Fasting glucose: a cardiometabolic indicator for subclinical atherosclerosis on excess weight adolescents

Abstract Objective: To build a model based on cardiometabolic indicators that allow the identification of overweight adolescents at higher risk of subclinical atherosclerotic disease (SAD). Methods: Cross-sectional study involving 161 adolescents with a body mass index ≥ + 1 z-Score, aged 10 to 19 years. Carotid intima-media complex thickness (IMT) was evaluated using ultrasound to assess subclinical atherosclerotic disease. Cardiometabolic indicators evaluated included nutritional status, central adiposity, blood pressure, lipidic profile, glycemic profile, as well as age and sex. Data was presented using measures of central tendency and dispersion, as well as absolute and relative frequency. The relationship between IMT measurement (outcome variable) and other variables (independent variables) was assessed using Pearson or Spearman correlation, followed by multiple regression modeling with Gamma distribution to analyze predictors of IMT. Statistical analysis was performed using SPSS and R software, considering a significance level of 5 %. Results: It was observed that 23.7 % had Carotid thickening, and the prevalence of abnormal fasting glucose was the lowest. Age and fasting glucose were identified as predictors of IMT increase, with IMT decreasing with age by approximately 1 % per year and increasing with glucose by around 0.24 % per mg/dL. Conclusion: The adolescent at higher risk is younger with higher fasting glycemia levels.

A proposed simplified definition of metabolic syndrome in children and adolescents: a global perspective.

Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice.We proposed a simplified definition for assessing MetS risk in youths aged 6-17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89-0.92) and 0.79 (0.78-0.81) when using the IDF or NCEP definition as the gold standard, respectively.The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally.

Utility of waist-to-height ratio, waist circumference and body mass index in predicting clustered cardiometabolic risk factors and subclinical vascular phenotypes in children and adolescents: A pooled analysis of individual data from 14 countries.

AIMS: The clinical utility of waist-to-height ratio (WHtR) in predicting cardiometabolic risk factors (CMRFs) and subclinical markers of cardiovascular disease remains controversial. We aimed to compare the utility of WHtR with waist circumference (WC) and body mass index (BMI) in identifying children and adolescents (youths) at risk for cardiometabolic outcomes, including clustered CMRFs, high carotid intima-media thickness (cIMT), and arterial stiffness (assessed as high pulse wave velocity, PWV). METHODS: We analyzed data from 34,224 youths (51.0 % boys, aged 6-18 years) with CMRFs, 5004 (49.5 % boys, aged 6-18 years) with cIMT measurement, and 3100 (56.4 % boys, aged 6-17 years) with PWV measurement from 20 pediatric samples across 14 countries. RESULTS: WHtR, WC, and BMI z-scores had similar performance in discriminating youths with ≥3 CMRFs, with the area under the curve (AUC) (95 % confidence interval, CI)) ranging from 0.77 (0.75-0.78) to 0.78 (0.76-0.80) using the modified National Cholesterol Education Program (NCEP) definition, and from 0.77 (0.74-0.79) to 0.77 (0.74-0.80) using the International Diabetes Federation (IDF) definition. Similarly, all three measures showed similar performance in discriminating youths with subclinical vascular outcomes, with AUC (95 % CI) ranging from 0.67 (0.64-0.71) to 0.70 (0.66-0.73) for high cIMT (≥P95 values) and from 0.60 (0.58-0.66) to 0.62 (0.58-0.66) for high PWV (≥P95 values). CONCLUSIONS: Our findings suggest that WHtR, WC, and BMI are equally effective in identifying at-risk youths across diverse pediatric populations worldwide. Given its simplicity and ease of use, WHtR could be a preferable option for quickly screening youths with increased cardiometabolic risk in clinical settings.

Analysis of modified ilib therapy in patients submitted to plastic surgery.

The sample comprised 44 volunteers who had undergone some surgical procedure and were equally divided into four groups. G1 started the therapy 24 h after the surgical procedure with the device off. G2 followed the same time pattern, 24 h, but with the device turned on. G3 and G4 started therapy three days after the surgical procedure; in G3, the device was turned off, and in G4, the device remained on during therapy; each session lasted 30 min, using 660 nm (red), energy 180 J. For all groups, the therapy started with daily use for seven days and followed the interval use of three times a week until completed 21 days. The revaluation was performed after 7 and 21 days. The results found show changes in HR at rest, systolic and diastolic BP, and in peripheral oxygen saturation, which showed a significant difference in the groups that used on-therapy (p < 0.05). In the MCGILL Scale evaluation, the mean total score showed a more accentuated drop in the groups that used ILIB, (p < 0.05). ILIB may have prevented a more significant evolution of firosis levels; however, no changes were observed in the evaluation of sleep and anxiety. The application of the ILIB in patients undergoing plastic surgery was supported in terms of hemodynamics and pain; in addition, starting the ILIB application 24 h after the procedure proved to be more advantageous.

