Lopinavir and atazanavir in pregnancy: comparable infant outcomes, virological efficacies and preterm delivery rates.

OBJECTIVES: The aim of the study was to identify differences in infant outcomes, virological efficacy, and preterm delivery (PTD) outcome between women exposed to lopinavir/ritonavir (LPV/r) and those exposed to atazanavir/ritonavir (ATV/r). METHODS: A retrospective case note review was carried out. The case notes of 493 women who conceived while on LPV/r or ATV/r or initiated LPV/r or ATV/r during pregnancy and who delivered between 1 September 2007 and 30 August 2012 were reviewed. Data collected included demographics, antiretroviral use, HIV markers, and pregnancy and infant outcomes. Infant outcomes, virological efficacies and PTD rates for LPV/r and ATV/r were compared. RESULTS: A total of 306 women received LPV/r (82 conceiving while on the drug and 224 commencing it post-conception) and 187 received ATV/r (96 conceiving while on the drug and 91 commencing it post-conception). Comparing the two protease inhibitors (PIs), viral suppression rates were similar and, in women starting antiretroviral therapy (ART) post-conception, the median times to first undetectable HIV viral load were not significantly different (P = 0.64). PTD rates did not differ by therapy overall (ATV/r, 13%; LPV/r, 14%) or when considering the timing of first exposure (conceiving on ART, P = 0.81; commencing ART in pregnancy, P = 0.08). Poor fetal outcomes were very uncommon. There were two transmissions, giving a mother-to-child transmission (MTCT) rate of 0.4% (95% confidence interval 0.05-1.5%). CONCLUSIONS: Both ART regimens were well tolerated and successful in preventing MTCT. No significant differences in tolerability or in pregnancy or infant outcomes were observed, which supports the provision of a choice of PI in pregnancy.

A case of oral ulceration and disseminated histoplasmosis in HIV infection.

A 51-year-old Malawian woman presented with persistent mouth ulceration and an eight-month history of non-specific respiratory symptoms. Histoplasma capsulatum was diagnosed on gum, gastric and lymph node biopsies. Identification of H. capsulatum prompted HIV testing and the patient tested positive with a CD4 count of 40 cells/mm(3). The diagnosis of histoplasmosis was delayed due to its unusual presentation.

The effect of betamethasone treatment on neuroactive steroid synthesis in a foetal Guinea pig model of growth restriction.

There are ongoing concerns that antenatal corticosteroids, which are administered to women at high risk of delivering preterm to reduce the incidence of respiratory distress syndrome, have adverse effects on foetal brain development and subsequent effects on behaviour and learning, when administered as repeated courses. The present study aimed to examine whether repeated betamethasone treatment alters the expression of the key-rate limiting enzyme, 5alpha-reductase, in the synthetic pathway of the potent neuroactive steroid allopregnanolone in the brain and placenta and whether this effect is potentiated in growth restricted foetuses. To investigate this, pregnant guinea pigs carrying either control (sham surgery) or growth-restricted foetuses were treated with vehicle or betamethasone (1 mg/kg/day) for 4 days prior to sacrifice (65d). Placental insufficiency was induced by the ablation of uterine artery branches supplying each placenta at mid gestation, resulting in foetal growth restriction characterised by 'brain sparing'. Real-time reverse transcriptase polymerase chain reaction was used to determine relative 5alpha-reductase type 1 and 2 mRNA expression in the placenta and brain. Immunohistochemistry was used to examine the glial fibrillary acidic protein (GFAP) expression in the subcortical white matter, CA1 and dentate regions of the hippocampus. 5alpha-reductase type 2 mRNA expression in the brain was markedly reduced by betamethasone treatment in male foetuses compared to vehicle-treated controls but not in female foetuses. In addition, 5alpha-reductase type 1 expression in the brain was increased by growth restriction and/or betamethasone treatment in female foetuses but expression in males foetuses did not increase. 5alpha-reductase type 2 expression in the placenta was markedly reduced by betamethasone treatment compared to vehicle-treated control. Intrauterine growth restriction and betamethasone treatment reduced GFAP expression in the CA1 region of the hippocampus in the brains of male but not female foetuses. These data indicate that betamethasone treatment suppresses placental expression and has sexually dimorphic effects on expression of neuroactive steroid synthetic enzymes in the brain. These actions may lead to adverse effects on the developing brain, particularly in male foetuses, such as the observed effects on GFAP expression.

QTL associated with Fusarium head blight resistance in the soft red winter wheat Ernie.

