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1.
Arterioscler Thromb Vasc Biol ; 43(1): 79-91, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36325902

RESUMO

BACKGROUND: Reactive oxygen species (ROS) contribute to platelet hyperactivation during aging. Several oxidative pathways and antioxidant enzymes have been implicated; however, their mechanistic contributions during aging remain elusive. We hypothesized that mitochondria are an important source of platelet ROS and that mitochondrial SOD2 (superoxide dismutase) protects against mitochondrial ROS-driven platelet activation and thrombosis during aging. METHODS: We studied littermates of platelet-specific SOD2-knockout (SOD2fl/flPf4Cre, pSOD2-KO) and control (SOD2fl/fl) mice at young (4-5 months) or old (18-20 months) ages. We examined agonist-induced platelet activation, platelet-dependent thrombin generation potential, and susceptibility to in vivo thrombosis. RESULTS: Platelet αIIbß3 activation, aggregation, and adhesion were increased to similar extents in aged mice of both genotypes compared with young mice. In contrast, the age-dependent increases in mitochondrial and total cellular ROS, calcium elevation, and phosphatidylserine exposure were augmented in platelets from pSOD2-KO mice compared with control mice. Aged pSOD2-KO mice showed increased platelet-dependent thrombin generation compared with aged control mice. In vivo, aged pSOD2-KO mice exhibited enhanced susceptibility to carotid artery and pulmonary thrombosis compared to aged control mice. Adoptive transfer of platelets from aged pSOD2-KO but not aged control mice increased thrombotic susceptibility in aged host mice, suggesting a prothrombotic effect of platelet pSOD2 deficiency. Treatment with avasopasem manganese (GC4419), a SOD mimetic, decreased platelet mitochondrial pro-oxidants, cellular ROS levels, and inhibited procoagulant platelet formation and arterial thrombosis in aged mice. CONCLUSIONS: Platelet mitochondrial ROS contributes to age-related thrombosis and endogenous SOD2 protects from platelet-dependent thrombin generation and thrombosis during aging.


Assuntos
Trombina , Trombose , Camundongos , Animais , Trombina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos Knockout , Plaquetas/metabolismo , Trombose/genética , Trombose/prevenção & controle , Trombose/induzido quimicamente , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/metabolismo , Envelhecimento/metabolismo
2.
Int J Behav Nutr Phys Act ; 20(1): 118, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37789328

RESUMO

BACKGROUND: Through the Children's Food and Beverage Advertising Initiative (CFBAI), U.S. food companies pledge to only advertise healthier products in children's television (TV) programming, but previous research shows that highly advertised products do not qualify as nutritious according to independent nutrition criteria. In 2020, the CFBAI implemented stricter nutrition criteria for products that may be advertised to children, but the potential impact of these changes has not been assessed. This observational study evaluates (1) improvements in energy and individual nutrient composition of products that companies indicated may be advertised to children (i.e., CFBAI-listed products) in 2020 versus 2017, (2) amount of advertising on children's TV for CFBAI-listed versus other products in 2021, and 3) the nutrition quality of advertised versus non-advertised CFBAI-listed products. METHODS: Data include energy, saturated fat, sodium, and sugar content and overall nutrition quality (Nutrition Profile Index [NPI] scores) of CFBAI-listed products in 2017 (n = 308) and 2020 (n = 245). Nielsen data provided total ad spending and children's exposure to ads on children's TV channels for all foods and beverages in 2021. RESULTS: From 2017 to 2021, energy, saturated fat and sugar declined for CFBAI-listed products in three of six food categories (yogurt, sweet and salty snacks). Although CFBAI-listed products accounted for 79% of food ads viewed by children on children's TV channels, just 50% of CFBAI-listed food and 36% of drink brands were advertised on children's TV. Moreover, advertised products were significantly less nutritious than non-advertised CFBAI-listed products. CONCLUSION: Despite revised nutrition standards and improvements in nutrient content of some product categories, participating companies continued to primarily advertise nutritionally poor food and beverages on children's TV. CFBAI companies have not delivered on their promises to advertise healthier products to children.


