Long‐Term Mechanical Circulatory Support in Pediatric Patients

This retrospective study reviews our results regarding the long‐term support in pediatric patients using two ventricular assist systems between January 2008 and April 2014. We implanted the Berlin Heart EXCOR in 29 patients (median age 3.4 years [interquartile range (IQR) 0.2–16.5], median weight 13 kg [IQR 4.2–67.2]). Twenty‐two patients (75.8%) received a left ventricular assist device. Three patients (10.3%) had single‐ventricle physiology. One patient (3.4%) had mechanical mitral valve prosthesis. The HeartWare System was implanted in nine patients. The median age was 15.6 years (IQR 12.2–17.9), and the median weight was 54.9 kg (IQR 27.7–66). In the Berlin Heart group, the median support time was 65 days (IQR 4–619), with 3647 days of cardiac support. Nineteen patients (65.5%) were transplanted, six patients (20.7%) recovered, one patient (3.4%) is on support, and three patients (10.3%) died on support. Survival rate was 89.7%. Fourteen blood pumps had been exchanged. Four patients (13.8%) had local signs of infection, and three patients (10.3%) had neurological complications. In the HeartWare group, the median support time was 180 days (IQR 1–1124), with 2839 days of cardiac support. Four patients (44.4%) had local signs of infection, and three (33.3%) had neurological complications. Eight patients (88.9%) have been transplanted, and one patient (11.1%) died on support. Survival rate was 88.9%. Excellent survival is possible after long‐term mechanical circulatory support in patients with two‐ and single‐ventricle physiology with a low rate of adverse events.     

The association between maternal height and pregnancy outcomes in twin gestations

Objective: We sought to assess the association between maternal height and the risk of preterm birth, fetal growth restriction and mode of delivery in twin gestations.

Study design: Cohort study of patients with twin pregnancies delivered from 2005 to 2014. We compared pregnancy outcomes between patients of short stature?≤159?cm to those of normal stature?≥160?cm. Patients with monoamniotic twins and major fetal anomalies were excluded. Pearson’s correlation, Chi-square and Student’s t-test were used as appropriate.

Results: Six hundred and sixty-six patients were included, 159 (23.9%) of whom had short stature (mean height 155.8?±?2.5?cm) and 507 (76.1%) of whom had normal stature (mean height 167.2?±?5.5?cm). There were no differences in outcomes between the groups in regards to preterm birth, gestational age (GA) at delivery, birth weight of either twin, preeclampsia, gestational diabetes or cesarean section rate. Results were similar when the groups were stratified by parity. As a continuous variable, maternal height did not correlate with GA at delivery (p=?0.388), cesarean delivery (p?=?0.522) nor the birth weight of the larger (p?=?0.206) or smaller (p?=?0.307) twin.

Conclusion: In twin pregnancies, maternal short stature is not associated with preterm birth, fetal growth restriction or cesarean section rate. This suggests that although anthropometric measurements have long been used to counsel patients in regards to outcomes, patients of short stature should be reassured that their height does not appear to lead to adverse twin pregnancy outcomes.     

Nutritional Status Prior to Laparoscopic Sleeve Gastrectomy Surgery

Background

Two main causes for nutrient deficiencies following bariatric surgery (BS) are pre-operative deficiencies and favoring foods with high-energy density and poor micronutrient content. The aims of this study were to evaluate nutritional status and gender differences and the prevalence of nutritional deficiencies among candidates for laparoscopic sleeve gastrectomy (LSG) surgery.

Methods

A cross-sectional analysis of pre-surgery data collected as part of a randomized clinical trial on 100 morbidly obese patients with non-alcoholic fatty liver disease (NAFLD) admitted to LSG surgery at Assuta Medical Center between February 2014 and January 2015. Anthropometrics, food intake, and fasting blood tests were evaluated during the baseline visit.

Results

One-hundred patients completed the pre-operative measurements (60 % female) with a mean age of 41.9?±?9.8 years and a mean BMI of 42.3?±?4.7 kg/m². Pre-operatively, deficiencies for iron, ferritin, folic acid, vitamin B1, vitamin B12, vitamin D, and hemoglobin were 6, 1, 1, 6, 0, 22, and 6 %, respectively. Pre-surgery, mean energy, protein, fat, and carbohydrate intake were 2710.7?±?1275.7 kcal/day, 114.2?±?48.5, 110.6?±?54.5, and 321.6?±?176.1 gr/day, respectively. The intakes for iron, calcium, folic acid, vitamin B12, and vitamin B1 were below the Dietary Reference Intake (DRI) recommendations for 46, 48, 58, 14, and 34 % of the study population, respectively.

