RESUMO
The specificity and efficiency of enzyme-mediated reactions have the potential to positively impact many biotechnologies; however, many enzymes are easily degraded. Immobilization on a solid support has recently been explored to improve enzyme stability. This study aims to gain insights and facilitate enzyme adsorption onto gold nanoparticles (AuNPs) to form a stable bioconjugate through the installation of thiol functional groups that alter the protein chemistry. In specific, the model enzyme, horseradish peroxidase (HRP), is thiolated via Traut's reagent to increase the robustness and enzymatic activity of the bioconjugate. This study compares HRP and its thiolated analog (THRP) to deduce the impact of thiolation and AuNP-immobilization on the enzyme activity and stability. HRP, THRP, and their corresponding bioconjugates, HRP-AuNP and THRP-AuNP, were analyzed via UV-vis spectrophotometry, circular dichroism, zeta potential, and enzyme-substrate kinetics assays. Our data show a 5-fold greater adsorption for THRP on the AuNP, in comparison to HRP, that translated to a 5-fold increase in the THRP-AuNP bioconjugate activity. The thiolated and immobilized HRP exhibited a substantial improvement in stability at elevated temperatures (50 °C) and storage times (1 month) relative to the native enzyme in solution. Moreover, HRP, THRP, and their bioconjugates were incubated with trypsin to assess the susceptibility to proteolytic digestion. Our results demonstrate that THRP-AuNP bioconjugates maintain full enzymatic activity after 18 h of incubation with trypsin, whereas free HRP, free THRP, and HRP-AuNP conjugates are rendered inactive by trypsin treatment. These results highlight the potential for protein modification and immobilization to substantially extend enzyme shelf life, resist protease digestion, and enhance biological function to realize enzyme-enabled biotechnologies.
Assuntos
Estabilidade Enzimática , Enzimas Imobilizadas , Ouro , Peroxidase do Rábano Silvestre , Nanopartículas Metálicas , Compostos de Sulfidrila , Ouro/química , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Compostos de Sulfidrila/química , Nanopartículas Metálicas/química , Proteólise , Adsorção , CinéticaRESUMO
BACKGROUND: The influence of obesity on the development of prediabetes among African American women (AAW) remains uncertain. Thus, we investigated whether the pathogenic mechanisms of prediabetes differ in obese (OB, BMI<35 kg/m2) and very obese (VOB, BMI>35 kg/m2) AAW. SUBJECTS/METHODS: We recruited 26-OB and 41-VOB, AAW with prediabetes, mean age (46.3 ± 10.3 years), A1C (5.9 ± 0.4%) and BMI (38.3 ± 8.2 kg/m2). OGTT and FSIVGT were performed in each subject. Body composition (% body fat) was measured using DEXA. Si, Sg acute insulin response to glucose (AIRg) and disposition index (DI) were calculated using minimal model method. RESULTS: Mean BMI (32.6 ± 1.9 vs. 42.8 ± 5.5 kg/m2) and %body fat (44.7 ± 2.0 vs. 49.6 ± 2.2%) were significantly (p = 0.0001) lower in OB vs VOB. Mean fasting and post-glucose challenge, (glucose, insulin, c-peptide) levels were significantly (p = 0.03-0.0001) lower in OB vs VOB. Mean Si and Sg was not different. Mean AIRg tended to be higher (808 ± 776 vs. 535 ± 443 (x min [uU/L] -1), p = 0.106) whereas DI was greater (1999 ± 1408 vs. 1511 ± 1033, (×10-2 x min-1), p = 0.01) in OB vs VOB subjects. CONCLUSION: We found that OB and VOB AAW had similar Si and Sg, but VOB showed attenuated AIRg and DI. These parameters should be considered when developing primary prevention programs in AAW with prediabetes.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Diabetes Mellitus Tipo 2/prevenção & controle , Obesidade/complicações , Estado Pré-Diabético/etiologia , Composição Corporal , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/etnologia , Feminino , Teste de Tolerância a Glucose , Humanos , Pessoa de Meia-Idade , Obesidade/etnologia , Estado Pré-Diabético/etnologiaRESUMO
AIMS: To determine whether baseline metabolic syndrome (MetS) modifies the effect of intensive blood pressure control on cardiovascular (CV) outcomes, and whether the effects varied by race/ethnicity. METHODS: We performed post hoc analyses among non-Hispanic black, non-hispanic white and Hispanic participants, with and without MetS, in the Systolic Blood Pressure Intervention Trial (SPRINT), who were randomized to a systolic blood pressure (SBP) target of <120 mm Hg (intensive group, N = 4544) or an SBP target of <140 mm Hg (standard group, N = 4553). The median follow-up was 3.26 years. The primary outcome was the composite of the first occurrence of myocardial infarction, stroke, heart failure, non-myocardial infarction acute coronary syndrome or CV death. RESULTS: Overall, 3521/9097 participants (38.7%) met the criteria for MetS at baseline. Baseline characteristics were similar in the two SBP target groups within each MetS subgroup, except body mass index was slightly higher in the standard arm of the MetS subgroup (33.3 ± 5.6 vs 33.0 ± 5.3 kg/m2 ; P < .01), but were similar across treatment arms in the non-MetS subgroup. The hazard ratio for the primary outcome was similarly reduced in participants with or without baseline MetS: 0.75 (95% confidence interval [CI] 0.57, 0.96) and 0.71 (95% CI 0.57, 0.87), respectively (adjusted P value for treatment by subgroup interaction = .98). Similarly, there was no evidence of treatment × MetS subgroup interaction for all-cause mortality (adjusted interaction P value = .98). The findings were also similar across race/ethnic subgroups. CONCLUSIONS: In this analysis the CV benefit of intensive SBP control did not differ among participants by baseline MetS status, regardless of race/ethnicity.
Assuntos
Hipertensão/prevenção & controle , Síndrome Metabólica/complicações , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Término Precoce de Ensaios Clínicos , Feminino , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/mortalidade , Humanos , Hipertensão/etnologia , Hipertensão/mortalidade , Masculino , Síndrome Metabólica/etnologia , Síndrome Metabólica/mortalidade , Infarto do Miocárdio/etnologia , Infarto do Miocárdio/mortalidade , Fatores Raciais , Grupos Raciais/etnologia , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/mortalidade , Estados Unidos/epidemiologiaRESUMO
AIMS/HYPOTHESIS: The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to identify determinants associated with insulin resistance and beta cell dysfunction among this population. METHODS: Data from the cross-sectional multicentre Research on Obesity and Diabetes among African Migrants (RODAM) study were analysed. Participants included Ghanaian individuals without diabetes, aged 18-96 years old, who were residing in Amsterdam (n = 1337), Berlin (n = 502), London (n = 961), urban Ghana (n = 1309) and rural Ghana (n = 970). Glucose and insulin were measured in fasting venous blood samples. Anthropometrics were assessed during a physical examination. Questionnaires were used to assess demographics, physical activity, smoking status, alcohol consumption and energy intake. Insulin resistance and beta cell function were determined using homeostatic modelling (HOMA-IR and HOMA-B, respectively). Logistic regression analysis was used to study the contribution of HOMA-IR and inverse HOMA-B (beta cell dysfunction) to geographical differences in IFBG (fasting glucose 5.6-6.9 mmol/l). Multivariate linear regression analysis was used to identify determinants associated with HOMA-IR and inverse HOMA-B. RESULTS: IFBG was more common in individuals residing in urban Ghana (OR 1.41 [95% CI 1.08, 1.84]), Amsterdam (OR 3.44 [95% CI 2.69, 4.39]) and London (OR 1.58 [95% CI 1.20 2.08), but similar in individuals living in Berlin (OR 1.00 [95% CI 0.70, 1.45]), compared with those in rural Ghana (reference population). The attributable risk of IFBG per 1 SD increase in HOMA-IR was 69.3% and in inverse HOMA-B was 11.1%. After adjustment for HOMA-IR, the odds for IFBG reduced to 0.96 (95% CI 0.72, 1.27), 2.52 (95%CI 1.94, 3.26) and 1.02 (95% CI 0.78, 1.38) for individuals in Urban Ghana, Amsterdam and London compared with rural Ghana, respectively. In contrast, adjustment for inverse HOMA-B had very minor impact on the ORs of IFBG. In multivariate analyses, BMI (ß = 0.17 [95% CI 0.11, 0.24]) and waist circumference (ß = 0.29 [95%CI 0.22, 0.36]) were most strongly associated with higher HOMA-IR, whereas inverse HOMA-B was most strongly associated with age (ß = 0.20 [95% CI 0.16, 0.23]) and excess alcohol consumption (ß = 0.25 [95% CI 0.07, 0.43]). CONCLUSIONS/INTERPRETATION: Our findings suggest that insulin resistance, rather than beta cell dysfunction, is more important in accounting for the geographical differences in IFBG among sub-Saharan African individuals. We also show that BMI and waist circumference are important factors in insulin resistance in this population.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Jejum/sangue , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/fisiologia , Adolescente , Adulto , África , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Europa (Continente) , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Circunferência da Cintura/fisiologia , Adulto JovemRESUMO
BACKGROUND: The study aims to determine whether the route of insulin administration influences glycaemic variability and inflammatory or neurohormonal markers in patients with type 2 diabetes and congestive heart failure (CHF) exacerbation. METHODS: Patients (n = 65) were randomized to intravenous (IV) insulin (duration 48 h) or subcutaneous (SQ) insulin. Inflammatory cytokines and markers of lipid oxidation, high-frequency heart rate variability (n = 27) and cardiac impedance (pre-ejection period, n = 28) were used to estimate parasympathetic and sympathetic tone in patients with valid cardiac data. Glycaemic variability was measured using a continuous glucose monitor. RESULTS: Mean glucose was lower (7.7 ± 1.2 vs 9.4 ± 2.7 mmol/L, p = 0.004), coefficient of variation was higher (p = 0.03) and glycaemic lability index was similar on day 1 in the IV group compared with the SQ group, but groups were similar by day 2. The IV group had more confirmed hypoglycaemia (p = 0.005). There were no differences in hospital readmission or hospital length of stay between groups. There were no differences in CHF biomarkers, heart rate variability or pre-ejection period between groups. Increasing log glycaemic lability index was associated with lower on-treatment pre-ejection period (p = 0.03) while increasing coefficient of variation was associated with increasing brain natriuretic peptide (p = 0.004) and paroxonase-1 (p = 0.02). Other univariable analyses were not significant. CONCLUSIONS: There were modest, transient differences in glucose control between IV and SQ insulin in hospitalized CHF patients. However, the analyses do not support a link between insulin route and inflammatory markers or autonomic tone. Further study is needed to assess outcomes in hospitalized CHF patients.
