Yield of dual endoscopy for positive fecal occult blood test

OBJECTIVES: Dual endoscopy is frequently performed on the same day in patients whose stools are found to be positive on fecal occult blood testing (FOBT). This is often done to localize the potential sources of GI bleed. The diagnostic yield of same day dual upper endoscopy (EGD) and lower endoscopy (colonoscopy) for the detection of positive FOBT is uncertain. In the era of cost-efficient medical practice, we investigated whether a more evidence-based and structured approach could be used to guide physicians to the workup of patients who present with positive FOBT. METHODS: We performed a retrospective analysis of 309 patients, and 260 patients from this population met our inclusion criteria. Inclusion criteria included FOBT without acute GI hemorrhage, hematochezia, or melena. Patients were required to have had EGD and colonoscopy within the same day (<24 h). RESULTS: Of 260 patients, a total of 135 (52%) patients had positive findings on colonoscopy and a total of 42 (16.1%) patients had positive findings on EGD. Sixteen (6.1%) had positive EGD and negative colonoscopy; 109 (42%) had positive colonoscopy and negative EGD; and 26 (10%) had positive findings on both EGD and colonoscopy. CONCLUSIONS: Colonoscopy should be chosen as the initial procedure of choice in the evaluation of patients who present with positive FOBT. Same day dual endoscopy does not seem to be cost-effective.     

Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations

Zika virus (ZIKV) is one of the mosquito borne flavivirus with several outbreaks in past few years in tropical and subtropical regions. The non-structural proteins of flaviviruses are suitable active targets for inhibitory drugs due to their role in pathogenicity. In ZIKV, the non-structural protein 5 (NS5) RNA-Dependent RNA polymerase replicates its genome. Here we have performed virtual screening to identify suitable ligands that can potentially halt the ZIKV NS5 RNA dependent RNA polymerase (RdRp). During this process, we searched and screened a library of ligands against ZIKV NS5 RdRp. The selected ligands with significant binding energy and ligand-receptor interactions were further processed. Among the selected docked conformations, top five was further optimized at atomic level using molecular dynamic simulations followed by binding free energy calculations. The interactions of ligands with the target structure of ZIKV RdRp revealed that they form strong bonds within the active sites of the receptor molecule. The efficacy of these drugs against ZIKV can be further analyzed through in-vitro and in-vivo studies.     

What works? Interventions for maternal and child undernutrition and survival

We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0.25 (95% CI 0.01-0.49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0.41 (0.05-0.76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0.45, 0.32-0.62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2.93-21.07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0.84, 0.74-0.95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment.     

Imaging-Based Diagnosis of Autosomal Dominant Polycystic Kidney Disease

The clinical use of conventional ultrasonography (US) in autosomal dominant polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic sensitivity, especially in at-risk subjects younger than 30 years of age. In this single-center prospective study, we compared the diagnostic performance of MRI with that of high-resolution (HR) US in 126 subjects ages 16–40 years born with a 50% risk of ADPKD who underwent both these renal imaging studies and comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control subjects without a family history of ADPKD completed the same imaging protocol. We analyzed 110 at-risk subjects whose disease status was unequivocally defined by molecular testing and 45 unaffected healthy control subjects. Using a total of >10 cysts as a test criterion in subjects younger than 30 years of age, we found that MRI provided both a sensitivity and specificity of 100%. Comparison of our results from HR US with those from a previous study of conventional US using the test criterion of a total of three or more cysts found a higher diagnostic sensitivity (approximately 97% versus approximately 82%) with a slightly decreased specificity (approximately 98% versus 100%) in this study. Similar results were obtained in test subjects between the ages of 30 and 40 years old. These results suggest that MRI is highly sensitive and specific for diagnosis of ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is both center- and operator-dependent.     

Super absorption of solar energy using a plasmonic nanoparticle based CdTe solar cell

Improving the photon absorption in thin-film solar cells with plasmonic nanoparticles is essential for the realization of extremely efficient cells with substantial cost reduction. Here, a comprehensive study of solar energy enhancement in a cadmium telluride (CdTe) thin-film solar cell based on the simple design of a square array of plasmonic titanium nanoparticles, has been reported. The excitation of localized plasmons in the metallic nanostructures together with the antireflection coating (ARC) significantly enhances the absorption of photons in the active CdTe layer. The proposed structure attained super absorption with a mean absorbance of more than 97.27% covering a wide range from visible to near-infrared (i.e., from 300 nm to 1200 nm), presenting a 90% absorption bandwidth over 900 nm, and the peak absorption is up to 99.9%. For qualitative analysis, the photocurrent density is also estimated for AM 1.5 solar illumination (global tilt), whose value reaches 40.36 mA cm⁻², indicating the highest value reported to date. The impact of nanoparticle dimensions, various metal materials, shapes, and random arrangement of nanoparticles on optical absorption are discussed in detail. Moreover, the angle insensitivity is essentially validated by examining the absorption performance with oblique incidences and it is found that the solar cell keeps high absorption efficiency even when the incidence angle is greater than 0°. Therefore, these findings suggest that the proposed broadband structure has good prospect in attaining high power conversion efficiency while reducing the device cost.

Improving the photon absorption in thin-film solar cells with plasmonic nanoparticles is essential for the realization of extremely efficient cells with substantial cost reduction.     

Clinical and economic burden of invasive fungal diseases in Europe: focus on pre-emptive and empirical treatment of Aspergillus and Candida species

Invasive fungal diseases (IFDs) have been widely studied in recent years, largely because of the increasing population at risk. Aspergillus and Candida species remain the most common causes of IFDs, but other fungi are emerging. The early and accurate diagnosis of IFD is critical to outcome and the optimisation of treatment. Rapid diagnostic methods and new antifungal therapies have advanced disease management in recent years. Strategies for the prevention and treatment of IFDs include prophylaxis, and empirical and pre-emptive therapy. Here, we review the available primary literature on the clinical and economic burden of IFDs in Europe from 2000 to early 2011, with a focus on the value and outcomes of different approaches.     

Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models

Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4⁺ T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8⁺ T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4⁺ T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models.     

Hypocapnia during hypoxic exercise and its impact on cerebral oxygenation,ventilation and maximal whole body O2 uptake

With hypoxic exposure ventilation is elevated through the hypoxic ventilatory response. We tested the hypothesis that the resulting hypocapnia reduces maximal exercise capacity by decreasing (i) cerebral blood flow and oxygenation and (ii) the ventilatory drive.