Predictors of breastfeeding duration among women in Kuwait: results of a prospective cohort study

The purposes of this paper are to report the prevalence of breastfeeding to six months among women in Kuwait and to determine the factors that are associated with the duration of breastfeeding. A cohort of 373 women recruited from maternity wards in four hospitals in Kuwait city were followed from birth to 26 weeks postpartum. The association of any and full breastfeeding duration and predictor variables were explored using multivariate Cox’s proportional hazards models. At six months, 39% of all infants were receiving some breast milk and only 2% of infants had been fully breastfed to 26 weeks. Women born in other Arab countries were less likely to discontinue breastfeeding than women born in Kuwait. Other factors positively associated with breastfeeding duration were level of maternal education, higher parity, infant being demand fed in hospital and a preference for breastfeeding on the part of the infant’s father and maternal grandmother. The introduction of a pacifier before four weeks of age and the mother intending to return to work by six months were negatively associated with duration. These findings present a number of opportunities for prolonging breastfeeding duration in Kuwait

Weight gain and dietary intake during pregnancy in industrialized countries - a systematic review of observational studies

Background: Gestational weight gain (GWG) above the recently recommended ranges is likely to be related to adverse pregnancy outcomes and therefore a challenge in industrialized countries. Aims: We conducted a systematic review on observational studies in order to gain more evidence on whether diets with lower caloric/protein content or other diets might be associated with lower GWG. Methods: We searched in MEDLINE and EMBASE for observational studies written in English or German reporting associations between diet and GWG in singleton pregnancies of healthy women in industrialized countries. Results: We identified 12 studies which met the inclusion criteria. Five studies suggested significant positive associations between energy intake and GWG, whereas three found no significant association. Further significant positive associations of GWG were reported with respect to protein intake, animal lipids, energy density and a number of different food servings per day, whereas intake of carbohydrates and vegetarian diet were associated with less GWG. Conclusions: We suggest that GWG might be reduced by lower energy intake in pregnancy

Factorization and Nonfactorization in B Decays

Using NLL values for Wilson coefficients and including the contributions from the penguin diagrams, we estimate the amount of nonfactorization in two-body hadronic B decays. Also, we investigate the model dependence of the nonfactorization parameters by performing the calculation using different models for the form factors. The results support the universality of nonfactorizable contributions in both Cabibbo-favored and Cabibbo-suppressed B decays.Comment: 17 pages, 5 figures, revte

Triple-Product Correlations in B -> V1 V2$ Decays and New Physics

In this paper we examine T-violating triple-product correlations (TP's) in B -> V1 V2 decays. TP's are excellent probes of physics beyond the standard model (SM) for two reasons: (i) within the SM, most TP's are expected to be tiny, and (ii) unlike direct CP asymmetries, TP's are not suppressed by the small strong phases which are expected in B decays. TP's are obtained via the angular analysis of B -> V1 V2. In a general analysis based on factorization, we demonstrate that the most promising decays for measuring TP's in the SM involve excited final-state vector mesons, and we provide estimates of such TP's. We find that there are only a handful of decays in which large TP's are possible, and the size of these TP's depends strongly on the size of nonfactorizable effects. We show that TP's which vanish in the SM can be very large in models with new physics. The measurement of a nonzero TP asymmetry in a decay where none is expected would specifically point to new physics involving large couplings to the right-handed b-quark.Comment: 42 pages, LaTeX, no figures. Title changed, several explanatory paragraphs added, references added, analysis and conclusions unchange

Radio telemetry devices to monitor breathing in non-sedated animals

Radio telemetry equipment has significantly improved over the last 10-15 years and is increasingly being used in research for monitoring a variety of physiological parameters in non-sedated animals. The aim of this review is to provide an update on the current state of development of radio telemetry for recording respiration. Our literature review found only rare reports of respiratory studies via radio telemetry. Much of this article will hence report our experience with our custom-built radio telemetry devices designed for recording respiratory signals, together with numerous other physiological signals in lambs. Our current radio telemetry system allows to record 24 simultaneous signals 24h/day for several days. To our knowledge, this is the highest number of physiological signals, which can be recorded wirelessly. Our devices have been invaluable for studying respiration in our ovine models of preterm birth, reflux laryngitis, postnatal exposure to cigarette smoke, respiratory syncytial virus infection and nasal ventilation, all of which are relevant to neonatal respiratory problems

Temporal trends and lesion sets for persistent atrial fibrillation ablation: a meta-analysis with trial sequential analysis and meta-regression

BACKGROUND: Ablation for persistent atrial fibrillation (PsAF) has been performed for over 20 years, although success rates have remained modest. Several adjunctive lesion sets have been studied but none have become standard of practice. We sought to describe how the efficacy of ablation for PsAF has evolved in this time period with a focus on the effect of adjunctive ablation strategies. METHODS: Databases were searched for prospective studies of PsAF ablation. We performed meta-regression and trial sequential analysis. RESULTS: A total of 99 studies (15 424 patients) were included. Ablation for PsAF achieved the primary outcome (freedom of atrial fibrillation/atrial tachycardia rate at 12 months follow-up) in 48.2% (5% CI, 44.0-52.3). Meta-regression showed freedom from atrial arrhythmia at 12 months has improved over time, while procedure time and fluoroscopy time have significantly reduced. Through the use of cumulative meta-analyses and trial sequential analysis, we show that some ablation strategies may initially seem promising, but after several randomized controlled trials may be found to be ineffective. Trial sequential analysis showed that complex fractionated atrial electrogram ablation is ineffective and further study of this treatment would be futile, while posterior wall isolation currently does not have sufficient evidence for routine use in PsAF ablation. CONCLUSIONS: Overall success rates from PsAF ablation and procedure/fluoroscopy times have improved over time. However, no adjunctive lesion set, in addition to pulmonary vein isolation, has been conclusively demonstrated to be beneficial. Through the use of trial sequential analysis, we highlight the importance of adequately powered randomized controlled trials, to avoid reaching premature conclusions, before widespread adoption of novel therapies

Progressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems

Mutations in HACD1/PTPLA cause recessive congenital myopathies in humans and dogs. Hydroxyacyl-coA dehydratases are required for elongation of very long chain fatty acids, and HACD1 has a role in early myogenesis, but the functions of this striated muscle-specific enzyme in more differentiated skeletal muscle remain unknown. Canine HACD1 deficiency is histopathologically classified as a centronuclear myopathy (CNM). We investigated the hypothesis that muscle from HACD1-deficient dogs has membrane abnormalities in common with CNMs with different genetic causes. We found progressive changes in tubuloreticular and sarcolemmal membranes and mislocalized triads and mitochondria in skeletal muscle from animals deficient in HACD1. Furthermore, comparable membranous abnormalities in cultured HACD1-deficient myotubes provide additional evidence that these defects are a primary consequence of altered HACD1 expression. Our novel findings, including T-tubule dilatation and disorganization, associated with defects in this additional CNM-associated gene provide a definitive pathophysiologic link with these disorders, confirm that dogs deficient in HACD1 are relevant models, and strengthen the evidence for a unifying pathogenesis in CNMs via defective membrane trafficking and excitation-contraction coupling in muscle. These results build on previous work by determining further functional roles of HACD1 in muscle and provide new insight into the pathology and pathogenetic mechanisms of HACD1 CNM. Consequently, alterations in membrane properties associated with HACD1 mutations should be investigated in humans with related phenotypes

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation