Identifying the best cutoff value of the fecal occult blood immunochemical test in the detection of advanced and neoplastic colorectal lesions.

Objective: Screening is an effective tool for detecting colorectal lesions in asymptomatic subjects. There is a positive correlation between fecal immunochemical test (FIT) values and the size of tumors. Despite the efficacy of screening, the detection of colorectal cancer (CRC) remains low. The primary objective was to evaluate the best FIT cutoff value for detecting advanced adenomas and CRC among individuals at average risk in a country with a high incidence and morbidity from CRC. Methods: This observational and prospective study analyzed consecutive cases in 1461 asymptomatic subjects with a positive FIT (≥ 100 ng hemoglobin [Hb]/mL) referred for colonoscopy (2012-2015) at a tertiary center in Uruguay. Results: Colorectal lesions were detected in 35.3% (516/1461) of cases, with a mean age of 62.8 ± 8.3 years. About 53.2% were men and 65.1% of the tumors were located in the left side of the colon. The size of the lesion and FIT values (p = 0.001) were positively correlated. Laterally spreading tumors predominated in the right colon (586 ng Hb/mL; 95% Confidence interval [CI] 443.4-760). One hundred and thirty-five (26%) lesions were advanced adenomas (15 ± 6.7 mm); 694.6 ng/mL; 95% CI 632.4-756.9). The highest diagnostic yield (0.5112) for advanced adenomas was at a FIT level of 400 ng Hb/mL (accuracy 88.6%). There were significant differences in FIT values early and advanced CRC (927 ng/mL; [95% CI: 637-1082] vs. 1453 [95% CI: 1352-1594; p = 0.001]). Conclusion: A FIT value of 400 ng Hb/mL was the best diagnostic yield to detect advanced adenomas and CRC. This value is useful during the COVID-19 pandemic as it allows prioritization of colonoscopy to those most at risk of significant disease, thus reducing risks to both patients and healthcare workers.

Objetivo: El cribado es una herramienta eficaz para detectar lesiones colorrectales en sujetos asintomáticos. Existe una correlación positiva entre los valores de la prueba inmunoquímica fecal (FIT) y el tamaño de los tumores. A pesar de la eficacia del cribado, la detección del cáncer colorrectal (CCR) sigue siendo baja. El objetivo principal fue evaluar el mejor valor de corte FIT para detectar adenomas avanzados y CCR entre personas con riesgo promedio en un país con alta incidencia y morbilidad por CCR. Métodos: Este estudio observacional y prospectivo analizó 1461 sujetos asintomáticos con FIT positivo (≥ 100 ng de hemoglobina [Hb]/mL) remitidos para colonoscopia (2012-2015) en un centro terciario en Uruguay. Resultados: Se detectaron lesiones colorrectales en el 35,3% (516/1461) de los casos, con una edad media de 62,8 ± 8,3 años. Alrededor del 53,2% eran hombres y el 65,1% de los tumores estaban ubicados en el lado izquierdo del colon. El tamaño de la lesión y los valores FIT (p = 0,001) se correlacionaron positivamente. Los tumores con extensión lateral predominaron en el colon derecho (586 ng Hb/mL; intervalo de confianza [IC] del 95%: 443,4-760). Ciento treinta y cinco (26%) lesiones fueron adenomas avanzados (15 ± 6,7 mm); 694,6 ng/ml; IC 95% 632,4-756,9). El rendimiento diagnóstico más alto (0,5112) para los adenomas avanzados se obtuvo con un nivel FIT de 400 ng Hb/ml (precisión del 88,6%). Hubo diferencias significativas en los valores de FIT de CCR temprano y avanzado (927 ng/mL; [IC 95%: 637-1082] vs. 1453 [IC 95%: 1352-1594; p = 0,001]). Conclusión: Un valor FIT de 400 ng Hb/mL fue el mejor rendimiento diagnóstico para detectar adenomas avanzados y CCR. Este valor es útil durante la pandemia de COVID-19, ya que permite priorizar la colonoscopia a aquellos con mayor riesgo de padecer una enfermedad importante, reduciendo así los riesgos tanto para los pacientes como para los trabajadores de la salud.

Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial.

BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.

Effect of Insulin Resistance on Abdominal Obesity, Liver Fat Infiltration, and Body Mass Index in Youngsters.

AIM: Evaluate insulin resistance (IR) as a mediator of the effect of body fat distribution on liver fat infiltration and stiffness (LSt) in young adults using structural equation modeling (SEM). METHODS: We invited 500 first year students from two universities and evaluated their family history to determine the risk for cardiometabolic disease. Of these, 174 students (age 19 ± 1 years) were assessed for total body fat percentage (BF%), LSt, fat infiltration (Coefficient attenuated parameter CAP), and serum biochemical analysis. We performed a mediation analysis using two different structural equation models to determine the relationship between BMI, BF%, abdominal obesity (AO), IR, LSt, and fat infiltration using standardized ß coefficients. The symbol "->" means "explains/causes". RESULTS: Model#1 supported that mediation analysis and had a better fit than the direct effect. AO->IR (b = 0.62, p = 0.005), AO->CAP (b = 0.63, p <0.001), and CAP->IR (b = 0.23, p = 0.007), with negligible effect of BMI on CAP and IR. Model#2 showed direct effect of BMI on LSt was a better fit than mediation. BMI->LSt (b = 0.17, p = 0.05) but no effect AO->LSt. Interestingly, LSt->IR (b = 0.18, p = 0.001), but bi-directional IR->LSt (b = 0.23, p = 0.001). CONCLUSIONS: AO and BMI in young adults have differential phenotypic effects on liver CAP and LSt. Visceral fat had a direct effect on IR and CAP. Meanwhile, BMI was associated with LSt. Our findings shed light on the complex interplay of factors influencing liver stiffness, particularly in young individuals. Further research is needed to elucidate the precise mechanisms underlying these associations and their implications for liver health.

Getting Ahead: A Resident Led Quality Improvement Project to Increase Diabetic Nephropathy Screening in an Underserved Hispanic-Predominant Population.

Introduction: Diabetes is the leading cause of end-stage renal disease (ESRD) in the United States (US), with 37 million having chronic kidney disease. Despite national guidelines recommendations for diabetic nephropathy screening with urine albumin-to-creatinine ratio (UACR), less than 50% receive full screening.Our Internal Medicine residents led a quality improvement project to increase diabetic nephropathy screening rate with UACR in our resident clinic by 50% in one academic year. Methods: We conducted the resident-led quality improvement project from July 2021 to April 2022. We reviewed the electronic medical records (EMR) from our clinic pre-intervention July 2020 to June 2021 and compared this to post intervention July 2021 to March 2022 determining the nephropathy screening rates in patients with diabetes. Our interventions included resident education, pre and post surveys to test foundational knowledge, adding UACR in the affordable laboratory order form and establishing normal reference range of UACR in the EMR. Results: We collected 217 patients with diabetes, 27% were uninsured, 38% had Medicare/Medicaid and 90% identified as Hispanic. Comparing pre to post intervention, there was a significant change of 45 (20.7%) vs 71 (32.7%) patients screened for diabetic nephropathy with a UACR. The correct average score of knowledge-based questions was 82% on the pre survey, which increased to 88% in the post survey. Conclusion: Our study showed promising results on improving diabetic nephropathy screening. The comprehensive approach including resident education about diabetic nephropathy screening with UACR and more so facilitating the order set in the EMR were key to achieve this goal.

Vaccination in the context of the COVID-19 pandemic.