Application of experimental design as a statistical approach to recover bioactive peptides from different food sources.

Bioactive peptides (BAPs) derived from samples of animals and plants have been widely recommended and consumed for their beneficial properties to human health and to control several diseases. This work presents the applications of experimental designs (DoE) used to perform factor screening and/or optimization focused on finding the ideal hydrolysis condition to obtain BAPs with specific biological activities. The collection and discussion of articles revealed that Box Behnken Desing and Central Composite Design were the most used. The main parameters evaluated were pH, time, temperature and enzyme/substrate ratio. Among vegetable protein sources, soy was the most used in the generation of BAPs, and among animal proteins, milk and shrimp stood out as the most explored sources. The degree of hydrolysis and antioxidant activity were the most investigated responses in obtaining BAPs. This review brings new information that helps researchers apply these DoE to obtain high-quality BAPs with the desired biological activities.

Fasting glucose: a cardiometabolic indicator for subclinical atherosclerosis on excess weight adolescents.

OBJECTIVE: To build a model based on cardiometabolic indicators that allow the identification of overweight adolescents at higher risk of subclinical atherosclerotic disease (SAD). METHODS: Cross-sectional study involving 161 adolescents with a body mass index ≥ +1 z-Score, aged 10 to 19 years. Carotid intima-media complex thickness (IMT) was evaluated using ultrasound to assess subclinical atherosclerotic disease. Cardiometabolic indicators evaluated included nutritional status, central adiposity, blood pressure, lipidic profile, glycemic profile, as well as age and sex. Data was presented using measures of central tendency and dispersion, as well as absolute and relative frequency. The relationship between IMT measurement (outcome variable) and other variables (independent variables) was assessed using Pearson or Spearman correlation, followed by multiple regression modeling with Gamma distribution to analyze predictors of IMT. Statistical analysis was performed using SPSS and R software, considering a significance level of 5 %. RESULTS: It was observed that 23.7 % had Carotid thickening, and the prevalence of abnormal fasting glucose was the lowest. Age and fasting glucose were identified as predictors of IMT increase, with IMT decreasing with age by approximately 1 % per year and increasing with glucose by around 0.24 % per mg/dL. CONCLUSION: The adolescent at higher risk is younger with higher fasting glycemia levels.

Establishing international optimal cut-offs of waist-to-height ratio for predicting cardiometabolic risk in children and adolescents aged 6-18 years.

BACKGROUND: Waist-to-height ratio (WHtR) has been proposed as a simple and effective screening tool for assessing central obesity and cardiometabolic risk in both adult and pediatric populations. However, evidence suggests that the use of a uniform WHtR cut-off of 0.50 may not be universally optimal for pediatric populations globally. We aimed to determine the optimal cut-offs of WHtR in children and adolescents with increased cardiometabolic risk across different countries worldwide. METHODS: We used ten population-based cross-sectional data on 24,605 children and adolescents aged 6-18 years from Brazil, China, Greece, Iran, Italy, Korea, South Africa, Spain, the UK, and the USA for establishing optimal WHtR cut-offs. We performed an external independent test (9,619 children and adolescents aged 6-18 years who came from other six countries) to validate the optimal WHtR cut-offs based on the predicting performance for at least two or three cardiometabolic risk factors. RESULTS: Based on receiver operator characteristic curve analyses of various WHtR cut-offs to discriminate those with ≥ 2 cardiometabolic risk factors, the relatively optimal percentile cut-offs of WHtR in the normal weight subsample population in each country did not always coincide with a single fixed percentile, but varied from the 75th to 95th percentiles across the ten countries. However, these relatively optimal percentile values tended to cluster irrespective of sex, metabolic syndrome (MetS) criteria used, and WC measurement position. In general, using ≥ 2 cardiometabolic risk factors as the predictive outcome, the relatively optimal WHtR cut-off was around 0.50 in European and the US youths but was lower, around 0.46, in Asian, African, and South American youths. Secondary analyses that directly tested WHtR values ranging from 0.42 to 0.56 at 0.01 increments largely confirmed the results of the main analyses. In addition, the proposed cut-offs of 0.50 and 0.46 for two specific pediatric populations, respectively, showed a good performance in predicting ≥ 2 or ≥ 3 cardiometabolic risk factors in external independent test populations from six countries (Brazil, China, Germany, Italy, Korea, and the USA). CONCLUSIONS: The proposed international WHtR cut-offs are easy and useful to identify central obesity and cardiometabolic risk in children and adolescents globally, thus allowing international comparison across populations.

