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1.
Am J Hum Genet ; 105(5): 1005-1015, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31630790

RESUMO

Lissencephaly comprises a spectrum of malformations of cortical development. This spectrum includes agyria, pachygyria, and subcortical band heterotopia; each represents anatomical malformations of brain cortical development caused by neuronal migration defects. The molecular etiologies of neuronal migration anomalies are highly enriched for genes encoding microtubules and microtubule-associated proteins, and this enrichment highlights the critical role for these genes in cortical growth and gyrification. Using exome sequencing and family based rare variant analyses, we identified a homozygous variant (c.997C>T [p.Arg333Cys]) in TUBGCP2, encoding gamma-tubulin complex protein 2 (GCP2), in two individuals from a consanguineous family; both individuals presented with microcephaly and developmental delay. GCP2 forms the multiprotein γ-tubulin ring complex (γ-TuRC) together with γ-tubulin and other GCPs to regulate the assembly of microtubules. By querying clinical exome sequencing cases and through GeneMatcher-facilitated collaborations, we found three additional families with bi-allelic variation and similarly affected phenotypes including a homozygous variant (c.1843G>C [p.Ala615Pro]) in two families and compound heterozygous variants consisting of one missense variant (c.889C>T [p.Arg297Cys]) and one splice variant (c.2025-2A>G) in another family. Brain imaging from all five affected individuals revealed varying degrees of cortical malformations including pachygyria and subcortical band heterotopia, presumably caused by disruption of neuronal migration. Our data demonstrate that pathogenic variants in TUBGCP2 cause an autosomal recessive neurodevelopmental trait consisting of a neuronal migration disorder, and our data implicate GCP2 as a core component of γ-TuRC in neuronal migrating cells.

3.
MMWR Morb Mortal Wkly Rep ; 68(25): 568-572, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31246941

RESUMO

Cryptosporidium is a parasite that causes cryptosporidiosis, a profuse, watery diarrhea that can last up to 3 weeks in immunocompetent patients and can lead to life-threatening malnutrition and wasting in immunocompromised patients.* Fecal-oral transmission can occur by ingestion of contaminated recreational water, drinking water, or food, or through contact with infected persons or animals. For the period 2009-2017, public health officials from 40 states and Puerto Rico voluntarily reported 444 cryptosporidiosis outbreaks resulting in 7,465 cases. Exposure to treated recreational water (e.g., in pools and water playgrounds) was associated with 156 (35.1%) outbreaks resulting in 4,232 (56.7%) cases. Other predominant outbreak exposures included contact with cattle (65 outbreaks; 14.6%) and contact with infected persons in child care settings (57; 12.8%). The annual number of reported cryptosporidiosis outbreaks overall increased an average of approximately 13% per year over time. Reversing this trend will require dissemination of prevention messages to discourage swimming or attending child care while ill with diarrhea and encourage hand washing after contact with animals. Prevention and control measures can be optimized by improving understanding of Cryptosporidium transmission through regular analysis of systematically collected epidemiologic and molecular characterization data.


Assuntos
Criptosporidiose/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Creches , Pré-Escolar , Criptosporidiose/transmissão , Cryptosporidium/isolamento & purificação , Diarreia/microbiologia , Humanos , Lactente , Piscinas , Estados Unidos/epidemiologia , Microbiologia da Água
4.
Mil Med ; 184(11-12): 647-652, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31132088

