Surrogate Index Research Articles

Assessment of insulin resistance and metabolic syndrome in young reproductive aged women with polycystic ovarian syndrome: analogy of surrogate indices

Background Polycystic ovarian syndrome has emerged as a cardiometabolic disorder and aim of this study was to evaluate various surrogate indices and their diagnostic potential to determine the most convenient and cost-effective marker of IR, CVD, and MetS in these women. Materials and methods Ninety-five PCOS women and 45 age matched healthy women were enrolled. Measures included anthropometric and biochemical parameters, BMI, WHR, WHtR, BAI, VAI, LAP, HOMA-IR, and lipid profile. Results LAP has highest AUC value 0.781 with cut-off value = 39.73 (sensitivity = 75% and specificity = 79.5%) for predicting IR and AUC value 0.83 with cut-off value = 35.63 (sensitivity = 94.4% and specificity = 77.3%) for predicting MetS in women with PCOS. LAP had statistically strong positive correlation with WC, BMI, WHR, fasting glucose, fasting insulin, HOMA-IR, TC, TG, and SBP. Conclusions LAP is a powerful and reliable marker for assessment of IR, CVD, and MetS risk in young Indian women with PCOS.

The effect of coffee consumption on insulin sensitivity and other biological risk factors for type 2 diabetes: a randomized placebo-controlled trial

In observational studies, coffee consumption has been consistently associated with a lower risk of type 2 diabetes mellitus. Trials examining the effect of coffee consumption on glucose metabolism have been limited by the use of surrogate insulin sensitivity indices, small sample sizes, lack of blinding, and short follow-up duration. We aimed to overcome limitations of previously conducted coffee trials in a randomized placebo-controlled trial of the effect of coffee consumption on insulin sensitivity. We conducted a 24-wk randomized placebo-controlled trial in 126 overweight, non-insulin sensitive (HOMA-IR≥1.30), Chinese, Malay, and Asian-Indian males and females aged 35-69 y. Participants were randomly assigned to receive 4 cups of instant regular coffee (n=62) or 4 cups of a coffee-like placebo beverage (n =64) per day. The primary outcome was the amount of glucose metabolized per kilogram of body weight per minute (Mbw) assessed during steady-state conditions with a hyperinsulinemic euglycemic clamp. Secondary outcomes included other clamp-based insulin sensitivity measures, biological mediators of insulin sensitivity, and measures of fasting glucose metabolism. Coffee consumption did not significantly change insulin sensitivity compared with placebo (percentage mean difference in Mbw = 4.0%; 95% CI: -8.3, 18.0%; P=0.53). Furthermore, no significant differences in fasting plasma glucose (2.9%; 95% CI: -0.4, 6.3%; P=0.09) or biological mediators of insulin resistance, such as plasma adiponectin (2.3%; 95% CI: -1.4, 6.2%; P=0.22), were observed between coffee and placebo groups over 24 wk of intervention. Participants in the coffee arm experienced a loss of fat mass (FM) (-3.7%; 95% CI: -6.3, -1.1%; P=0.006) and reduction in urinary creatinine concentrations (-21.2%; 95% CI: -31.4, -9.5%; P=0.001) compared with participants in the placebo arm over 24 wk of intervention. Consuming 4 cups/d of caffeinated coffee for 24 wk had no significant effect on insulin sensitivity or biological mediatorsof insulin resistance but was associated with a modest lossofFM and reduction in urinary creatinine concentrations.Thistrial was registered at clinicaltrials.gov as NCT01738399. Registered on November 28, 2012. Trial sponsor: Nestlé Research, Lausanne, Switzerland. Trial site: National University of Singapore.

Trends in Glaucoma Filtration Procedures: A Retrospective Administrative Health Records Analysis Over a 13-Year Period in Canada.

BackgroundGlaucoma surgical management has evolved significantly with the introduction of minimally invasive glaucoma surgery. Our aim was to evaluate trends in Canadian glaucoma surgery billing code usage as a surrogate index of the current impact of this new technology in Canada’s publicly funded health-care system.MethodsRetrospective administrative health records analysis of all patients who underwent a publicly funded glaucoma filtration procedure from January 2003 to December 2016 in the 6 largest Canadian provinces. The frequency of glaucoma-related procedures was adjusted against primary open-angle glaucoma prevalence data. Frequency of all glaucoma filtration procedures with and without implantation of a drainage device in each province per year is reported.ResultsNationwide, glaucoma filtration procedures per 1000 primary open-angle glaucoma patients per year remained constant, with increased drainage device implantation over time (P<0.0001). Ontario and Nova Scotia mirrored the overall population. British Columbia and Saskatchewan showed increased rates of glaucoma filtration surgery, with increased drainage device implantations. In Quebec, overall filtration surgery decreased, while the rate of device implantation increased (p<0.0001). Alberta showed a decline in filtration surgery and device implantations from 2003 to 2008, and then increased thereafter.ConclusionOver the study period, there was a distinct trend towards billing code usage for implanted devices. Challenges encountered during this investigation highlight the need for identifiers in provincial health databases to accommodate the introduction of novel technologies. The absence of specific billing codes for newer technologies prevents accurate analyses of impact, utilization, efficacy and cost implications in contemporary patient management.

Mapping of fatty acid composition with free-breathing MR spectroscopic imaging and compressed sensing.

Nonalcoholic fatty liver disease (NAFLD) is a growing health problem, and a major challenge in NAFLD management is identifying which patients are at risk of progression to more serious disease. Simple measurements of liver fat content are not strong predictors of clinical outcome, but biomarkers related to fatty acid composition (ie, saturated vs. unsaturated fat) may be more effective. MR spectroscopic imaging (MRSI) methods allow spatially resolved, whole‐liver measurements of chemical composition but are traditionally limited by slow acquisition times. In this work we present an accelerated MRSI acquisition based on spin echo single point imaging (SE‐SPI), which, using appropriate sampling and compressed sensing reconstruction, allows free‐breathing acquisition in a mouse model of fatty liver disease. After validating the technique's performance in oil/water phantoms, we imaged mice that had received a normal diet or a methionine and choline deficient (MCD) diet, some of which also received supplemental injections of iron to mimic hepatic iron overload. SE‐SPI was more resistant to the line‐broadening effects of iron than single‐voxel spectroscopy measurements, and was consistently able to measure the amplitudes of low‐intensity spectral peaks that are important to characterizing fatty acid composition. In particular, in the mice receiving the MCD diet, SE‐SPI showed a significant decrease in a metric associated with unsaturated fat, which is consistent with the literature. This or other related metrics may therefore offer more a specific biomarker of liver health than fat content alone. This preclinical study is an important precursor to clinical testing of the proposed method.MR‐based quantification of fatty acid composition may allow for improved characterization of non‐alcoholic fatty liver disease. A spectroscopic imaging method with appropriate sampling strategy allows whole‐liver mapping of fat composition metrics in a free‐breathing mouse model. Changes in metrics like the surrogate unsaturation index (UIs) are visible in mice receiving a diet which induces fat accumulation in the liver, as compared to a normal diet; such metrics may prove useful in future clinical studies of liver disease.

Daily high-dose aspirin does not lower APRI in the Aspirin-Myocardial Infarction Study.

Antiplatelet agents reduce liver fibrosis by inhibiting platelet activation and platelet-derived growth factor production. Previous cross-sectional epidemiological studies suggest that the use of aspirin is related to reduced liver fibrosis. The Aspirin-Myocardial Infarction Study (AMIS) aims to examine this relationship in a multicenter, randomized, double-blind and placebo-controlled trial. The existing clinical trial of aspirin was conducted to study the benefit of one gram aspirin daily among 4 524 individuals who had experienced at least one documented myocardial infarction. The aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI) was calculated at baseline and annually from the platelet count and AST levels. Participants in the AMIS trial had a mean baseline APRI of 0.34±0.36, and only 1% individuals had APRI scores higher than 1.0, a common cutoff for cirrhosis. The daily use of aspirin was associated with an increase, rather than a reduction of APRI, by 0.007 per year (95% CI 0.002-0.015, P=0.12). The use of aspirin did not significantly affect platelet counts. In a sensitivity analysis of individuals with probable significant fibrosis at baseline (APRI≥0.7), the aspirin group had a sustained reduction in APRI over time, although this change was not significant compared to that in the placebo group. In the AMIS trial, the daily use of high-dose aspirin did not significantly affect APRI, a surrogate index of liver fibrosis. This study highlights the need for de novo clinical trials to investigate the potential benefit of antiplatelet agents on liver fibrosis.

