Health literacy and diabetic retinopathy.

Health literacy (HL) is defined as a cognitive and social skill that determines the motivation and ability of individuals to understand and use information to promote and maintain proper health. Inadequate HL has been associated with worse outcomes in diabetes control, poor self-care, and higher hospitalization rates for some chronic diseases. We hypothesized that HL influences the prevalence of diabetic retinopathy (DR) among individuals with type 2 diabetes mellitus (T2DM) and that inadequate glycemic control would mediate this association. This was a cross-sectional study carried out with 288 participants of the "Brazilian Diabetes Study" cohort. Inclusion criteria were people diagnosed with T2DM aged between 40 and 70 years and ability to read and write. In the adequate HL group, DR was found in 16.5% of participants and in the inadequate HL group, it was found in 32.8% (P=0.0081). Individuals with inadequate HL had a higher risk of having DR, and this association was still statistically significant after adjusting for HbA1c, low-density lipoprotein cholesterol, systolic blood pressure, and diastolic blood pressure. In conclusion, HL is related to DR without the mediation of classical clinical variables.

Health literacy and diabetic retinopathy

Health literacy (HL) is defined as a cognitive and social skill that determines the motivation and ability of individuals to understand and use information to promote and maintain proper health. Inadequate HL has been associated with worse outcomes in diabetes control, poor self-care, and higher hospitalization rates for some chronic diseases. We hypothesized that HL influences the prevalence of diabetic retinopathy (DR) among individuals with type 2 diabetes mellitus (T2DM) and that inadequate glycemic control would mediate this association. This was a cross-sectional study carried out with 288 participants of the "Brazilian Diabetes Study" cohort. Inclusion criteria were people diagnosed with T2DM aged between 40 and 70 years and ability to read and write. In the adequate HL group, DR was found in 16.5% of participants and in the inadequate HL group, it was found in 32.8% (P=0.0081). Individuals with inadequate HL had a higher risk of having DR, and this association was still statistically significant after adjusting for HbA1c, low-density lipoprotein cholesterol, systolic blood pressure, and diastolic blood pressure. In conclusion, HL is related to DR without the mediation of classical clinical variables.

Dissecção de aorta evoluindo com insuficiência aórtica: relato de caso / Aortic dissection evolving with aortic insufficiency: case report

INTRODUÇÃO: A dissecção de aorta é um evento cardiovascular com elevada taxa de mortalidade, caso ocorra atraso no seu diagnóstico e tratamento, e que possui como diagnóstico diferencial as síndromes coronarianas agudas. Aponta-se uma incidência de 5 a 30 casos por milhão de pessoas por ano, sendo necessário um alto nível de suspeita clínica para o seu diagnóstico. O avanço da técnica operatória e a intervenção precoce são apontados como fatores essenciais na melhora dos resultados do tratamento cirúrgico no que se refere às taxas de mortalidade. DESCRIÇÃO DO CASO: Esse trabalho teve como objetivos a descrição de um caso típico de dissecção de aorta que se destacou pela gravidade da sua apresentação clínica e rapidez na investigação diagnóstica. Além disso, busca-se, através desse relato, realizar a revisão dessa importante patologia em diversos aspectos. Relatou-se o caso de um paciente do sexo masculino, 49 anos, tabagista, que se apresentou com dor torácica, sem irradiação, associada a dispneia e que foi tratado, inicialmente, como um caso de edema agudo de pulmão, evoluindo com instabilidade clínica e necessidade de intubação orotraqueal e início de noradrenalina. O paciente foi avaliado, posteriormente, com ecocardiograma e angiotomografia de tórax e de abdome, sendo confirmado o diagnóstico de dissecção de aorta que complicou com insuficiência valvar aórtica e foi iniciado o tratamento clínico. O início da dissecção era no bulbo e essa se estendia até a bifurcação da aorta e pela artéria ilíaca comum esquerda. O paciente evolui, novamente, com instabilidade hemodinâmica, durante a internação, porém houve resposta ao tratamento cirúrgico, com remissão dos sintomas. O caso descrito se apresentou como uma síndrome de insuficiência respiratória e edema agudo de pulmão, refratário ao tratamento clínico inicial, com uma dor típica associada, o que motivou a investigação diagnóstica. Buscou-se, inicialmente, o controle do duplo produto do paciente com o esmolol e foi indicado, posteriormente, o tratamento cirúrgico, com correção da insuficiência aórtica, para o paciente, após a estabilização do quadro. CONCLUSÕES: Percebe-se que a dissecção de aorta é uma condição de elevada gravidade, que possui uma diversidade de fatores de risco e de apresentações clínicas. A agilidade no diagnóstico e tratamento dependem da suspeita dessa condição. Destaca-se a importância do diagnóstico dessa condição e do reconhecimento das indicações cirúrgicas, pois está comprovado seu impacto na sobrevida do paciente.

Reagent integration and controlled release for multiplexed nucleic acid testing in disposable thermoplastic 2D microwell arrays.

The seamless integration of reagents into microfluidic devices can serve to significantly reduce assay complexity and cost for disposable diagnostics. In this work, the integration of multiplexed reagents into thermoplastic 2D microwell arrays is demonstrated using a scalable pin spotting technique. Using a simple and low-cost narrow-bore capillary spotting pin, high resolution deposition of concentrated reagents within the arrays of enclosed nanoliter-scale wells is achieved. The pin spotting method is further employed to encapsulate the deposited reagents with a chemically modified wax layer that serves to prevent disruption of the dried assay components during sample introduction through a shared microchannel, while also enabling temperature-controlled release after sample filling is complete. This approach supports the arbitrary patterning and release of different reagents within individual wells without crosstalk for multiplexed analyses. The performance of the in-well spotting technique is characterized using on-chip rolling circle amplification to evaluate its potential for nucleic acid-based diagnostics.

Low empowerment and diabetes regimen distress are related to HbA1c in low income type 1 diabetes patients in a Brazilian tertiary public hospital.

BACKGROUND: Adults with type 1 diabetes (T1D) have a high risk of developing depressive symptoms and diabetes-related distress (DD). Low socioeconomic level is associated with increased risk of poor self-management, treatment difficulties and psychological distress. The goals of this study were to document the frequency of major depressive disorder (MDD), high depressive symptoms and high DD, to assess levels of empowerment and to determine the association with each of these measures and glycemic control in a low-income Brazilian sample of adults with T1D. METHODS: In a cross-sectional study, inclusion criteria were age > 18 years and diagnosis of T1D > 6 months. Exclusion criteria were cognitive impairment, history of major psychiatric disorders, severe diabetes-related complications and pregnancy. Diagnoses of MDD were made using interview-based DSM-5 criteria. Depressive symptoms were evaluated by the depression subscale of the Hospital Anxiety and Depression Scale (HAD-D). The Diabetes Distress Scale (DDS) assessed DD. Empowerment levels were evaluated by the Diabetes Empowerment Scale short form (DES-SF). Glycemic control was measured by HbA1c. The latest lipid panel results were recorded. Number of complications was obtained from medical records. RESULTS: Of the 63 T1D patients recruited, 36.5% were male, mean age was 31.5 (± 8.9), mean number of complications was 1 (± 1.1), and mean HbA1c was 10.0% (± 2). Frequency of MDD was 34.9% and 34.9% reported high depressive symptoms. Fifty-seven percent reported clinically meaningful DD. High diabetes regimen distress and low empowerment were associated to HbA1c (p = 0.003; p = 0.01, respectively). In multivariate analyses, lower empowerment levels were associated to higher HbA1c (beta - 1.11; r-partial 0.09; p value 0.0126). MDD and depressive symptoms were not significantly correlated with HbA1c in this expected direction (p = 0.72; p = 0.97, respectively). CONCLUSIONS: This study showed high rates of MDD, high depressive symptoms and high DD and low levels of empowerment in this low income population. Empowerment and diabetes regimen distress were linked to glycemic control. The results emphasize the need to incorporate the psychological and psychosocial side of diabetes into strategies of care and education for T1D patients.