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Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/patologia , Insulina/administração & dosagem , Administração Intravenosa , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Progressão da Doença , Feminino , Humanos , Injeções Subcutâneas , Insulina/efeitos adversos , Insulina Aspart/administração & dosagem , Insulina Aspart/efeitos adversos , Sistemas de Infusão de Insulina , Insulina Lispro/administração & dosagem , Insulina Lispro/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
African-Americans with type 2 diabetes (T2DM) have higher morbidity and mortality partly attributed to poor glucose control and lack of formal diabetes self-management education and support (DSMES) programs compared to Whites. Therefore, the objective of this study was to compare the clinical and metabolic parameters during DSMES vs. standard care in African-Americans with T2DM attending primary care inner city clinics. We recruited 124 African-American patients with T2DM, randomized into Group 1-DSMES (n = 58) and Group 2-standard care group (n = 38) for 6 months. Body weight, blood pressure, random blood sugars and point-of-care (POC) hemoglobin A1C (A1C) and lipids/lipoproteins were measured at 0, 3, and 6 months. At 6 months, Group 1 had significant reduction in A1C (8.2 ± 1.4% vs. 7.5 ± 1.5%, p = 0.02) and random glucose (190.4 ± 77.6 vs. 160.6 ± 59.8 mg/dl, p = 0.03). However, there were no changes in body weight, blood pressure, or lipids/lipoprotein levels. We found no significant changes in the clinical/metabolic parameters in Group 2. We concluded that DSMES, supplemented with POC testing, was associated with significant improvements in glycemic control without changes in body weight, blood pressure, or lipids/lipoproteins. We recommend the inclusion of DSMES with POC testing in managing African-American patients with T2DM attending inner city primary care clinics.
Assuntos
População Negra , Glicemia/análise , Diabetes Mellitus Tipo 2/etnologia , Educação de Pacientes como Assunto/organização & administração , Assistência Centrada no Paciente/organização & administração , Sistemas Automatizados de Assistência Junto ao Leito , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: As a major safety intervention, infrastructural facilities such as footbridges, underpasses or signals are provided for pedestrians to remove their direct interactions with vehicles and consequently ensure safe crossing as they attempt to cross roadways. Interestingly, it is evident that even within the proximity of footbridges or underpasses, some individuals are more willing to take the risk of crossing at-grade even where there are no signals or crosswalk markings to separate their movement from vehicles. These crossing alternatives may have different utilization depending on location and road user types. Therefore, sustainable crossing facilities are needed to meet pedestrian needs. This study attempts to investigate the factors that influence pedestrians to avoid provided footbridges and engage in at-grade crossing behaviors. METHODS: The crossing point preference is an interpersonal behavior which is a multifaceted and complex phenomenon involving conscious (intentions) and subconscious (habits) factors. This study employs Triandis' Theory of Interpersonal Behavior (TIB) as a theoretical framework and structural equation modeling to achieve study objectives. Pedestrians were intercepted randomly and socio-demographics, trip characteristics and perceptions data collected through a stated preference survey. RESULTS: Perceived consequence, affect, and social factors were found as significant antecedents of at-grade crossing intentions. Habits and facilitating conditions significantly moderate the impact of crossing intentions on actual at-grading crossing behavior. Pedestrians' perceived consequence was found to significantly mediate the impact of social factors and affective factors on intention to cross at-grade. Apart from gender, age, satisfaction with footbridge features, work trips, and crossing frequency were all significant determinants of actual crossing at-grade behavior. CONCLUSIONS: The study findings can help road safety agencies provide acceptable sustainable facilities that will be used by pedestrians to ensure that the purpose of investments toward pedestrian crossing safety is achieved. Effective road safety education and awareness campaigns on negative consequences of crossing at-grade, while highlighting the benefits of using provided footbridges are suggested to be undertaken by government agencies.
Assuntos
Pedestres , Humanos , Acidentes de Trânsito/prevenção & controle , Acidentes de Trânsito/psicologia , Caminhada/psicologia , Segurança , IntençãoRESUMO
PURPOSE: The purpose of the study is to examine the psychological impact of COVID-19 on health workers' career satisfaction and intention to leave the health profession, with neurotic personality type as a moderator. DESIGN/METHODOLOGY/APPROACH: A total of 277 health workers in two public hospitals in Ghana were included in this study. Purposive and convenience sampling techniques were adopted for the study, focusing on eight departments that were involved in the management of COVID-19 cases. Validated instruments were used to measure burnout, intention to leave, neurotic personality and career satisfaction. Using AMOS and partial least squares structural equation modeling (PLS-SEM), various techniques were employed to analyze mediating and moderating mechanisms. FINDINGS: The departments had staff sizes ranging from 19 to 40, with 67% female and 33% male, with an average age of 31. Nurses accounted for the majority of responses (67.8%), followed by physicians (13.9%), sonographers (0.9%), lab technicians (0.9%) and other respondents (16.5%). The study found that health workers' level of burnout during COVID-19 had a positive effect on their intention to leave the health profession. Career satisfaction does not mediate this relationship; however, career satisfaction negatively influences the intention to leave the health profession. A neurotic personality does not moderate this relationship. ORIGINALITY/VALUE: This study provides validation of burnout and intention to leave among health workers in Ghana during COVID-19 and supports the proposition that threats to resources (burnout) and having a resource (career satisfaction) have effects on the intention to leave one's profession.
Assuntos
Esgotamento Profissional , COVID-19 , Pessoal de Saúde , Satisfação no Emprego , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Masculino , Feminino , Adulto , Esgotamento Profissional/psicologia , Gana , Pessoal de Saúde/psicologia , Intenção , SARS-CoV-2 , Inquéritos e Questionários , Personalidade , Reorganização de Recursos Humanos , Estudos Transversais , Pessoa de Meia-Idade , Hospitais PúblicosRESUMO
The goal of this systematic review was to assess the current understanding of the effects of exercise intervention on high-density lipoprotein (HDL) cholesterol (HDL-C) and changes in HDL function as well as modification of these effects by genomic factors. The reviewed studies demonstrate that exercise has modest effects on HDL-C with limited data suggesting an effect on HDL function. Genetic polymorphisms in proteins associated with HDL metabolism play a role in modifying the HDL-C response to exercise and possibly its function. Exercise as an intervention for patients at risk for cardiovascular events can lead to small improvements in HDL-C and potential changes in HDL function. There is an important modifier effect of genetics in determining these changes.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Exercício Físico/fisiologia , Lipoproteínas HDL/sangue , Lipoproteínas HDL/fisiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , LDL-Colesterol/sangue , LDL-Colesterol/genética , LDL-Colesterol/fisiologia , Humanos , Lipoproteínas HDL/genética , Fatores de RiscoRESUMO
BACKGROUND: Obesity is often associated with high cardiovascular disease risk factors. Obesity is common in African American women. We investigated the characteristics of metabolically healthy and metabolically unhealthy overweight/obese African American women based on the presence of insulin resistance. MATERIALS/METHODS: We studied 196 apparently healthy overweight/obese African American women with family history of type 2 diabetes. Waist circumference, fasting glucose, insulin, c-peptide, lipids and lipoproteins, and systolic and diastolic blood pressure were obtained in each subject. In addition, insulin sensitivity was calculated using Bergman's Minimal Model Method. We defined insulin-sensitive metabolically healthy African American women as individuals with insulin sensitivity greater than 2.7 x 10(-4) x min(-1) (uU/ mL)(-1) and insulin resistant, metabolically unhealthy as insulin sensitivity less than 2.7 x 10(-4) x min(-1) (uU/mL)(-1). RESULTS: Thirty-three percent of our subjects were metabolically healthy African American women, while 67% were metabolically unhealthy African American women. The metabolically healthy subjects were significantly younger and less obese than the metabolically unhealthy subgroup. Mean fasting serum glucose, insulin, and c-peptide were significantly lower (P = .001) in the metabolically healthy than in metabolically unhealthy subjects. However, the mean blood pressures were within normal in both subgroups. Mean serum cholesterol (p < .05) and triglyceride (p < .001) levels were significantly lower, whereas high-density lipoprotein cholesterol (p < .03) was significantly higher in the metabolically healthy than in the metabolically unhealthy subjects. We found 25.5% of our subjects had metabolic syndrome (30.3% metabolically unhealthy and 15.6% metabolically healthy). CONCLUSION: We concluded that: (1) despite obesity, metabolically healthy African American women appear to be less prone to type 2 diabetes and cardiovascular disease and (2) in view of the higher prevalence of metabolic syndrome, metabolically unhealthy African American women should be targeted for primary prevention of type 2 diabetes and cardiovascular disease.