858: Leptin and the association between breastfeeding and insulin resistance in women with current gestational diabetes

Although breastfeeding is considered to have a protective effect against the development of diabetes in women with gestational diabetes (GDM), the mechanism remains obscure. In this pilot study, we investigated factors associated with breastfeeding and insulin resistance (IR) at six months postpartum. In this prospective observational study, we included Japanese singleton pregnant women with a diagnosis of GDM. At 6 months postpartum when they underwent a follow-up 75-g oral glucose tolerance tests (OGTT), we collected serum samples for the measurement of serum factors, including TNF-alpha, leptin, adiponectin, prolactin (PRL), oxytocin, and IgA, as well as insulin, in the fasting state. We used homeostasis model of assessment (HOMA)-IR as a surrogate index of IR. We defined the condition in which infants were fed by breastfeeding greater than 80% of the volume as high-intensity breastfeeding (HIB), while other statuses, including partial and non-breastfeeding, were non-HIB. We investigated the association between HOMA-IR, breastfeeding status, and endocrine factors. In 72 women with current GDM, we found that the breastfeeding status and body mass index (BMI) were independently associated with HOMA-IR at 6 months postpartum. The TNF-alpha (p< 0.0001), leptin (p< 0.0001) and IgA (p< 0.05) levels were also significantly and positively associated with HOMA-IR in a multivariate analysis after adjusting for the age and BMI. Among those factors, only leptin (p< 0.05) was associated with breastfeeding status (HIB vs. non-HIB: 14.9±9.0 vs. 21.3±17.3, p< 0.05), and it remained significant after adjusting for the age and BMI. PRL and oxytocin were significantly associated with the breastfeeding status but not with HOMA-IR. Adiponectin was associated with neither HOMA-IR nor the breastfeeding status. Breastfeeding is significantly and independently associated with decreasing insulin resistance at six months postpartum. Leptin may play a key role in the association between breastfeeding and insulin sensitivity.

Pharmacokinetics of marbofloxacin in Green sea turtles (Chelonia mydas) following intravenous and intramuscular administration at two dosage rates.

Limited pharmacokinetic information to establish suitable therapeutic plans is available for green sea turtles. Therefore, the present study was conducted to evaluate the pharmacokinetic characteristics of marbofloxacin (MBF) in the green sea turtle, Chelonia mydas, following single intravenous (i.v.) or intramuscular (i.m.) administration at two dosages of 2 and 4mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168hr. MBF in plasma was extracted using liquid-liquid extraction and analyzed by a validated high-performance liquid chromatography (HPLC). MBF was quantifiable from 15min to 96hr after i.v. and i.m. administrations at two dose rates. A noncompartmental model was used to fit the plasma concentration of MBF versus time curve for each green sea turtle. The t1/2λz value, similar for both the dosages (22-28hr), indicated that the overall rate of elimination of MBF in green sea turtles is relatively slow. The average i.m. F% ranged 88%-103%. MBF is a concentration-dependent drug and the AUC/MIC ratio is the best PK/PD predictor for its efficacy. The MBF dosage of 4mg/kg appeared to produce an appropriate value of the PK-PD surrogate that predicts antibacterial success for disease caused by susceptible bacteria. In contrast, i.m. administration of MBF at a dosage of 2mg/kg b.w. was not found to produce a suitable PK-PD surrogate index. However, further studies of multiple doses and plasma binding proteins are warranted to confirm an appropriate dosage regimen.

Surrogate indices of aortic peak systolic velocity variation to monitor fluid responsiveness in pediatric non-cardiac surgery: a prospective observational study.