In this review, we described the history of vaccination, the different types of vaccines, and how vaccination coverage has been affected by the current COVID-19 pandemic. The effectiveness of the vaccines under metabolic host conditions is analyzed, especially when people have lost their immunocompetence, such as in patients with chronic kidney disease who are in dialysis treatment. Vaccines are produced in a variety of industrial methods, modifying costs. The novel field of vaccinomics includes the set of immune responses, the satisfactory levels of neutralizing antibodies, the production of metabolites, and the induction of protein expression. Finally, an analysis is made of the confusing messages regarding vaccination that are disseminated on social networks, and general recommendations are given.

En esta revisión se describen el historial de vacunación, los diferentes tipos de vacunas y cómo la cobertura de vacunación se ha visto afectada por la pandemia actual de COVID-19. Se analiza la efectividad de las vacunas en condiciones metabólicas del huésped, especialmente cuando las personas han perdido su inmunocompetencia, como los pacientes con enfermedad renal crónica que están en tratamiento de diálisis. Las vacunas se producen con una variedad de métodos industriales, modificando los costos. El nuevo campo de la vacunómica incluye el conjunto de respuestas inmunitarias, los niveles satisfactorios de anticuerpos neutralizantes, la producción de metabolitos y la inducción de la expresión de proteínas. Finalmente, se analizan los confusos mensajes sobre vacunación que se difunden en las redes sociales y se dan recomendaciones generales.

Looking for Crumbs in the Obesity Forest: Anti-obesity Interventions and Obesity-Associated Cardiometabolic Traits in the Mexican Population. History and Systematic Review With Meta-Analyses.

Mexicans and Mexican Americans share culture, genetic background, and predisposition for chronic complications associated with obesity and diabetes making imperative efficacious treatments and prevention. Obesity has been treated for centuries focused-on weight loss while other treatments on associated conditions like gout, diabetes (T2D), and hypertriglyceridemia. To date, there is no systematic review that synthesizes the origin of obesity clinics in Mexico and the efforts to investigate treatments for obesity tested by randomized clinical trials (RCT). We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve anti-obesity RCT through 2019 and without an inferior temporal limit. The systematic review included RCT of anti-obesity treatments in the Mexican adult population, covering alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions reporting metabolism-associated traits such as BMI, weight, waist circumference, triglycerides, glucose, among others. Only the studies with at least 3 months of treatment were included in the meta-analyses in order to reduce placebo effects. We found 634 entries, after removal of duplicates and screening the studies based on eligibility criteria, we analyzed 43 national, and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and the implemented strategies do not have replications in the population. The nutrition/behavioral interventions were difficult to blind, and most studies have medium-to-high risk of bias. Nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like pure water instead of sweet beverages decrease triglycerides and systolic blood pressure. Dark chocolate showed the highest effect for BMI and high blood pressure, and treatment with insulin increased weight in those with T2D. The study of obesity in Mexico has been on-going for more than four decades, the interest on RCT just increased until this millennium, but with small sample sizes and lack of replication. The interventions affect different cardiometabolic associated traits, which should be analyzed in detail in the population living near the Mexico-U.S. border; therefore, bi-national collaboration is desirable to disentangle the cultural effects on this population's treatment response. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020221436, identifier: CRD42020221436.

[Consenso experto en tiempos de COVID-19: aplicaciones del método Delphi en materia de salud].

La epidemia de COVID-19 ha modificado la cultura de la comunicación. La solución para los problemas de salud puede ser asertiva cuando es consensuada. El método Delphi es una herramienta de consenso que emplea rondas de listas de preguntas para recopilar información del conocimiento de un panel de expertos que analizan planteamientos y posibles soluciones a problemas. Se basa en la premisa de que, con la libertad del anonimato, la inteligencia combinada mejora el juicio individual y captura la opinión colectiva experta. El proceso del método es muy flexible, pues las rondas de preguntas pueden realizarse de manera presencial o remota. En este artículo se describe cómo implementar el método Delphi convencional en tiempos de confinamiento, y se analizan la utilidad y las limitaciones del método para su uso por expertos en salud para la resolución de problemas de tratamiento, diagnóstico o administrativos. Las tecnologías actuales para recolectar los datos permiten gran flexibilidad en el formato de los cuestionarios y facilitan la recopilación de la opinión experta. Gracias a su adaptabilidad, el método Delphi se está convirtiendo en una estrategia popular que involucra los ámbitos cualitativo y cuantitativo.