RESUMO

INTRODUCTION: Effective, standardized, and easily accessible weight management programs are urgently needed for military beneficiaries. Videoconference interventions have the potential for widespread scaling, and can provide both real time interaction and flexibility in delivery times regardless of location, but there is little information on their effectiveness and acceptability. MATERIALS AND METHODS: This study as part of a larger weight loss trial describes the videoconference adaption of Group Lifestyle Balance (GLB) program, a community group-based Diabetes Prevention Program intervention, and provides a comparison of weight loss and meeting attendance between in-person and videoconference delivery modes over 12 weeks in adult family members of military service members. Forty-three participants were enrolled from two military installations and received either the videoconference-adapted or an in-person GLB program in a non-randomized trial design. Differences in program attendance and percent weight lost at 12 weeks were compared by independent samples t-tests and nonparametric methods. Group differences in the percentage of weight lost over the 12-week period were analyzed using a linear mixed model. RESULTS: All GLB intervention components were successfully delivered by videoconference with minor adaptations for the different delivery mechanism. Participant retention was 70% and 96% in the in-person and videoconference groups, respectively (p = 0.04). Completing participants in both groups lost a significant percent body weight over the 12 week intervention (p < 0.001) and there was no difference in percent body weight after 12 weeks of intervention (6.2 ± 3.2% and 5.3 ± 3.4% for in-person and videoconference at 12 weeks, respectively; p = 0.60). CONCLUSION: This study describes the first videoconference adaption of the GLB program for use in military families. Attrition was lower in the videoconference group, and there were a similar levels of weight loss in both groups regardless of delivery modality. Videoconference weight loss interventions are effective and feasible for scaling to support healthy weight management in military as well as civilian populations.

5.
Clin Ophthalmol ; 13: 147-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30666085

RESUMO

Purpose: To evaluate anatomical differences between laser (VICTUS) and manual constructed phacoemulsification incisions. Setting: Study was conducted at the Hospital de Olhos Paulista, Sao Paulo, Brazil. Design: This is a prospective, observational, consecutive nonrandomized cohort. Patients and methods: Sixteen patients (18 eyes) had phacoemulsification surgery, nine eyes had manual incisions and nine eyes had femtosecond incisions. All incisions were performed by the same surgeon. All incisions were evaluated at the 1st and 30th postoperative day with anterior segment optical coherence tomography to evaluate anatomical features. Inclusion criterion was presence of low visual acuity due to cataract. Exclusion criteria were other ocular pathologies, previous trauma, or corneal wound healing disease, as any intra or postoperative complication. Three different corneal specialists analyzed wound architecture features (epithelial or endothelial gap, incision edema, number of planes, Descemet's detachment, and loss of wound sealing) at both visits. ImageJ (National Institutes of Health) software was also used to analyze anatomical features of incisions. Results: Almost all incisions had edema at the first postoperative day. All femto incisions were triplanar, as intended, unlike manual incisions, which showed two uniplanar incisions (P=0.009). All laser incisions presented partial loss of wound sealing, while five keratome incisions had no loss of wound sealing at the first postoperative day (P=0.03). Conclusion: These findings support the hypothesis that laser constructed incisions are more precisely constructed than manual, although corneal wound healing was similar between the two groups at the 30th postoperative day, with a tendency to a faster anatomical improvement in the keratome group.

6.
Am J Obstet Gynecol ; 220(1): 120, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30171844
7.
Nutrients ; 10(12)2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30513876

RESUMO

Gluten-free (GF) eating patterns are frequently perceived to be healthier than gluten-containing (GC) ones, but there has been very little research to evaluate this viewpoint. The effect of GF eating patterns on dietary composition was assessed using two independent approaches. One approach compared macronutrients and typical shortfall nutrients between MyPlate example menus developed with either GC or equivalent GF foods. In this analysis, the GF menus were significantly lower in protein, magnesium, potassium, vitamin E, folate, and sodium (p = 0.002⁻0.03), with suggestive trends towards lower calcium and higher fat (p = 0.06⁻0.08). The second approach was a meta-analysis of seven studies comparing information on the nutrient intakes of adults with celiac disease following a GF diet with control subjects eating a GC diet, and differences were evaluated using paired t-tests or Wilcoxon Signed rank tests. In this analysis, consuming a GF diet was associated with higher energy and fat intakes, and lower fiber and folate intakes compared to controls (p < 0.001 to p = 0.03). After adjusting for heterogeneity and accounting for the large mean effect size (-0.88 ± 0.09), the lower fiber remained significant (p < 0.001). These combined analyses indicate that GF diets are not nutritionally superior except for sodium, and in several respects are actually worse.