Effects of exergaming on the microcirculation of adolescents with overweight or obesity-a clinical trial efficacy.

To assess the effect of exergaming on the microcirculation function of adolescents with overweight or obesity, this non-randomized clinical trial efficacy was conducted with 61 adolescents aged between 10 and 16 years. The intervention group (n = 31) performed exergaming three times per week for 8 weeks. Both groups received guidelines for a healthy diet and staying physically active. Microcirculation was assessed using a laser Doppler flowmetry (LDF) at baseline and after intervention. Primary outcomes derived from LDF assessment included resting flow, maximum flow, maximum/resting flow ratio, area under hyperemia, and post-occlusive reactive hyperemia (PORH). Secondary outcomes were body mass index and systemic blood pressure. Unpaired Student's t test compared intergroup analyses, and paired Student's t test compared intragroup analyses. The significance was set at 5%. Statistical analysis intergroup and intragroup was done by fitting a two-way mixed effects model. Microcirculation was similar between groups. Maximum flow (109.0 ± 38.3 versus 124.6 ± 43.0, P = 0.022), area under hyperemia (1614 ± 472 versus. 1755 ± 461, P = 0.023), and PORH (2.18 ± 0.49 versus 2.01 ± 0.52, P = 0.031) were statistically different after intervention. Body mass index decreased in intervention (24.5 ± 3.8-24.1 ± 4.0 kg/m2, P = 0.002) and control (25.2 ± 3.2-25.1 ± 3.3 kg/m2, P = 0.031) groups. Systolic blood pressure decreased significantly in the intervention group (110 ± 10-106 ± 9 mm Hg; P = 0.041) but not diastolic blood pressure (66.0 ± 7-68.8 ± 8 mm Hg; P = 0.089). Exergaming for 8 weeks led to improvements in the microcirculation function in adolescents with overweighed or obesity. Clinical trials: NTC03532659.

Relação das práticas parentais com sobrepeso e obesidade em adolescentes escolares: estudo de caso-controle / Relación de las prácticas parentales sobrepeso y obesidad en adolescentes escolares: estudio de casos y controles / Relation of parental practices overweight and obesity in school adolescents: case-control study

Objetivo: avaliar as práticas parentais educativas relativas à alimentação e sua relação com sobrepeso/obesidade em adolescentes escolares. Método: estudo de caso-controle com adolescentes de escolas públicas, mediante investigação das dimensões restritivas em relação ao consumo de doces e alimentos calóricos, pressão para comer, comer de acordo com a determinação e monitoramento-controle sobre consumo de doces e alimentos calóricos. Aplicou-se teste qui-quadrado com intervalo de confiança de 95%. Resultados: participaram 148 adolescentes (80 casos-sobrepeso/obesidade e 68 controles-eutróficos). Houve associação entre estado nutricional do cuidador e do adolescente (OR=5,688; p<0,01), maior percentual de sobrepeso/obesidade entre adolescentes submetidos a práticas restritivas de consumo de doces; em pressão para comer, proporção maior de adolescentes com sobrepeso/obesidade entre os cuidadores que discordaram; maior percentual de adolescentes com sobrepeso/obesidade entre as mães/cuidadores que relataram monitorar o consumo de alimentos calóricos na maior parte do tempo. Conclusão: as práticas parentais educativas relacionaram-se com o sobrepeso/obesidade em adolescentes escolares.

Objetivo: avaliar as práticas parentais educativas relativas à alimentação e sua relação com sobrepeso/obesidade em adolescentes escolares. Método: estudo de caso-controle com adolescentes de escolas públicas, mediante investigação das dimensões restritivas em relação ao consumo de doces e alimentos calóricos, pressão para comer, comer de acordo com a determinação e monitoramento-controle sobre consumo de doces e alimentos calóricos. Aplicou-se teste qui-quadrado com intervalo de confiança de 95%. Resultados: participaram 148 adolescentes (80 casos-sobrepeso/obesidade e 68 controles-eutróficos). Houve associação entre estado nutricional do cuidador e do adolescente (OR=5,688; p<0,01), maior percentual de sobrepeso/obesidade entre adolescentes submetidos a práticas restritivas de consumo de doces; em pressão para comer, proporção maior de adolescentes com sobrepeso/obesidade entre os cuidadores que discordaram; maior percentual de adolescentes com sobrepeso/obesidade entre as mães/cuidadores que relataram monitorar o consumo de alimentos calóricos na maior parte do tempo. Conclusão: as práticas parentais educativas relacionaram-se com o sobrepeso/obesidade em adolescentes escolares. Considerações finais: revelaram-se atendimentos influenciados por estereótipos de gênero e sexualidade, o que reduz o acesso a uma Atenção Primária à Saúde de qualidade, promotora do cuidado para com a saúde de mulheres lésbicas.

Objective: to evaluate the educational parental practices related to food and its relationship with overweight/obesity in school adolescents. Method: case-control study with adolescents from public schools, through investigation of the restrictive dimensions-in relation to the consumption of sweets and caloric foods, pressure to eat, eating according to determination and monitoring-control on consumption of sweets and caloric foods. Chi-square test was applied with a 95% confidence interval. Results: the participants were 148 adolescents (80 cases-overweight/obesity and 68 controls-eutrophic). There was an association between nutritional status of the caregiver and adolescents (OR=5.688; p<0.01), a higher percentage of overweight/obesity among adolescents submitted to restrictive practices of sweet consumption; pressure to eat, a higher proportion of overweight/obese adolescents among caregivers who disagreed; higher percentage of overweight/obese adolescents among mothers/caregivers who reported monitoring caloric food consumption most of the time. Conclusion: educational parenting practices were related to overweight/obesity in school adolescents.

Association between breakfast omission and abdominal adiposity in low-income adolescents / Associação entre a omissão do desjejum e a adiposidade abdominal em adolescentes de baixa renda

ABSTRACT Objective To assess the association between breakfast omission, overweight/obesity, abdominal adiposity, and unhealthy lifestyle of low-income adolescents. Methods A cross-sectional population study involving 571 public school students aged between 15 and 19 years old. The habit of having breakfast was assessed using a form, checking the weekly frequency of a given meal and considered as breakfast omission when these adolescents did not have breakfast for at least 5 days in the past week. Sociodemographic and lifestyle variables (sedentarism, physical activity level, and sleep duration) were also assessed. Overweight/obesity was defined as a body mass index above a Z-score of +1, and the presence of abdominal adiposity was determined by a waist circumference/height ratio greater than 0.5. The association between breakfast omission and lifestyle variables was assessed using the chi-square test and a multivariate logistic regression of the anthropometric indicators. Results The omission of breakfast was found in 31% of the adolescents and was associated with physical inactivity (p<0.001). Regarding anthropometric indicators, breakfast omission was an independent factor for determining abdominal adiposity, with a 1.8 times greater chance of having this condition among those who omitted breakfast (p=0.037). Conclusions Omitting breakfast was frequent among the students assessed, and was associated with abdominal adiposity, a cardiometabolic risk factor. Investigation and early intervention are fundamental to change this behavior.

RESUMO Objetivo O estudo objetivou avaliar a associação entre omissão do desjejum, sobrepeso/obesidade, adiposidade abdominal e estilo de vida não saudável em adolescentes de baixa renda. Methods Este foi um estudo populacional com delineamento transversal, envolvendo 571 adolescentes de escolas públicas, entre 15 e 19 anos. O hábito do desjejum foi avaliado através de formulário que verificou a frequência semanal da realização dessa refeição, sendo considerado omissão do desjejum quando os adolescentes não o realizaram por pelo menos cinco dias na última semana. Variáveis sociodemográficas e de estilo de vida (sedentarismo, nível de atividade física e horas de sono) também foram analisadas. A classificação em sobrepeso/obesidade contemplou o índice de massa corporal acima do +1 escore-z, e definiu-se adiposidade abdominal quando a relação circunferência abdominal/estatura foi maior que 0,5. A associação entre a omissão do desjejum e as variáveis de estilo de vida foi avaliada através do teste do qui-quadrado e com os indicadores antropométricos por regressão logística multivariada Results O hábito de omitir o desjejum esteve presente em 31% dos adolescentes e apresentou associação com a inatividade física (p<0,001). Em relação aos indicadores antropométricos, a omissão do desjejum foi um fator independente para determinação da adiposidade abdominal, verificando-se uma chance 1,8 vezes maior de presença dessa condição entre os que omitiam o desjejum (p=0,037). Conclusions A omissão do desjejum foi frequente entre os estudantes avaliados e esteve associada à adiposidade abdominal, um fator de risco cardiometabólico, sendo fundamental a investigação e a intervenção precoce para a mudança desse comportamento.