Monocytes of patients with unstable angina express high levels of chemokine and pattern-recognition receptors.

BACKGROUND AND AIMS: Macrophages derived from monocytes play an important role in atherosclerosis progression. Subpopulations of circulating classical, intermediate, and non-classical monocytes possess distinct functions and phenotypes, and participate in the pathogenesis of disease. The aim of this study was to compare the quantity and phenotypes of circulating monocyte subpopulations in patients with established atherosclerosis and healthy control individuals. Additionally, the study aimed to provide insight into the functional activity of monocytes against a heat shock protein (HSP60). METHODS: Chemokine and pattern recognition receptors in monocyte subsets obtained from peripheral blood of acute and chronic coronary artery disease patients and controls were quantified by flow cytometry. Furthermore, monocytes from healthy controls were stimulated in vitro with HSP60, and the cytokines produced by them were evaluated by flow cytometry. RESULTS: Eighteen controls (C), 34 individuals with risk factors for cardiovascular disease (RF), 32 patients with stable angina (SA), and 16 patients with unstable angina (UA) were enrolled in the study. The absolute count of intermediate monocytes was found to be increased in patients of the UA group; high frequencies of the chemokine receptors CCR2, CCR5, and CX3CR1 were also observed in this subpopulation. Moreover, the pattern recognition receptors TLR2 and TLR4 were more frequent in intermediate monocytes from the UA group. Furthermore, the intermediate monocytes from healthy individuals produced IL-12p70 after stimulation with HSP60. CONCLUSIONS: Our results show that intermediate monocytes of UA patients exhibited an enhanced expression of the receptors involved in the recognition of damage-associated molecular patterns (DAMPs) and enhancement of the migratory function. Hence, they might contribute to the propagation and progression of inflammation observed in atherosclerosis, especially in the acute setting.

Staggered trap arrays for robust microfluidic sample digitization.

A sample digitization method that exploits the controlled pinning of fluid at geometric discontinuities within an array of staggered microfluidic traps is presented. The staggered trap design enables reliable sample filling within high aspect ratio microwells, even when employing substrate materials such as thermoplastics that are not gas permeable. A simple geometric model is developed to predict the impact of device geometry on sample filling and discretization, and validated experimentally using fabricated cyclic olefin polymer devices. Using the developed design guidelines, a 768-element staggered trap array is demonstrated, with reliable passive loading and discretization achieved within 5 min. The resulting discretization platform offers a simplified workflow with flexible trap design, reliable discretization, and repeatable operation using low-cost thermoplastic substrates.

Rapid real-time PCR and high resolution melt analysis in a self-filling thermoplastic chip.

A microfluidic platform designed for point-of-care PCR-based nucleic acid diagnostics is described. Compared to established microfluidic PCR technologies, the system is unique in its ability to achieve exceptionally rapid PCR amplification in a low cost thermoplastic format, together with high temperature accuracy enabling effective validation of reaction product by high resolution melt analysis performed in the same chamber as PCR. In addition, the system employs capillary pumping for automated loading of sample into the reaction chamber, combined with an integrated hydrophilic valve for precise self-metering of sample volumes into the device. Using the microfluidic system to target a mutation in the G6PC gene, efficient PCR from human genomic DNA template is achieved with cycle times as low as 14 s, full amplification in 8.5 min, and final melt analysis accurately identifying the desired amplicon.

Arterial tissue and plasma concentration of enzymatic-driven oxysterols are associated with severe peripheral atherosclerotic disease and systemic inflammatory activity.

INTRODUCTION: Cholesterol undergoes oxidation via both enzymatic stress- and free radical-mediated mechanisms, generating a wide range of oxysterols. In contrast to oxidative stress-driven metabolites, enzymatic stress-derived oxysterols are scarcely studied in their association with atherosclerotic disease in humans. METHODS: 24S-hydroxycholesterol (24S-HC), 25-hydroxycholesterol (25-HC), and 27-hydroxycholesterol (27-HC) were assessed in plasma and arteries with atherosclerotic plaques from 10 patients (54-84 years) with severe peripheral artery disease (PAD) as well as arteries free of atherosclerotic plaques from 13 individuals (45-78 years, controls). RESULTS: Plasma 25-HC was higher in PAD individuals than in controls (6.3[2] vs. 3.9[1.9] ng/mgCol; p = 0.004). 24S-HC and 27-HC levels were, respectively, five- and 20-fold higher in the arterial tissue of PAD individuals than in those of the controls (p = 0.016 and p = 0.001). Plasma C-reactive protein correlated with plasma 24-HC (r = 0.51; p = 0.010), 25-HC (r = 0.75; p < 0.001), 27-HC (r = 0.48; p = 0.015), and with tissue 24S-HC (r = 0.4; p = 0.041) and 27-HC (r = 0.46; p = 0.023). CONCLUSION: Arterial intima accumulation of 27-HC and 24S-HC is associated with advanced atherosclerotic disease and systemic inflammatory activity in individuals with severe PAD.

Laser-Induced Forward Transfer-printing of focused ion beam pre-machined crystalline magneto-optic yttrium iron garnet micro-discs.

We present femtosecond laser-induced forward transfer of focused ion beam pre-machined discs of crystalline magneto-optic yttrium iron garnet (YIG) films. Debris-free circular micro-discs with smooth edges and surface uniformity have been successfully printed. The crystalline nature of the printed micro-discs has not been altered by the LIFT printing process, as was confirmed via micro-Raman measurements.

Endothelial nitric oxide synthase gene variant modulates the relationship between serum cholesterol levels and blood pressure in the general population: new evidence for a direct effect of lipids in arterial blood pressure.

BACKGROUND: A causal relationship between plasma cholesterol and blood pressure remains poorly understood. It has been postulated that the decrease in nitric oxide (NO) availability is a potential mechanism by which hypercholesterolemia may stimulate blood pressure elevation. However, evidence supporting the role of the L-arginine-NO pathway on the relationship between hypertension and hypercholesterolemia is still lacking. METHODS AND RESULTS: We tested for an association of the expressed NO synthase (eNOS) Glu298Asp gene variant and plasma levels of lipids and lipoproteins in the determination of systolic blood pressure levels in a 1577 individuals randomly selected from the general population. Significant interactions could be disclosed either between the Glu298Asp gene variant and total-cholesterol (p = 0.02), log-transformed triglycerides (p = 0.004) or non-HDL-cholesterol (p = 0.003) in the determination of systolic blood pressure. In addition, although the presence of the AspAsp genotype did not significantly increase the risk of hypertension in individuals in the 50% lowest percentile of total-cholesterol, presence of this genotype significantly increased the risk of hypertension in individuals in the 50% highest percentile. Finally, in a multiple logistic regression model adjusting for age, sex, diabetes, ethnicity, smoking status and BMI, the AspAsp genotype significantly increased the risk of hypertension only in individuals with total-cholesterol above 209 mg/dL (p = 0.05, odds ratios (OR) = 2.0). CONCLUSION: Taken together, these results provide evidence supporting the role of the eNOS Glu298Asp gene variant in modulating blood pressure through a relationship with lipid levels.

Cholesterol lowering with statins reduces exercise-induced myocardial ischemia in hypercholesterolemic patients with coronary artery disease.