Acanthosis nigricans as a composite marker of cardiometabolic risk and its complex association with obesity and insulin resistance in Mexican American children.

AIM: Acanthosis nigricans (AN) is a strong correlate of obesity and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMRFs). However, the direct causal relationship of IR with AN in obesity has been debated. Therefore, we aimed to examine the complex causal relationships among the troika of AN, obesity, and IR in Mexican Americans (MAs). METHODS: We used data from 670 non-diabetic MA children, aged 6-17 years (49% girls). AN (prevalence 33%) severity scores (range 0-5) were used as a quasi-quantitative trait (AN-q) for analysis. We used the program SOLAR for determining phenotypic, genetic, and environmental correlations between AN-q and CMRFs (e.g., BMI, HOMA-IR, lipids, blood pressure, hs-C-reactive protein (CRP), and Harvard physical fitness score (PFS)). The genetic and environmental correlations were subsequently used in mediation analysis (AMOS program). Model comparisons were made using goodness-of-fit indexes. RESULTS: Heritability of AN-q was 0.75 (p<0.0001). It was positively/significantly (p<0.05) correlated with traits such as BMI, HOMA-IR, and CRP, and negatively with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMI→HOMA-IR→AN-q yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN-q simultaneously. Using complex models, BMI was associated with AN-q and IR mediating most of the CMRFs; but no relationship between IR and AN-q. CONCLUSION: Our study suggests that obesity explains the association of IR with AN, but no causal relationship between IR and AN in Mexican American children.

CARDIOMETABOLIC RISK FACTORS ASSOCIATED WITH RENAL FUNCTION IN APPARENTLY HEALTHY YOUNG STUDENTS: A CROSS-SECTIONAL STUDY.

BACKGROUND: Cardiometabolic risk factors (CMRFs) appear decades before developing chronic kidney disease (CKD) in adulthood. OBJECTIVE: The objective of the study was to identify the prevalence and association between CMRFs and kidney function in apparently healthy young adults (18-25 years old). METHODS: We included 5531 freshman year students. Data collected on CMRFs included central obesity, high body mass index (hBMI >25), blood pressure, glycemia, lipids, uric acid (UA >6.8 mg/dL), and insulin. Glomerular filtration rate (GFR) was estimated by CKD-Epidemiology Collaboration formula. We used logistic regression and a log linear for odds ratio (OR) (95% confidence level) and probabilities. RESULTS: The presence of any CMRF was observed in 78% (4312) of individuals; GFR ≥120/130 mL/min/1.73 m2sc was found in 33%, GFR <90 mL/min/1.73 m2sc in 3%, and proteinuria in 3%. Factors associated with high GFR were hBMI (OR 1.3 [1.14, 1.47]), UA (OR 0.2 [0.15, 0.26]), high-density lipoprotein (HDL) (OR 1.4 [1.2, 1.6]), and insulin resistance (OR 1.3 [1.05, 1.7]). CMRF associated with low GFR was UA (OR 1.8 [1.3, 2.6]), low-density lipoprotein cholesterol (OR 1.66 [1.05, 2.6]), and proteinuria (OR 3.4 [2.07, 5.7]). Proteinuria was associated with high UA (OR 1.59 [1.01, 2.5]) and hypercholesterolemia (OR 1.8 [1.03, 3.18]). The sole presence of hBMI+UA predicted low GFR with p = 0.6 and hBMI+UA+low HDL predicted proteinuria with p = 0.55. CONCLUSIONS: CMRFs were highly prevalent among this freshman student population and were associated with proteinuria and GFR abnormalities. Future studies should focus on public health programs to prevent or delay the development of CKD.