Corneal nerves anatomy, function, injury and regeneration.

The cornea is a highly innervated tissue, exhibiting a complex nerve architecture, distribution, and structural organization. Significant contributions over the years have allowed us to come to the current understanding about the corneal nerves. Mechanical or chemical trauma, infections, surgical wounds, ocular or systemic comorbidities, can induce corneal neuroplastic changes. Consequently, a cascade of events involving the corneal wound healing, trophic functions, neural circuits, and the lacrimal products may interfere in the corneal homeostasis. Nerve physiology drew the attention of investigators due to the popularization of modern laser refractive surgery and the perception of the destructive potential of the excimer laser to the corneal nerve population. Nerve fiber loss can lead to symptoms that may impact the patient's quality of life, and impair the best-corrected vision, leading to patient and physician dissatisfaction. Therefore, there is a need to better understand preoperative signs of corneal nerve dysfunction, the postoperative mechanisms of nerve degeneration and recovery, aiming to achieve the most efficient way of treating nerve disorders related to diseases and refractive surgery.

Use of Static Cutoffs of Hypertension to Determine High cIMT in Children and Adolescents: An International Collaboration Study.

BACKGROUND: Pediatric hypertension is typically defined as blood pressure ≥ sex-, age-, and height-specific 95th percentile (high) cutoffs. Given the number of strata, there are hundreds of cutoffs for defining elevated and high blood pressure that make it cumbersome to use in clinical practice. This study aimed to evaluate the utility of the static cutoffs for pediatric hypertension (120/80 mm Hg for children and 130/80 mm Hg for adolescents) in determining high carotid intimamedia thickness (cIMT) in children and adolescents. METHODS: Data were from 6 population-based cross-sectional studies in Brazil, China, Greece, Italy, Spain, and the United Kingdom. A total of 4280 children and adolescents, aged 6 to 17 years, were included. High cIMT was defined as cIMT ≥ sex-, age- and cohort-specific 90th percentile cutoffs. RESULTS: Compared with normal blood pressure, hypertension defined using the percentile-based cutoffs from 2017 American Academy of Pediatrics guideline, and the static cutoffs were associated with similar higher odds for high cIMT (percentile-based cutoffs: odds ratio [OR], 1.46, 95% confidence interval [CI], 1.15-1.86; static cutoffs: OR, 1.65, 95% CI, 1.25-2.17), after adjustment for sex, age, race/ethnicity, body mass index, high-density lipoprotein-cholesterol, triglyceride, and fasting blood glucose. The similar utility of 2 definitions in determining high cIMT was further confirmed by area under the receiver operating characteristic curve and net reclassification improvement methods (P for difference > 0.05). CONCLUSION: Static cutoffs (120/80 mm Hg for children, 130/80 mm Hg for adolescents) performed similarly compared with percentile-based cutoffs in determining high cIMT, supporting the use of static cutoffs in identifying pediatric hypertension in clinical practice.

Antihypertensive effect of carvacrol is improved after incorporation in ß-cyclodextrin as a drug delivery system.

Carvacrol (CARV), has been shown to possess various pharmacological properties, especially in the treatment of cardiovascular diseases. We evaluated the antihypertensive effect of the CARV free and encapsulation of CARV in ß-cyclodextrin (CARV/ß-CD), and whether CARV/ß-CD is able to improve the antihypertensive effects of CARV free in spontaneously hypertensive rats (SHR). The rats were randomly divided into four groups, each treated daily for 21 days and the mean arterial pressure and heart rate was measured every 5 days: group 1, Wistar-vehicle solution; group 2, SHR-vehicle; group 3, SHR-CARV 50 mg/kg/d; and group 4, CARV/ß-CD 50 mg/kg/d. After 21 days of treatment, the mesenteric artery from treated animals was tested for phenylephrine (Phe) and sodium nitroprusside (SNP) sensitivity. In addition, administration of CARV/ß-CD induced important antihypertensive activity when compared with the uncomplexed form, reducing the progression of arterial hypertension in SHR. Moreover, pharmacological potency to Phe in the SHR-CARV and CARV/ß-CD groups was increased, approaching values expressed in the Wistar-vehicle. Furthermore, CARV/ß-CD reduced the production of the pro-inflammatory mediator, IL-1ß, and increased anti-inflammatory cytokine, IL-10. Together, these results produced evidence that the encapsulation of CARV in ß-CD can improve cardiovascular activity, showing potential anti-inflammatory and antihypertensive effects.