Assuntos
População Negra , Resistência à Insulina/fisiologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Adulto , Fatores Etários , Glicemia/análise , Pressão Sanguínea , Peptídeo C/sangue , Colesterol/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Insulina/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Triglicerídeos/sangueRESUMO
Dried cashew nut testa (DCNT) was characterized with respect to proximate, mineral, and energy profile. The crude protein, crude fibre, and fat and ash contents were, in g kg(-1)DM, 190.0, 103.0, 20.1, and 20.2, respectively, with metabolizable energy of 7.12 MJ kg(-1) DM. In a feeding trial, isoproteic diets containing DCNT (O, 50, 100, and 150 g kg(-1)) were fed ad libitum to 4 groups of Sprague-Dawley male rats (110 g body weight, n = 20) for a period of 4 weeks. The rats, used as model for pigs, had free access to water. As the dietary DCNT content was increased from 0 to 150 g kg(-1), there was a significant (P < 0.01) decrease in feed intake (r = -0.99), water intake (r = -0.87), and a reduction in body weight gain (r = -0.93) and efficiency of feed utilization (r = 0.78). However, no deaths or health-related problems were recorded during the study. Dietary treatments had no impact on liver, heart, lungs, kidneys, and intestinal weights. Cost per gram feed and feed cost per gram live weight gain were reduced when DCNT was used. The experimental diet containing 50 g DCNT kg(-1) supported the best growth performance with the lowest feed cost per gram live weight gain of GH¢0.18. Seasonal increases in the prices of conventional feedstuffs like maize and fishmeal would make the use of agroindustrial by-products such as DCNT in pig diets even more attractive.
Assuntos
Anacardium/química , Fenômenos Fisiológicos da Nutrição Animal , Nozes/química , Sementes/química , Ração Animal/economia , Animais , Peso Corporal/efeitos dos fármacos , Cálcio/análise , Fibras na Dieta/análise , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Magnésio/análise , Masculino , Modelos Animais , Valor Nutritivo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas de Plantas/análise , Ratos , Ratos Sprague-Dawley , Suínos , Aumento de Peso/efeitos dos fármacos , Zea mays/químicaRESUMO
INTRODUCTION: The Emergency Medicine Education and Research by Global Experts (EMERGE) network was formed to generate and translate evidence to improve global emergency care. We share the challenges faced and lessons learned in establishing a global research network. METHODS: We describe the challenges encountered when EMERGE proposed the development of a global emergency department (ED) visit registry. The proposed registry was to be a six-month, retrospective, deidentified, minimal dataset of routinely collected variables, such as patient demographics, diagnosis, and disposition. RESULTS: Obtaining reliable, accurate, and pertinent data from participating EDs is challenging in a global context. Barriers experienced ranged from variable taxonomies, need for language translation, varying site processes for curation and transfer of deidentified data, navigating institution- and country-specific data protection regulations, and substantial variation in each participating institution's research infrastructure including training in research-related activities. We have overcome many of these challenges by creating detailed data-sharing agreements with bilateral regulatory oversight agreements between EMERGE and participating EDs, developing relationships with and training health informaticians at each site to ensure secure transfer of deidentified data, and formalizing an electronic transfer process ensuring data privacy. CONCLUSION: We believe that networks like EMERGE are integral to providing the necessary platforms for education, training, and research collaborations for emergency care. We identified substantial challenges in data sharing and variation in local sites' research infrastructure and propose potential approaches to address these challenges.
Assuntos
Serviços Médicos de Emergência , Medicina de Emergência , Humanos , Estudos Retrospectivos , Medicina de Emergência/educação , Serviço Hospitalar de Emergência , Coleta de DadosRESUMO
Disproportionate hyperproinsulinemia is an indicator of ß-cell dysfunction in diabetes and the basis underlying this abnormality remains obscure. Recently, we have found proinsulin is an aggregation-prone molecule inherent with a low relative folding rate and maintains a homeostatic balance of natively and plentiful non-natively folded states (i.e., proinsulin homeostasis, PIHO) in normal ß-cells as a result of the integration of maturation and disposal processes. PIHO is susceptible to environmental and genetic influences. Perturbation of PIHO produces a number of toxic consequences with known association to ß-cell failure in diabetes. To explore whether the perturbation of PIHO has a link to disproportionate hyperproinsulinemia, we investigated proinsulin conversion and the involved prohormone convertase 1/3 (PC1/3) and 2 (PC2) in mouse Ins2(+/Akita) islets/ß-cells that preserve a primary PIHO disorder due to a mutation (C96Y) in the insulin 2 (Ins2) gene. Our metabolic-labeling studies found an increased ratio of proinsulin to insulin in the cellular or released proteins of Ins2(+/Akita) islets. Histological, metabolic-labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2 immunoreactivities in the ß-cells of Ins2(+/Akita) islets in spite of no declines of these two convertases at the transcriptional and translational levels. Immunoblot analyses in cloned Ins2(+/Akita) ß-cells further confirmed the increased ratio of proinsulin to insulin despite the levels of PC1/3 and PC2 proteins were not reduced somehow. The findings demonstrate that the perturbation of PIHO results in defects in the subsequent conversion process of proinsulin and is a contributor to the occurrence of disproportionate hyperproinsulinemia in diabetes.
Assuntos
Hiperinsulinismo/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Proinsulina/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Proinsulina/genéticaRESUMO
BACKGROUND: diabetes and CHF are common comorbidities in hospitalized patients but the relationship between glycaemic control, glycaemic variability, and mortality in patients with both conditions is unclear. METHODS: we used administrative data to retrospectively identify patients with a diagnosis of CHF who underwent frequent glucose assessments. TWMG was compared with other measures of glycaemic control and a time-weighted measure of glycaemic variability, the glycaemic lability index. The outcome was hospital mortality. RESULTS: a total of 748 patients were included in the final analysis. Time-weighted mean glucose was higher than unadjusted mean glucose (137 + /- 44.7 mg/dL versus 167 + /- 54.9, p < 0.001), due in part to shorter sampling intervals at higher glucose levels. Hypoglycaemia, defined as a glucose level < 70 mg/dL, occurred during 6.3% of patient-days in survivors and 8.4% of patient-days among nonsurvivors (p = 0.05). Time-weighted mean glucose was similar (128 + /- 33.1 mg/dL versus 138 + /- 45.1 mg/dL) in nonsurvivors versus survivors, p = 0.19). However, relatively few patients had were significantly elevated readings. Median GLI was higher in nonsurvivors compared with that in survivors (18.1 versus 6.82, p = 0.0003). Increasing glycaemic lability index (odds ratio 1.32, 95% confidence interval 1.05-1.65), and hypoglycaemia (odds ratio 2.21, 95% confidence interval 1.07-4.65), were independently associated with higher mortality in logistic regression analysis. Respiratory failure was associated with mortality, but not standard deviation of glucose. CONCLUSIONS: future studies analysing glycaemic control should control for variable sampling intervals. In this analysis, glycaemic lability index was independently associated with increased mortality, independent of hypoglycaemia. Prospective studies are needed to evaluate these findings.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/mortalidade , Insuficiência Cardíaca/mortalidade , Hospitalização/estatística & dados numéricos , Idoso , Comorbidade , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Índice Glicêmico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Voltage-gated ion channels are responsible for generating electrical impulses in nerves and other excitable cells. The fourth transmembrane helix (S4) in voltage-gated channels is the primary voltage-sensing unit that mediates the response to a changing membrane electric field. The molecular mechanism of voltage sensing, particularly with respect to the magnitude of the transmembrane movement of S4, remains controversial. To determine the extent of this transmembrane movement, we use fluorescent resonance energy transfer between the S4 domain and a reference point in the lipid bilayer. The lipophilic ion dipicrylamine distributes on either side of the lipid bilayer depending on the membrane potential, and is used here as a resonance-energy-transfer acceptor from donor molecules attached to several positions in the Shaker K+ channel. A voltage-driven transmembrane movement of the donor should produce a transient fluorescence change because the acceptor also translocates as a function of voltage. In Shaker K+ channels no such transient fluorescence is observed, indicating that the S4 segment does not translocate across the lipid bilayer. Based on these observations, we propose a molecular model of voltage gating that can account for the observed 13e gating charge with limited transmembrane S4 movement.