Assuntos
Publicidade , Autocontrole , Criança , Humanos , Indústria Alimentícia , Alimentos , Bebidas , Televisão , Lanches , Açúcares
3.
Health Promot Int ; 38(3)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37184579

RESUMO

This study aimed to exhaustively explore the characteristics of food advertising on TV in Guatemala and Costa Rica. The International Network for Food and Obesity Non-Communicable Diseases (NCDs) Research, Monitoring and Action Support (INFORMAS) methodology was applied. In 2016, we recorded 1440 h of video among 10 TV channels. We used the Pan American Health Organization (PAHO) Nutrient Profile (NP) Model to identify 'critical nutrients', whose excessive consumption is associated with NCDs. We created a nutritional quality score (0 if the product did not exceed any critical nutrient, 1 if the product exceeded one and 2 if it exceeded ≥2). We classified food ads as permitted (score = 0) and not-permitted (score 1 or 2) for marketing. Persuasive marketing techniques were classified as promotional characters (e.g. Batman), premium offers (e.g. toys), brand benefit claims (e.g. tasty) and health-related claims (e.g. nutritious). In Guatemala, foods that exceeded one critical nutrient were more likely to use persuasive marketing techniques, and in Costa Rica were those with an excess of ≥2 critical nutrients, compared with foods without any excess in critical nutrients [Guatemala: promotional characters (odds ratio, OR = 16.6, 95% confidence interval, CI: 5.8, 47.3), premium offers (OR = 3.4, 95% CI: 1.4, 8.2) and health-related claims (OR = 3.5, 95% CI: 2.2, 5.7); Costa Rica: health-related claims (OR = 4.2, 95% CI: 2.0, 8.5)]. In conclusion, Guatemalan and Costa Rican children are exposed to an overabundance of not-permitted food ads on TV. This justifies implementing national policies to reduce exposure to not-permitted food for marketing, including on TV and other media.


This study aimed to exhaustively explore the characteristics of food advertising on TV in Guatemala and Costa Rica. In 2016, we recorded 1440 h of video among 10 TV channels. We used the PAHO Nutrient Profile Model to identify 'critical nutrients' (e.g. sodium) whose excessive consumption is associated with Non-Communicable Chronic Diseases (e.g. hypertension). We created a nutritional quality score (0 if the product did not exceed any critical nutrient, 1 if the product exceeded one and 2 if it exceeded ≥2). We classified food ads as permitted (score = 0) and not-permitted (score 1 or 2) for marketing. Persuasive marketing techniques were classified as promotional characters, premium offers, brand benefit claims and health-related claims. In Guatemala, foods that exceeded one critical nutrient had a high probability of using promotional characters, premium offers and health-related claims than foods without any excess in critical nutrients. However, in Costa Rica health-related claims had a high probability of appearing with foods that exceeded ≥2 critical nutrients. In conclusion, Guatemalan and Costa Rican children are exposed to an overabundance of not-permitted food ads on TV. This justifies implementing national policies to reduce exposure to not-permitted food for marketing.


Assuntos
Publicidade , Alimentos , Criança , Humanos , Costa Rica , Marketing/métodos , Televisão , Valor Nutritivo , Indústria Alimentícia , Bebidas
4.
Public Health Nutr ; : 1-9, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35440350

RESUMO

OBJECTIVE: Drinks containing added sugar and/or non-nutritive sweeteners are not recommended for children under 6 years. Yet, most young children consume these products. The current study examined factors associated with caregivers' provision of sweetened drinks to their young child. DESIGN: Caregivers reported frequency of providing sweetened fruit-flavoured drinks (fruit drinks and flavoured water) and unsweetened juices (100 % juice and juice/water blends) to their 1- to 5-year-old child in the past month and perceived importance of product attributes (healthfulness, product claims and other characteristics), other drinks provided, reading the nutrition facts panel and socio-demographic characteristics. A partial proportional odds model measured the relationship between these factors and frequency of providing sweetened fruit-flavoured drinks. SETTING: Online cross-sectional survey. PARTICIPANTS: U.S. caregivers (n 1763) with a young child (ages 1-5). RESULTS: The majority (74 %) of caregivers provided sweetened fruit-flavoured drinks to their child in the past month; 26 % provided them daily. Provision frequency was positively associated with some drink attributes, including perceived healthfulness, vitamin C claims and box/pouch packaging; child requests and serving other sweetened drinks and juice/water blends. Provision frequency was negatively associated with perceived importance of 'no/less sugar' and 'all natural' claims. Reading nutrition facts panels, serving water to their child and child's age were not significant. CONCLUSION: Misunderstanding of product healthfulness and other marketing attributes contribute to frequent provision of sweetened drinks to young children. Public health efforts to address common misperceptions, including counter marketing, may raise awareness among caregivers about the harms of providing sweetened drinks to young children.