Assuntos
Dieta Livre de Glúten , Valor Nutritivo , Adulto , Doença Celíaca/dietoterapia , Alimentos Especializados , Humanos , Refeições , Estado Nutricional
8.
BMJ ; 363: k4864, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541752

RESUMO

OBJECTIVE: To measure the energy content of frequently ordered meals from full service and fast food restaurants in five countries and compare values with US data. DESIGN: Cross sectional survey. SETTING: 223 meals from 111 randomly selected full service and fast food restaurants serving popular cuisines in Brazil, China, Finland, Ghana, and India were the primary sampling unit; 10 meals from five worksite canteens were also studied in Finland. The observational unit was frequently ordered meals in selected restaurants. MAIN OUTCOME MEASURE: Meal energy content, measured by bomb calorimetry. RESULTS: Compared with the US, weighted mean energy of restaurant meals was lower only in China (719 (95% confidence interval 646 to 799) kcal versus 1088 (1002 to 1181) kcal; P<0.001). In analysis of variance models, fast food contained 33% less energy than full service meals (P<0.001). In Finland, worksite canteens provided 25% less energy than full service and fast food restaurants (mean 880 (SD 156) versus 1166 (298); P=0.009). Country, restaurant type, number of meal components, and meal weight predicted meal energy in a factorial analysis of variance (R2=0.62, P<0.001). Ninety four per cent of full service meals and 72% of fast food meals contained at least 600 kcal. Modeling indicated that, except in China, consuming current servings of a full service and a fast food meal daily would supply between 70% and 120% of the daily energy requirements for a sedentary woman, without additional meals, drinks, snacks, appetizers, or desserts. CONCLUSION: Very high dietary energy content of both full service and fast food restaurant meals is a widespread phenomenon that is probably supporting global obesity and provides a valid intervention target.


Assuntos
Ingestão de Energia , Fast Foods/análise , Análise de Alimentos/estatística & dados numéricos , Refeições , Análise de Variância , Brasil , China , Comportamento do Consumidor , Estudos Transversais , Análise Fatorial , Finlândia , Gana , Humanos , Índia , Necessidades Nutricionais , Restaurantes , Estados Unidos
9.
MMWR Morb Mortal Wkly Rep ; 67(37): 1032-1035, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30235182

RESUMO

Campylobacter causes an estimated 1.3 million diarrheal illnesses in the United States annually (1). In August 2017, the Florida Department of Health notified CDC of six Campylobacter jejuni infections linked to company A, a national pet store chain based in Ohio. CDC examined whole-genome sequencing (WGS) data and identified six isolates from company A puppies in Florida that were highly related to an isolate from a company A customer in Ohio. This information prompted a multistate investigation by local and state health and agriculture departments and CDC to identify the outbreak source and prevent additional illness. Health officials from six states visited pet stores to collect puppy fecal samples, antibiotic records, and traceback information. Nationally, 118 persons, including 29 pet store employees, in 18 states were identified with illness onset during January 5, 2016-February 4, 2018. In total, six pet store companies were linked to the outbreak. Outbreak isolates were resistant by antibiotic susceptibility testing to all antibiotics commonly used to treat Campylobacter infections, including macrolides and quinolones. Store record reviews revealed that among 149 investigated puppies, 142 (95%) received one or more courses of antibiotics, raising concern that antibiotic use might have led to development of resistance. Public health authorities issued infection prevention recommendations to affected pet stores and recommendations for testing puppies to veterinarians. This outbreak demonstrates that puppies can be a source of multidrug-resistant Campylobacter infections in humans, warranting a closer look at antimicrobial use in the commercial dog industry.


Assuntos
Infecções por Campylobacter/epidemiologia , Campylobacter jejuni/efeitos dos fármacos , Surtos de Doenças , Cães/microbiologia , Farmacorresistência Bacteriana Múltipla , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Campylobacter/tratamento farmacológico , Infecções por Campylobacter/prevenção & controle , Campylobacter jejuni/isolamento & purificação , Criança , Pré-Escolar , Busca de Comunicante , Surtos de Doenças/prevenção & controle , Fezes/microbiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem , Zoonoses
10.
J Genet Couns ; 27(5): 1130-1147, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29516345

RESUMO

The introduction of chromosomal microarray (CMA) into the prenatal setting has involved considerable deliberation due to the wide range of possible outcomes (e.g., copy number variants of uncertain clinical significance). Such issues are typically discussed in pre-test counseling for pregnant women to support informed decision-making regarding prenatal testing options. This research study aimed to assess the level of informed decision-making with respect to prenatal CMA and the factor(s) influencing decision-making to accept CMA for the selected prenatal testing procedure (i.e., chorionic villus sampling or amniocentesis). We employed a questionnaire that was adapted from a three-dimensional measure previously used to assess informed decision-making with respect to prenatal screening for Down syndrome and neural tube defects. This measure classifies an informed decision as one that is knowledgeable, value-consistent, and deliberated. Our questionnaire also included an optional open-ended question, soliciting factors that may have influenced the participants' decision to accept prenatal CMA; these responses were analyzed qualitatively. Data analysis on 106 participants indicated that 49% made an informed decision (i.e., meeting all three criteria of knowledgeable, deliberated, and value-consistent). Analysis of 59 responses to the open-ended question showed that "the more information the better" emerged as the dominant factor influencing both informed and uninformed participants' decisions to accept prenatal CMA. Despite learning about the key issues in pre-test genetic counseling, our study classified a significant portion of women as making uninformed decisions due to insufficient knowledge, lack of deliberation, value-inconsistency, or a combination of these three measures. Future efforts should focus on developing educational approaches and counseling strategies to effectively increase the rate of informed decision-making among women offered prenatal CMA.


Assuntos
Aberrações Cromossômicas , Tomada de Decisões , Diagnóstico Pré-Natal/psicologia , Adolescente , Adulto , Amniocentese , Síndrome de Down/genética , Feminino , Aconselhamento Genético/psicologia , Testes Genéticos/métodos , Humanos , Defeitos do Tubo Neural/genética , Gravidez
11.
Emerg Infect Dis ; 23(13)2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29155664

RESUMO

Zoonotic diseases represent critical threats to global health security. Effective mitigation of the impact of endemic and emerging zoonotic diseases of public health importance requires multisectoral collaboration and interdisciplinary partnerships. The US Centers for Disease Control and Prevention created the One Health Zoonotic Disease Prioritization Tool to help countries identify zoonotic diseases of greatest national concern using input from representatives of human health, agriculture, environment, and wildlife sectors. We review 7 One Health Zoonotic Disease Prioritization Tool workshops conducted during 2014-2016, highlighting workshop outcomes, lessons learned, and shared themes from countries implementing this process. We also describe the tool's ability to help countries focus One Health capacity-building efforts to appropriately prevent, detect, and respond to zoonotic disease threats.


Assuntos
Fortalecimento Institucional , Saúde Global , Prioridades em Saúde , Zoonoses/epidemiologia , Animais , Humanos , Zoonoses/prevenção & controle
12.
Invest Ophthalmol Vis Sci ; 58(11): 4569-4578, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28892825

RESUMO

Purpose: There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD. Methods: Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient. Results: There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant. Conclusions: A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.


Assuntos
Dieta , Atrofia Geográfica/prevenção & controle , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Degeneração Macular Exsudativa/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Registros de Dieta , Suplementos Nutricionais , Progressão da Doença , Ingestão de Energia , Feminino , Seguimentos , Atrofia Geográfica/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fenômenos Fisiológicos da Nutrição , Estudos Prospectivos , Fatores de Risco , Degeneração Macular Exsudativa/epidemiologia
13.
Invest Ophthalmol Vis Sci ; 58(9): 3519-3529, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28715590

