The structure and organization within the membrane of the helices composing the pore-forming domain of Bacillus thuringiensis δ-endotoxin are consistent with an “umbrella-like” structure of the pore

The aim of this study was to elucidate the mechanism of membrane insertion and the structural organization of pores formed by Bacillus thuringiensis δ-endotoxin. We determined the relative affinities for membranes of peptides corresponding to the seven helices that compose the toxin pore-forming domain, their modes of membrane interaction, their structures within membranes, and their orientations relative to the membrane normal. In addition, we used resonance energy transfer measurements of all possible combinatorial pairs of membrane-bound helices to map the network of interactions between helices in their membrane-bound state. The interaction of the helices with the bilayer membrane was also probed by a Monte Carlo simulation protocol to determine lowest-energy orientations. Our results are consistent with a situation in which helices α4 and α5 insert into the membrane as a helical hairpin in an antiparallel manner, while the other helices lie on the membrane surface like the ribs of an umbrella (the “umbrella model”). Our results also support the suggestion that α7 may serve as a binding sensor to initiate the structural rearrangement of the pore-forming domain.     

Rotary-door flap in laryngotracheal reconstruction

A newly described vascularized myocutaneous flap based on the infrahyoid muscles is presented. The blood supply originating at the superior and inferior thyroid arteries is preserved. This flap is rotated axially, 180 degrees, to augment and resurface the lumen of the stenosed airway. Stenting is achieved by means of a silicone T tube topped by a custom-carved laryngeal stent. Hyoid transposition may be included when required. We successfully reconstructed 15 cases of laryngotracheal stenosis by this method. The regional flap provides a dependable, readily applicable technique for reconstruction of difficult laryngotracheal stenoses.     

Duration and outcome of persistent candidaemia in newborn infants

The aims of the study were to define the duration of candidaemia in newborn infants and to determine the incidence of persistent hospital-acquired candidaemia and its associated morbidity and mortality compared with non-persistent candidaemia. This retrospective study, included 56 neonates admitted to the neonatal intensive care unit from 1996 to 2000 who had one or more positive blood cultures for Candida spp. The most prevalent pathogen was Candida albicans (64.3%). Mean disease duration was 6.9 +/- 5.5 days (median 6 days). Twenty-nine patients (52%) had a positive blood culture for >5 days (persistent candidaemia). There were no statistically significant differences between the infants with persistent and non-persistent candidaemia in background or predisposing clinical factors. Fungal endocarditis was present in four patients (13.7%) with persistent disease and one patient (3.7%) with non-persistent disease (odds ratio 4.19), and uveitis developed in one patient. Ten patients (17.8%) died--five with persistent and five with non-persistent disease (P = 1.0). These findings indicate that persistent neonatal candidaemia may be associated with an increased risk of Candida endocarditis, but not with other complications or increased mortality.     

Perspective: chromosomal aneuploidy in leukemia--lessons from down syndrome

Abnormal number of chromosomes, aneuploidy, is the most common abnormality in leukemia and cancer. However, the casual relationship between aneuploidy and cancer is unclear. Additional copies of chromosome 21 are frequently found in leukemic cells. Constitutional trisomy 21 that characterizes Down Syndrome is associated with markedly increased risk for childhood leukemia. In this perspective I review recent studies that suggest that constitutional trisomy 21 promotes leukemic transformation during fetal hematopoiesis. As most of childhood leukemias arise in-utero, these studies are of general relevance to sporadic childhood leukemias.     

Talc sclerodhesis of persistent Morel-Lavallée lesions (posttraumatic pseudocysts): case report of 4 patients

Large posttraumatic pseudocysts are infamous for their tendency to recur despite repeated aspiration. The standard practice has been repeated extensive surgical debridement. To avoid the need for such treatment, talc was used to sclerose the lesion in 4 patients treated between 2000 and 2003. The patients were between the ages of 20 and 73 and had thigh and buttock pseudocysts that persisted for an average of 3 months. Talc was administered under fluoroscopic guidance and suction drainage (wall suction followed by a bulb vacuum drainage system) was applied for an average of 12 days. The patients were followed for an average period of 27 months after talc sclerodhesis. All persistent pseudocysts showed an immediate cessation of fluid accumulation in the treated space without reccurence. One case which was complicated by infection, had to be treated twice with talc to cease the accumulation. In this case, the infection recurred, although fluid accumulation did not recur. Talc sclerodhesis proved to be a simple and rapid method of treatment in posttraumatic cases classically treated by repeated and aggressive surgical methods.     