5.
Appetite ; 168: 105670, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478756

RESUMO

Screen time has been associated with overweight and obesity, as well as with poorer dietary quality. However, the reasons explaining these associations are not well understood. The objectives of this cross-sectional study were [1] to determine the extent of overall TV viewing as well as using screens while eating (e.g., watching TV or using a tablet), [2] to compare food and nutrient consumption of on-versus off-screen eating occasions, and [3] to determine whether TV viewing and using screens while eating is associated with overall dietary intake. Participants were from the Food Environment Chilean Cohort (n = 938, 4-6 y) and the Growth and Obesity Cohort Study (n = 752, 12-14 y). Dietary data was collected via one 24-h food recall. For each eating occasion, activity performed during consumption (e.g., watching TV, playing sports) was reported. Weekly TV viewing time was collected via an additional survey instrument. Analyses included multivariable linear and logistic regression. Post-hoc pairwise comparisons examined differences in outcomes by tertiles. Our sample reported a median of 9-13.5 weekly hours of TV viewing and 87.5% reported consuming at least one meal or snack per day while using screens. The median kilocalories contributed by eating during screen use was 387 kcal/d in children and 848 kcal/day in adolescents, which represents 34.7% and 42.3% of daily energy intake, respectively. There were no consistent differences when comparing eating occasions consumed on-screen versus off-screen. Higher weekly TV viewing was associated with elements of a less healthy diet including more sweets and desserts in children, and more sugar sweetened beverages in adolescents. A large percentage of Chilean children and adolescents' daily energy is consumed while using screens. In depth, longitudinal work is needed to understand how screen time eating affects diet quality and nutritional status.


Assuntos
Comportamento Alimentar , Televisão , Adolescente , Criança , Estudos de Coortes , Estudos Transversais , Ingestão de Alimentos , Ingestão de Energia , Humanos , Lanches
6.
Int J Behav Nutr Phys Act ; 18(1): 60, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947436

RESUMO

BACKGROUND: The first phase of a comprehensive marketing policy was implemented in Chile in 2016. The policy restricted child-directed marketing of foods and beverages considered high in energy, total sugars, sodium or saturated fat ("high-in"). The objective of this study was to examine the role of high-in TV food advertising as a mediator in the association between policy implementation and consumption of high-in foods and beverages between 2016 and 2017. METHODS: Dietary data were from 24-hour diet recalls collected in 2016 and 2017 in a cohort of 12-14 y children (n = 721). Television use was assessed concurrently and linked to analyses of food advertisements on broadcast and paid television to derive individual-level estimates of exposure to high-in food advertising. A multilevel mediation analysis examined direct and indirect effects of the policy through advertising exposure. RESULTS: Following the policy implementation, high-in advertising exposure was significantly reduced (p < 0.01). High-in food intake decreased in adolescents with lower levels, but not higher levels, of high-in advertising at baseline. We did not find evidence of mediation by changes in high-in ad exposure. CONCLUSIONS: Adolescents' exposure to high-in TV advertising decreased after the 2016 implementation of the Chilean Food Labeling and Marketing Law. However, evidence that changes in advertisement mediated dietary changes was not found. Further research is needed to understand how marketing changes will relate to dietary changes after full implementation of the law and in the long term.


Assuntos
Dieta , Comportamento Alimentar/fisiologia , Marketing , Política Nutricional , Televisão , Adolescente , Criança , Chile , Rotulagem de Alimentos , Humanos
7.
Public Health Nutr ; 24(18): 6499-6511, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34407907

RESUMO

OBJECTIVE: To assess the extent to which mandatory Guidelines to improve the school food environment were being implemented in Costa Rican high schools and to explore the perspectives of key policy actors towards the Guidelines. DESIGN: Semi-structured interviews and site observations. Interviews were recorded, transcribed verbatim and imported to NVivo 12 for analysis. Inductive and deductive themes were identified, and elements of the RE-AIM framework and the social process framework were used when classifying these themes. SETTING: Sixteen public high schools in San José, Costa Rica. PARTICIPANTS: High school principal and kiosk concessionaires. RESULTS: Products that did not adhere to the Guidelines were still widely available in schools, and amongst the most prevalent challenges to implementation that emerged from our interviews, were a lack of understanding of the policy content, a lack of monitoring and accountability, and competing values amongst actors which affected their views on the role that the school must have in offering a healthy food environment. CONCLUSION: Most products offered in high schools did not meet the criteria required by the mandatory Guidelines, and several contextual factors were found to influence implementation. Strengthening the implementation of the Costa Rican Guidelines will require further actions at the governmental and school levels.