RESUMO

Purpose: Age-related macular degeneration (AMD) is a progressive disease with multifactorial etiology. There is a need to identify clinical features that are harbingers of advanced disease. We evaluated morphologic features of the retina and choroid on optical coherence tomography (OCT) to determine if they predict progression to advanced disease. Methods: Progressors transitioned from early or intermediate AMD to advanced disease (n = 40 eyes), and were matched on baseline AMD grade and follow-up interval to nonprogressors who did not develop advanced AMD (n = 40 eyes). Features of the neurosensory retina, photoreceptors, retinal pigment epithelium (RPE), and choroid were evaluated. Logistic regression was used to evaluate univariate associations between features and progression to overall advanced AMD, geographic atrophy (GA), and neovascular disease (NV). Multivariate associations based on stepwise regression models were also assessed. Results: Ellipsoid zone disruption was associated with progression to overall advanced AMD and NV (odds ratios [ORs]: 17.9 and 30.6; P < 0.001), with a similar trend observed for GA. Drusenoid RPE detachment, RPE thickening, and retinal pigmentary hyperreflective material were significantly associated with higher risk of progression to advanced AMD (ORs: 5.0-8.5) and NV (ORs: 10.8-17.2). Pigmentary hyperreflective material was associated with progression to GA (OR: 7.5, P = 0.009). Total retinal thickness, pigmentary hyperreflective material, nascent GA features, and choroidal vessel abnormalities were independently associated with progression to advanced AMD in a multivariate stepwise model. Conclusions: Abnormalities in the photoreceptors, retinal thickness, RPE, and choroid were associated with higher risk of developing advanced AMD. These findings provide insights into disease progression, and may be helpful to identify earlier endpoints for clinical studies.


Assuntos
Corioide/diagnóstico por imagem , Neovascularização de Coroide/diagnóstico , Atrofia Geográfica/diagnóstico , Retina/diagnóstico por imagem , Drusas Retinianas/diagnóstico , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Progressão da Doença , Feminino , Angiofluoresceinografia , Seguimentos , Atrofia Geográfica/tratamento farmacológico , Humanos , Injeções Intravítreas , Masculino , Estudos Prospectivos , Ranibizumab/uso terapêutico , Drusas Retinianas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/tratamento farmacológico
15.
Invest Ophthalmol Vis Sci ; 57(14): 5843-5855, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27802514

RESUMO

Purpose: Increasing evidence suggests a role for macrophages in the pathogenesis of age-related macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD. Methods: Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLA-DR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1- and HLA-DR-positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis. Results: In aged control eyes, the mean number of submacular IBA1+ and HLA-DR+ macrophages was 433/mm2 and 152/mm2, respectively. In early AMD eyes, there was a significant increase in IBA1+ and HLA-DR+ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR+ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls. Conclusions: The average number of IBA1+ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR+ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease.


Assuntos
Corioide/patologia , Neovascularização de Coroide/patologia , Macrófagos/patologia , Degeneração Macular/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Contagem de Células , Feminino , Humanos , Masculino
16.
Am J Hum Genet ; 99(5): 1005-1014, 2016 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-27745832

RESUMO

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.


Assuntos
Complemento C1r/genética , Complemento C1s/genética , Síndrome de Ehlers-Danlos/genética , Deleção de Genes , Mutação de Sentido Incorreto , Periodontite/genética , Adolescente , Adulto , Criança , Pré-Escolar , Mapeamento Cromossômico , Cromossomos Humanos Par 12/genética , Síndrome de Ehlers-Danlos/diagnóstico , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Exoma , Feminino , Loci Gênicos , Humanos , Masculino , Linhagem , Periodontite/diagnóstico , Conformação Proteica , Adulto Jovem
17.
JAMA Ophthalmol ; 134(11): 1272-1280, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27657855