Fusarium head blight (FHB), mainly caused by Fusarium graminearum Schwabe [telomorph: Gibberella zeae Schw. (Petch)], is an increasingly important disease of wheat (Triticum aestivum L.). Host-plant resistance provides the best hope for reducing economic losses associated with FHB, but new sources of resistance are limited. The moderately resistant winter wheat cultivar, Ernie, may provide a source of resistance that differs from Sumai 3 but these genes have not been mapped. Also hindering resistance breeding may be associations of resistance with agronomic traits such as late maturity that may be undesirable in some production environments. This research was conducted to identify QTL associated with type II FHB resistance (FHB severity, FHBS), and to determine if they are associated with days to anthesis (DTA), number of spikelets (NOS), and the presence/absence of awns. Two hundred and forty-three F(8) recombinant inbred lines from a cross between the resistant cultivar, Ernie and susceptible parent, MO 94-317 were phenotyped for type II FHB resistance using point inoculation in the greenhouse during 2002 and 2003. Genetic linkage maps were constructed using 94 simple sequence repeat (SSR) and 146 amplified fragment length polymorphic (AFLP) markers. Over years four QTL regions on chromosomes 2B, 3B, 4BL and 5A were consistently associated with FHB resistance. These QTL explained 43.3% of the phenotypic variation in FHBS. Major QTL conditioning DTA and NOS were identified on chromosome 2D. Neither the QTL associated with DTA and NOS nor the presence/absence of awns were associated with FHB resistance in Ernie. Our results suggest that the FHB resistance in Ernie appears to differ from that in Sumai 3, thus pyramiding the QTL in Ernie with those from Sumai 3 could result in enhanced levels of FHB resistance in wheat.

Inheritance of Fusarium head blight resistance in the soft red winter wheat Ernie.

Fusarium head blight (FHB), caused by Fusarium graminearum Schwabe [telomorph:Gibberella zeae Schw. (Petch)], is an increasingly important disease of wheat (Triticum aestivum L.). Host-plant resistance is considered to be the most economical means of control, but a lack of unique sources of resistance has hindered efforts to breed resistant varieties. The soft red winter wheat, Ernie, has moderately high FHB resistance and is widely used in U.S. breeding programs; however, the genetics of resistance have not been studied. The objectives of this study were to estimate the genetic effects, gene numbers, and heritability for traits related to FHB resistance in Ernie through generation means analyses and variance analyses of 243 F3-derived F8 and F9 recombinant inbred lines (RILs). Replicated experiments were grown in the greenhouse, inoculated with F. graminearum, and evaluated for disease spread and the FHB index (FHBI). The latter was calculated as the percentage of diseased spikelets in inoculated spikes and is often referred to as type-II resistance. Gene action for both disease spread and FHBI was primarily additive with partial dominance for low disease. Broad-sense heritabilities for spread and FHBI were 78.2% and 78.3%, respectively, while the narrow-sense heritabilities were 51.3% and 55.4%, respectively. Line-mean heritabilities from analyses of variance of RILs were 0.70 and 0.87 for spread and FHBI, respectively. A minimum of four genes conditioned both disease spread and FHBI. These results suggest that breeders should be able to enhance FHB resistance by combining the resistance in Ernie with other complementary additive sources of resistance.

Evaluation of Components of Fusarium Head Blight Resistance in Soft Red Winter Wheat Germ Plasm Using a Detached Leaf Assay.

A large environmental influence on phenotypic estimates of disease resistance and the complex polygenic nature of Fusarium head blight (FHB) resistance in wheat (Triticum aestivum) are impediments to developing resistant cultivars. The objective of this research was to investigate the utility of a detached leaf assay, inoculated using inoculum from isolates of Microdochium nivale var. majus, to identify components of FHB resistance among 30 entries of U.S. soft red winter wheat in the 2002 Uniform Southern FHB Nursery (USFHBN). Whole plant FHB resistance of the USFHBN entries was evaluated in replicated, mist-irrigated field trials at 10 locations in eight states during the 2001-2002 season. Incubation period (days from inoculation to the first appearance of a dull gray-green water-soaked lesion) was the only detached leaf variable significantly correlated across all FHB resistance parameters accounting for 45% of the variation in FHB incidence, 27% of FHB severity, 30% of Fusarium damaged kernels, and 26% of the variation in grain deoxynivalenol (DON) concentration. The results for incubation period contrasted with previous studies of moderately resistant European cultivars, in that longer incubation period was correlated with greater FHB susceptibility, but agreed with previous findings for the Chinese cultivar Sumai 3 and CIMMYT germ plasm containing diverse sources of FHB resistance. The results support the view that the detached leaf assay method has potential for use to distinguish between specific sources of FHB resistance when combined with data on FHB reaction and pedigree information. For example, entry 28, a di-haploid line from the cross between the moderately resistant U.S. cultivar Roane and the resistant Chinese line W14, exhibited detached leaf parameters that suggested a combination of both sources of FHB resistance. The USFHBN represents the combination of adapted and exotic germ plasm, but four moderately resistant U.S. commercial cultivars (Roane, McCormick, NC-Neuse, and Pat) had long incubation and latent periods and short lesion lengths in the detached leaf assay as observed in moderately FHB resistant European cultivars. The dichotomy in the relationship between incubation period and FHB resistance indicates that this may need to be considered to effectively combine exotic and existing/adapted sources of FHB resistance.