GeneXpert MTB/RIF Version G4 for Identification of Rifampin-Resistant Tuberculosis in a Programmatic Setting

A recent Cochrane review estimated GeneXpert MTB/RIF specificity for rifampin resistance as 98% (95% confidence interval [CI], 97 to 99), based on results from earlier test versions. The measured positive predictive value of the new generation test from programmatic implementation in Cape Town, South Africa, was 99.5% (95% CI, 98.5 to 100), confirming excellent specificity.     

Quantification of the area and shunt volume of multiple,circular, and noncircular ventricular septal defects: A 2D/3D echocardiography comparison and real time 3D color Doppler feasibility determination study

Background

Quantification of defect size and shunt flow is an important aspect of ventricular septal defect (VSD) evaluation. This study compared three‐dimensional echocardiography (3DE) with the current clinical standard two‐dimensional echocardiography (2DE) for quantifying defect area and tested the feasibility of real time 3D color Doppler echocardiography (RT3D‐CDE) for quantifying shunt volume of irregular shaped and multiple VSDs.

Methods

Latex balloons were sutured into the ventricles of 32 freshly harvested porcine hearts and were connected with tubing placed in septal perforations. Tubing was varied in area (0.13–5.22 cm²), number (1–3), and shape (circle, oval, crescent, triangle). A pulsatile pump was used to pump “blood” through the VSD (LV to RV) at stroke volumes of 30–70 mL with a stroke rate of 60 bpm. Two‐dimensional echocardiography (2DE), 3DE, and RT3D‐CDE images were acquired from the right side of the phantom.

Results

For circular VSDs, both 2DE and 3DE area measurements were consistent with the actual areas (R² = 0.98 vs 0.99). For noncircular/multiple VSDs, 3DE correlated with the actual area more closely than 2DE (R² = 0.99 vs 0.44). Shunt volumes obtained using RT3D‐CDE positively correlated with pumped stroke volumes (R² = 0.96).

Conclusions

Three‐dimensional echocardiography (3DE) is a feasible method for determining VSD area and is more accurate than 2DE for evaluating the area of multiple or noncircular VSDs. Real‐time 3D color Doppler echocardiography (RT3D‐CDE) is a feasible method for quantifying the shunt volume of multiple or noncircular VSDs.     

Hematobiochemical effects of cadmium intoxication in male Japanese quail (Coturnix japonica) and its amelioration with silymarin and milk thistle

The present study was designed to investigate the toxico-pathological effect of cadmium (Cd) and its amelioration with silymarin (SL) and milk thistle (MT) in male Japanese quail (Coturnix japonica). A total of 144 male quail were divided into nine equal groups (A–I). Experimental feeds were offered to these groups containing different combinations of Cd chloride (Cd1: 150 and Cd2: 300?mg/kg feed), SL (250?mg/kg of feed), and MT (10?g/kg of feed). The duration of the experiment was 60 days. The physical parameters studied included feed intake and body weight. Hematobiochemical parameters included total protein, albumin, ALT, AST, creatinine, urea, hemoglobin, and hematocrit. The data were analyzed by analysis of variance (ANOVA) technique, and group means were compared by Duncan’s multiple range test. The body weight decreased significantly in Cd-treated groups while SL and MT ameliorated the toxic effects of Cd as compared to control group. The hemoglobin (Hb) concentration and hematocrit (Hct) values were decreased significantly in Cd2-treated group, while Hb and Hct decreased nonsignificantly in Cd1-treated group compared with control. Similar hematological findings were observed, when Cd was used in combinations with SL and MT. Urea, creatinine, and AST increased significantly, while ALT increased nonsignificantly in Cd-treated groups as compared to control group, while total protein, albumin, and globulin decreased significantly in Cd-treated groups as compared to control group. The SL and MT completely ameliorated these toxic effects at low dose of Cd; however, amelioration was partial at higher doses of Cd. These compounds (SL &; MT) might be used to ameliorate toxic effects of Cd in Japanese quail.     

Novel insights into the SLC7A11-mediated ferroptosis signaling pathways in preeclampsia patients: identifying pannexin 1 and toll-like receptor 4 as innovative prospective diagnostic biomarkers

Journal of Assisted Reproduction and Genetics - Ferroptosis is associated with oxidative stress (OS) and is caused by iron-dependent lipid-peroxidative damage, but its role in PE is unclear. The...     