Conclusion

We found a low prevalence of nutritional deficiencies pre-operatively except for vitamin D. Most micronutrient intake did not reach the DRI recommendations, despite high-caloric and macronutrient intake indicating a poor dietary quality.

     

Potential therapeutic value of TRPV1 and TRPA1 in diabetes mellitus and obesity

Diabetes mellitus and obesity, which is a major risk factor in the development of type 2 diabetes mellitus, have reached epidemic proportions worldwide including the USA. The current statistics and forecasts, both short- and long-term, are alarming and predict severe problems in the near future. Therefore, there is a race for developing new compounds, discovering new receptors, or finding alternative solutions to prevent and/or treat the symptoms and complications related to obesity and diabetes mellitus. It is well demonstrated that members of the transient receptor potential (TRP) superfamily play a crucial role in a variety of biological functions both in health and disease. In the recent years, transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) were shown to have beneficial effects on whole body metabolism including glucose homeostasis. TRPV1 and TRPA1 have been associated with control of weight, pancreatic function, hormone secretion, thermogenesis, and neuronal function, which suggest a potential therapeutic value of these channels. This review summarizes recent findings regarding TRPV1 and TRPA1 in association with whole body metabolism with emphasis on obese and diabetic conditions.     

Cryo-electron microscopy study of bacteriophage T4 displaying anthrax toxin proteins

The bacteriophage T4 capsid contains two accessory surface proteins, the small outer capsid protein (Soc, 870 copies) and the highly antigenic outer capsid protein (Hoc, 155 copies). As these are dispensable for capsid formation, they can be used for displaying proteins and macromolecular complexes on the T4 capsid surface. Anthrax toxin components were attached to the T4 capsid as a fusion protein of the N-terminal domain of the anthrax lethal factor (LFn) with Soc. The LFn-Soc fusion protein was complexed in vitro with Hoc(-)Soc(-)T4 phage. Subsequently, cleaved anthrax protective antigen heptamers (PA63)(7) were attached to the exposed LFn domains. A cryo-electron microscopy study of the decorated T4 particles shows the complex of PA63 heptamers with LFn-Soc on the phage surface. Although the cryo-electron microscopy reconstruction is unable to differentiate on its own between different proposed models of the anthrax toxin, the density is consistent with a model that had predicted the orientation and position of three LFn molecules bound to one PA63 heptamer.     

Modular architecture of the T4 phage superfamily: a conserved core genome and a plastic periphery

Among the most numerous objects in the biosphere, phages show enormous diversity in morphology and genetic content. We have sequenced 7 T4-like phages and compared their genome architecture. All seven phages share a core genome with T4 that is interrupted by several hyperplastic regions (HPRs) where most of their divergence occurs. The core primarily includes homologues of essential T4 genes, such as the virion structure and DNA replication genes. In contrast, the HPRs contain mostly novel genes of unknown function and origin. A few of the HPR genes that can be assigned putative functions, such as a series of novel Internal Proteins, are implicated in phage adaptation to the host. Thus, the T4-like genome appears to be partitioned into discrete segments that fulfil different functions and behave differently in evolution. Such partitioning may be critical for these large and complex phages to maintain their flexibility, while simultaneously allowing them to conserve their highly successful virion design and mode of replication.     

CFTR (ABCC7) is a hydrolyzable-ligand-gated channel

As the product of the gene mutated in cystic fibrosis, the most common genetic disease of Caucasians, CFTR is an atypical ABC protein. From an evolutionary perspective, it is apparently a relatively young member of the ABC family, present only in metazoans where it plays a critical role in epithelial salt and fluid homeostasis. Functionally, the membrane translocation process it mediates, the passive bidirectional diffusion of small inorganic anions, is simpler than the vectorial transport of larger more complex substrates (“allocrites”) by most ABC transporters. However, the control of the permeation pathway which cannot go unchecked is necessarily more stringent than in the case of the transporters. There is tight regulation by the phosphorylation/dephosphorylation of the unique CFTR R domain superimposed on the basic ABC regulation mode of ATP binding and hydrolysis at the dual nucleotide binding sites. As with other ABCC subfamily members, only the second of these sites is hydrolytic in CFTR. The phosphorylation and ATP binding/hydrolysis events do not strongly influence each other; rather, R domain phosphorylation appears to enable transduction of the nucleotide binding allosteric signal to the responding channel gate. ATP hydrolysis is not required for either the opening or closing gating transitions but efficiently clears the ligand-binding site enabling a new gating cycle to be initiated.