To The Suburbs Of Baghdad: Clinton\u27s Extension Of The Southern Iraqi No-Fly Zone

In the early morning hours of September 3, 1996, the United States conducted military strikes against an old foe., Once again United States guns were discharging upon the nation of Iraq and its obstinate leader, Saddam Hussein

Mutations in STAT3 and IL12RB1 impair the development of human IL-17–producing T cells

The cytokines controlling the development of human interleukin (IL) 17–producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17–producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) β, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17–producing T cells. These data suggest that IL-12Rβ1– and STAT-3–dependent signals play a key role in the differentiation and/or expansion of human IL-17–producing T cell populations in vivo

Molecular analysis and intestinal expression of <it>SAR1 </it>genes and proteins in Anderson's disease (Chylomicron retention disease)

<p>Abstract</p> <p>Background</p> <p>Anderson's disease (AD) or chylomicron retention disease (CMRD) is a very rare hereditary lipid malabsorption syndrome. In order to discover novel mutations in the <it>SAR1B </it>gene and to evaluate the expression, as compared to healthy subjects, of the Sar1 gene and protein paralogues in the intestine, we investigated three previously undescribed individuals with the disease.</p> <p>Methods</p> <p>The <it>SAR1B, SAR1A </it>and <it>PCSK9 </it>genes were sequenced. The expression of the <it>SAR1B </it>and <it>SAR1A </it>genes in intestinal biopsies of both normal individuals and patients was measured by RTqPCR. Immunohistochemistry using antibodies to recombinant Sar1 protein was used to evaluate the expression and localization of the Sar1 paralogues in the duodenal biopsies.</p> <p>Results</p> <p>Two patients had a novel <it>SAR1B </it>mutation (p.Asp48ThrfsX17). The third patient, who had a previously described <it>SAR1B </it>mutation (p.Leu28ArgfsX7), also had a p.Leu21dup variant of the <it>PCSK9 </it>gene. The expression of the <it>SAR1B </it>gene in duodenal biopsies from an AD/CMRD patient was significantly decreased whereas the expression of the <it>SAR1A </it>gene was significantly increased, as compared to healthy individuals. The Sar1 proteins were present in decreased amounts in enterocytes in duodenal biopsies from the patients as compared to those from healthy subjects.</p> <p>Conclusions</p> <p>Although the proteins encoded by the <it>SAR1A </it>and <it>SAR1B </it>genes are 90% identical, the increased expression of the <it>SAR1A </it>gene in AD/CMRD does not appear to compensate for the lack of the SAR1B protein. The PCSK9 variant, although reported to be associated with low levels of cholesterol, does not appear to exert any additional effect in this patient. The results provide further insight into the tissue-specific nature of AD/CMRD.</p

High burden of recurrent cardiovascular events in heterozygous familial hypercholesterolemia: The French Familial Hypercholesterolemia Registry

International audienceBackground and aims: Cardiovascular risk is high in heterozygous familial hypercholesterolemia (HeFH). The objective of this study was to describe recurrent cardiovascular events in selected patients with HeFH attending lipid clinics in France. Methods: We included 781 patients with a clinical (Dutch Lipid Clinic Network score >= 6) or genetic diagnosis of HeFH who had experienced a first cardiovascular event (myocardial infarction, percutaneous coronary intervention or coronary bypass, unstable angina, stroke, peripheral arterial revascularization or cardiovascular death) and were enrolled in the French Familial Hypercholesterolemia Registry (November 2015 to March 2018). Results: The first cardiovascular event occurred at the mean age of 47 years (interquartile range 39-55) in a predominantly male population (72%); 48% of patients were on statin therapy. Overall, 37% of patients had at least one recurrent cardiovascular event (mean of 1.8 events per patient), of which 32% occurred in the 12 months after the index event; 55% of events occurred > 3 years after the first event. Mean LDL-C at the last clinic visit was 144 +/- 75 mg/dL (132 +/- 69 mg/dL for patients on high-potency statin therapy and 223 +/- 85 mg/dL for untreated patients). Conclusions: The rate of recurrent cardiovascular events was high in French patients with HeFH in secondary prevention. The detection of FH during childhood is crucial to prevent CV events at a young age by early initiating statin therapy. There is a clear urgent need to expand the actual very small target population which can be treated with the PCSK9 inhibitor in France

Survival and Morbidity of Preterm Children Born at 22 Through 34 Weeks’ Gestation in France in 2011

International audienceImportance Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. Objectives To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks’ gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. Design, Setting, and Participants The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks’ gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. Main Outcomes and Measures Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). Results A total of 0.7% of infants born before 24 weeks’ gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. Conclusions and Relevance The substantial improvement in survival in France for newborns born at 25 through 31 weeks’ gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard