Clinical spectrum and predictive risk factors of major infections in hospitalized children with nephrotic syndrome

This observational study was conducted with the primary objective of studying the incidence of major infections in nephrotic syndrome (NS), while the secondary objectives were to evaluate the risk factors for and the etiological spectrum of major infections. Eighty six children up to 13 years of age fulfilling the International Study of Kidney Disease in Children (ISKDC) criteria for NS, who required 101 hospital admissions were recruited from November 2010 to July 2012. Major infections were defined as those that are disseminated, affecting deep organs, requiring hospitalization or potentially life-threatening. The incidence of major infections was 36.6%. Among the major infections, peritonitis and pneumonia together accounted for 72.9%, while urinary tract infections and cellulitis accounted for 16.2%. On logistic regression, severe ascites and more severe clinical types of NS independently predicted major infections, while serum cholesterol >400 mg/dL was the sole predictor of peritonitis.     

Genomic medicine in non-small cell lung cancer: paving the path to personalized care

Lung cancer is the commonest cause of cancer-related mortality and non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancer. The prognosis of NSCLC remains poor across all stages, despite advances in staging techniques and treatments. The findings of recent high-throughput mRNA microarray studies have shown potential in refining current NSCLC diagnosis, classification, prognosis and treatment paradigms. Emerging microarray studies of microRNA, DNA copy number and methylation profiles are also providing novel insights into the biology of NSCLC. Currently there are several challenges, such as the reproducibility and cost of microarray platforms that will need to be addressed prior to the implementation of these genomic technologies to routine thoracic oncology practice. In addition, genomic tests (such as prognosis and prediction gene expression signatures) will need to be validated in well designed prospective studies that aim to answer clinically relevant questions. If successful, the integration of microarray-based genomic information with existing clinicopathological models may enhance the ability of clinicians to match the most effective treatment to an individual patient. Such a strategy may improve survival and reduce treatment-related morbidity in NSCLC patients.     

Nonunion in a distal radius metaphyseal fracture in a child: Role of intact periosteal sleeve in management

We present an adolescent with distal radius nonunion following an open fracture and failed surgery which eventually united when the length and stability was restored for eight weeks duration. The intact periosteal sleeve at the nonunion site formed new bone when its tension was restored by gradual differential distraction. This case report highlights the possibility of stimulating bony union in an established atrophic nonunion by distracting the minimally disturbed soft tissue and thick osteogenic periosteal envelope in the paediatric age group.     

Generation of cellular immunity to lymphocytic choriomeningitis virus is independent of CD1d1 expression.

CD1 molecules are cell surface glycoproteins, structurally similar to major histocompatibility complex (MHC) class I molecules. The murine CD1d1 molecule has been shown to be essential for the positive selection of a unique subpopulation of T cells [the natural killer (NK) T cells], as CD1d1-deficient mice lack NK T cells. These cells have recently been suggested to play an important role in the induction of innate immunity (i.e. NK cells) and the regulation of immune homeostasis. As such, it was asked whether NK T cells were necessary for the generation of cellular immunity to an acute virus infection. In these studies, the Armstrong strain of lymphocytic choriomeningitis virus (LCMV), a classic inducer of NK cells, and its pathogenic variant clone 13 were used. When NK-cell activity was assessed on day 3 post-LCMV infection, surprisingly, it was found that CD1d1-deficient mice could generate NK-cell activity at wild-type levels. Likewise, LCMV-specific cytotoxic T-lymphocyte (CTL) activity in CD1d1-deficient mice was indistinguishable from that generated in wild-type mice. Additionally, viral titres in the spleen (LCMV Armstrong) and blood (LCMV clone 13) of infected CD1d1-deficient mice were at comparable levels to those found in wild-type mice, as were virus infection-induced increases in cell surface H-2Kb in the spleen. Therefore, these results suggest that the LCMV-induced generation of NK-cell and virus-specific CTL activity, as well as viral clearance, are independent of CD1d1 expression.     

Real‐time measurement of hyperpolarized lactate production and efflux as a biomarker of tumor aggressiveness in an MR compatible 3D cell culture bioreactor

We have developed a 3D cell/tissue culture bioreactor compatible with hyperpolarized (HP) ¹³C MR and interrogated HP [1‐¹³C]lactate production and efflux in human renal cell carcinoma (RCC) cells. This platform is capable of resolving intracellular and extracellular HP lactate pools, allowing the kinetic measurement of lactate production and efflux in the context of cancer aggressiveness and response to therapy. HP ¹³C MR studies were performed on three immortalized human renal cell lines: HK2, a normal renal proximal tubule cell line from which a majority of RCCs arise, UMRC6, a cell line derived from a localized RCC, and UOK262, an aggressive and metastatic RCC. The intra‐ (Lac_in) and extracellular (Lac_ex) HP lactate signals were robustly resolved in dynamic ¹³C spectra of the cell lines due to a very small but reproducible chemical shift difference (0.031 ± 0.0005 ppm). Following HP [1‐¹³C]pyruvate delivery, the ratio of HP Lac_in/Lac_ex was significantly lower for UOK262 cells compared with both UMRC6 and HK2 cells due to a significant (p < 0.05) increase in the Lac_ex pool size. Lac_in/Lac_ex correlated with the MCT4 mRNA expression of the cell lines, and inhibition of MCT4 transport using DIDS resulted in a significant reduction in the HP Lac_ex pool size. The extension of these studies to living patient‐derived RCC tissue slices using HP [1,2‐¹³C₂]pyruvate demonstrated a similarly split lactate doublet with a high Lac_ex pool fraction; in contrast, only a single NMR resonance is noted for HP [5‐¹³C]glutamate, consistent with intracellular localization. These studies support the importance of lactate efflux as a biomarker of cancer aggressiveness and metastatic potential, and the utility of the MR compatible 3D cell/tissue culture bioreactor to study not only cellular metabolism but also transport. Additionally, this platform offers a sophisticated way to follow therapeutic interventions and screen novel therapies that target lactate export. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis of novel 4,5-dihydropyrrolo[1,2-a]quinoxalines,pyrrolo[1,2-a]quinoxalin]-2-ones and their antituberculosis and anticancer activity

A facile strategy was developed for the synthesis of biologically important 4,5-dihydropyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin]-2-ones by treating 2-(1H-pyrrol-1-yl)anilines with imidazo[1,2-a]pyridine-3-carbaldehyde or isatin, using amidosulfonic acid (NH₃SO₃) as a solid catalyst in water at room temperature. The protocol has been extended to electrophile ninhydrin. The catalyst could be recycled for six times without the loss of activity. The compounds were evaluated for their antituberculosis, antibacterial, and anticancer activities. It is worth noting that compounds 3d and 3e demonstrated a minimum inhibitory concentration value of 6.25 µM against Mycobacterium tuberculosis H37Rv, whereas compounds 3d , 3g , 5d , 5e , and 5i showed a remarkable inhibition of A549, DU145, HeLa, HepG2, MCF-7, and B16-F10 cell lines, respectively. Staphylococcus aureus was inhibited by compounds 5b , 5e , 5d , 5g , and 5l at 32 µg/ml.