Validation and Calibration of a Computer Simulation Model of Pediatric HIV Infection

Background

Computer simulation models can project long-term patient outcomes and inform health policy. We internally validated and then calibrated a model of HIV disease in children before initiation of antiretroviral therapy to provide a framework against which to compare the impact of pediatric HIV treatment strategies.

Methods

We developed a patient-level (Monte Carlo) model of HIV progression among untreated children <5 years of age, using the Cost-Effectiveness of Preventing AIDS Complications model framework: the CEPAC-Pediatric model. We populated the model with data on opportunistic infection and mortality risks from the International Epidemiologic Database to Evaluate AIDS (IeDEA), with mean CD4% at birth (42%) and mean CD4% decline (1.4%/month) from the Women and Infants’ Transmission Study (WITS). We internally validated the model by varying WITS-derived CD4% data, comparing the corresponding model-generated survival curves to empirical survival curves from IeDEA, and identifying best-fitting parameter sets as those with a root-mean square error (RMSE) <0.01. We then calibrated the model to other African settings by systematically varying immunologic and HIV mortality-related input parameters. Model-generated survival curves for children aged 0-60 months were compared, again using RMSE, to UNAIDS data from >1,300 untreated, HIV-infected African children.

Results

In internal validation analyses, model-generated survival curves fit IeDEA data well; modeled and observed survival at 16 months of age were 91.2% and 91.1%, respectively. RMSE varied widely with variations in CD4% parameters; the best fitting parameter set (RMSE = 0.00423) resulted when CD4% was 45% at birth and declined by 6%/month (ages 0-3 months) and 0.3%/month (ages >3 months). In calibration analyses, increases in IeDEA-derived mortality risks were necessary to fit UNAIDS survival data.

Conclusions

The CEPAC-Pediatric model performed well in internal validation analyses. Increases in modeled mortality risks required to match UNAIDS data highlight the importance of pre-enrollment mortality in many pediatric cohort studies.     

Effect of concentration and shell thickness on the optical behavior of aqueous CdTe/ZnSe core/shell quantum dots (QDs) exposed to ionizing radiation

In this work CdTe/ZnSe core/shell quantum dots (QDs) were synthesized via a simple, rapid and room temperature photochemical approach. Optical properties of aqueous prepared CdTe/ZnSe QDs were studied systematically under gamma irradiation with dose range of 0 Gy to 20 kGy. The obtained results showed a regular red shift behavior versus gamma irradiation dose, in photoluminescence peak and absorption edge of the CdTe/ZnSe QDs. Structural properties of CdTe/ZnSe QDs before and after gamma irradiation were characterized by means of X-ray diffraction (XRD), Raman and Fourier-transform infrared (FT-IR) analyses. The obtained results showed that the crystalline structure of CdTe/ZnSe core/shell QDs did not change after gamma irradiation. Concentration and shell thickness as two important factors on the sensitivity of CdTe/ZnSe QDs in front of gamma irradiation have been investigated. Based on this study, CdTe/ZnSe QDs are suggested as good candidates for gamma dosimeter.     

Resveratrol treatment reduces expression of MCP-1, IL-6, IL-8 and RANTES in endometriotic stromal cells

Endometriosis is an inflammatory disease affecting reproductive-aged women. Immunologic disturbance, as well as inflammation, have crucial roles in the pathogenesis of endometriosis. In this study, we evaluated the effects of resveratrol treatment on expression of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), IL-8, and regulated upon activation, normal T cell expressed and secreted (RANTES) in endometrial stromal cells from patients with endometriosis compared with non-endometriotic controls. Thirteen eutopic (EuESCs) and nine ectopic (EESCs) endometrial stromal cells from endometriotic patients as well as eleven endometrial stromal cells from non-endometriotic controls (CESCs) were treated with resveratrol (100 μmol/L) or ethanol, and gene and/or protein expression of MCP-1, IL-6, IL-8 and RANTES was examined at 6, 24 and 48 hours following treatment in the cells from all origins. Resveratrol treatment significantly reduced gene and protein expression of MCP-1, IL-6, and IL-8 in EuESCs and EESCs compared with CESCs (P < .05-.001, P < .05-.001 and P < .05-<.01, respectively), and this reduction was more noticeable in EESCs than EuESCs (P < .05-<.001). Besides, resveratrol treatment significantly reduced RANTES protein expression in EESCs in all time intervals (P < .05). Resveratrol treatment significantly reduced the expression of MCP-1, IL-6, IL-8 and RANTES in EESCs.     

The Incidence of Coronary Heart Disease and the Population Attributable Fraction of Its Risk Factors in Tehran: A 10-Year Population-Based Cohort Study

Background

Data on incidence of coronary heart disease (CHD) is scarce in the Middle East and little is known about the contribution of known risk factors in this area.

Methods

The incidence of CHD and the effect of modifiable risk factors were explored in 2889 men and 3803 women aged 30–74 years in the population based cohort of the Tehran Lipid and Glucose Study, during 1999–2010. Average population attributable fraction (aPAF) was calculated for any risk factor using direct method based on regression model.

Results

The crude incidence rate in men was about twice that in women (11.9 vs. 6.5 per 1000 person-years). The aPAF of hypertension, diabetes, high total cholesterol and low-HDL cholesterol was 9.4%, 6.7%, 7.3% and 6.1% in men and 17%, 16.6%, 12% and 4.6% in women respectively. This index was 7.0% for smoking in men. High risk age contributed to 42% and 22% of risk in men and women respectively.

