Bacteriological Profile and Outcome of Culture-Positive Neonatal Sepsis in a Special Newborn Care Unit Setting, Odisha.

INTRODUCTION: Nearly one-third of neonatal mortality in India is due to neonatal sepsis and death occurs in 30% of culture-positive neonates. Pathogens such as Klebsiella pneumoniae and Escherichia coli are the most common bacteria responsible for neonatal sepsis in India and South Asia. MATERIALS AND METHODS: It was an observational study, conducted in special newborn care units (SNCUs) of Capital Hospital in Bhubaneswar, Odisha from May 2017 to October 2019. All neonates (<28 days of life) with blood culture-positive sepsis were included in this study. Blood cultures were sent in all the babies with features of clinical sepsis. The demographic profile of neonates, clinical presentations, isolated organisms, and their sensitive patterns was recorded for analysis. RESULTS: Blood culture was sent in 445 suspected neonates with clinical sepsis out of which 115 blood culture positive organisms were isolated. Among the isolated organisms, 42 (35.6%) cases were Staphylococcus aureus followed by Coagulase negative Staphylococcus (CONS) (20.8%), E. coli (19.1%), K. pneumoniae (10.4%), Acinetobacter baumannii (2.7%), Enterobacter spp.(4.3%), Enterococcus spp. (4.3%), and Pseudomonas aeruginosa (2.7%). S. aureus was the predominant organism found in both early and late-onset sepsis. All Gram-negative bacilli (GNB) are resistant to ampicillin whereas cephalosporin resistance was found in 68% of cases. Mortality due to sepsis was 8%. CONCLUSION:  S. aureus followed by CONS was found to be the most common cause of sepsis in SNCU. A high degree of resistance of organisms to penicillins and cephalosporins calls for a re-evaluation of antibiotic policy and protocols for empirical treatment in neonatal sepsis.

Robust Second-Order Consensus Using a Fixed-Time Convergent Sliding Surface in Multiagent Systems.

Faster convergence is always sought in many applications. Designing fixed-time control has recently gained much attention since, for this type of control structure, the convergence time of the states does not depend on initial conditions, unlike other control methods providing faster convergence. This paper proposes a new distributed algorithm for second-order consensus in multiagent systems by using a full-order fixed-time convergent sliding surface. The stability analysis is performed using the Lyapunov function and bi-homogenous property. Moreover, the proposed control is smooth and free from any singularity. The robustness of the proposed scheme is verified both in the presence of Lipschitz disturbances and uncertainties in the network. The proposed method is compared with a state-of-the-art method to show the effectiveness.

Photostimulable near-infrared persistent luminescent nanoprobes for ultrasensitive and longitudinal deep-tissue bio-imaging.

In vivo fluorescence imaging suffers from suboptimal signal-to-noise ratio and shallow detection depth, which is caused by the strong tissue autofluorescence under constant external excitation and the scattering and absorption of short-wavelength light in tissues. Here we address these limitations by using a novel type of optical nanoprobes, photostimulable LiGa5O8:Cr(3+) near-infrared (NIR) persistent luminescence nanoparticles, which, with very-long-lasting NIR persistent luminescence and unique photo-stimulated persistent luminescence (PSPL) capability, allow optical imaging to be performed in an excitation-free and hence, autofluorescence-free manner. LiGa5O8:Cr(3+) nanoparticles pre-charged by ultraviolet light can be repeatedly (>20 times) stimulated in vivo, even in deep tissues, by short-illumination (~15 seconds) with a white light-emitting-diode flashlight, giving rise to multiple NIR PSPL that expands the tracking window from several hours to more than 10 days. Our studies reveal promising potential of these nanoprobes in cell tracking and tumor targeting, exhibiting exceptional sensitivity and penetration that far exceed those afforded by conventional fluorescence imaging.

Cyclosporin A and FK506 inhibit IL-12p40 production through the calmodulin/calmodulin-dependent protein kinase-activated phosphoinositide 3-kinase in lipopolysaccharide-stimulated human monocytic cells.

Cyclosporine-A (CyA) and FK506 are potent immunosuppressive agents because of their ability to suppress the production of Th1 cytokines including interleukin (IL)-12. However, the mechanisms underlying the inhibitory effects of CyA and FK506 on the production of IL-12p40, a critical component of IL-12, remain unknown. Both CyA and FK506 are potent inhibitors of calcineurin in the calcium signaling pathway. Interestingly, calcium and phosphoinositide 3-kinase (PI3K) signaling pathways have been shown to negatively regulate lipopolysaccharide (LPS)-induced murine IL-12p40 production. Contrary to these observations, we show that LPS-induced IL-12p40 production in human monocytic cells is positively regulated by the calcium pathway and in particular by calmodulin-(CaM) and CaM-dependent protein kinase-II (CaMK-II)-activated PI3K. Furthermore, LPS-induced IL-12p40 production was regulated by the p110alpha catalytic subunit of PI3K. Moreover, LPS induced IL-12p40 production through the CaM/CaMK-II-activated NFkappaB and AP-1 transcription factors. LPS-induced IL-12p40 production is known to be regulated by the c-Jun N-terminal kinase (JNK) pathway. Importantly, both CyA and FK506 down-regulated LPS-induced IL-12p40 transcription by inhibiting CaM/CaMK-II-activated PI3K and their downstream transcription factors NFkappaB and AP-1 independent of the JNK pathway.