RESUMO

Importance: Age-related macular degeneration (AMD) is a multifactorial disease with genetic and environmental factors contributing to risk. Histopathologic changes underlying AMD are not fully understood, particularly the relationship between choriocapillaris (CC) dysfunction and phenotypic variability of this disease. Objective: To examine histopathologic changes in the CC of eyes with clinically documented AMD. Design, Setting, and Participants: The study was designed in 2011. Tissues were collected post mortem (2012-2016), and histopathological images were obtained from participants enrolled in AMD studies since 1988. Clinical records and images were collected from participants as standard protocol. Eyes without AMD (n = 4) and eyes with early (n = 9), intermediate (n = 5), and advanced stages of AMD (geographic atrophy, n = 5; neovascular disease, n = 13) were evaluated. Choroidal vasculature was labeled using Ulex europaeus agglutinin lectin and examined using confocal microscopy. Main Outcomes and Measures: A standardized classification system was applied to determine AMD stage. Ocular records and images were reviewed and histopathologic analyses performed. Viability of the choroidal vasculature was analyzed for each AMD stage. Results: All participants were white. Fourteen were male, and 16 were female. The mean age was 90.5 years among AMD patients and 88.5 years among control participants. Submacular CC dropout without retinal pigment eipthelial (RPE) loss was observed in all cases with early stages of AMD. Higher vascular area loss for each AMD stage was observed compared with control participants: 20.5% in early AMD (95% CI, 11.2%-40.2%; P < .001), 12.5% in intermediate AMD (95% CI, 2.9%-21.4%; P = .01), 39.0% loss in GA (95% CI, 32.1%-45.4%; P < .001), and 38.2% loss in neovascular disease where RPE remained intact (95% CI, 27.7%-47.9%; P < .001). Hypercellular, apparent neovascular buds were adjacent to areas of CC loss in 22.2% of eyes with early AMD and 40% of eyes with intermediate AMD. Conclusions and Relevance: Retinal pigment epithelial atrophy preceded CC loss in geographic atrophy, but CC loss occurred in the absence of RPE atrophy in 2 of 9 eyes with early-stage AMD. Given the cross-sectional nature of this study and the small number of eyes evaluated, definitive conclusions regarding this progression cannot be determined with certainty. We speculate that neovascular buds may be a precursor to neovascular disease. Hypoxic RPE resulting from reduced blood supply might upregulate production of vascular endothelial growth factor, providing the stimulus for neovascular disease.


Assuntos
Corioide/irrigação sanguínea , Neovascularização de Coroide/diagnóstico , Degeneração Macular/diagnóstico , Epitélio Pigmentado da Retina/patologia , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/etiologia , Estudos Transversais , Progressão da Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Degeneração Macular/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo
18.
Br J Ophthalmol ; 100(12): 1731-1737, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27471039

RESUMO

BACKGROUND/AIMS: The Age-Related Eye Disease Study (AREDS) reported the beneficial impact of antioxidant and zinc supplements on the risk of progression to advanced stages of age-related macular degeneration (AMD). We evaluated the role of genetic variants in modifying the relationship between supplementation and progression to advanced AMD. METHODS: Among 4124 eyes (2317 subjects with a genetic specimen), 882 progressed from no AMD, early or intermediate AMD to overall advanced disease, including geographic atrophy (GA) and neovascular disease (NV) over the course of the clinical trial. Survival analysis using individual eyes as the unit of analysis was used to assess the effect of supplementation on AMD outcomes, with adjustment for demographic, environmental, ocular and genetic covariates. Interaction effects between supplement groups and individual complement factor H (CFH) Y402H and age-related maculopathy susceptibility 2 (ARMS2) genotypes, and composite genetic risk groups combining the number of risk alleles for both loci, were evaluated for their association with progression. RESULTS: Among antioxidant and zinc supplement users compared with the placebo group, subjects with a non-risk genotype for CFH (TT) had a lower risk of progression to advanced AMD (HR: 0.55, 95% CI 0.32 to 0.95, p=0.033). No significant treatment effect was apparent among subjects who were homozygous for the CFH risk allele (CC). A protective effect was observed among high-risk ARMS2 (TT) carriers (HR: 0.52, 95% CI 0.33 to 0.82, p=0.005). Similar results were seen for the NV subtype but not GA. CONCLUSIONS: The effectiveness of antioxidant and zinc supplementation appears to differ by genotype. Further study is needed to determine the biological basis for this interaction. TRIAL REGISTRATION NUMBER: NCT00594672, pre-results.