Assuntos
Serviços de Alimentação , Instituições Acadêmicas , Costa Rica , Alimentos , Humanos , Política Nutricional , Obesidade
8.
Public Health Nutr ; 22(13): 2509-2520, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31109393

RESUMO

OBJECTIVE: To examine the frequency of television (TV) food and beverage advertisements (F&B ads) to which children (4-11 years) are likely exposed and the nutrient profile of products advertised. DESIGN: TV broadcasting between September and November 2016 was recorded (288 h of children's programming; 288 h of family programming) resulting in 8980 advertisements, of which 1862 were F&B ads. Of those, 1473 could be classified into one of the seventeen food groups, and into permitted/non-permitted according to the WHO-EU nutrient profile model. Persuasive marketing techniques used were also identified. SETTING: TV programming was recorded for four weekdays and four weekend days, between 06.00 and 00.00 hours (576 total hours), for four channels (two national and two cable), in Costa Rica. RESULTS: Mean (sd) number of F&B ads/h was greater in cable than national channels (3·7 (0·4) v. 2·8 (0·4), P < 0·05) and during children's peak viewing hours (4·4 (0·4) v. 2·9 (0·3)). Of F&B ads classified with WHO-EU nutrient profile model (n 1473, 71·1 %), 91·1 % were non-permitted to be marketed to children. Categories most frequently advertised were ready-made/convenience foods (16 %), chocolates/confectionery/desserts (15 %), breakfast cereals (14 %), beverages (15 %), edible ices (9 %) and salty snacks (8 %). Non-permitted F&B ads were more likely to use promotional characters, brand benefit claims, and nutrition and health claims than permitted F&B ads. CONCLUSIONS: Children watching popular TV channels in Costa Rica are exposed to a high number of unhealthy F&B ads daily. Our findings help justify the need for regulatory actions by national authorities.


Assuntos
Publicidade/estatística & dados numéricos , Bebidas/estatística & dados numéricos , Alimentos/estatística & dados numéricos , Televisão , Bebidas/classificação , Criança , Pré-Escolar , Costa Rica , Alimentos/classificação , Indústria Alimentícia , Humanos , Valor Nutritivo/fisiologia , Comunicação Persuasiva
9.
Public Health Nutr ; 22(15): 2803-2812, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31124768

RESUMO

OBJECTIVE: To examine snacking patterns, food sources and nutrient profiles of snacks in low- and middle-income Chilean children and adolescents. DESIGN: Cross-sectional. Dietary data were collected via 24 h food recalls. We determined the proportion of snackers, snacks per day and energy from top food and beverage groups consumed. We compared the nutrient profile (energy, sodium, total sugars and saturated fat) of snacks v. meals. SETTING: South-east region of Chile. PARTICIPANTS: Children and adolescents from two cohorts: the Food Environment Chilean Cohort (n 958, 4-6 years old) and the Growth and Obesity Cohort Study (n 752, 12-14 years old). RESULTS: With a mean of 2·30 (se 0·03) snacks consumed daily, 95·2 % of children and 89·9 % of adolescents reported at least one snacking event. Snacks contributed on average 1506 kJ/d (360 kcal/d) in snacking children and 2218 kJ/d (530 kcal/d) in snacking adolescents (29·0 and 27·4 % daily energy contribution, respectively). Grain-based desserts, salty snacks, other sweets and desserts, dairy foods and cereal-based foods contributed the most energy from snacks in the overall sample. For meals, cereal-based foods, dairy beverages, meat and meat substitutes, oils and fats, and fruits and vegetables were the top energy contributors. CONCLUSIONS: Widespread snacking among Chilean youth provides over a quarter of their daily energy and includes foods generally considered high in energy, saturated fat, sodium and/or total sugars. Future research should explore whether snacking behaviours change as the result of Chile's national regulations on food marketing, labelling and school environments.