Aortic peak systolic velocity variation (ΔVpeakAo) is a reliable dynamic indicator of preload in mechanically ventilated children. However, easily measurable alternative parameters like carotid peak systolic velocity variation (ΔVpeakCa) and suprasternal peak systolic velocity variation (ΔVpeakSs) are not well evaluated in children. The aim of the study was to find correlation between ΔVpeakCa and ΔVpeakSs to ΔVpeakAo, as potential surrogate markers of fluid responsiveness. 52 children, 1-12years old, undergoing major non-cardiac surgeries under general endotracheal anaesthesia were recruited for this single-centre prospective observational study. ΔVpeakAo, ΔVpeakCa and ΔVpeakSs were measured by pulsed wave Doppler in appropriate windows, measuring maximum and minimum peak flow velocity over a single respiratory cycle. Calculated parameters were compared by a repeated measures study design. Correlation coefficients were 0.82 between ΔVpeakAo and ΔVpeakSs and 0.73 between ΔVpeakAo and ΔVpeakCa. Bland-Altman analysis showed minimal bias of 1.86 percentage points with limits of agreement of 11.21 to - 7.49 (ΔVpeakAo and ΔVpeakSs) and 3.93 percentage points with limits of agreement of 14.04 to - 6.18 (ΔVpeakAo and ΔVpeakCa). ΔVpeakSs and ΔVpeakCa also showed good discrimination to predict ΔVpeakAo (lying in previously validated fluid responsive zones) with sensitivities and specificities of 82.25% and 85% with cut-off of 11% for ΔVpeakSs, and 88.52% and 70% with cut-off of 8.6% for ΔVpeakCa. Carotid peak systolic velocity variation (ΔVpeakCa) and suprasternal peak systolic velocity variation (ΔVpeakCa) can be potential surrogate markers for Aortic peak systolic velocity variation (ΔVpeakAo) in assessing fluid responsiveness in mechanically ventilated children.Study registration: Clinicaltrials.gov ID NCT03155555.

Fasting triglycerides and glucose index: a useful screening test for assessing insulin resistance in patients diagnosed with rheumatoid arthritis and systemic lupus erythematosus

BackgroundInsulin resistance (IR) is frequently observed in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). In clinical practice, IR assessment is limited to a low proportion of patients due to cost and equipment and technical expertise requirements. The surrogate index of triglycerides and glucose (TyG index) has been validated in non-rheumatic populations, showing adequate sensitivity and specificity for IR, although this index has not yet been used in connective tissue disorders. The aim of this study was to evaluate the frequency of insulin resistance (IR) using the validated surrogate index of triglycerides and glucose (TyG index) and to explore factors associated with IR in Mexican women with RA or SLE.MethodsNinety-five female RA and 57 SLE patients were included in a cross-sectional study. Clinical and epidemiological variables were evaluated. IR was assessed using the TyG index with a cutoff value of > 4.68. Logistic regression analysis was performed to identify factors associated with IR excluding confounders.ResultsIR frequency in the entire sample was 50%, higher than the 10% observed in non-rheumatic controls (p < 0.001). The frequency of IR was similar in SLE (49.1%) and RA (50.5%, p = 0.8) patients. IR was associated with a longer duration of hypertension and higher total cholesterol and low density lipoprotein cholesterol levels. Based on multivariate analysis, the duration of hypertension (OR: 1.06; 95% CI 1.002–1.12, p = 0.04), waist circumference (OR: 1.04; 95% CI 1.01–1.08, p = 0.007), uric acid levels (OR: 1.46; 95% CI 1.08–1.97, p = 0.01), RA (OR: 4.87; 95% CI 1.31–18.78, p = 0.01) and SLE (OR: 4.22; 95% CI 1.06–16.74, p = 0.04) were the main risk factors for IR.ConclusionsThis study shows that the TyG index is a useful screening test for IR in RA and SLE patients. Future longitudinal studies should be performed with the aim of identifying the predictive value of TyG index results for identifying complications linked to IR.