Assuntos
Membrana Celular/metabolismo , Ativação do Canal Iônico , Movimento , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Transferência Ressonante de Energia de Fluorescência , Bicamadas Lipídicas/metabolismo , Potenciais da Membrana , Modelos Moleculares , Sondas Moleculares , Picratos , Canais de Potássio/química , Canais de Potássio/genética , Canais de Potássio/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/química , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Conformação Proteica , Superfamília Shaker de Canais de PotássioRESUMO
The study seeks to identify bicycle ownership and ridership and gain insights into how demographics, perceptions and experiences of respondents influenced the status of cycling in Tamale Metropolis. Earlier studies have focused on examining the determinants of utility cycling among adults in the same metropolis, but this study assesses cycling from a broader perspective in terms of demographics, barriers, and promotional strategies. A cross-sectional survey was carried out with 500 semi-structured questionnaires through mainly a face-to-face approach. Five trained survey assistants administered the questionnaires within demarcated zones in the metropolis and tracked participants by geographic information system. Binary logistic regression, chi-squared test and descriptive statistics were employed in the analysis of the data. Out of the 439 valid questionnaires, bicycle ownership and ridership were 56% and 78% respectively. Gender and occupation were significant in owning and riding bicycles, where p < 0.05. Males and the non-income earners (i.e., students, apprentices and unemployed) were more likely to ride and own bicycles. Cycling was prevalent among low-income individuals and in households where bicycles were available. The major motivation of bicycle riders was affordability. Age was statistically insignificant to owning or riding bicycles since every age group cycled as much. Despite the existing infrastructure provision for cycling and its associated benefits, there is a latent desire to shift from bicycles by 85% of the riders. A chi-square test conducted revealed that the desire to shift from bicycle use was independent of one's gender, age and occupation, but associated with bicycle ownership. Moreover, speed, fatigue endured in riding and inadequate infrastructure were mentioned as part of the factors that discourage cycling. This study, therefore, recommends government interventions such as a reduction in bicycle cost, and the introduction of electric bicycles to meet the respondents' transport needs of speed and travelling with less fatigue.
RESUMO
INTRODUCTION: Emergency departments (ED) globally are addressing the coronavirus disease 2019 (COVID-19) pandemic with varying degrees of success. We leveraged the 17-country, Emergency Medicine Education & Research by Global Experts (EMERGE) network and non-EMERGE ED contacts to understand ED emergency preparedness and practices globally when combating the COVID-19 pandemic. METHODS: We electronically surveyed EMERGE and non-EMERGE EDs from April 3-June 1, 2020 on ED capacity, pandemic preparedness plans, triage methods, staffing, supplies, and communication practices. The survey was available in English, Mandarin Chinese, and Spanish to optimize participation. We analyzed survey responses using descriptive statistics. RESULTS: 74/129 (57%) EDs from 28 countries in all six World Health Organization global regions responded. Most EDs were in Asia (49%), followed by North America (28%), and Europe (14%). Nearly all EDs (97%) developed and implemented protocols for screening, testing, and treating patients with suspected COVID-19 infections. Sixty percent responded that provider staffing/back-up plans were ineffective. Many sites (47/74, 64%) reported staff missing work due to possible illness with the highest provider proportion of COVID-19 exposures and infections among nurses. CONCLUSION: Despite having disaster plans in place, ED pandemic preparedness and response continue to be a challenge. Global emergency research networks are vital for generating and disseminating large-scale event data, which is particularly important during a pandemic.
Assuntos
COVID-19 , Serviço Hospitalar de Emergência/organização & administração , Pandemias , Triagem , Estudos Transversais , Saúde Global , Humanos , SARS-CoV-2RESUMO
Blacks have a lower prevalence of metabolic syndrome (MetS) that can be partly ascribed to the lower prevalent rates of some major components of MetS, namely the lower serum triglycerides and higher high-density lipoprotein cholesterol levels in blacks when compared with whites. Blacks manifest greater insulin resistance, the pivotal lesion underpinning MetS than whites. However, the relationships among insulin resistance and cardiovascular disease (CVD) risk factors are weaker in blacks than whites. The international bodies have recommended the use of European-based cutoff points for MetS for blacks. However, with the emerging inconsistencies in the association of insulin resistance and CVD risk factors in blacks, the use of these definitions and the cutoff points for MetS have become problematic. Therefore, it is important to review the limitations in the use of the current criteria and cutoff points of MetS in blacks to lessen the CVD risk burden in blacks.