Assuntos
Dieta/estatística & dados numéricos , Comportamento Alimentar , Refeições , Lanches , Adolescente , Criança , Pré-Escolar , Chile , Estudos Transversais , Inquéritos sobre Dietas , Ingestão de Energia , Feminino , Humanos , Masculino
10.
S D Med ; 71(8): 362-366, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30110527

RESUMO

Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal inflammatory disease that is becoming more widely recognized as a cause of feeding difficulties in infants and young children, as well as gastroesophageal reflux disease (GERD)-like symptoms, dysphagia, and food impaction in children and adolescents. The diagnosis of EoE is clinicopathologic, based on endoscopic, histologic, and clinical findings. Patients with suspected eosinophilic esophagitis require an endoscopy with biopsies. The diagnosis requires the presence of 15 or more intraepithelial eosinophils/HPF in at least one endoscopic esophageal mucosal biopsy. Histology will reveal mucosal eosinophilia isolated to the esophagus, which does not improve following Proton Pump Inhibitor (PPI) trial. Other disorders causing esophageal eosinophilia, such as GERD, celiac disease, Crohn's disease, infection, hypereosinophilic syndrome, achalasia, and drug hypersensitivity must be ruled out. The goals of treatment should include both histologic healing of the esophageal mucosa, as well as resolution of clinical symptoms. Treatment options include food elimination diets, topical steroids, and/or esophageal dilatation. While the understanding of EoE has evolved over the past twenty years, it continues to be a challenging diagnosis due to the clinical and histopathologic similarities to GERD. Much remains to be studied regarding the underlying pathology, as well as appropriate biomarkers to better evaluate response to therapy.


Assuntos
Esofagite Eosinofílica/patologia , Adolescente , Biópsia , Criança , Pré-Escolar , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/tratamento farmacológico , Humanos , Lactente , Inibidores da Bomba de Prótons/uso terapêutico
11.
J Nutr ; 146(8): 1593-600, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27358419

RESUMO

BACKGROUND: Food assistance programs may alter food choices, but factors determining households' decisions regarding food acquisition, preparation, and consumption in the context of food aid are not well understood. OBJECTIVE: This study aimed to understand how the Programa Comunitario Materno Infantil de Diversificación Alimentaria (Mother-Child Community Food Diversification Program; PROCOMIDA), a food-assisted maternal and child health and nutrition program in rural Alta Verapaz, Guatemala, altered household food choices. METHODS: We conducted semistructured interviews and focus groups with 63 households in 3 participating (n = 32 households) and 3 control (n = 31) villages. A last-day food recall (without estimating quantities) and food-frequency questionnaire that used food cards assessed dietary choices. Qualitative analysis used thematic a priori and emergent coding; food group consumption frequencies were analyzed by using 2-level, logistic, mixed modeling, and chi-square testing while accounting for community clustering. RESULTS: Compared with control households, PROCOMIDA changed household food choices through a combination of providing food resources (with monthly food rations) and new knowledge and skills related to health and food (in the program's behavior change communication component) while reinforcing existing knowledge and beliefs. PROCOMIDA families consumed rice, red beans, and oil more frequently than did control families (differences of 2.20 (P < 0.001), 2.68 (P < 0.001), and 1.64 (P = 0.038) times/wk, respectively); these foods were in the rations. PROCOMIDA families also ate chicken, local plants, and some vegetables more frequently. The importance of these foods was emphasized in the behavioral change communication component; these foods may have been more accessible because provision of food rations freed resources. CONCLUSION: Our findings suggest that if a program provides food free of cost to rural indigenous families in the context of a maternal and child nutrition and health program, it may be important to include a well-designed behavioral change communication component to improve household food choices.


Assuntos
Comportamento de Escolha , Comunicação , Dieta , Características da Família , Comportamento Alimentar , Assistência Alimentar , Promoção da Saúde/métodos , Adulto , Terapia Comportamental , Saúde da Criança , Feminino , Guatemala , Conhecimentos, Atitudes e Prática em Saúde , Serviços de Saúde do Indígena , Humanos , Lactente , Recém-Nascido , Masculino , Saúde Materna , População Rural , Adulto Jovem
12.
J Pediatr Gastroenterol Nutr ; 61(2): 187-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25651487

RESUMO

OBJECTIVES: Oral high-dose repletion vitamin D therapy, also known as stoss therapy, can be effective in the treatment of nutritional vitamin D deficiency rickets in infants and young children without liver disease and in patients with cystic fibrosis. There is no literature about this approach in infants with new-onset cholestasis. METHODS: This was a retrospective chart review of infants with cholestasis from March 2010 to March 2012 at a pediatric tertiary care center. Four cases satisfied the inclusion criteria, and were described in detail. RESULTS: All of the patients received oral high-dose repletion therapy with ergocalciferol (vitamin D2) 300,000 IU daily for 2 to 3 days. Follow-up vitamin D levels approximately 4 weeks later showed failure to achieve sufficiency levels (>20 ng/dL) in any patient. CONCLUSIONS: Unlike infants without liver disease, use of oral high-dose repletion therapy may not be adequate as treatment of vitamin D deficiency in the setting of cholestasis.


