Invasive Obstetric Procedures and Cesarean Sections in Women With Known Herpes Simplex Virus Status During Pregnancy.

BackgroundNeonatal herpes is a potentially devastating infection that results from acquisition of herpes simplex virus (HSV) type 1 or 2 from the maternal genital tract at the time of vaginal delivery. Current guidelines recommend (1) cesarean delivery if maternal genital HSV lesions are present at the time of labor and (2) antiviral suppressive therapy for women with known genital herpes to decrease HSV shedding from the genital tract at the time of vaginal delivery. However, most neonatal infections occur in infants born to women without a history of genital HSV, making current prevention efforts ineffective for this group. Although routine serologic HSV testing of women during pregnancy could identify women at higher risk of intrapartum viral shedding, it is uncertain how this knowledge might impact intrapartum management, and a potential concern is a higher rate of cesarean sections among women known to be HSV-2 seropositive.MethodsTo assess the effects of prenatal HSV-2 antibody testing, history of genital herpes, and use of suppressive antiviral medication on the intrapartum management of women, we investigated the frequency of invasive obstetric procedures and cesarean deliveries. We conducted a retrospective cohort study of pregnant women delivering at the University of Washington Medical center in Seattle, Washington. We defined the exposure of interest as HSV-2 antibody positivity or known history of genital herpes noted in prenatal records. The primary outcome was intrapartum procedures including fetal scalp electrode, artificial rupture of membranes, intrauterine pressure catheter, or operative vaginal delivery (vacuum or forceps). The secondary outcome was incidence of cesarean birth. Univariate and multivariable logistic regressions were performed.ResultsFrom a total of 449 women included in the analysis, 97 (21.6%) were HSV-2 seropositive or had a history of genital herpes (HSV-2/GH). Herpes simplex virus-2/GH women not using suppressive antiviral therapy were less likely to undergo intrapartum procedures than women without HSV-2/GH (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.95; P = .036), but this relationship was attenuated after adjustment for potential confounders (adjusted OR, 0.69; 95% CI, 0.34-1.41; P = .31). There was no difference in intrapartum procedures for women on suppressive therapy versus women without HSV-2/GH (OR, 1.17; 95% CI, 0.66-2.07; P = .60). Similar proportions of cesarean sections were performed within each group of women: 25% without history of HSV-2/GH, 30% on suppressive treatment, and 28.1% without suppressive treatment (global, P = .73).ConclusionsIn this single-site study, provider awareness of genital herpes infection either by HSV serotesting or history was associated with fewer invasive obstetric procedures shown to be associated with neonatal herpes, but it was not associated with an increased rate of cesarean birth

Contribución a la identificación de esporas del Reino Fungi en la atmósfera de La Plata, Argentina

Based on the aeromycological analysis of La Plata city, artificial Morphological Groups of fungal spores were defined. This study is a methodological contribution to the identification and counting of a fraction of the atmospheric micobiota. For the definition of groups, the criteria of Saccardo (1886) were taken into account and the groupings created by Díaz et al. (1998) and Aira et al. (2005) have been reformulated. Four new groups have been created and other sporal types have been incorporated to previous classifications. Each of them includes 2 to 6 spore types belonging to the Phylum Zygomycota, Basidiomycota and Ascomycota and their anamorphs, assigned to generic level. Characters that define such associations are: Absidia Group, hyaline amerospores; Cortinarius Group, pigmented amerospores; Didymella Group, hyalines or slightly colored didymospores; Didymosphaeria Group, pigmented didymospores and didymoconidia; Leptosphaeria Group, hyaline to pigmented phragmospores and Helminthosporium Group, hyaline to pigmented distoseptated phragmoconidia. The aim of this work is to give a tool to facilitate the task of data processing by providing new qualitative elements to prior classifications and contributing to the complex problem of identification of fungal spores presents in atmosphere.A partir del análisis del registro aeromicológico de la ciudad de La Plata se propone la definición de Grupos Morfológicos de esporas del Reino Fungi. Este estudio constituye un aporte metodológico a la identificación y recuento de una fracción de la micobiota atmosférica. Para la definición de los grupos, se han tenido en cuenta los criterios de Saccardo (1886) y reformulado los agrupamientos de Díaz et al. (1998) y Aira et al. (2005). Se han creando 4 nuevos grupos y se han incorporando otros tipos esporales a las clasificaciones previas. Cada grupo, incluye entre 2 y 6 tipos de esporas pertenecientes a los Phylum Zygomycota, Basidiomycota y Ascomycota y sus anamorfos, que han sido asignados a nivel genérico. Los caracteres que definen dichas asociaciones son: Grupo Absidia, amerosporas hialinas; Grupo Cortinarius, amerosporas pigmentadas amigdaliformes; Grupo Didymella, didimosporas hialinas o levemente coloreadas; Grupo Didymosphaeria, didimosporas y didimoconidios pigmentados; Grupo Lepthosphaeria, fragmosporas septadas hialinas a pigmentadas y Grupo Helminthosporium, fragmosporas distoseptadas hialinas a pigmentadas. Esta investigación aspira a proporcionar una herramienta que facilite el procesamiento de datos y aporte nuevos elementos cualitativos a las clasificaciones previas, contribuyendo en la compleja problemática de identificación de las esporas fúngicas

Prevalence and characterization of methicillin-resistant Staphylococcus aureus among healthy children in a city of Argentina

