Georgia College & State University

About: Georgia College & State University is a education organization based out in Milledgeville, Georgia, United States. It is known for research contribution in the topics: Population & Higher education. The organization has 950 authors who have published 1591 publications receiving 37027 citations.

Activity and Mechanism of Action of HDVD, a Novel Pyrimidine Nucleoside Derivative with High Levels of Selectivity and Potency against Gammaherpesviruses

Abstract: A novel nucleoside analogue, 1-[(2S,4S-2-(hydroxymethyl)-1,3-dioxolan-4-yl]5-vinylpyrimidine-2,4(1H,3H)-dione, or HDVD, was evaluated against a wide variety of herpesviruses and was found to be a highly selective inhibitor of replication of the gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). HDVD had also a pronounced inhibitory activity against murine herpesvirus 68 (MHV-68) and herpes simplex virus 1 (HSV-1). In contrast, replication of herpesvirus saimiri (HVS), HSV-2, and varicella-zoster virus (VZV) was weakly inhibited by the compound, and no antiviral activity was determined against human cytomegalovirus (HCMV) and rhesus rhadinovirus (RRV). The HDVD-resistant virus phenotype contained point mutations in the viral thymidine kinase (TK) of HSV-1, MHV-68, and HVS isolates. These mutations conferred cross-resistance to other TK-dependent drugs, with the exception of an MHV-68 mutant (E358D) that exhibited resistance only to HDVD. HSV-1 and HVS TK-mutants isolated under selective pressure with bromovinyldeoxyuridine (BVDU) also showed reduced sensitivity to HDVD. Oral treatment with HDVD and BVDU was assessed in an intranasal model of MHV-68 infection in BALB/c mice. In contrast to BVDU treatment, HDVD-treated animals showed a reduction in viral DNA loads and diminished viral gene expression during acute viral replication in the lungs in comparison to levels in untreated controls. The valyl ester prodrug of HDVD (USS-02-71-44) suppressed the latent infection in the spleen to a greater extent than HDVD. In the present study, HDVD emerged as a highly potent antiviral with a unique spectrum of activity against herpesviruses, in particular, gammaherpesviruses, and may be of interest in the treatment of virus-associated diseases.

Novel coordination of lipopolysaccharide modifications in Vibrio cholerae promotes CAMP resistance.

Abstract: In the environment and during infection, the human intestinal pathogen Vibrio cholerae must overcome noxious compounds that damage the bacterial outer membrane. The El Tor and classical biotypes of O1 V. cholerae show striking differences in their resistance to membrane disrupting cationic antimicrobial peptides (CAMPs), such as polymyxins. The classical biotype is susceptible to CAMPs, but current pandemic El Tor biotype isolates gain CAMP resistance by altering the net charge of their cell surface through glycine modification of lipid A. Here we report a second lipid A modification mechanism that only functions in the V. cholerae El Tor biotype. We identify a functional EptA ortholog responsible for the transfer of the amino-residue phosphoethanolamine (pEtN) to the lipid A of V. cholerae El Tor that is not functional in the classical biotype. We previously reported that mildly acidic growth conditions (pH 5.8) downregulate expression of genes encoding the glycine modification machinery. In this report, growth at pH 5.8 increases expression of eptA with concomitant pEtN modification suggesting coordinated regulation of these LPS modification systems. Similarly, efficient pEtN lipid A substitution is seen in the absence of lipid A glycinylation. We further demonstrate EptA orthologs from non-cholerae Vibrio species are functional.

Mothers satisfaction with planned vaginal and planned cesarean birth

Abstract: We sought to describe maternal satisfaction with childbirth among women planning either cesarean or vaginal birth. We enrolled primiparous women planning cesarean birth and a comparison group planning vaginal birth. After delivery, the maternal subjective experience was assessed with a visual analogue satisfaction scale and the Salmon questionnaire, with scale scores for these aspects of the maternal experience of birth: fulfillment, distress, and difficulty. The sample included 160 women planning vaginal birth and 44 women planning cesarean. Eight weeks postpartum, women planning cesarean reported higher satisfaction ratings ( P = 0.023), higher scores for fulfillment ( P = 0.017), lower scores for distress ( P = 0.010), and lower scores for difficulty ( P < 0.001). The least favorable scores were associated with unplanned cesarean ( N = 48). Women planning cesarean reported a more favorable birth experience than women planning vaginal birth, due in part to low satisfaction associated with unplanned cesarean. Maternal satisfaction with childbirth may be improved by efforts to reduce unplanned cesarean, but also by support for maternal-choice cesarean.