Surrogate indexes of insulin resistance and risk of metabolic syndrome in non-Hispanic White, non-Hispanic Black and Mexican American

AimTo compare the strength of associations between surrogate indexes of insulin resistance (sIR) and risk of metabolic syndrome (MetS) in non-Hispanic White (NHW), non-Hispanic Black (NHB) and Mexican American (MA) adults. MethodsThe 2013–2016 US National Health and Nutrition Examination Survey data (n = 3435) were used for this study. The associations between sIR that includes Triglyceride/HDL cholesterol ratio (TG/HDL-C), triglyceride glucose (TG) index, visceral adiposity index (VAI), lipid accumulation product (LAP), TG-body mass index (TG-BMI), and TG-waist circumference (TG-WC) and risk for MetS were determined using the prevalence odds ratio (OR) from the logistic regression analyses. Pseudo-R-squared tests were used to estimate the proportion of variance in MetS accounted for by each sIR. Akaike Information Criterion and Bayesian Information Criterion from the multinomial logistic regression analysis were used to compare models that included each sIR and its components separately as predictors of MetS. Areas under curves (AUC) from the receiver-operating characteristic (ROC) were used to detect their diagnostic capabilities. ResultsCompared with other sIR, TG-WC (AUC = 0.899; 95% CI: 0.884–0.913 in NHW) and (AUC = 0.893; 95% CI:0.871–0.915 in NHB), and LAP (AUC = 877; 95% CI: 0.861–0.894 in MA) exhibited the highest diagnostic and predictive accuracy for MetS. Compared with other sIR, TG-WC (OR = 22.8; 95% CI:16.6–31.0 in NHW) and (OR = 22.7; 95% CI:13.1–39.3 in NHB), and LAP (OR = 10.6; 95%:6.6–17.0 in MA) were most significantly associated with increased odds of MetS, adjusting for eGFR, age, marital status, CHD, CHF, income, education, physical activity, alcohol use, smoking and use of cholesterol-lowering medication. ConclusionsTG-WC in NHW and NHB, and LAP in MA are more powerful than other proxies of IR in predicting MetS. TG-WC and LAP can serve as adjunctive tools for screening for MetS in NHW, NHB, and MA.

Pharmacokinetic and tissue analyses of levofloxacin in sheep (Ovis aries Linnaeus) after multiple-dose administration

The aim of this study was to assess the pharmacokinetic profile of LFX in sheep after intravenous (IV) and oral (PO) administration of 2 mg/kg LFX once a day for 5 days and to evaluate its tissue depletion in the muscles, heart, liver, lungs, and kidneys. Twenty healthy female sheep were randomly divided into two equal groups. Each group was further randomly subdivided into two equal subgroups (n = 5). Group 1 was used for blood collection and underwent a crossover design (2 × 2 Latin square). Group 2 was randomly subdivided into two equal subgroups (n = 5) for IV and PO route respectively, and used for tissue collection. A single sheep was sacrificed at each time point and the organs were harvested. Samples were analyzed using a validated HPLC method with fluorescence detection. LFX administered orally was rapidly absorbed with a peak plasma concentration of 2866 ± 239 ng/mL and an absolute oral bioavailability of 114 ± 27.7%. The pharmacokinetic estimates were comparable between PO and IV administration. According to the pharmacokinetic/pharmacodynamic surrogate index (area under the curve / minimum inhibitory concentration) of 100–125, LFX has the potential to be an effective treatment for infections caused by bacteria with a MIC of 0.049–0.061 μg/mL. LFX was detected for up to 48 h in all the tissues samples. The kidney had the highest LFX concentration after IV and PO administration. The AUCtissue/plasma ratio was lower than 1 in all tissues indicating absence of LFX tissue accumulation.

Relationships of surrogate indexes of insulin resistance with insulin sensitivity assessed by euglycemic hyperinsulinemic clamp and subclinical vascular damage

IntroductionInsulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular disease. The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, visceral adiposity index (VAI), lipid accumulation...

A Study on the Potential of IAD as a Surrogate Index of Quality and Storability in cv. ‘Gala’ Apple Fruit