Assuntos
Colestase/complicações , Ergocalciferóis/administração & dosagem , Deficiência de Vitamina D/tratamento farmacológico , Administração Oral , Atresia Biliar/complicações , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária , Falha de Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/etiologia , Deficiência de alfa 1-Antitripsina/complicações
13.
S D Med ; 68(1): 9-11, 13, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25638903

RESUMO

Cyclic vomiting syndrome (CVS) is characterized by stereotypical episodes of intense vomiting separated by periods where the individual feels completely well. There is a strong link between CVS and migraine headaches, with many overlapping symptoms and similarities in treatment. There are consensus criteria for CVS diagnosis, but there is no specific diagnostic test, and there is often a delay in diagnosis resulting in a high degree of morbidity. Recognizing the CVS vomiting pattern can facilitate earlier diagnosis and treatment, which can greatly improve the quality of life for CVS patients.


Assuntos
Vômito/diagnóstico , Vômito/terapia , Criança , Humanos , Vômito/etiologia
14.
Blood ; 120(26): 5224-30, 2012 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-22983446

RESUMO

Epidemiologic studies suggest that elevated VWF levels and reduced ADAMTS13 activity in the plasma are risk factors for myocardial infarction. However, it remains unknown whether the ADAMTS13-VWF axis plays a causal role in the pathophysiology of myocardial infarction. In the present study, we tested the hypothesis that ADAMTS13 reduces VWF-mediated acute myocardial ischemia/reperfusion (I/R) injury in mice. Infarct size, neutrophil infiltration, and myocyte apoptosis in the left ventricular area were quantified after 30 minutes of ischemia and 23.5 hours of reperfusion injury. Adamts13(-/-) mice exhibited significantly larger infarcts concordant with increased neutrophil infiltration and myocyte apoptosis compared with wild-type (WT) mice. In contrast, Vwf(-/-) mice exhibited significantly reduced infarct size, neutrophil infiltration, and myocyte apoptosis compared with WT mice, suggesting a detrimental role for VWF in myocardial I/R injury. Treating WT or Adamts13(-/-) mice with neutralizing Abs to VWF significantly reduced infarct size compared with control Ig-treated mice. Finally, myocardial I/R injury in Adamts13(-/-)/Vwf(-/-) mice was similar to that in Vwf(-/-) mice, suggesting that the exacerbated myocardial I/R injury observed in the setting of ADAMTS13 deficiency is VWF dependent. These findings reveal that ADAMTS13 and VWF are causally involved in myocardial I/R injury.


Assuntos
Metaloendopeptidases/deficiência , Metaloendopeptidases/fisiologia , Traumatismo por Reperfusão Miocárdica/genética , Fator de von Willebrand/fisiologia , Proteína ADAMTS13 , Animais , Anticorpos Neutralizantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/fisiologia , Cardiotônicos/farmacologia , Progressão da Doença , Masculino , Metaloendopeptidases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/complicações , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miócitos Cardíacos/fisiologia , Infiltração de Neutrófilos/genética , Fator de von Willebrand/antagonistas & inibidores , Fator de von Willebrand/genética , Fator de von Willebrand/imunologia
15.
Blood ; 119(13): 3176-83, 2012 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-22186991

RESUMO

Hyperhomocysteinemia confers a high risk for thrombotic vascular events, but homocysteine-lowering therapies have been ineffective in reducing the incidence of secondary vascular outcomes, raising questions regarding the role of homocysteine as a mediator of cardiovascular disease. Therefore, to determine the contribution of elevated homocysteine to thrombosis susceptibility, we studied Cbs(-/-) mice conditionally expressing a zinc-inducible mutated human CBS (I278T) transgene. Tg-I278T Cbs(-/-) mice exhibited severe hyperhomocysteinemia and endothelial dysfunction in cerebral arterioles. Surprisingly, however, these mice did not display increased susceptibility to arterial or venous thrombosis as measured by photochemical injury in the carotid artery, chemical injury in the carotid artery or mesenteric arterioles, or ligation of the inferior vena cava. A survey of hemostatic and hemodynamic parameters revealed no detectible differences between control and Tg-I278T Cbs(-/-) mice. Our data demonstrate that severe elevation in homocysteine leads to the development of vascular endothelial dysfunction but is not sufficient to promote thrombosis. These findings may provide insights into the failure of homocysteine-lowering trials in secondary prevention from thrombotic vascular events.