Conclusions

The incidence in this population of Iran was comparable to those in the US in the seventies. Well known modifiable risk factors explained about 40% and 50% of CHD burden in men and women respectively. Aging, as a reflection of unmeasured or unknown risk factors, bears the most burden of CHD, especially in men; indicating more age-related health care is required.     

Single-cell analysis of tumors: Creating new value for molecular biomarker discovery of cancer stem cells and tumor-infiltrating immune cells

Biomarker-driven individualized treatment in oncology has made tremendous progress through technological developments, new therapeutic modalities and a deeper understanding of the molecular biology for tumors, cancer stem cells and tumor-infiltrating immune cells. Recent technical developments have led to the establishment of a variety of cancer-related diagnostic, prognostic and predictive biomarkers. In this regard, different modern OMICs approaches were assessed in order to categorize and classify prognostically different forms of neoplasia. Despite those technical advancements, the extent of molecular heterogeneity at the individual cell level in human tumors remains largely uncharacterized. Each tumor consists of a mixture of heterogeneous cell types. Therefore, it is important to quantify the dynamic cellular variations in order to predict clinical parameters, such as a response to treatment and or potential for disease recurrence. Recently, single-cell based methods have been developed to characterize the heterogeneity in seemingly homogenous cancer cell populations prior to and during treatment. In this review, we highlight the recent advances for single-cell analysis and discuss the challenges and prospects for molecular characterization of cancer cells, cancer stem cells and tumor-infiltrating immune cells.     

Vectorcardiography analysis of the repolarization response to pharmacologically induced autonomic nervous system modulation in healthy subjects

Autonomic nervous system activity is essential for regulation of ventricular repolarization (VR) and plays an important role in several arrhythmogenic conditions. This study in 31 healthy adult subjects (16 men, 15 women) evaluated the VR response to pharmacologically modulated autonomic nervous system activity applying vectorcardiography (VCG) analysis. During continuous VCG recording, 0.01-0.1 μg·kg(-1)·min(-1) isoprenaline (Iso) was infused at an increasing flow rate until three targeted heart rates (HR) were reached. After Iso washout, one intravenous bolus of 0.04 mg/kg atropine was given followed by an intravenous bolus of 0.2 mg/kg propranolol. A 5-min steady-state VCG recording was analyzed for each of the seven phases (including baseline 1 and 2). Furthermore, during the first 4 min following atropine, six periods of 10-s VCG were selected for subanalysis to evaluate the time course of change. The analysis included QRS, QT, and T-peak to T-end intervals, measures of the QRS and T vectors and their relation, as well as T-loop morphology parameters. By increasing HR, Iso infusion decreased HR dependent parameters reflecting total heterogeneity of VR (T area) and action potential morphology (ventricular gradient). In contrast, Iso prolonged QT HR corrected according to Bazett and increased the T-peak to T-end-to-QT ratio to levels observed in arrhythmogenic conditions. HR acceleration after atropine was accompanied by a transient paradoxical QT prolongation and delayed HR adaptation of T area and ventricular gradient. In addition to the expected HR adaptation, the VR response to β-adrenoceptor stimulation with Iso and to muscarinic receptor blockade with atropine thus included alterations previously observed in congenital and acquired long QT syndromes, demonstrating substantial overlap between physiological and pathophysiological electrophysiology.     

Race analysis of Puccinia striiformis f.sp. tritici in Iran

The wheat stripe (yellow) rust is one of the most important diseases in Iran. In this study, 41 races out of 104 isolates in greenhouse were determined from 2008 to 2010. Races 6E6A+, 6E10A+ and 6E0A+ were more common. Races 0E0A+ was less aggressive than races 166E158A+ and 134E158A+ with virulence on 11 known genes. Virulence on plant/s with gene/s Yr1, Yr2, Yr4, Yr6, Yr7, Yr8, Yr9, Yr10, Yr25, Yr27, YrSU, YrSD, YrND, Yr3, Yr2+, Yr6+, Yr9+, Yr7+, YrCV and YrA was detected. The majority of isolates with high frequency (more than 70%) showed virulence on plant/s with Yr2, Yr7, Yr9 and YrA genes. No virulence was detected on plant/s with Yr3, Yr5 and YrSP. In greenhouse test, frequency of virulence to wheat genotypes with Yr1, Yr4, Yr10, YrCV (32+) and YrSD gene was less than 7%. Frequency of virulence to other wheat genotypes was between 8 and 100%.     

Changing the convexity and concavity of nasal cartilages and cartilage grafts with horizontal mattress sutures: part II. Clinical results

Horizontal mattress sutures have previously been shown to remove unwanted bulbosity and convexity of nasal tip cartilages. The purpose of this study was to extend that concept by investigating the universal applicability of the horizontal mattress suture to change and control the curvature (e.g., convexity or concavity) of a wide variety of nasal cartilages and warped cartilage grafts. The horizontal mattress suture was applied to a variety of clinical situations, including nasal tip bulbosity caused by convex lateral crura, collapsed external nasal valves, warped grafts and struts, crooked L-shaped septal struts, and collapsed internal nasal valves. Twenty-nine cases were studied over a period of 10 to 23 months. The horizontal mattress suture proved to be a simple, effective means of achieving satisfactory control of the curvature of various cartilages of the nose (including external valves, internal valves, and septum) and warped cartilage grafts. Curvature control was obtained in all cases where the cartilage was supple. Moreover, the resultant strength was increased above normal. Partial recurrence of the curvature was seen in only two cases. Clinical results indicated that the horizontal mattress suture is universally applicable to a variety of situations in which the curvature of nasal cartilage and cartilage grafts needs to be removed or modified. The mattress suture drastically reduces the need for scoring (with its inherent problems of weakness) and the need for cartilage grafting.