The Global Distribution and Burden of Dengue and Japanese Encephalitis Co-Infection in Acute Encephalitis Syndrome

Dengue is widespread throughout the tropics globally in more than hundred countries and coincides with various climatic factors for co-infection with other flaviviral infections of the central nervous system (CNS). Dengue and Japanese encephalitis virus co-infection are highly prevalent, with diagnosis dilemma including significant mortality and morbidity in Southeast Asia. Both dengue and Japanese encephalitis transmissions intensify during the rainy season, during which the vector population increases. CNS involvement during dengue and Japanese encephalitis co-infection-associated acute encephalitis syndrome (AES) is still poorly understood, and therefore, there is a desperate need to understand the etiology, therapeutics, clinical management, and prevention of these tropically neglected diseases. AES can be differentiated from other etiologies of encephalopathy through considering its essential features: sudden onset of fever, cerebrospinal fluid (CSF) comprising inflammatory cells, magnetic resonance imaging (MRI)-based confirmation, and presence of pathogen or pathogen-specific antibodies. Complementary and alternative medicine is progressively being used globally and can be effective for the overall management of this co-infection

Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-Gingerol in cervical cancer cells

Human papilloma virus (HPV) expressing E6 and E7 oncoproteins, is known to inactivate the tumor suppressor p53 through proteasomal degradation in cervical cancers. Therefore, use of small molecules for inhibition of proteasome function and induction of p53 reactivation is a promising strategy for induction of apoptosis in cervical cancer cells. The polyphenolic alkanone, 6-Gingerol (6G), present in the pungent extracts of ginger (Zingiber officinale Roscoe) has shown potent anti-tumorigenic and pro-apoptotic activities against a variety of cancers. In this study we explored the molecular mechanism of action of 6G in human cervical cancer cells in vitro and in vivo. 6G potently inhibited proliferation of the HPV positive cervical cancer cells. 6G was found to: (i) inhibit the chymotrypsin activity of proteasomes, (ii) induce reactivation of p53, (iii) increase levels of p21, (iv) induce DNA damage and G2/M cell cycle arrest, (v) alter expression levels of p53-associated apoptotic markers like, cleaved caspase-3 and PARP, and (vi) potentiate the cytotoxicity of cisplatin. 6G treatment induced significant reduction of tumor volume, tumor weight, proteasome inhibition and p53 accumulation in HeLa xenograft tumor cells in vivo. The 6G treatment was devoid of toxic effects as it did not affect body weights, hematological and osteogenic parameters. Taken together, our data underscores the therapeutic and chemosensitizing effects of 6G in the management and treatment of cervical cancer

Transverse-momentum and event-shape dependence of D-meson flow harmonics in Pb–Pb collisions at √sNN = 5.02 TeV

The elliptic and triangular flow coefficients v2 and v3 of prompt D0, D+, and D∗+ mesons were measured at midrapidity (|y| < 0.8) in Pb–Pb collisions at the centre-of-mass energy per nucleon pair of √sNN = 5.02 TeV with the ALICE detector at the LHC. The D mesons were reconstructed via their hadronic decays in the transverse momentum interval 1 < pT < 36 GeV/c in central (0–10%) and semi-central (30–50%) collisions. Compared to pions, protons, and J/ψ mesons, the average D-meson vn harmonics are compatible within uncertainties with a mass hierarchy for pT 3 GeV/c, and are similar to those of charged pions for higher pT. The coupling of the charm quark to the light quarks in the underlying medium is further investigated with the application of the event-shape engineering (ESE) technique to the D-meson v2 and pT-differential yields. The D-meson v2 is correlated with average bulk elliptic flow in both central and semi-central collisions. Within the current precision, the ratios of per-event Dmeson yields in the ESE-selected and unbiased samples are found to be compatible with unity. All the measurements are found to be reasonably well described by theoretical calculations including the effects of charm-quark transport and the recombination of charm quarks with light quarks in a hydrodynamically expanding medium

Multiplicity dependence of inclusive J/ψ production at midrapidity in pp collisions at √s=13 TeV

Measurements of the inclusive J/ψ yield as a function of charged-particle pseudorapidity density dNch/dη in pp collisions at √s = 13 TeV with ALICE at the LHC are reported. The J/ψ meson yield is measured at midrapidity (|y| < 0.9) in the dielectron channel, for events selected based on the charged-particle multiplicity at midrapidity (|η| < 1) and at forward rapidity (−3.7 < η < −1.7 and 2.8 < η < 5.1); both observables are normalized to their corresponding averages in minimum bias events. The increase of the normalized J/ψ yield with normalized dNch/dη is significantly stronger than linear and dependent on the transverse momentum. The data are compared to theoretical predictions, which describe the observed trends well, albeit not always quantitatively