Cardiometabolic risk factors associated with renal function in apparently healthy young students: a cross-sectional study

ABSTRACT Background: Cardiometabolic risk factors (CMRFs) appear decades before developing chronic kidney disease (CKD) in adulthood. Objective: The objective of the study was to identify the prevalence and association between CMRFs and kidney function in apparently healthy young adults (18-25 years old). Methods: We included 5531 freshman year students. Data collected on CMRFs included central obesity, high body mass index (hBMI >25), blood pressure, glycemia, lipids, uric acid (UA >6.8 mg/dL), and insulin. Glomerular filtration rate (GFR) was estimated by CKD-Epidemiology Collaboration formula. We used logistic regression and a log linear for odds ratio (OR) (95% confidence level) and probabilities. Results: The presence of any CMRF was observed in 78% (4312) of individuals; GFR ≥120/130 mL/min/1.73 m2sc was found in 33%, GFR <90 mL/min/1.73 m2sc in 3%, and proteinuria in 3%. Factors associated with high GFR were hBMI (OR 1.3 [1.14, 1.47]), UA (OR 0.2 [0.15, 0.26]), high-density lipoprotein (HDL) (OR 1.4 [1.2, 1.6]), and insulin resistance (OR 1.3 [1.05, 1.7]). CMRF associated with low GFR was UA (OR 1.8 [1.3, 2.6]), low-density lipoprotein cholesterol (OR 1.66 [1.05, 2.6]), and proteinuria (OR 3.4 [2.07, 5.7]). Proteinuria was associated with high UA (OR 1.59 [1.01, 2.5]) and hypercholesterolemia (OR 1.8 [1.03, 3.18]). The sole presence of hBMI+UA predicted low GFR with p = 0.6 and hBMI+UA+low HDL predicted proteinuria with p = 0.55. Conclusions: CMRFs were highly prevalent among this freshman student population and were associated with proteinuria and GFR abnormalities. Future studies should focus on public health programs to prevent or delay the development of CKD.

Efficacy of the Combination of Pinaverium Bromide 100 mg Plus Simethicone 300 mg in Abdominal Pain and Bloating in Irritable Bowel Syndrome: A Randomized, Placebo-controlled Trial.

GOALS: We aimed to evaluate the efficacy and safety of PB+S (pinaverium bromide 100 mg plus simethicone 300 mg) in patients with irritable bowel syndrome (IBS). BACKGROUND: IBS is a multifactorial disorder; thus, combination therapy with different mechanisms of action is expected to be useful. PB+S has shown effectiveness in an open-label clinical study in IBS. However, there are no placebo-controlled trials. MATERIALS AND METHODS: IBS-Rome III patients with abdominal pain/discomfort for at least 2 days within the week prior to baseline assessment were included in this 12-week, randomized, double-blind, placebo-controlled study of PB+S versus placebo, bid. The primary endpoint was overall symptom improvement, evaluated weekly by the patient (Likert Scale). Secondary endpoints included the weekly improvement in the severity of abdominal pain and bloating assessed both by patients (10-cm Visual Analogue Scale) and investigators (Likert Scale); frequency of Bristol Scale stool types (consistency) evaluated by patients and the IBS Quality of Life scores. RESULTS: A total of 285 patients (female: 83%; 36.5±8.9 y old) received at least 1 dose of PB+S (n=140) or placebo (n=145). No difference was observed in overall symptom improvement between the groups (P=0.13). However, PB+S was superior in abdominal pain (effect size: 31%, P=0.038) and bloating (33%, P=0.019). Patients with IBS-C and IBS-M showed the best improvement in the frequency of stool types with PB+S. No differences were observed in IBS Quality of Life scores and adverse events. CONCLUSIONS: PB+S was superior to placebo in improving abdominal pain and bloating in patients with active IBS. The effect on the frequency of stool consistency was particularly significant in IBS-C and IBS-M.

