across 5 sites (Illinois, California, Iowa, Texas, and Puerto Rico). PARTICIPANTS: Mexican American and Puerto Rican families (parent and 1 child aged 6-18 years). A sample size of 100 families (50 intervention and 50 control) per site (nâ¯=â¯500) will provide adequate power to detect intervention effects. INTERVENTION: Families will participate in 6 weekly, 2-hour group workshops on nutrition education through combined presentations and activities, family wellness, and physical activity. MAIN OUTCOME MEASURES: The primary outcome is prevention of excess weight gain in children; secondary outcomes include changes in child diet, specifically fruit, vegetable, and sugar-sweetened beverage consumption, and changes in parents' diets and improvement of family routines. Measures will be collected at baseline, postintervention, and 6 months after. ANALYSIS: Modeling to assess changes within and between experimental groups will be checked using standard methods including assessment of model fit, influence diagnostics, adjusted R2, and multicollinearity. Significance of effects will be examined using Type III tests.
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Dieta , Exercício Físico/fisiologia , Promoção da Saúde/métodos , Adolescente , Criança , Currículo , Feminino , Hispânico ou Latino , Humanos , Masculino , Obesidade Infantil/prevenção & controle , Porto Rico , Estados Unidos , Aumento de PesoRESUMO
The most common malignancy of the biliary tract, gallbladder cancer (GBC) often has a dismal prognosis. The aggressive nature of the tumor, delayed diagnosis at advanced stages of the disease, and lack of effective treatment options are some of the factors that contribute to a poor outcome. Early detection and accurate assessment of disease burden is critical to optimize management and improve long-term survival, as well as identify patients for adjuvant therapy and clinical trials. With recent advances in the understanding of the molecular pathogenesis of GBC, several specific diagnostic and biomarkers have been proposed as being of diagnostic and prognostic importance. Indeed, identification of novel diagnostic and prognostic markers has an important role in early diagnosis and development of targeted therapies among patients with GBC. Next-generation sequencing technology and genomewide data analysis have provided novel insight into understanding the molecular pathogenesis of biliary tract cancers, thereby identifying potential biomarkers for clinical use. We herein review available GBC biomarkers and the potential clinical implications in the management of GBC.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/terapia , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Animais , Neoplasias da Vesícula Biliar/metabolismo , Humanos , PrognósticoRESUMO
BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD. METHODOLOGY/PRINCIPAL FINDINGS: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p≤0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence ≥5% and significant association with MSD. CONCLUSIONS/SIGNIFICANCE: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%.
Assuntos
Escherichia coli Enterotoxigênica/genética , Escherichia coli Enterotoxigênica/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Proteínas de Fímbrias/genética , Fatores de Virulência/genética , África/epidemiologia , Ásia/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase , PrevalênciaRESUMO
INTRODUCTION: Cigarette smoking is a major environmental risk factor for many diseases, including chronic obstructive pulmonary disease (COPD). There are shared genetic influences on cigarette smoking and COPD. Genetic risk factors for cigarette smoking in cohorts enriched for COPD are largely unknown. METHODS: We performed genome-wide association analyses for average cigarettes per day (CPD) across the Genetic Epidemiology of COPD (COPDGene) non-Hispanic white (NHW) (n = 6659) and African American (AA) (n = 3260), GenKOLS (the Genetics of Chronic Obstructive Lung Disease) (n = 1671), and ECLIPSE (the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) (n = 1942) cohorts. In addition, we performed exome array association analyses across the COPDGene NHW and AA cohorts. We considered analyses across the entire cohort and stratified by COPD case-control status. RESULTS: We identified genome-wide significant associations for CPD on chromosome 15q25 across all cohorts (lowest p = 1.78 × 10-15), except in the COPDGene AA cohort alone. Previously reported associations on chromosome 19 had suggestive and directionally consistent associations (RAB4, p = 1.95 × 10-6; CYP2A7, p = 7.50 × 10-5; CYP2B6, p = 4.04 × 10-4). When we stratified by COPD case-control status, single nucleotide polymorphisms on chromosome 15q25 were nominally associated with both NHW COPD cases (ß = 0.11, p = 5.58 × 10-4) and controls (ß = 0.12, p = 3.86 × 10-5) For the gene-based exome array association analysis of rare variants, there were no exome-wide significant associations. For these previously replicated associations, the most significant results were among COPDGene NHW subjects for CYP2A7 (p = 5.2 × 10-4). CONCLUSIONS: In a large genome-wide association study of both common variants and a gene-based association of rare coding variants in ever-smokers, we found genome-wide significant associations on chromosome 15q25 with CPD for common variants, but not for rare coding variants. These results were directionally consistent among COPD cases and controls. IMPLICATIONS: We examined both common and rare coding variants associated with CPD in a large population of heavy smokers with and without COPD of NHW and AA descent. We replicated genome-wide significant associations on chromosome 15q25 with CPD for common variants among NHW subjects, but not for rare variants. We demonstrated for the first time that common variants on chromosome 15q25 associated with CPD are similar among COPD cases and controls. Previously reported associations on chromosome 19 showed suggestive and directionally consistent associations among common variants (RAB4, CYP2A7, and CYP2B6) and for rare variants (CYP2A7) among COPDGene NHW subjects. Although the genetic effect sizes for these single nucleotide polymorphisms on chromosome 15q25 are modest, we show that this creates a substantial smoking burden over the lifetime of a smoker.