Coronary flow reserve is mainly influenced by the combination of luminal stenosis and vascular dilation capacity. Thus, after statin treatment, the reduction of ischemic threshold in patients submitted to exercise testing could be intensely influenced by angiographic severity. In this study, we verify the effect of statin treatment on exercise-induced myocardial ischemia in hypercholesterolemic patients with a broad range of coronary angiographic severities. Patients with 2 consecutive positive exercise tests, coronary stenosis > or =70%, total cholesterol > or =300 mg/dl, and triglycerides < or =200 mg/dl were randomly assigned to a 16-week treatment period with either diet alone (n = 39) or diet plus statins (simavastatin, n = 31 and pravastatin, n = 10). Statin-treated patients had a significant variation in total cholesterol (-46% vs -2.7%; p <0.01), low-density lipoprotein cholesterol (-58% vs 0.8%; p <0.01), and high-density cholesterol (+28% vs -6%; p <0.05) in comparison with the diet-only group. After 16 weeks of treatment, 36 patients (92%) in the diet group still had positive exercise tests, whereas only 7 patients (15%) of the statin group had a positive test (p <0.01). The proportion of positive tests was significantly reduced in subgroups of patients with 1-, 2-, or 3-vessel disease. Regarding the severity of coronary stenosis, the proportion of positive tests was significantly reduced in patients with stenosis between 70% and 90% and in patients with stenosis > or =90%. Moreover, the proportion of positive tests tended to decrease to a greater extent in patients with mild coronary disease. In conclusion, cholesterol-lowering treatment with statins reduces exercise-induced myocardial ischemia in hypercholesterolemic patients with mild or severe epicardial coronary stenosis.

Triglyceride and lipoprotein (a) are markers of coronary artery disease severity among postmenopausal women.

OBJECTIVE: After menopause, some women manifest coronary artery disease (CAD) with highly variable angiographic severity. For these women, postmenopausal appearing of some CAD risk factors may have differently influenced the CAD risk and severity. In this study, we attempt to unravel differences in the frequency or intensity of CAD risk factors among postmenopausal women with different angiographic severity. METHODS: We studied 182 postmenopausal women (64+/-6 years) who underwent coronary angiography to investigate thoracic pain. Subjects with no detectable coronary lesions at angiography were recruited to the non-obstructive group and patients with CAD were grouped in one-vessel or multi-vessel groups. We compared clinical variables as the body mass index (BMI), age at menopause, age, hypertension, diabetes and cigarette smoking, and lipid measurements as plasma levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein (apo) A1, apo B and lipoprotein(a) (Lp(a)). RESULTS: Comparing to the non-obstructive group, Lp(a) was twofold higher in the one-vessel group and threefold higher in the multi-vessel group and triglycerides were 34% higher in the one-vessel group and 50% higher in the multi-vessel group. No further difference was found among the three groups. After multivariate logistic regression analysis, triglyceride (odds ratio: 1.01; P=0.0013) and Lp(a) (odds ratio: 1.006; P<0.0001) were independently indicative of the presence of obstructive CAD. CONCLUSIONS: We found that both Lp(a) and triglycerides constitute useful markers of CAD severity among postmenopausal women.

Effects of etofibrate upon the metabolism of chylomicron-like emulsions in patients with coronary artery disease.

Slow chylomicron intravascular catabolism has been associated with coronary artery disease and screening for drugs that can speed-up this process can be important. In this study, the effects of etofibrate upon chylomicron metabolism was tested by determination of the plasma kinetics of a chylomicron-like emulsion model in 12 patients with coronary artery disease, aged 59+/-11 years, (total cholesterol: 240+/-41 mg/dl; triglycerides: 188+/-42 mg/dl) submitted to a randomized, crossover, double-blind, placebo-controlled study with administration of 1 g per day etofibrate or placebo for 1-month. A 1-month washout period was inserted between the treatment periods. Patients were intravenously injected a chylomicron-like emulsion doubly labeled with 14C-cholesteryl oleate and 3H-triolein at baseline and after treatments. After etofibrate treatment, there was decrease of total cholesterol and triglyceride plasma levels and a trend to increase high-density lipoprotein cholesterol plasma levels. Etofibrate elicited 62% enhancement of post-heparin lipolytic activity and 100% increase of 3H-triglyceride fractional clearance rate compared with placebo treatment. 14C-cholesterol ester fractional clearance rate was 260% greater after etofibrate than after placebo. Therefore, a potent effect of etofibrate on both chylomicron lipolysis and remnant removal was achieved, indicating that this drug can be used to improve this metabolism in future prospective studies.

