Human Genetics of Tricuspid Atresia and Univentricular Heart.

Tricuspid atresia (TA) is a rare congenital heart condition that presents with a complete absence of the right atrioventricular valve. Because of the rarity of familial and/or isolated cases of TA, little is known about the potential genetic abnormalities contributing to this condition. Potential responsible chromosomal abnormalities were identified in exploratory studies and include deletions in 22q11, 4q31, 8p23, and 3p as well as trisomies 13 and 18. In parallel, potential culprit genes include the ZFPM2, HEY2, NFATC1, NKX2-5, MYH6, and KLF13 genes. The aim of this chapter is to expose the genetic components that are potentially involved in the pathogenesis of TA in humans. The large variability in phenotypes and genotypes among cases of TA suggests a genetic network that involves many components yet to be unraveled.

Antibiotic duration and gastric dysmotility in preterm neonates.

OBJECTIVES: Prolonged antibiotic use after birth is associated with neonatal feeding intolerance and functional gastrointestinal disorders (FGIDs). A gastric dysrhythmia (tachygastria) with frequencies >4-9 cycles per minute, measured by electrogastrography (EGG), is associated with FGIDs. The relationship between prolonged antibiotic use and % time spent in tachygastria is unknown in preterm infants. We aimed to compare weekly changes in % tachygastria between preterm infants receiving long (>48 h) versus short (≤48 h) courses of antibiotics for early onset sepsis evaluation (initiated at <3 days of life). METHODS: This was a longitudinal, prospective cohort study of 88 preterm infants (<34 weeks' gestation) with weekly EGG recordings from the first week of life until 40 weeks' post-menstrual age, discharge, or death. We calculated % of EGG recording time in tachygastria and determined the mean across weekly sessions. A mixed effects model assessed variance in % tachygastria between the short- and long-antibiotic exposure groups across all weeks. RESULTS: Baseline characteristics were similar between the two groups. There was no difference in % tachygastria between short and long antibiotic exposure groups across nine postnatal weeks (p = 0.08). CONCLUSIONS: Early, prolonged antibiotic exposure among preterm infants may not lead to significant gastric dysrhythmia. Future studies including larger sample sizes and a "no antibiotic" exposure arm are essential in elucidating this potential relationship.

Biomarkers detected in cord blood predict vaccine responses in young infants.

Introduction: Factors influencing vaccine immune priming in the first year of life involve both innate and adaptive immunity but there are gaps in understanding how these factors sustain vaccine antibody levels in healthy infants. The hypothesis was that bioprofiles associated with B cell survival best predict sustained vaccine IgG levels at one year. Methods: Longitudinal study of plasma bioprofiles in 82 term, healthy infants, who received standard recommended immunizations in the United States, with changes in 15 plasma biomarker concentrations and B cell subsets associated with germinal center development monitored at birth, soon after completion of the initial vaccine series at 6 months, and prior to the 12-month vaccinations. Post vaccination antibody IgG levels to Bordetella pertussis, tetanus toxoid, and conjugated Haemophilus influenzae type B (HiB) were outcome measures. Results: Using a least absolute shrinkage and selection operator (lasso) regression model, cord blood (CB) plasma IL-2, IL-17A, IL-31, and soluble CD14 (sCD14) were positively associated with pertussis IgG levels at 12 months, while CB plasma concentrations of APRIL and IL-33 were negatively associated. In contrast, CB concentrations of sCD14 and APRIL were positively associated with sustained tetanus IgG levels. A separate cross-sectional analysis of 18 mother/newborn pairs indicated that CB biomarkers were not due to transplacental transfer, but rather due to immune activation at the fetal/maternal interface. Elevated percentages of cord blood switched memory B cells were positively associated with 12-month HiB IgG levels. BAFF concentrations at 6 and 12 months were positively associated with pertussis and HiB IgG levels respectively. Discussion: Sustained B cell immunity is highly influenced by early life immune dynamics beginning prior to birth. The findings provide important insights into how germinal center development shapes vaccine responses in healthy infants and provide a foundation for studies of conditions that impair infant immune development.

Awareness and attitudes of the Lebanese population with regard to physician-pharmaceutical company interaction: a survey study.

OBJECTIVE: To assess the awareness and attitudes of the general public in Lebanon regarding the interactions between physicians and pharmaceutical companies. SETTING: Primary healthcare clinics and shopping malls in the Greater Beirut Area. PARTICIPANTS: 263 participants completed the questionnaire, of whom 62% were female and 38% were male. Eligible participants were Arabic-speaking or English-speaking adults (age≥18 years) residing in Lebanon for at least 5 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Awareness, attitudes and beliefs of the general public. RESULTS: 263 out of 295 invited individuals (89% completion rate) completed the questionnaire. While the majority of participants were aware of pharmaceutical company presence (or absence) in physicians' offices (range of 71-76% across questions), smaller percentages were aware of gift-related practices of physicians (range of 26-69% across questions). 40% thought that the acceptance of small gifts or meals by physicians is wrong/unethical. The percentage of participants reporting lower trust in physicians due to their participation in various pharmaceutical company-related activities ranged from 12% to 45% (the highest percentage being for large gifts). Participants who reported receiving free medication samples were significantly more likely to consider physicians' acceptance of small gifts as 'not a problem' than 'unethical' (OR=1.53; p=0.044). CONCLUSIONS: Participants in our survey were generally more aware of pharmaceutical company presence (or absence) in physicians' offices than of gift-related practices of physicians. While the level of trust was not affected for the majority of participants for various types of interactions, it was affected the most for accepting large gifts.