The re-emerging association between tuberculosis and diabetes: Lessons from past centuries.

The association between tuberculosis (TB) and diabetes mellitus (DM) had a common place in the literature up to the first half of the 20th century, but virtually disappeared with the discovery of insulin to treat DM and antibiotics to cure TB. In the late 1990s the literature began to re-emerge with the worldwide increase in type 2 DM, particularly in TB-endemic countries. Today, type 2 DM is the most prevalent comorbidity among TB patients and the World Health Organization considers it a threat to TB control. We summarize the literature on TB and DM up to the 1960s. Then we evaluate unique aspects of this comorbidity in older times, such as the frequent diabetic comas that suggest challenges for proper DM management as insulin was being implemented, or the absence of antibiotics to cure TB. Despite the unique aspects of each study period, the literature across times is consistent in key aspects of the association. Namely, a higher TB prevalence among DM (versus non-DM patients), the importance of glucose control and chronic DM on TB susceptibility and the higher risk of death among patients with the co-morbidity. From the older literature, we can infer the likely contribution of type 1 DM to TB (in addition to type 2), regardless of their differing autoimmune or metabolic pathophysiology, respectively. Furthermore, in the older literature there was a notable reporting of DM development among TB patients, even though DM usually preceded TB. This observation deserves further epidemiological and basic studies to elucidate this intriguing aspect of the relationship between TB and DM.

Clinical Significance of Serum Uric Acid Levels in Mexican Young Adults.

BACKGROUND: High serum uric acid concentration (SUA >6 for women [W] or 7 mg/dL for men [M]) in adults is an independent risk factor for causing cardiovascular disease and chronic kidney disease (CKD); the risk of high SUA in young population is still being debated. SUMMARY: We conducted an epidemiological study to determine the association between SUA quartiles with cardiometabolic risk factors (CRF) and renal impairment in apparently healthy young adults. CRF (dyslipidemia, overweight [Ow], obesity [Ob], blood pressure [BP], hyperglycemia, insulin resistance [IR]) and renal impairment were defined as glomerular filtration rate (GFR) by CKD-Epidemiology Collaboration formula >130/120, <90 mL/min/1.73 m2, and proteinuria were measured in 18- to 25-year-old students (total n = 5,531). Adjusted ORs by sex were calculated using logistic regression. RESULTS: The mean SUA was 4.5 ± 1.04 and 6.2 ± 1.2 mg/dL in W and M respectively. High SUA was found in 13.9% (n = 767); prevalence of Ow/Ob 69% (528 of 767), high BP 9% (67), hyperglycemia 15% (112), IR 47% (214), hypertriglyceridemia 35% (269), high LDL-c 16% (120), low HDL-c 52% (399), and metabolic syndrome 33% (249). Prevalence of high GFR was 13% (103), low GFR 8% (62) and proteinuria 5% (37). All risk factors showed a positive relationship with the SUA quartiles with high LDL-c with lowest risk (OR 1.7) and Ow/Ob with highest risk (OR 4.1), independent of sex. Key Messages: High SUA concentrations (M ≥6.2/W ≥4.5 mg/dL) are associated with CRF and renal impairment in young adults. It is necessary to reevaluate the cutoff points for UA in young adults.

Nonalcoholic fatty liver disease can be predicted by retinal vascular changes in patients with obesity without hypertension or diabetes.

