Economic and Diagnostic Biomarker Tests of Neonatal Sepsis: A Prospective Study from a Tertiary Care Hospital in a Low-Income Country.

Background: Neonatal sepsis is a leading cause of morbidity and mortality in low-and middle-income countries (LMICs). There are several sophisticated biomarkers; however, they are still insufficient in precision. In this perspective, our study aims to search for a pragmatic diagnostic biomarker in the age category. Methods: A cross-sectional study was conducted over six months(April-September 2018). All neonates with a diagnosis of probable sepsis were included. Logistic regression analysis of demographic variables was done to elucidate any association with confirmed sepsis cases. The median with interquartile range (IQR)] and mean with standard deviation (SD) were calculated, and then compared. The area under the receiver operating characteristic curve (AUROC) of the commonly opted biomarker tests [distribution width of red blood cells (RDW) and platelets(PDW), mean platelet volume(MPV), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] was compared to the culture-confirmed case. Results: Of the 171 suspected sepsis subjects, we discovered a significant burden of newborn sepsis, with 18.7% of cases being culture-confirmed. 66 Early-onset sepsis(EOS) and 105 Late-onset sepsis(LOS) probable sepsis cases were enrolled. A higher incidence was revealed among male infants 24(14%) compared to females 8(4.7%). On logistic regression analysis, preterm birth [odds ratio (OR): 10.9, 95% confidence interval (CI): 4.5-26.9] and low birth weight (OR: 6.5, 95% CI: 2.4-17.9) were significantly associated. Coagulase-negative Staphylococcus aureus (CoNS) (n =6) among gram-positive, and Pseudomonas aeruginosa (n =6) was among gram-negative, were the leading etiologies. Escherichia coli (n =3) was the predominant bacteria in EOS subjects, while Pseudomonas aeruginosa (n =6) among LOS. Median interquartile range(IQR): platelet count 144.5(99-192), red cell distribution width 18(16.9-20), CRP 6(3-18.3); and mean ± SD: MPV (11.7 ± 1.7); PDW (15.2 ± 3.5) were attained, among confirmed cases. The AUROC, of biomarker tests was attained in the order: PDW(0.86) > MPV(0.81) > RDW(0.76) > CRP(0.67) > ESR(0.59); similarly, the cut-off order was >11.2, >10.4, >16.8, >2.9, >4.5, respectively. Conclusions: Our finding shows an increment in the width and volume of RBCand platelet: RDW, MPV, and PDW have a diagnostic role in neonatal sepsis.

A comparison of techniques to address the frequency of Helicobacter pylori positive dyspeptic patient.

OBJECTIVES: The study was aimed to compare the diagnostic techniques, for the detection of Helicobacter pylori infection, available in low-income countries, where molecular testing is not available or inaccessible to anyone. RESULTS: Of total enrolled patient, with the mean age of 41.4 ± 13.33 years, 24 (14 female; 10 male) were diagnosed to have been infected. The diagnosis was established based upon the gold standard test [either two of three tests: Rapid Urease Test (RUT), culture and histological examinations]. Of clinical presentation, the epigastric pain (75%) was the commonest; nevertheless, the endoscopic findings had shown an equivocal specificity since the larger percentile (58.3%) reported as normal findings, in a presumed dyspepsia. Based on the premise-with calculated sensitivity, specificity, and predictive values; the accuracy order observed as histology > RUT > serology > stool antigen test, in H. pylori detection from the clinical samples. The accuracy order of the diagnostic test may vary depending upon the laboratory settings and study population. Therefore, in reference to low-income countries, the clinicians must resort any available positive test so that the supporting positive rudiments would be an ancillary in augmenting the diagnostic accuracy.

Inhibiting G protein ßγ signaling blocks prostate cancer progression and enhances the efficacy of paclitaxel.

Aberrant activation of G protein-coupled receptors (GPCRs) is implicated in prostate cancer progression, but targeting them has been challenging because multiple GPCRs are involved in cancer progression. In this study, we tested the effect of blocking signaling via a hub through which multiple GPCRs converge - the G-protein Gßγ subunits. Inhibiting Gßγ signaling in several castration-resistant prostate cancer cell lines (i.e. PC3, DU145 and 22Rv1), impaired cell growth and migration in vitro, and halted tumor growth and metastasis in nude mice. The blockade of Gßγ signaling also diminished prostate cancer stem cell-like activities, by reducing tumorsphere formation in vitro and tumor formation in a limiting dilution assay in nude mice. Furthermore, Gßγ blockade enhanced the sensitivity of prostate cancer cells to paclitaxel treatment, both in vitro and in vivo. Together, our results identify a novel function of Gßγ in regulating prostate cancer stem-cell-like activities, and demonstrate that targeting Gßγ signaling is an effective approach in blocking prostate cancer progression and augmenting response to chemotherapy.

Grb7 and Filamin-a associate and are colocalized to cell membrane ruffles upon EGF stimulation.

Grb7 is an adaptor molecule mediating signal transduction from multiple cell surface receptors to diverse downstream pathways. Grb7, along with Grb10 and Grb14, make up the Grb7 protein family. This protein family has been shown to be overexpressed in certain cancers and cancer cell lines. Grb7 and a receptor tyrosine kinase, ErbB2, are overexpressed in 20-30% of breast cancers. Grb7 overexpression has been linked to enhanced cell migration and metastasis, although the participants in these pathways have not been fully determined. In this study, we report the Grb7 protein interacts with Filamin-a, an actin-crosslinking component of the cell cytoskeleton. Additionally, we have demonstrated the interaction between Grb7 and Flna is specific to the RA-PH domains of Grb7, and the immunoglobulin-like repeat 16-19 domains of Flna. We demonstrate that full-length Grb7 and Flna interact in the mammalian cellular environment, as well as in vitro. Immunofluorescent microscopy shows potential co-localization of Grb7 and Flna in membrane ruffles upon epidermal growth factor stimulation. These studies are amongst the first to establish a clear connection between Grb7 signaling and cytoskeletal remodeling.