The effects of gemfibrozil upon the metabolism of chylomicron-like emulsions in patients with endogenous hypertriglyceridemia.

OBJECTIVE: To evaluate the effects of gemfibrozil upon the intravascular metabolism of chylomicron-like emulsions in endogenous hypertriglyceridemia. METHODS: We evaluated the plasma kinetics of a chylomicron-like emulsion in 39 subjects: 27 hypertriglyceridemics, total cholesterol (TC) expressed as median (%25; %75) 7.47 (6.1; 8.19) mmol/l and plasma triglycerides (TG) 4.28 (3.6; 18.5) mmol/l and in 12 normolipidemics, TC 4.7 (3.85; 5.37) mmol/l and TG 0.91 (0.64; 1.75) mmol/l. Hypertriglyceridemics were evaluated at baseline and after a 30-day 1200-mg/day gemfibrozil (n=8) or placebo treatment (n=7). The emulsion labelled with 14C-cholesteryl oleate (14C-CO) and 3H-triolein (3H-TO) was injected intravenously after a 12-h fast. The plasma kinetics of 3H-TO and 14C-CO were determined to assess, respectively, lipolysis and clearance of chylomicron and remnants by compartmental analysis. RESULTS: The residence times (in minutes) of 3H-TO and 14C-CO of hypertriglyceridemics were roughly twice the values of normolipidemics, i.e. 8.0 (5.5; 12.0) versus 15.0 (11.0; 24.0) and 21.5 (14.0; 33.0) versus 44.0 (32.0; 72.0), P=0.001. Gemfibrozil treatment of hypertriglyceridemic patients reduced the residence times of 3H-TO and 14C-CO, respectively, by 46% (P=0.003) and 53% (P=0.008). Effects were noted on the slow phase of emulsion plasma removal, which was reduced in hypertriglyceridemics. After treatment, the emulsion residence times determined in hypertriglyceridemics attained the values of the normolipidemic group. CONCLUSIONS: Gemfibrozil treatment normalised the defects in chylomicron-like emulsion catabolism observed in endogenous hypertriglyceridemia patients.

Etofibrate but not controlled-release niacin decreases LDL cholesterol and lipoprotein (a) in type IIb dyslipidemic subjects.

Etofibrate is a hybrid drug which combines niacin with clofibrate. After contact with plasma hydrolases, both constituents are gradually released in a controlled-release manner. In this study, we compared the effects of etofibrate and controlled-release niacin on lipid profile and plasma lipoprotein (a) (Lp(a)) levels of patients with triglyceride levels of 200 to 400 mg/dl, total cholesterol above 240 mg/dl and Lp(a) above 40 mg/dl. These patients were randomly assigned to a double-blind 16-week treatment period with etofibrate (500 mg twice daily, N = 14) or niacin (500 mg twice daily, N = 11). In both treatment groups total cholesterol, VLDL cholesterol and triglycerides were equally reduced and high-density lipoprotein cholesterol was increased. Etofibrate, but not niacin, reduced Lp(a) by 26% and low-density lipoprotein (LDL) cholesterol by 23%. The hybrid compound etofibrate produced a more effective reduction in plasma LDL cholesterol and Lp(a) levels than controlled-release niacin in type IIb dyslipidemic subjects.