OBJECTIVE: To evaluate the utility of predicting nonalcoholic fatty liver disease (NAFLD) and obesity by retinal vascular changes (RVC) found in fundoscopy and to determine whether this is related to a low-grade inflammatory process. METHODS: We carried out a cross-sectional analysis that included 152 (ages 18-45 years) patients divided into four groups: NAFLD and BMI less than 25, absence of NAFLD and BMI less than 25, NAFLD and BMI more than 30, and absence of NAFLD and BMI more than 30. Retinal fundoscopy, hepatic ultrasound, metabolic profile, and cytokine measurement were performed. We calculated odds ratio [95% confidence interval (CI)], performed diagnostic utility tests, and carried out a 2 factorial analysis. RESULTS: Obesity was associated with RVC (odds ratio: 21.25; 95% CI: 8.79-51.4) and NAFLD [25 (9.07-72.6)]. NAFLD was associated with RVC [11.24 (4.98-26.48)], and the prediction of NAFLD showed a sensitivity of 75% (95% CI: 68-82) and a specificity of 81% (75-86); when RVC-obesity were combined, sensitivity increased to 90% (88-91.7), with a specificity of 85% (84-85.8). C-reactive protein was associated with the three factors, suggesting an independent contribution. Thin patients with RVC and NAFLD had higher concentrations of interleukin-2, interleukin-6, tumor necrosis factor-α, and interferon-γ. CONCLUSION: NAFLD in patients with obesity without diabetes or hypertension can be predicted by RVC, a noninvasive technique carried out by eye fundoscopy. NAFLD alone can drive inflammatory conditions in the absence of obesity that manifests as RVC.

Heritability of ambulatory and beat-to-beat office blood pressure in large multigenerational Arab pedigrees: the 'Oman Family study'.

OBJECTIVE: To estimate the heritability of ambulatory blood pressure (BP), heart rate (HR), and beat-to-beat office BP and HR in an isolated, environmentally and genetically homogeneous Omani Arab population. METHODS: Ambulatory BP measurements were recorded in 1,124 subjects with a mean age of 33.8 ± 16.2 years, using the auscultatory mode of the validated Schiller ambulatory BP Monitor. Beat-to-beat BP and HR were recorded by the Task Force Monitor. Heritability was estimated using quantitative genetic analysis. This was achieved by applying the maximum-likelihood-based variance decomposition method implemented in SOLAR software. RESULTS: We detected statistically significant heritability estimates for office beat-to-beat, 24-hour, daytime, and sleep HR of 0.31, 0.21, 0.20, and 0.07, respectively. Heritability estimates in the above mentioned conditions for systolic BP (SBP)/diastolic BP (DBP)/mean BP (MBP)were all significant and estimated at 0.19/0.19/0.19, 0.30/0.44/0.41, 0.28/0.38/0.39, and 0.21/0.18/0.20,respectively. Heritability estimates for 24-hour and daytime ambulatory SBP, DBP, and MBP ranged from 0.28 to 0.44, and were higher than the heritability estimates for beat-to-beat recordings and sleep periods,which were estimated within a narrow range of 0.18-0.21. CONCLUSION: In this cohort, because shared environments are common to all, the environmental influence that occurs is primarily due to the variation in non-shared environment that is unique to the individual. We demonstrated significant heritability estimates for both beat-to-beat office and ambulatory BP and HR recordings, but 24-hour and daytime ambulatory heritabilities are higher than those from beat-to-beat resting levels and ambulatory night-time recordings.

Impact of an exercise program on acylcarnitines in obesity: a prospective controlled study.

BACKGROUND: Acylcarnitine (AC) transport dysfunction into the mitochondrial matrix is one of the pathophysiological mechanisms of type 2 diabetes mellitus (DM). The effect of an aerobic exercise (AE) program on this condition in obese subjects without DM is unclear. METHODS: A prospective, randomized, longitudinal, interventional study in a University Research Center involved a 10-week AE program in 32 women without DM and a body mass index (BMI) greater than 27 kg/m2. (Cases n = 17; Controls n = 15). The primary objective was to evaluate the influence of a controlled AE program on beta-oxidation according to modifications in short, medium, and long-chain ACs. Secondary objectives were to define the behavior of amino acids, and the correlation between these modifications with metabolic and anthropometric markers. RESULTS: The proportion of dropouts was 17% and 6% in controls and cases, respectively. In cases there was a significant reduction in total carnitine (30.40 [95% CI 28.2 to 35.6]) vs. (29.4 [CI 95% 25.1 to 31.7]) p = 0.0008 and long-chain AC C14 (0.06 [95% CI 0.05 to 0.08]) vs. (0.05 [95% CI 0.05 to 0.09]) p = 0.005 and in C18 (0.31 [95% CI 0.27 to 0.45]) vs. (0.28 [95% CI 0.22 to 0.32]) p = 0.03. Free fatty acid levels remained without change during the study in both groups. CONCLUSION: In conclusion, a controlled 10-week AE program improved beta-oxidation by reducing long-chain ACs. This finding highlights the importance that AE might have in avoiding or reverting lipotoxicity, and in consequence, improving insulin sensitivity and pancreatic beta cell functional reserve.