Insulin-like growth factor binding protein-1 detection in preterm labor: evaluation of a bedside test

Phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) is secreted by decidual cells and may leak into cervical secretions during detachment of the fetal membrane. The aim of this study was to determine whether a rapid bedside test for phIGFBP-1 predicts preterm birth in women with preterm uterine contractions. This was a prospective study of pregnant women who sought medical care for symptoms of preterm labor. Cervical swabs were assayed for the presence of phIGFBP-1 by a rapid bedside test. Sixty-four patients were enrolled. Eleven of them (17%) delivered preterm (< 35 weeks). phIGFBP-1 in cervical secretions predicted preterm birth with a sensitivity of 72.7%, a specificity of 83.0%, a positive predictive value of 47.0%, and negative predictive value of 93.6%. Positive phIGFBP-1 bedside test in women with preterm uterine contractions may indicate a significant risk for subsequent preterm birth. The absence of phIGBP-1 is a reassuring sign that the likelihood of preterm birth is low.     

Cancer incidence and survival among children and adolescents in Israel during the years 1998 to 2007

Our goal was to describe childhood cancer incidence and survival in Israel and to identify demographic and epidemiologic variations among children and adolescents with cancer. We used data from the Israel National Cancer Registry to examine the incidence and survival of pediatric cancer in Israeli children aged 0 to 19 years, diagnosed during the years 1998 to 2007. Cases were analyzed according to sex, age, ethnicity, and geographic region. Among the 4255 cases of childhood cancer, there was a total age-adjusted incidence rate of 172.4 per million for children aged 0 to 19 years and 153.4 per million for children aged 0 to 14 years. The incidence rate for boys was higher than for girls (192.5 and 153.3, respectively) and higher for Jewish children than for Arab children (177.6 and 156.8, respectively). The largest groups were leukemias (22%), lymphomas (20.2%), and central nervous system tumors (17.4%). The number of new cases increased each year, but the incidence rate remained steady. The survival probability updated to December 2008 was estimated and the 5-year survival was calculated for the new cases until the end of 2003. The overall survival at 5 years was 80.8%, with 72.8% for the Arabic population and 83.2% for the Jewish population, and depended on the diagnosis. Incidence and survival in childhood cancer in Israel is at the same medium level compared with other parts of the world. This study may set the basis for investigating the genetic and environmental factors that cause pediatric cancer in Israel, delineating the genetic basis for ethnic origin disparities in survival.     

Meta-analysis comparing Mediterranean to low-fat diets for modification of cardiovascular risk factors

Background

Evidence from individual trials comparing Mediterranean to low-fat diets to modify cardiovascular risk factors remains preliminary.

Methods

We systematically searched MEDLINE, EMBASE, Biosis, Web of Science, and the Cochrane Central Register of Controlled Trials from their inception until January 2011, as well as contacted experts in the field, to identify randomized controlled trials comparing Mediterranean to low-fat diets in overweight/obese individuals, with a minimum follow-up of 6 months, reporting intention-to-treat data on cardiovascular risk factors. Two authors independently assessed trial eligibility and quality.

Results

We identified 6 trials, including 2650 individuals (50% women) fulfilling our inclusion criteria. Mean age of enrolled patients ranged from 35 to 68 years, mean body mass index from 29 to 35 kg/m². After 2 years of follow-up, individuals assigned to a Mediterranean diet had more favorable changes in weighted mean differences of body weight (−2.2 kg; 95% confidence interval [CI], −3.9 to −0.6), body mass index (−0.6 kg/m²; 95% CI, −1 to −0.1), systolic blood pressure (−1.7 mm Hg; 95% CI, −3.3 to −0.05), diastolic blood pressure (−1.5 mm Hg; 95% CI, −2.1 to −0.8), fasting plasma glucose (−3.8 mg/dL, 95% CI, −7 to −0.6), total cholesterol (−7.4 mg/dL; 95% CI, −10.3 to −4.4), and high-sensitivity C-reactive protein (−1.0 mg/L; 95% CI, −1.5 to −0.5). The observed heterogeneity across individual trials could, by and large, be eliminated by restricting analyses to trials with balanced co-interventions or trials with restriction of daily calorie intake in both diet groups.

Conclusion

Mediterranean diets appear to be more effective than low-fat diets in inducing clinically relevant long-term changes in cardiovascular risk factors and inflammatory markers.