FIBCD1 ameliorates weight loss in chemotherapy-induced murine mucositis.

PURPOSE: Chemotherapy-induced gastrointestinal toxicity is a common adverse event during chemotherapeutic treatment. No uniformly applicable strategies exist to predict, prevent, or treat gastrointestinal toxicity. Thus, a goal of mucositis research is to identify targets for therapeutic interventions and individualized risk prediction. Fibrinogen C domain containing 1 (FIBCD1) is a transmembrane protein expressed in human intestinal epithelial cells with functions in the innate immune system. Previous observations have shown that FIBCD1 ameliorates dextran sulfate sodium (DSS)-induced intestinal inflammation in vivo. We evaluated the effect of FIBCD1 in a murine model of chemotherapy-induced gastrointestinal toxicity and inflammation. METHODS: Transgenic (Tg) mice overexpressing FIBCD1 in the intestinal epithelium (Fibcd1Tg) and wild-type (WT) littermates (C57BL/6N) were randomized to receive an intraperitoneal injection of doxorubicin 20 mg/kg or saline and were terminated 2 or 7 days after the injection. Gastrointestinal toxicity was evaluated by weight change, intestinal length, villus height/crypt depth, and histological mucositis score. Expression of inflammatory markers (IL-6, IL-1ß, and Tnfα) was measured by quantitative real-time PCR in intestinal tissue samples. RESULTS: Following doxorubicin treatment, WT mice exhibited an increased weight loss compared with Tg littermates (p < 0.001). No differences between genotypes were seen in mucositis score, intestinal length, villus height/crypt depth, or IL-6, IL-1ß, and Tnfα expression. CONCLUSION: Our findings suggest that FIBCD1 could ameliorate chemotherapy-induced gastrointestinal toxicity by reducing weight loss; however, the mechanism of this possible protective effect remains to be defined warranting additional investigations.

Stoma Closure Improves Head Circumference Growth in Very Preterm Infants after Necrotizing Enterocolitis.

INTRODUCTION: Very preterm infants (VPIs) surgically treated for necrotizing enterocolitis (NEC) are at risk of growth retardation. The aim of this study was to demonstrate and compare growth during the first 6 years of life in VPIs with stoma after NEC surgery with VPIs without NEC surgery. MATERIALS AND METHODS: We included all VPIs surgically treated due to NEC at the Odense University Hospital from August 1, 2004, to July 31, 2008. Outcome on growth was compared with a group of VPIs without NEC. The VPIs with NEC were identified searching the local database using the International Classification of Diseases, 10th Revision diagnosis of NEC (DP77.9). Data on growth were collected from medical files and if not present, the parents reported the data. RESULTS: Nineteen VPIs, surgically treated due to NEC, survived to 6 years of age. Median gestational age was 283/7 weeks (245/7-313/7). Median age at NEC surgery and stoma formation was 2.3 weeks (0.1-6.3) and median age at stoma closure was 2.5 months corrected age (CA) (postmenstrual age 36 weeks to CA 6.7 months). Compared with the non-NEC group, VPIs with NEC and stoma demonstrated poor growth, especially in head circumference (HC) with no increase in growth velocity before the time of stoma closure between 2.5- and 3-month CAs. CONCLUSION: Our findings demonstrate poor growth in VPIs after NEC surgery and improved HC growth after stoma closure.

Late-onset group B streptococcus infections and severe bronchopulmonary dysplasia in an extremely preterm born infant.

This case report is about a boy born extremely preterm at gestational age of 24 weeks, with extremely low birth weight, developing severe bronchopulmonary dysplasia and in need of mechanical ventilation for 155 days. He also had five recurrent infections with group B streptococcus (GBS) within 4 months from birth, and his respiratory condition clearly deteriorated with every GBS infection. It was difficult to wean him from mechanical ventilation. Finally he was extubated when he was 7 months old and kept out of mechanical ventilation after receiving high-dose methylprednisolone, given according to international recommendations. After GBS was cultured for the fifth time, he received oral rifampicin along with intravenous penicillin and after this treatment, GBS did not occur again. At the age of 22 months, the boy no longer needed any respiratory support and he was about 6 months late in his neurological development.

Contrasting Models of Posttraumatic Stress Disorder: Reply to.

We address the four main points in Monroe and Mineka (2008)'s Comment. First, we first show that the DSM PTSD diagnosis includes an etiology and that it is based on a theoretical model with a distinguished history in psychology and psychiatry. Two tenets of this theoretical model are that voluntary (strategic) recollections of the trauma are fragmented and incomplete while involuntary (spontaneous) recollections are vivid and persistent and yield privileged access to traumatic material. Second, we describe differences between our model and other cognitive models of PTSD. We argue that these other models share the same two tenets as the diagnosis and we show that these two tenets are largely unsupported by empirical evidence. Third, we counter arguments about the strength of the evidence favoring the mnemonic model, and fourth, we show that concerns about the causal role of memory in PTSD are based on views of causality that are generally inappropriate for the explanation of PTSD in the social and biological sciences.

[Maternal diabetes and congenital malformations]. / Maternel diabetes og medfødte misdannelser.

Maternal diabetes is a known risk factor for congenital malformations. Maternal hyperglycemia is a non-specific teratogen. The risk of congenital malformations, even with optimal metabolic control, is considerably elevated compared with non-diabetic pregnancies. The relationship between maternal hyperglycemia in early pregnancy and the risk of congenital malformations seems to be linear without any threshold level. To diminish the risk of congenital malformations, close preconceptional and first-trimester diabetic control and folic acid supplementation of 5 mg/day are recommended.