Heart rate is associated with markers of fatty acid desaturation: the GOCADAN study.

OBJECTIVES: To determine if heart rate (HR) is associated with desaturation indexes as HR is associated with arrhythmia and sudden death. STUDY DESIGN: A community based cross-sectional study of 1214 Alaskan Inuit. METHODS: Data of FA concentrations from plasma and red blood cell membranes from those ≥35 years of age (n = 819) were compared to basal HR at the time of examination. Multiple linear regression with backward stepwise selection was employed to analyze the effect of the desaturase indexes on HR, after adjustment for relevant covariates. RESULTS: The Δ(5) desaturase index (Δ(5)-DI) measured in serum has recently been associated with a protective role for cardiovascular disease. This index measured here in plasma and red blood cells showed a negative correlation with HR. The plasma stearoyl-CoA-desaturase (SCD) index, previously determined to be related to cardiovascular disease (CVD) mortality, on the other hand, was positively associated with HR, while the Δ(6) desaturase index (Δ(6)-DI) had no significant effect on HR. CONCLUSION: Endogenous FA desaturation is associated with HR and thereby, in the case of SCD, possibly with arrhythmia and sudden death, which would at least partially explain the previously observed association between cardiovascular mortality and desaturase activity.

Genome-wide linkage analysis of hemodynamic parameters under mental and physical stress in extended Omani Arab pedigrees: the Oman Family Study.

BACKGROUND: We performed a genome-wide scan in a homogeneous Arab population to identify genomic regions linked to blood pressure (BP) and its intermediate phenotypes during mental and physical stress tests. METHODS: The Oman Family Study subjects (N = 1277) were recruited from five extended families of ~10 generations. Hemodynamic phenotypes were computed from beat-to-beat BP, electrocardiography and impedance cardiography. Multi-point linkage was performed for resting, mental (word conflict test, WCT) and cold pressor (CPT) stress and their reactivity scores (s), using variance components decomposition-based methods implemented in SOLAR. RESULTS: Genome-wide scans for BP phenotypes identified quantitative trait loci (QTLs) with significant evidence of linkage on chromosomes 1 and 12 for WCT-linked cardiac output (LOD = 3.1) and systolic BP (LOD = 3.5). Evidence for suggestive linkage for WCT was found on chromosomes 3, 17 and 1 for heart rate (LOD = 2.3), DBP (LOD = 2.4) and left ventricular ejection time (LVET), respectively. For △WCT, suggestive QTLs were detected for CO on chr11 (LOD = 2.5), LVET on chr3 (LOD = 2.0) and EDI on chr9 (LOD = 2.1). For CPT, suggestive QTLs for HR and LVET shared the same region on chr22 (LOD 2.3 and 2.8, respectively) and on chr9 (LOD = 2.3) for SBP, chr7 (LOD = 2.4) for SV and chr19 (LOD = 2.6) for CO. For △CPT, CO and TPR top signals were detected on chr15 and 10 (LOD; 2.40, 2.08) respectively. CONCLUSION: Mental stress revealed the largest number of significant and suggestive loci for normal BP reported to date. The study of BP and its intermediate phenotypes under mental and physical stress may help reveal the genes involved in the pathogenesis of essential hypertension.