Itaconimides derivatives induce relaxation in mesenteric artery and negative inotropism by inhibition of CA2+ influx.

BACKGROUND: The aim of this study was to evaluate the cardiovascular effects of N-phenyl-itaconimide (Imide-1), N-4-methyl-phenyl-itaconimide (Imide-2), N-4-methoxy-phenyl-itaconimide (Imide-3) and N-4-chloro-phenyl-itaconimide (Imide-4), and investigate the mechanisms of action involved in the observed responses. METHODS: The relaxant effect was investigated in rat superior mesenteric arteries by using isometric tension measurements. Additionally, in isolated atria were evaluated the heart rate and force of cardiac contraction and in vivo experiments was evaluated blood pressure and heart rate. RESULTS: Cumulative administration of itaconimides (3 × 10-8 to 3 × 10-4 M) in pre-contracted mesenteric artery rings with phenylephrine, 1 µM, induced endothelium-independent vasorelaxation. The itaconimides showed similar maximum efficacies. Additionally, Imide-3 induced vasorelaxation in rings exposed to a depolarizing-tyrode solution containing 60 mM KCl or 20 mM KCl similar to the control, suggesting the non-participation of K+ channels. Imide-3 attenuated Ca2+ influx in a concentration-dependent manner. As well, imide-3 reduced CaCl2-induced contraction in nominally calcium-free medium, in the presence of cyclopiazonic acid (20 µM), phenylephrine (1 µM) and nifedipine (1 µM), indicating a reduction of Ca2+ influx by receptor-operated channels (ROC) and store-operated channels (SOC). The presence of SKF 96365 (10-5 M), SOC blocker, did not significantly alter the vasorelaxant effect induced by imide-3. Moreover, imide-3 induced a negative inotropic effect. In vivo studies, in non-anesthetized normotensive rats, imide-3 lowered blood pressure and induced bradycardia. CONCLUSIONS: These results suggest that itaconimides have concentration-dependent vascular effects and the vasorelaxation seems to be endothelium-independent. The vasodilatory effect induced by imide-3 may be due to a possible influence on the CaV and ROC. In addition, imide-3 is able to reduce force of cardiac contraction, blood pressure and promote bradycardia.

Metabolic syndrome, clustering of cardiovascular risk factors and high carotid intima-media thickness in children and adolescents.

OBJECTIVE: The clinical utility of screening for pediatric metabolic syndrome (MetS) in children and adolescents is still controversial. We examined the performance of pediatric MetS vs. clustering of cardiovascular risk factors (which are the components of MetS) for predicting high carotid intima-media thickness (cIMT) in children and adolescents. METHODS: Participants included 2427 children and adolescents aged 6-17 years from population-based studies in three countries (Brazil, China and Italy). Pediatric MetS was defined using either the modified National Cholesterol Education Program Adult Treatment Panel III criteria or the modified International Diabetes Federation criteria. Clustering of cardiovascular risk factors was calculated as the sum of five components of MetS (i.e. central obesity, elevated blood pressure, elevated triglycerides, reduced HDL-cholesterol and elevated fasting blood glucose). High cIMT was defined as cIMT at least 95th percentile values for sex and age developed from European children. RESULTS: Presence of one, two or at least three cardiovascular risk factors (using the National Cholesterol Education Program Adult Treatment Panel III criteria), as compared with none, was associated with gradually increasing odds of high cIMT [odds ratios (95% confidence intervals): 1.60 (1.29-1.99), 2.89 (2.21-3.78) and 4.24 (2.81-6.39), respectively]. High cIMT was also associated with presence (vs. absence) of MetS (odds ratio = 2.88, 95% confidence interval = 1.95-4.26). However, clustering of cardiovascular risk factors predicted high cIMT markedly better than MetS (area under the curve of 0.66 vs. 0.54, respectively). Findings were similar using the International Diabetes Federation criteria for pediatric MetS. CONCLUSION: In children and adolescents, a graded score based on five cardiovascular risk factors (used to define MetS) predicted high cIMT markedly better than MetS. These findings do not support the clinical utility of MetS for screening youth at increased cardiovascular risk, as expressed in this study by high cIMT.