Molecular Characterization of β-Thalassemia Mutations Via the Amplification Refractory Mutation System-Polymerase Chain Reaction Method at the North Waziristan Agency,Pakistan

β-Thalassemia (β-thal) is a monogenic disease characterized by mutations on the HBB gene, affecting the production of globin that results in hypochromic and microcytic anemia. The aim of this study was to determine the prevalence of six common β-thal mutations, and their frequency and inheritance pattern in affected populations of North Waziristan Agency, Pakistan. In this study, 130 blood samples from 37 unrelated β-thalassemic families having a minimum of one transfusion-dependent child with β-thal major (β-TM), were retrieved either from the Thalassaemia Centre for Women and Children Hospital Bannu or their home towns situated in Noth Waziristan Agency. All samples were analyzed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) using six allele-specific primers for the presence of the six β-thal mutations common in the Pakistani population. Of the six common mutations, our study demonstrated five HBB mutations comprising HBB: c.27_28insG, HBB: c.92+5G>C, HBB: c.126_129delCTTT, HBB: c.92+1G>T and HBB: c.17_18delCT from the families studied, while mutation HBB: c.47G>A [codon 15 (G>A)] was not detected in any of the studied families. Furthermore, the HBB: c.27_28insG and HBB: c.92+5G>C were noted to be the most common with frequencies of 42.85 and 31.42%, respectively. The findings of the present study may be useful in launching carrier screening and prenatal diagnosis (PND) programs by screening analyzed and other unanalyzed affected families for the possible presence of common mutations through the ARMS-PCR technique that will help to control the disease.     

Risk assessment of Pakistani individuals for diabetes (RAPID)

ObjectiveTo develop and evaluate a risk score to predict people at high risk of developing type 2 diabetes in Pakistan.MethodologyCross sectional data regarding primary prevention of diabetes in Pakistan. Diabetes risk score was developed by using simple parameters namely age, waist circumference, and family history of diabetes. Odds ratios of the model were used to assign a score value for each variable and the diabetes risk score was calculated as the sum of those scores.ResultsWe externally validated the score using two data from 1264 subjects and 856 subjects aged 25 years and above from two separate studies respectively. Validating this score using the first data from the second screening study gave an area under the receive operator characteristics curve [AROC] of 0.758. A cut point of 4 had a sensitivity of 47.0% and specificity of 88% and in the second data AROC is 0.7 with 44% sensitivity and 89% specificity.ConclusionsA simple diabetes risk score, based on a set of variables can be used for the identification of high risk individuals for early intervention to delay or prevent type 2 diabetes in Pakistani population.     

Spores of Clostridium engineered for clinical efficacy and safety cause regression and cure of tumors in vivo

Spores of some species of the strictly anaerobic bacteria Clostridium naturally target and partially lyse the hypoxic cores of tumors, which tend to be refractory to conventional therapies. The anti-tumor effect can be augmented by engineering strains to convert a non-toxic prodrug into a cytotoxic drug specifically at the tumor site by expressing a prodrug-converting enzyme (PCE). Safe doses of the favored prodrug CB1954 lead to peak concentrations of 6.3 μM in patient sera, but at these concentration(s) known nitroreductase (NTR) PCEs for this prodrug show low activity. Furthermore, efficacious and safe Clostridium strains that stably express a PCE have not been reported. Here we identify a novel nitroreductase from Neisseria meningitidis, NmeNTR, which is able to activate CB1954 at clinically-achievable serum concentrations. An NmeNTR expression cassette, which does not contain an antibiotic resistance marker, was stably localized to the chromosome of Clostridium sporogenes using a new integration method, and the strain was disabled for safety and containment by making it a uracil auxotroph. The efficacy of Clostridium-Directed Enzyme Prodrug Therapy (CDEPT) using this system was demonstrated in a mouse xenograft model of human colon carcinoma. Substantial tumor suppression was achieved, and several animals were cured. These encouraging data suggest that the novel enzyme and strain engineering approach represent a promising platform for the clinical development of CDEPT.