The decline of relative chlorophyll contents during fruit ripening is considered to be an important indicator of fruit physiological condition. The recent availability of low-cost portable visible spectrum (VIS) spectrometers has spurred research interest towards optical sensing of chlorophyll changes in intact fruit, with many scientists attempting to link the shifts in optical signals, attributed to chlorophyll changes, to different maturity and quality parameters. One of the widely available portable devices for non-destructive estimation of relative chlorophyll contents is the DA meter, which provides a maturity index that is calculated as a difference between absorption at 670 nm (near the chlorophyll-a absorption peak) and 720 nm (background of the spectrum), abbreviated as IAD. In the present study, the evolution of IAD and its relation to starch pattern index (SPI) and fruit flesh firmness (FFF) was monitored in fruit of two cv. ‘Gala’ clones during maturation and storage, aiming to identify a potential existence of a usable IAD range for the assessment and prediction of the optimal harvest window and storage potential. In both clones, canopy positions, fruit sides, and seasons IAD, SPI, and FFF generally changed in a linear fashion over time, but with partially very different slopes, i.e., they were changing at different rates. What all of these parameters had in common was the presence of a very high biological variability, which is typical of apple fruit. Significantly powerful estimations of SPI (r2 &gt; 0.7, p &lt; 0.005) and pre- and post-storage FFF (r2 &gt; 0.6, p &lt; 0.005) were achieved. However, the very large biological variability could not be neutralized, which means that the predictions always included large confidence intervals of up to 0.46–0.59 units for SPI and 0.82–1.1 kgF FFF, which ultimately makes them unusable for practical applications. Experiments done under real-life conditions in a commercial fruit storage facility on several different fruit batches confirmed that IAD measured at harvest cannot be used indiscriminately for predicting post-storage FFF of cv. ‘Gala’ originating from different orchards. Nevertheless, mean IAD values that were obtained at optimal maturity from samples of the same orchards remained stable over seasons (0.8–1.2), which strongly suggests that, provided that the calibrations and validations are not only cultivar, but also orchard-specific, IAD has a potential for estimating maturity and storability of apple fruit. In this case, IAD could replace standard maturity indices, otherwise it would be suited for use as a supplementary index for determining fruits physiological maturity status.

The Triglyceride and Glucose Index Is a Predictor of Incident Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study

Background The triglyceride and glucose index (TyG), defined as the product of triglycerides (TG) and fasting plasma glucose (FPG), is reported as a surrogate index for insulin resistance. Although a cross-sectional study revealed the association between the TyG-index and the prevalence of nonalcoholic fatty liver disease (NAFLD), few studies have investigated the association between the TyG-index and incident NAFLD. Here we investigated whether the TyG-index can be used to predict incident NAFLD. Methods This historical cohort study included 16,093 apparently healthy Japanese individuals. The TyG-index was calculated by the established formula: TyG = Ln [TG (mg/dl) × FPG (mg/dl)/2]. Fatty liver was diagnosed based on the subjects' abdominal ultrasonography results. We divided the subjects into tertiles according to the levels of TyG-index. Hazard ratios (HRs) of the TyG-index for incident NAFLD were calculated by a Cox proportional hazards regression model. Results During the observation period, 27.4% of the men and 11.0% of the women developed NAFLD. The highest TyG-index tertile (men, 8.48 ≤ TyG and women, 7.97 ≤ TyG) (adjusted HR 1.67, 95% CI 1.44–1.94, p < 0.001 in the men and 2.06, 1.59–2.70, p < 0.001 in the women) and the middle TyG-index tertile (men, 8.00 < TyG ≤ 8.48 and women, 7.53 <TyG ≤7.97) (1.33, 1.15–1.54, p < 0.001 in the men and 1.52, 1.16–2.01, p < 0.001 in the women) presented a significantly higher risk of incident NAFLD compared to the lowest TyG-index tertile (men, TyG < 8.00 and women, TyG < 7.53). Conclusions Our findings demonstrate that the TyG-index is significantly associated with incident NAFLD.

Is there a relationship between dopamine and rhegmatogenous retinal detachment?

Dopamine and its receptors have been widely studied in the neurological conditions and in the retina. In this study, we evaluated the possible role of dopamine in rhegmatogenous retinal detachment (RRD) by comparing the amount of 3,4-dihydroxyphenylacetic acid (DOPAC), a surrogate index of retinal dopamine levels, in the vitreous sample of patients affected by RRD with those affected by macular pucker and vitreous hemorrhage. Our results showed that significantly higher levels of DOPAC were found in the vitreous sample of patients affected by RRD compared with those affected by vitreous hemorrhage and macular pucker (P = 0.002). Specifically, no trace of the substance was found in vitreous hemorrhage and macular pucker samples. A slightly significant positive correlation was found among DOPAC and post-operative best corrected visual acuity (r = 0.470, P = 0.049). No correlation was found between DOPAC and the days elapsed between diagnosis and surgery (P = 0.317). For the first time our findings suggest that DOPAC is released in RRD, but not in other retinal diseases such as vitreous hemorrhage and macular pucker. Moreover, we showed a correlation between visual acuity outcome and the amount of DOPAC in the vitreous. This might have a potential, although still unknown, implication in the pathogenesis of the disease and/or in the associated photoreceptors loss. This study was approved by the Ethics Committee of Rome Tor Vergata University Hospital (R.S.92.10) on September 24, 2010.