Assuntos
Modelos Animais de Doenças , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/patologia , Camundongos , Trombose/etiologia , Animais , Cistationina beta-Sintase/genética , Feminino , Testes Hematológicos , Hemodinâmica/genética , Hemodinâmica/fisiologia , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Fatores de Risco , Índice de Gravidade de Doença
16.
J Thromb Haemost ; 22(9): 2514-2530, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38815756

RESUMO

BACKGROUND: COVID-19 can cause profound inflammation and coagulopathy, and while many mechanisms have been proposed, there is no known common pathway leading to a prothrombotic state. OBJECTIVES: From the beginning of the COVID-19 pandemic, elevated levels of extracellular histones have been found in plasma of patients infected with SARS-CoV-2. We hypothesized that platelet activation triggered by extracellular histones might represent a unifying mechanism leading to increased thrombin generation and thrombosis. METHODS: We utilized blood samples collected from an early clinical trial of hospitalized COVID-19 patients (NCT04360824) and recruited healthy subjects as controls. Using plasma samples, we measured the procoagulant and prothrombotic potential of circulating extracellular histones and extracellular vesicles (EVs). Platelet prothrombotic activity was assessed via thrombin generation potential and platelet thrombus growth. Circulating EVs were assessed for thrombin generation potential in vitro in plasma and enhancement of thrombotic susceptibility in vivo in mice. RESULTS: Compared with controls, COVID-19 patients had elevated plasma levels of citrullinated histone H3, cell-free DNA, nucleosomes, and EVs. Plasma from COVID-19 patients promoted platelet activation, platelet-dependent thrombin generation, thrombus growth under venous shear stress, and release of platelet-derived EVs. These prothrombotic effects of COVID-19 plasma were inhibited by an RNA aptamer that neutralizes both free and DNA-bound histones. EVs isolated from COVID-19 plasma enhanced thrombin generation in vitro and potentiated venous thrombosis in mice in vivo. CONCLUSION: We conclude that extracellular histones and procoagulant EVs drive the prothrombotic state in COVID-19 and that histone-targeted therapy may prove beneficial.


Assuntos
Plaquetas , COVID-19 , Vesículas Extracelulares , Histonas , Ativação Plaquetária , Trombose , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Coagulação Sanguínea , Plaquetas/metabolismo , Estudos de Casos e Controles , Citrulinação , COVID-19/sangue , COVID-19/complicações , Vesículas Extracelulares/metabolismo , Histonas/sangue , Camundongos Endogâmicos C57BL , Nucleossomos/metabolismo , Trombina/metabolismo , Trombose/sangue , Trombose/etiologia , Ensaios Clínicos Fase IV como Assunto
17.
Curr Dev Nutr ; 6(1): nzab151, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35047722

RESUMO

BACKGROUND: Against expert recommendations, sugar-sweetened beverages, especially fruit drinks, are consumed by young children. Misperceptions about drink ingredients and healthfulness can contribute to caregivers' provision. OBJECTIVES: To assess caregivers' reasons for serving sweetened fruit-flavored drinks and unsweetened juices to their young children (1-5 y) and perceptions of product healthfulness and drink ingredients. METHODS: A cross-sectional online survey assessed participants' (n = 1614) perceptions of sweetened fruit-flavored drinks (fruit drinks and flavored water) and unsweetened juices (100% juice and water/juice blends) provided to their child in the past month, including product healthfulness, reasons for providing, and knowledge of product ingredients [added sugar, nonnutritive sweeteners (NNSs), percentage juice]. One-factor ANOVA compared perceived healthfulness of drink categories and types of sugar and NNSs, and differences between participants who could compared with those who could not accurately identify drink ingredients. RESULTS: Participants' top reasons for providing sweetened drinks included child liking it, being inexpensive, child asking for it, and being a special treat. Participants perceived 100% juice as healthiest, followed by juice/water blends, flavored waters, and, lastly, fruit drinks (P < 0.05). Many participants inaccurately believed the fruit drink or flavored water they served their child most often did not contain NNSs (59.0% and 64.9%) and/or added sugars (20.1% and 42.2%), when in fact they did, and 81.3-91.1% overestimated the percentage juice in the drink. Perceived healthfulness of fruit drinks was associated with caregivers' belief that the drink contained added sugar (P < 0.05), but not with their belief that it contained NNS; increased accuracy was associated with decreased perceived healthfulness (P < 0.05). CONCLUSIONS: Inaccurate understanding of added sugar, NNSs, and percentage juice in drinks served to young children was common and could contribute to sugary drink provision. Public health efforts should seek to improve labeling practices and revise nutrition education messages.

18.
Pediatr Obes ; 16(4): e12735, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33105522

RESUMO

BACKGROUND: The Chilean government implemented the first phase of a comprehensive marketing policy in 2016, restricting child-directed marketing of products high in energy, total sugars, sodium or saturated fat (hereafter "high-in"). OBJECTIVES: To examine the role that high-in TV food advertising had in the effect of the policy on consumption of high-in products between 2016 and 2017. METHODS: Dietary data were obtained from 24-hour diet recall measured in 2016 (n = 940) and 2017 (n = 853), pre- and post-policy, from a cohort of 4 to 6 years children. Television use was linked to analyses of food advertisements to derive individual-level estimates of exposure to advertising. A multilevel mediation analysis examined direct and indirect effects of the policy through advertising exposure. RESULTS: Children's high-in food consumption and advertising exposure declined significantly from 2016 to 2017 (P < .01). Consumption changes were not significantly mediated by changes in advertising exposure, which might suggest other elements of the Chilean Law potentially driving decreases in consumption to a greater extent than TV ads. CONCLUSIONS: Preschoolers' exposure to high-in advertising and consumption of high-in products decreased post-policy. Further research is needed to understand how marketing changes will relate to dietary changes after full implementation of the law and in the long term.


Assuntos
Publicidade , Marketing , Pré-Escolar , Chile , Ingestão de Alimentos , Feminino , Alimentos , Indústria Alimentícia , Humanos , Política Nutricional , Televisão
19.
Obes Rev ; 22 Suppl 3: e13237, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34152071

RESUMO

The food environment is a major contributor to unhealthy diets in children and, therefore, to the increasing rates of obesity. Acclaimed by scholars across the world, Latin American countries have been leaders in implementing policies that target different aspects of the food environment. Evidence on the nature and to what extent children are exposed and respond to unhealthy food environments in the region and among Latinos in the United States is, however, deficient. The objective of this review is to use the integrated International Network for Food and Obesity/noncommunicable diseases (NCDs) Research, Monitoring and Action Support (INFORMAS) framework to create healthy food environment to (i) compare the key elements of childhood obesity-related food environments in Latin America and for Latinos living in the United States; (ii) describe the evidence on solutions to improve childhood obesity-related food environments; and (iii) identify research priorities to inform solutions to fight childhood obesity in these populations. We found that an integrated body of evidence is needed to inform an optimal package of policies to improve food environments to which children in Latin America and Latino children in the United States are exposed and more efficiently translate policy solutions to help curb growing childhood obesity levels across borders.


Assuntos
Obesidade Infantil , Criança , Dieta , Promoção da Saúde , Hispânico ou Latino , Humanos , América Latina/epidemiologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/prevenção & controle , Estados Unidos/epidemiologia
20.
Contemp Clin Trials Commun ; 20: 100660, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33094194

RESUMO

Within the military, cognitive readiness is essential to ensure the warfighter can return to highly demanding combat training and deployment operations. The warfighter must be able to make split second decisions and adapt to new tools and environments. After a traumatic brain injury, clinicians helping the warfighter must have techniques that address warfighter cognitive readiness. Current rehabilitation for cognitive complaints used in military medicine are modeled after civilian therapies which focus on remediating moderate to severe impairment through building compensatory strategies. This traditional approach to cognitive rehabilitation does not translate well to mild traumatic brain injury (mTBI) where impairments are subtle, nor does it meet the needs of our warfighters in deployed and combat training environments. Challenging our current methods is critical in adapting to the needs of this highly valued population to ensure that our warfighters are able to carry out mission critical decision making. Here we present a review of our best current practices for cognitive rehabilitation, describe the limitations our traditional approaches impose for mTBI in military personnel, and present an alternative treatment called Strategic Memory Advanced Reasoning Training (SMART) that can be adopted through a randomized clinical trial design. We propose directly comparing traditional treatment approaches with a novel cognitive rehabilitation strategy which has been well validated outside of the military setting. Procedures were developed to execute this clinical trial in a way that is most relevant to the study population by establishing ecologically valid outcome metrics.

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