Activation of JNK-dependent pathway is required for HIV viral protein R-induced apoptosis in human monocytic cells: involvement of antiapoptotic BCL2 and c-IAP1 genes.

Human immunodeficiency virus (HIV) accessory protein viral protein R (Vpr) plays a key role in virus replication and induces cell cycle arrest and apoptosis in various cell types including T cells and neuronal and tumor cells following infection with Vpr-expressing HIV isolates or exposure to the extracellular Vpr protein. The C-terminal Vpr peptide encompassing amino acids 52-96 (Vpr-(52-96)) is required for exerting the apoptotic effects, whereas the N-terminal Vpr-(1-45) peptide is responsible for virus transcription. We demonstrate that Vpr-(52-96) induced apoptosis in human promonocytic THP-1 cells and primary monocytes through the mitochondrial pathway in a caspase-dependent manner. To understand the regulation of Vpr-induced apoptosis, we investigated the signaling pathways, particularly the MAPKs, and the transcription factors involved. Although both Vpr-(52-96) and Vpr-(1-45) peptides induced phosphorylation of all the three members of the MAPKs, Vpr-(52-96)-activated JNK selectively induced apoptosis in monocytic cells through the mitochondrial pathway as determined by using JNK inhibitors SP60025, dexamethasone, curcumin, and JNK-specific small interfering RNAs. Furthermore Vpr-(52-96)-induced apoptosis was mediated by inhibition of downstream antiapoptotic Bcl2 and c-IAP1 genes whose expression could be restored following pretreatment with JNK-specific inhibitors. Overall the results suggest that Vpr-(52-96)-activated JNK plays a key role in inducing apoptosis through the down-regulation of antiapoptotic Bcl2 and c-IAP1 genes.

Distinct role of calmodulin and calmodulin-dependent protein kinase-II in lipopolysaccharide and tumor necrosis factor-alpha-mediated suppression of apoptosis and antiapoptotic c-IAP2 gene expression in human monocytic cells.

Exposure of phagocytic cells to bacterial endotoxin (lipopolysaccharide; LPS) or inflammatory cytokines confers antiapoptotic survival signals; however, in the absence of the appropriate stimulus, monocytes are programmed to undergo apoptosis. Macrophage survival may thus influence inflammatory and immune responses and susceptibility to microbial pathogens. Herein, we demonstrate that LPS and the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), enhance monocytic cell survival through the induction of the antiapoptotic c-IAP2 gene in a human promonocytic THP-1 cell line. We also investigated the role of upstream signaling molecules including the mitogen-activated protein kinases, phosphatidylinositol 3-kinase, and the calcium signaling pathways in the regulation of c-IAP2 expression and eventual survival of monocytic cells. Our results suggest that LPS and TNF-alpha-induced c-IAP2 expression was regulated by calmodulin (CaM) through the activation of calmodulin-dependent protein kinase-II (CaMKII). In addition, CaM and CaMKII regulated c-IAP2 expression in LPSand TNF-alpha-stimulated cells through NF-kappaB activation. Moreover, the CaM/CaMKII pathway also regulated LPS- and TNF-alpha-mediated inhibition of apoptosis in these cells. Taken together, these results suggest that LPS- and TNF-alpha-induced c-IAP2 expression and its associated antiapoptotic survival signals in THP-1 cells are regulated selectively by CaM/CaMKII through NF-kappaB activation.

Differential involvement of calmodulin-dependent protein kinase II-activated AP-1 and c-Jun N-terminal kinase-activated EGR-1 signaling pathways in tumor necrosis factor-alpha and lipopolysaccharide-induced CD44 expression in human monocytic cells.

CD44 plays a crucial role in cell migration, inflammation, and immune responses. Alteration in the levels of CD44 expression on monocytic cells by endotoxins and immunoregulatory cytokines may modulate the migration of immune cells to inflammatory sites and the development of immune responses. Lipopolysaccharide (LPS) and the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), act as important regulators of CD44 expression in human monocytic cells. We previously demonstrated that the c-Jun N-terminal kinase (JNK), a mitogen-activated protein kinase (MAPK), differentially regulated LPS- but not TNF-alpha-induced CD44 expression in monocytic cells. In this study, our results suggest that the calcium signaling pathway, in particular calmodulin (CaM) and CaM-dependent protein kinase II (CaMK-II), is involved in TNF-alpha- but not LPS-induced CD44 expression. CD44 promoter analysis suggested the participation of distinct transcription factors AP-1 and Egr-1 in TNF-alpha- and LPS-induced CD44 expression, respectively. Furthermore, TNF-alpha-induced CD44 expression was regulated by AP-1 through the activation of the CaMK-II pathway, whereas LPS-induced CD44 transcription was regulated specifically by Egr-1 through JNK activation. Overall, the results suggest the involvement of two distinct and independent signaling pathways involved in the regulation of CD44 transcription that may represent potential targets for anti-inflammatory agents capable of inhibiting CD44-mediated cell migration.