Descemet's Membrane Modulation of Posterior Corneal Fibrosis.

Purpose: The purpose of this study was to evaluate the effect of removal of Descemet's basement membrane and endothelium compared with removal of the endothelium alone on posterior corneal fibrosis. Methods: Twelve New Zealand White rabbits were included in the study. Six eyes had removal of the Descemet's membrane-endothelial complex over the central 8 mm of the cornea. Six eyes had endothelial removal with an olive-tipped cannula over the central 8 mm of the cornea. All corneas developed stromal edema. Corneas in both groups were cryofixed in optimum cutting temperature (OCT) formula at 1 month after surgery. Immunohistochemistry (IHC) was performed for α-smooth muscle actin (SMA), keratocan, CD45, nidogen-1, vimentin, and Ki-67, and a TUNEL assay was performed to detect apoptosis. Results: Six of six corneas that had Descemet's membrane-endothelial removal developed posterior stromal fibrosis populated with SMA+ myofibroblasts, whereas zero of six corneas that had endothelial removal alone developed fibrosis or SMA+ myofibroblasts (P < 0.01). Myofibroblasts in the fibrotic zone of corneas that had Descemet's membrane-endothelial removal were undergoing both mitosis and apoptosis at 1 month after surgery. A zone between keratocan+ keratocytes and SMA+ myofibroblasts contained keratocan-SMA-vimentin+ cells that were likely CD45- corneal fibroblasts and CD45+ fibrocytes. Conclusions: Descemet's basement membrane has an important role in modulating posterior corneal fibrosis after injury that is analogous to the role of the epithelial basement membrane in modulating anterior corneal fibrosis after injury. Fibrotic areas had myofibroblasts undergoing mitosis and apoptosis, indicating that fibrosis is in dynamic flux.

Metabolically Healthy Obesity and High Carotid Intima-Media Thickness in Children and Adolescents: International Childhood Vascular Structure Evaluation Consortium.

OBJECTIVE: It has been argued that metabolically healthy obesity (MHO) does not increase cardiovascular disease (CVD) risk. This study examines the association of MHO with carotid intima-media thickness (cIMT), a proxy of CVD risk, in children and adolescents. RESEARCH DESIGN AND METHODS: Data were available for 3,497 children and adolescents aged 6-17 years from five population-based cross-sectional studies in Brazil, China, Greece, Italy, and Spain. Weight status categories (normal, overweight, and obese) were defined using BMI cutoffs from the International Obesity Task Force. Metabolic status (defined as "healthy" [no risk factors] or "unhealthy" [one or more risk factors]) was based on four CVD risk factors: elevated blood pressure, elevated triglyceride levels, reduced HDL cholesterol, and elevated fasting glucose. High cIMT was defined as cIMT ≥90th percentile for sex, age, and study population. Logistic regression model was used to examine the association of weight and metabolic status with high cIMT, with adjustment for sex, age, race/ethnicity, and study center. RESULTS: In comparison with metabolically healthy normal weight, odds ratios (ORs) for high cIMT were 2.29 (95% CI 1.58-3.32) for metabolically healthy overweight and 3.91 (2.46-6.21) for MHO. ORs for high cIMT were 1.44 (1.03-2.02) for unhealthy normal weight, 3.49 (2.51-4.85) for unhealthy overweight, and 6.96 (5.05-9.61) for unhealthy obesity. CONCLUSIONS: Among children and adolescents, cIMT was higher for both MHO and metabolically healthy overweight compared with metabolically healthy normal weight. Our findings reinforce the need for weight control in children and adolescents irrespective of their metabolic status.

The Impact of Photorefractive Keratectomy and Mitomycin C on Corneal Nerves and Their Regeneration.