Assessment of Nutritional Status in Sri Lankan Children: Validity of Current Anthropometry Cutoffs?

Despite socioeconomic improvement, undernutrition rates stagnate in Sri Lanka, while a slow rise in obesity and noncommunicable diseases (NCD) is seen. Inability to improve undernutrition and detection of NCD could be due to overdiagnosing stunting/wasting and underdiagnosing overweight/obesity. Obesity, being a risk factor for NCDs, needs correct tools for early diagnosis. Although body mass index (BMI) is a commonly used surrogate index, the validity of universal cutoffs is questioned. Evidence shows that body composition varies with ethnic origin and cutoff value reflecting fat mass (FM) varies in different ethnic groups. This study was conducted in 12 788, 5- to 15-year-old children from 8 schools in Negombo, Sri Lanka, to identify the validity of current anthropometric cutoffs. Obesity prevalence identified by body fat content was high. International BMI cutoffs had high specificity but varied sensitivity. Locally developed BMI cutoffs had high sensitivity and specificity. Validity of internationally developed anthropometric cutoffs in South Asian children is unsatisfactory; hence, locally/regionally developed anthropometric tools should be used for screening of obesity.

Fusion OLAP: Fusing the Pros of MOLAP and ROLAP Together for In-Memory OLAP

OLAP models can be categorized with two types: MOLAP (multidimensional OLAP) and ROLAP (relational OLAP). In particular, MOLAP is efficient in multidimensional computing at the cost of cube maintenance, while ROLAP reduces the data storage size at the cost of expensive multidimensional join operations. In this paper, we propose a novel Fusion OLAP model to fuse the multidimensional computing model and relational storage model together to make the best aspects of both MOLAP and ROLAP worlds. This is achieved by mapping the relation tables into virtual multidimensional model and binding the multidimensional operations into a set of vector indexes to enable multidimensional computing on relation tables. The Fusion OLAP model can be integrated into the state-of-the-art in-memory databases with additional surrogate key indexes and vector indexes. We compared the Fusion OLAP implementations with three leading analytical in-memory databases. Our comprehensive experimental results show that Fusion OLAP implementation can achieve up to 35, 365, and 169 percent performance improvements based on the Hyper, Vectorwise, and MonetDB databases, respectively, for the Star Schema Benchmark (SSB) with scale factor 100.

Three-dimensional echocardiography investigation of the mechanisms of tricuspid annular dilatation.

Tricuspid annular (TA) size, assessed by 2D transthoracic echocardiography (TTE), has a well-established prognostic value in patients undergoing mitral valve surgery, with TA dilatation triggering simultaneous tricuspid annuloplasty. While TA dilatation is common in patients with dilated atria secondary to atrial fibrillation, little is known about the mechanisms of TA dilatation in patients with sinus rhythm (SR). This study aimed to identify echocardiographic parameters most closely related to the TA size as a potential tool for identification of patients prone to developing TA enlargement. 120 patients with SR underwent clinically indicated TTE, including 30 patients with normal hearts and 90 patients diagnosed with at least one right heart abnormality, defined as: right ventricular (RV) or right atrial (RA) dilatation, ≥ moderate tricuspid regurgitation (TR) and elevated systolic pulmonary artery pressure (sPAP). RA and RV end-diastolic and end-systolic volumes (EDV, ESV) and function were measured using commercial 3D software (TomTec). 3D RV long and short axes were used as surrogate indices of RV shape. Degrees of TR and sPAP were estimated by 2D TTE. 3D TA sizing was performed at end-diastole using 3D custom software. Linear regression analysis was used to identify variables best correlated with TA size, followed by multivariate analysis to identify independent associations. The highest correlations were found between TA area and: RA ESV (r = 0.73; p < 0.01), RV EDV (r = 0.58; p < 0.01), RV end-diastolic long and short axes (r = 0.53, 0.42; both p < 0.01), TR degree (r = 0.40; p < 0.01) and sPAP (r = 0.32; p < 0.01). Multivariate analysis revealed that RA ESV was the only parameter independently associated with TA area (p < 0.05, r = 0.85). In conclusion,RA volume plays an important role in TA dilatation even in patients with normal SR. Understanding of annular remodeling mechanisms could aid in identifying patients at higher risk for TA dilatation, especially those scheduled for mitral valve surgery.