Community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a major global problem. Healthy carriers of S. aureus strains have an important role in the dissemination of this bacterium. The aim of this study was to estimate the prevalence of S. aureus and methicillin-resistant S. aureus (MRSA) carriage among healthy children in a city of Buenos Aires province, Argentina, and to determine the potential risk factors for its acquisition. We also described the molecular features of MRSA strains circulating in this population. S. aureus carriage was investigated in all children attending the last year of kindergarten during the 2008 school- year period. Household contacts of MRSA carriers were also screened. Of 316 healthy children, 98 (31.0%) carried S. aureus, including 14 MRSA carriers (4.4%) and 84 methicillin susceptible S. aureus (MSSA) carriers (26.6%). All MRSA isolates carried the SCCmec type IV cassette. Eight of the fourteen isolates were closely related to the clone responsible for most severe community- acquired MRSA infections caused in our country (CAA: PFGE A, SCCmec IV, spa t311, ST5). Two subtypes (A1 and A2) were distinguished in this group by PFGE. Both had agr type II and presented the same virulence determinants, except for PVL coding genes and sea that were only harbored by subtype A1. Our results, based on the analysis of MRSA isolates recovered in the screening of healthy children, provide evidence of a community reservoir of the major CA-MRSA clone described in Argentina.Fil: Gardella, N.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Murzicato, S.. Hospital Municipal de San Antonio de Areco; ArgentinaFil: Di Gregorio, Sabrina Noelia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cuirolo, Arabela Ximena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Desse, J.. Hospital Paroissien; ArgentinaFil: Crudo, F.. Hospital Municipal de San Antonio de Areco; ArgentinaFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Mollerach, Marta Eugenia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Mild malformations of cortical development in sleep-related hypermotor epilepsy due to KCNT1 mutations

open14siMutations in the sodium-activated potassium channel gene KCNT1 have been associated with nonlesional sleep-related hypermotor epilepsy (SHE). We report the co-occurrence of mild malformation of cortical development (mMCD) and KCNT1 mutations in four patients with SHE. Focal cortical dysplasia type I was neuropathologically diagnosed after epilepsy surgery in three unrelated MRI-negative patients, periventricular nodular heterotopia was detected in one patient by MRI. Our findings suggest that KCNT1 epileptogenicity may result not only from dysregulated excitability by controlling Na+K+ transport, but also from mMCD. Therefore, pathogenic variants in KCNT1 may encompass both lesional and nonlesional epilepsies.openRubboli G.; Plazzi G.; Picard F.; Nobili L.; Hirsch E.; Chelly J.; Prayson R.A.; Boutonnat J.; Bramerio M.; Kahane P.; Dibbens L.M.; Gardella E.; Baulac S.; Moller R.S.Rubboli, G.; Plazzi, G.; Picard, F.; Nobili, L.; Hirsch, E.; Chelly, J.; Prayson, R. A.; Boutonnat, J.; Bramerio, M.; Kahane, P.; Dibbens, L. M.; Gardella, E.; Baulac, S.; Moller, R. S

Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding

Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required

Mesenchymal-epithelial signalling in tumour microenvironment: role of high-mobility group Box 1.

Glucose deprivation, hypoxia and acidosis are characteristic features of the central core of most solid tumours. Myofibroblasts are stromal cells present in many such solid tumours, including those of the colon, and are known to be involved in all stages of tumour progression. HMGB1 is a nuclear protein with an important role in nucleosome stabilisation and gene transcription; it is also released from immune cells and is involved in the inflammatory process. We report that the microenvironmental condition of glucose deprivation is responsible for the active release of HMGB1 from various types of cancer cell lines (HT-29, MCF-7 and A549) under normoxic conditions. Recombinant HMGB1 (10 ng/ml) triggered proliferation in myofibroblast cells via activation of PI3K and MEK1/2. Conditioned medium collected from glucose-deprived HT-29 colon cancer cells stimulated the migration and invasion of colonic myofibroblasts, and these processes were significantly inhibited by immunoneutralising antibodies to HMGB1, RAGE and TLR4, together with specific inhibitors of PI3K and MEK1/2. Our data suggest that HMGB1 released from cancer cells under glucose deprivation is involved in stimulating colonic myofibroblast migration and invasion and that this occurs through the activation of RAGE and TLR4, resulting in the activation of the MAPK and PI3K signalling pathways. Thus, HMGB1 might be released by cancer cells in areas of low glucose in solid tumours with the resulting activation of myofibroblasts and is a potential therapeutic target to inhibit solid tumour growth

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro

BACKGROUND: The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. METHODS: Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. RESULTS: Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. CONCLUSIONS: THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development of antiviral strategies utilizing non-psychoactive derivatives of THC

New Copy Number Variations in Schizophrenia

Genome-wide screenings for copy number variations (CNVs) in patients with schizophrenia have demonstrated the presence of several CNVs that increase the risk of developing the disease and a growing number of large rare CNVs; the contribution of these rare CNVs to schizophrenia remains unknown. Using Affymetrix 6.0 arrays, we undertook a systematic search for CNVs in 172 patients with schizophrenia and 160 healthy controls, all of Italian origin, with the aim of confirming previously identified loci and identifying novel schizophrenia susceptibility genes. We found five patients with a CNV occurring in one of the regions most convincingly implicated as risk factors for schizophrenia: NRXN1 and the 16p13.1 regions were found to be deleted in single patients and 15q11.2 in 2 patients, whereas the 15q13.3 region was duplicated in one patient. Furthermore, we found three distinct patients with CNVs in 2q12.2, 3q29 and 17p12 loci, respectively. These loci were previously reported to be deleted or duplicated in patients with schizophrenia but were never formally associated with the disease. We found 5 large CNVs (>900 kb) in 4q32, 5q14.3, 8q23.3, 11q25 and 17q12 in five different patients that could include some new candidate schizophrenia susceptibility genes. In conclusion, the identification of previously reported CNVs and of new, rare, large CNVs further supports a model of schizophrenia that includes the effect of multiple, rare, highly penetrant variants