PURPOSE: To determine how photorefractive keratectomy (PRK) and mitomycin C (MMC) affect corneal nerves and their regeneration over time after surgery. METHODS: Twenty-eight New Zealand rabbits had corneal epithelial scraping with (n = 3) and without (n = 3) MMC 0.02% or -9.00 diopter PRK with (n = 6) and without (n = 16) MMC 0.02%. Corneas were removed after death and corneal nerve morphology was evaluated using acetylcholinesterase immunohistochemistry and beta-III tubulin staining after 1 day for all groups, after 1 month for PRK with and without MMC, and 2, 3, and 6 months after PRK without MMC. Image-Pro software (Media Cybernetics, Rockville, MD) was used to quantitate the area of nerve loss after the procedures and, consequently, regeneration of the nerves over time. Opposite eyes were used as controls. RESULTS: Epithelial scraping with MMC treatment did not show a statistically significant difference in nerve loss compared to epithelial scraping without MMC (P = .40). PRK with MMC was significantly different from PRK without MMC at 1 day after surgery (P = .0009) but not different at 1 month after surgery (P = .90). In the PRK without MMC group, nerves regenerated at 2 months (P < .0001) but did not return to the normal preoperative level of innervation until 3 months after surgery (P = .05). However, the morphology of the regenerating nerves was abnormal-with more tortuosity and aberrant innervation compared to the preoperative controls-even at 6 months after surgery. CONCLUSIONS: PRK negatively impacts the corneal nerves, but they are partially regenerated by 3 months after surgery in rabbits. Nerve loss after PRK extended peripherally to the excimer laser ablated zone, indicating that there was retrograde degeneration of nerves after PRK. MMC had a small additive toxic effect on the corneal nerves when combined with PRK that was only significant prior to 1 month after surgery. [J Refract Surg. 2018;34(12):790-798.].

IL-1 and TGF-ß Modulation of Epithelial Basement Membrane Components Perlecan and Nidogen Production by Corneal Stromal Cells.

Purpose: To determine whether (1) the in vitro expression of epithelial basement membrane components nidogen-1, nidogen-2, and perlecan by keratocytes, corneal fibroblasts, and myofibroblasts is modulated by cytokines/growth factors, and (2) perlecan protein is produced by stromal cells after photorefractive keratectomy. Methods: Marker-verified rabbit keratocytes, corneal fibroblasts, myofibroblasts were stimulated with TGF-ß1, IL-1α, IL-1ß, TGF-ß3, platelet-derived growth factor (PDGF)-AA, or PDGF-AB. Real-time quantitative RT-PCR was used to detect expression of nidogen-1, nidogen-2, and perlecan mRNAs. Western blotting evaluated changes in protein expression. Immunohistochemistry was performed on rabbit corneas for perlecan, alpha-smooth muscle actin, keratocan, vimentin, and CD45 at time points from 1 day to 1 month after photorefractive keratectomy (PRK). Results: IL-1α or -1ß significantly upregulated perlecan mRNA expression in keratocytes. TGF-ß1 or -ß3 markedly downregulated nidogen-1 or -2 mRNA expression in keratocytes. None of these cytokines had significant effects on nidogen-1, -2, or perlecan mRNA expression in corneal fibroblasts or myofibroblasts. IL-1α significantly upregulated, while TGF-ß1 significantly downregulated, perlecan protein expression in keratocytes. Perlecan protein expression was upregulated in anterior stromal cells at 1 and 2 days after -4.5 or -9 diopters (D) PRK, but the subepithelial localization of perlecan became disrupted at 7 days and later time points in -9-D PRK corneas when myofibroblasts populated the anterior stroma. Conclusions: IL-1 and TGF-ß1 have opposing effects on perlecan and nidogen expression by keratocytes in vitro. Proximate participation of keratocytes is likely needed to regenerate normal epithelial basement membrane after corneal injury.

Basement membranes in the cornea and other organs that commonly develop fibrosis.

Basement membranes are thin connective tissue structures composed of organ-specific assemblages of collagens, laminins, proteoglycan-like perlecan, nidogens, and other components. Traditionally, basement membranes are thought of as structures which primarily function to anchor epithelial, endothelial, or parenchymal cells to underlying connective tissues. While this role is important, other functions such as the modulation of growth factors and cytokines that regulate cell proliferation, migration, differentiation, and fibrosis are equally important. An example of this is the critical role of both the epithelial basement membrane and Descemet's basement membrane in the cornea in modulating myofibroblast development and fibrosis, as well as myofibroblast apoptosis and the resolution of fibrosis. This article compares the ultrastructure and functions of key basement membranes in several organs to illustrate the variability and importance of these structures in organs that commonly develop fibrosis.