Assuntos
Antioxidantes/administração & dosagem , DNA/genética , Atrofia Geográfica/genética , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Compostos de Zinco/administração & dosagem , Idoso , Alelos , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Suplementos Nutricionais , Progressão da Doença , Método Duplo-Cego , Feminino , Seguimentos , Genótipo , Atrofia Geográfica/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas/metabolismo , Fatores de Risco , Análise de Sobrevida
19.
Am J Clin Nutr ; 103(4): 1135-44, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26961928

RESUMO

BACKGROUND: There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but few studies have explored associations with folate and B vitamins. No effective therapeutic strategy for geographic atrophy (GA) is available, and prevention could be of great value. OBJECTIVE: We investigated associations between dietary folate, B vitamins, and progression to GA and whether these associations might be modified by genetic susceptibility. DESIGN: Among 2525 subjects (4663 eyes) in the Age-Related Eye Disease Study, 405 subjects (528 eyes) progressed to GA over 13 y. Folate and B vitamins were log transformed and calorie adjusted separately for men and women. Ten loci in 7 AMD genes [complement factor H, age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1, complement component 2, complement component 3, complement factor B, collagen type VIII α 1, and RAD51 paralog B] were examined. Survival analysis was used to assess associations between incident GA and dietary intake of folate and B vitamins. Interaction effects between these nutrients and genetic variation on AMD risk were also evaluated. Subjects with at least one eye free of advanced AMD at baseline were included in these analyses. RESULTS: There was a reduced risk of progression to GA with increasing intake of thiamin, riboflavin, and folate after adjusting for age, sex, and total energy intake (P-trend = 0.01, 0.03, and 0.001, respectively). After adjustment for demographic, behavioral, ocular, and genetic covariates, trends remained statistically significant for folate (P-trend = 0.007) and were borderline for thiamin (P-trend = 0.05). Riboflavin did not retain statistical significance (P-trend = 0.20). Folate was significantly associated with lower risk of incident GA among subjects homozygous for the complement component 3 (C3) R102G rs2230199 nonrisk genotype (CC) (HR = 0.43; 95% CI: 0.27, 0.70; P = 0.0005) but not subjects carrying the risk allele (G) (P = 0.76). Neither folate nor any B vitamin was significantly associated with neovascular AMD. CONCLUSIONS: High folate intake was associated with a reduced risk of progression to GA. This relation could be modified by genetic susceptibility, particularly related to the C3 genotype. This trial was registered at clinicaltrials.gov as NCT00594672.


Assuntos
Ácido Fólico/administração & dosagem , Predisposição Genética para Doença , Atrofia Geográfica/genética , Degeneração Macular/genética , Complexo Vitamínico B/administração & dosagem , Idoso , Índice de Massa Corporal , Colágeno Tipo VIII/genética , Colágeno Tipo VIII/metabolismo , Complemento C2/genética , Complemento C2/metabolismo , Complemento C3/genética , Complemento C3/metabolismo , Fator B do Complemento/genética , Fator B do Complemento/metabolismo , Fator H do Complemento/genética , Fator H do Complemento/metabolismo , Progressão da Doença , Feminino , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas/genética , Proteínas/metabolismo , Riboflavina/administração & dosagem , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Tiamina/administração & dosagem
20.
Food Chem ; 197(Pt A): 872-80, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26617029

RESUMO

Considerable research is focused on understanding the functionality of starch hydrolysis products (SHP) consisting of glucose, maltose, maltooligosaccharides (MOS), and maltopolysaccharides (MPS). A confounding factor in this research is the high molecular dispersity of commercially available SHP. The study presented herein characterizes a flexible fractionation approach for lowering the dispersity of such products. This was accomplished by fractionating a corn syrup solids (CSS) preparation based on the differential solubility of its component saccharides in aqueous-ethanol solutions. Products obtained from selected fractionations were characterized with respect to degree of polymerization (DP; liquid chromatography), dextrose equivalency (reducing sugar assays), and prevalence of branching (NMR). Glucose and maltose were preferentially removed from CSS using high (⩾90%) ethanol extractants. Preparations with relatively narrow ranges of MOS, lower DP MPS, and higher DP MPS were obtained through repetitive 70%-ethanol extractions. Linear, as opposed to branched, MOS and MPS were preferentially extracted under all conditions tested.


Assuntos
Etanol/química , Glucose/análise , Maltose/análise , Oligossacarídeos/análise , Amido/química , Fracionamento Químico , Hidrólise , Solubilidade , Soluções
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