Assuntos
População Negra/etnologia , Síndrome Metabólica/etnologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Resistência à Insulina , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Síndrome Metabólica/fisiopatologia , Fatores de RiscoRESUMO
BACKGROUND: Comparing findings from separate trials is necessary to choose among treatment options, however differences among study cohorts may impede these comparisons. PURPOSE: As a case study, to examine the overlap of study cohorts in two large randomized controlled clinical trials that assess interventions to reduce risk of major cardiovascular disease events in adults with type 2 diabetes in order to explore the feasibility of cross-trial comparisons METHODS: The Action for Health in Diabetes (Look AHEAD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trials enrolled 5145 and 10,251 adults with type 2 diabetes, respectively. Look AHEAD assesses the efficacy of an intensive lifestyle intervention designed to produce weight loss; ACCORD tests pharmacological therapies for control of glycemia, hyperlipidemia, and hypertension. Incidence of major cardiovascular disease events is the primary outcome for both trials. A sample was constructed to include participants from each trial who appeared to meet eligibility criteria and be appropriate candidates for the other trial's interventions. Demographic characteristics, health status, and outcomes of members and nonmembers of this constructed sample were compared. RESULTS: Nearly 80% of Look AHEAD participants were projected to be ineligible for ACCORD; ineligibility was primarily due to better glycemic control or no early history of cardiovascular disease. Approximately 30% of ACCORD participants were projected to be ineligible for Look AHEAD, often for reasons linked to poorer health. The characteristics of participants projected to be jointly eligible for both trials continued to reflect differences between trials according to factors likely linked to retention, adherence, and study outcomes. LIMITATIONS: Accurate ascertainment of cross-trial eligibility was hampered by differences between protocols. CONCLUSIONS: Despite several similarities, the Look AHEAD and ACCORD cohorts represent distinct populations. Even within the subsets of participants who appear to be eligible and appropriate candidates for trials of both modes of intervention, differences remained. Direct comparisons of results from separate trials of lifestyle and pharmacologic interventions are compromised by marked differences in enrolled cohorts.
Assuntos
Estudos de Coortes , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Fatores Etários , Glicemia , Peso Corporal , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Etnicidade , Estudos de Viabilidade , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Grupos Raciais , Fatores de Risco , Fatores SexuaisRESUMO
According to the third National Health and Nutrition Examination Survey, African Americans have a lower prevalence of metabolic syndrome than do Whites. Recent reports in Blacks in other regions have confirmed these observations, but the rates vary. This lower rate of metabolic syndrome in Blacks can be partly ascribed to the lower prevalent rates of some major components of metabolic syndrome, namely serum triglyceride and high-density lipoprotein cholesterol levels in Blacks. This is in contrast with the higher prevalence of obesity (waist circumference) and blood pressure that meet National Cholesterol Education Program criteria in Blacks. Despite these seemingly favorable lipids and lipoprotein profiles, Blacks continue to have higher cardiovascular disease (CVD) mortality and morbidity, even in the absence of diabetes, than do Whites. Insulin resistance is more prevalent in Blacks than in Whites. However, the relationships among insulin resistance and CVD risk factors such as hypertension, high-density lipoprotein cholesterol, and triglycerides are weak in contrast with Whites. The paradox of more favorable lipid profile and conversely the higher rates of unfavorable blood pressure in Blacks calls into question the validity of the current criteria for metabolic syndrome in Blacks. Thus, it can be argued that each of the components of the metabolic syndrome carry different CVD risk factors in Blacks. The greater CVD mortality and morbidity in Blacks appear to be multifactorial. With the emerging epidemic of noncommunicable diseases, chronic kidney diseases due to both diabetes and hypertension have emerged as major CVD risks that are associated with increasing mortality and morbidity in Blacks. We need to emphasize specific components of metabolic syndrome, specifically blood pressure and chronic kidney disease, that carry higher CVD risk with associated greater morbidity and mortality for primary prevention of CVD and type 2 diabetes in Blacks. To this end, we believe the higher prevalence of hypertension and chronic kidney diseases in Blacks suggests that the current classification, definition, and criteria for metabolic syndrome in Blacks should be reconsidered.