Neonatal and two-year outcomes after rupture of membranes before 25 weeks of gestation

Objective

To assess the impact of extreme preterm premature rupture of membranes (PPROM) <25 weeks of gestation on preterm child outcome.

Study design

Retrospective study comparing the neonatal and 2-year outcomes of infants exposed to extremely PPROM <25 weeks with a non-exposed group of neonates in a tertiary care referral centre located in Paris, France, between 2003 and 2007. All women with singleton pregnancy and PPROM between 15^0/7 and 24^6/7 weeks of gestation were recruited. For each infant born alive, the next inborn neonate matched for gestational age and sex was selected as a control among neonates born alive after spontaneous preterm labour with intact membranes. The main outcome measures were neonatal outcome assessed by a combined criterion of adverse neonatal outcomes and the two-year neurodevelopmental outcome assessed by developmental Brunet–Lézine tests and neurological examinations.

Results

In 78 cases of extremely PPROM, 22 live births occurred at a mean gestational age of 26^5/7 weeks. The percentage of neonates with adverse neonatal outcomes was significantly higher among PPROM than non-exposed cases (68.2 versus 27.3%). At 2 years of age, children from the PPROM group were more likely to have delayed acquisitions (64.3 versus 15.8%) and behavioural disorders (57.1 versus 15.8%). Mean Brunet–Lézine language score was significantly lower among those infants (78.9 versus 96.8).

Conclusion

PPROM <25 weeks is associated with increased neonatal mortality and morbidity and with increased risks of delayed acquisitions, behavioural disorders and lower language performance scores at 2 years in comparison with matched preterm neonates born after spontaneous preterm labour with intact membranes.     

Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice

Ebola virus is a Filoviridae that causes hemorrhagic fever in humans and induces high morbidity and mortality rates. Filoviruses are classified as “Category A bioterrorism agents”, and currently there are no licensed therapeutics or vaccines to treat and prevent infection. The Filovirus glycoprotein (GP) is sufficient to protect individuals against infection, and several vaccines based on GP are under development including recombinant adenovirus, parainfluenza virus, Venezuelan equine encephalitis virus, vesicular stomatitis virus (VSV) and virus-like particles. Here we describe the development of a GP Fc fusion protein as a vaccine candidate. We expressed the extracellular domain of the Zaire Ebola virus (ZEBOV) GP fused to the Fc fragment of human IgG1 (ZEBOVGP-Fc) in mammalian cells and showed that GP undergoes the complex furin cleavage and processing observed in the native membrane-bound GP. Mice immunized with ZEBOVGP-Fc developed T-cell immunity against ZEBOV GP and neutralizing antibodies against replication-competent VSV-G deleted recombinant VSV containing ZEBOV GP. The ZEBOVGP-Fc vaccinated mice were protected against challenge with a lethal dose of ZEBOV. These results show that vaccination with the ZEBOVGP-Fc fusion protein alone without the need of a viral vector or assembly into virus-like particles is sufficient to induce protective immunity against ZEBOV in mice. Our data suggested that Filovirus GP Fc fusion proteins could be developed as a simple, safe, efficacious, and cost effective vaccine against Filovirus infection for human use.     

Resistance training attenuates fat mass regain after weight loss in ovariectomized rats

Objective

The aim of the present study was to investigate the effects of maintaining only one of the two components of a food restriction (FR) + resistance training (RT) regimen on the regain of body weight and fat mass (liver and adipocytes) in ovariectomized (Ovx) rats.

Methods

Five week Ovx rats were submitted to a weight loss program consisting of a 26% FR combined with RT (OvxFR + RT) for 8 weeks. RT consisted of climbing a 1.5 m vertical grid with a load attached to the tail, 20–40 times with progressively increasing loads 4 times/week. Following this weight loss intervention, OvxFR + RT rats were sub-divided into 3 groups for an additional 5 weeks: 2 groups went back to a normal ad libitum feeding with or without RT and the other group kept only FR.

Results

Combined FR + RT program in Ovx rats led to lower body mass gain, liver triacylglycerol (TAG) levels, and fat mass gain compared to sedentary normally fed Ovx rats (P < 0.01). Stopping both FR and RT over a 5 week period resulted in the regain of body weight, intra-abdominal fat pad weight and liver TAG (P < 0.01). When only FR was maintained, the regain of body and fat pad weight as well as liver and plasma TAG concentrations was completely prevented. However, when only RT was maintained, regain in the aforementioned parameters was attenuated but not prevented (P < 0.05).

Conclusion

It is concluded that following a FR + RT weight loss program, continuation of only RT constitutes an asset to attenuate body weight and fat mass regain in Ovx rats; although the impact is less than the maintaining FR alone. These results suggest that, in post-menopausal women, RT is a positive strategy to reduce body weight and fat mass relapse.     

Giant basal cell carcinoma with regional lymph node and distant lung metastasis

The prevalence of metastatic basal cell carcinoma (MBCC) varies between 0.0028% and 0.55% of all cases. In total, more than 300 MBCC have been reported in the literature. We report the case of a 72 year old lady, who presented in September 2009 with a 10-year history of a progressively growing, giant, facial basal cell carcinoma (BCC). Clinical and imaging evaluations identified large local invasion with bone and meningeal involvement. Treatment consisted of an extensive surgery including left eye exenteration and meningeal resection followed by radiotherapy. A solitary lung metastasis was identified five months after the primary tumor resection. As the lesion remained solitary but had increased in size five months later, the patient finally accepted a surgical resection. A right upper-lobe pneumonectomy was performed and pathologic examination confirmed the metastasis as a MBCC.     

Impaired activation and costimulation of T CD4+ lymphocytes during chronic hepatitis C infection

Hepatitis C chronic infection occurs in 80% of the cases and eventually leads to cirrhosis and hepatocellular carcinoma. A deficient adaptive immune response has been described during chronic infection which contributes to viral persistence. This altered T cell response could be associated to deficient costimulation signals during priming of T cells. We have conducted an in vitro study to explore the activation phenomenon of CD4+ T cells focusing on costimulation via the CD28 receptor, associated to stimulation with purified Hepatitis C (HCV) core antigen. Our study involved the induction of CD69, CD25 and CD40L activation receptors, along with detection of intracellular cytokines such as IFN-gamma, TGF-beta and IL-10. Analysis was performed in chronically HCV infected patients, intrafamilial members of HCV-infected patients and healthy individuals. HCV core antigen induced CD40L expression in CD4+ cells from intrafamilial members, in contrast to chronically infected patients and control individuals. Association of CD28 crosslinking increased CD69 and IFN-gamma expression in chronically infected patients, suggesting a detriment in this signaling pathway. Additionally, an increased TGF-beta expression was observed in CD4+ cells from HCV-infected patients, which was corrected by addition of CD28 crosslinking. Our results may contribute to understand the underlying mechanism of T cell tolerance against HCV during chronic infection, and to provide new targets for the designing of therapeutic strategies to control the infection and to offer protective immunity against the virus.