Stress sensitivity and cutaneous sensory thresholds before and after neuropathic injury in various inbred and outbred rat strains

Chronic pain is associated with altered affective state, stress, anxiety and depression. Conversely, stress, anxiety and depression can all modulate pain perception. The relative link between these behavioural constructs in different inbred and outbred rat strains, known to be variously hypo/hyperresponsive to stress has not been determined. Hindpaw sensory thresholds to repeated mechanical (von Frey filament and electronic Randall Selitto) and thermal (Hargreaves, cold plate and hot plate) stimulation were routinely assessed over three weeks in non-injured male rats of the following strains; WKY, LEW, F344, Hsd:SD and Crl:SD. Thereafter, threshold responses to Spared Nerve Injury (SNI) were assessed using von Frey, pin prick and Hargreaves testing in the same strains over a three month period. Finally, anxiolytic efficacy of the benzodiazepine drug diazepam was assessed using the Elevated Plus Maze (EPM), as a surrogate index of functional plasticity of circuits involved in affective processing. Repeated nociceptive testing was associated with distinct strain-dependent changes in sensory thresholds in naïve rats; stress-hyporesponsive LEW rats presented with a mechanical/thermal hyperalgesia phenotype, whereas stress-hyperresponsive WKY rats presented with an unexpected heat/cold hypoalgesia phenotype. After SNI, LEW rats showed minimal signs of neuropathic sensitivity. Diazepam was anxiolytic in all tested strains with the exception of LEW rats reflecting distinct inherent affective processing only in this strain. The contribution of stress reactivity to nociceptive sensory profiles appears to vary in the absence or presence of neuropathic injury. Intriguingly, the functional responsiveness of affective state prior to injury may be a predisposing factor to developing chronic pain.

Abstract 310: Time-Dependent Changes in Myocardial Edema Overestimate the Ischemic Area-at-Risk Up to One Week After Reperfused Myocardial Infarction in Swine

Objective: Assessment of tissue salvage after myocardial infarction (MI) requires accurate quantification of the ischemic area at risk (AAR). Although the AAR is typically measured retrospectively within one week after reperfusion, dynamic changes in tissue composition may affect the precision of this approach. Given recent cardiac MRI data demonstrating a transient reduction in myocardial edema 24 hours after reperfused MI, we tested the hypothesis that this is an optimal timepoint for accurate retrospective AAR assessment. Methods: Swine (n=27) were subjected to a 1 hour LAD occlusion, during which the AAR was assessed by contrast enhanced CT-derived quantification of the myocardial perfusion defect. Phthalocyanine blue was administered at the end of occlusion (n=7) or during re-occlusion of the LAD 3 hours (n=5), 24 hours (n=5) or 7 days (n=10) after reperfusion for pathologic determination of the AAR. Serial echocardiography was performed in the 24 hour reperfusion group to assess end diastolic wall thickness (EDWT) as a surrogate index of post-MI edema. Results: When assessed before reperfusion, the AAR was similar by CT and postmortem pathology ( Table ). However, AAR measurements 3 hours, 24 hours, and 7 days after reperfusion overestimated CT AAR mass by 38±7 %, 31±10 %, and 37±5%, respectively. Echocardiography showed a marked increase in EDWT 1 and 3 hours after reperfusion, followed by a decrease at 24 hours that remained significantly higher than pre-ischemia values. Conclusion: Despite partial resolution of edema 24 hours after reperfusion, AAR measurement at this time does not provide an accurate assessment of the AAR obtained during the initial coronary occlusion.