Isolated blunt liver trauma: is nonoperative treatment justified?

During the past 8 years 13 children with isolated blunt liver trauma were managed nonoperatively. All patients selected for this management were hemodynamically stable after initial resuscitation and were without signs of other associated intraabdominal injuries on ultrasonogram and/or computed tomography. Patients were observed in an intensive care unit for at least 48 hours with repeated clinical assessments, laboratory studies, and bed rest. One patient with type 3 injury was operated on 8 days after injury because of sudden intraperitoneal bleeding on ambulation. Five patients required blood transfusions of not more than 300 mL per patient. Laboratory values returned to normal from 7 to 21 days after injury. Resolution of hepatic injury on ultrasonogram took from 1 to 3 months. Complete bed rest was prescribed for at least 10 days depending on the type of injury, with restricted activities up to 3 months postinjury. No complications were seen in this series.     

Erythrocyte ferritin in patients on chronic hemodialysis treatment

Serum ferritin (SF) and erythrocyte ferritin (EF) were evaluated in 35 patients on chronic hemodialysis treatment (CHD), in 45 healthy subjects and in 22 nonnephropathic females with iron deficiency anemia. Twenty-five CHD patients with basal SF less than 500 micrograms/l were treated orally with 200 mg of Fe2+ for 2 months and the positive (hemoglobin increase greater than 1 g/dl) or negative response to the therapy was correlated to the basal levels of SF and EF. Three groups of CHD patients could be defined on the basis of their basal SF levels (hypo-, normo- or hyperferritinemic). Nine patients with increased SF levels had also EF levels significantly higher than the other CHD patients and controls since they were probably iron-overloaded. In the other 2 groups of CHD patients, EF levels were significantly higher than in controls for each level of SF probably because of the reduced utilization of iron by uremic bone marrow. Among the 25 treated CHD patients, only 5 responded to the therapy: 3 were hypoferritinemic while the other 2 responders had basal SF within the normal range. Four hypoferritinemic patients did not respond to the therapy. Four out of five responders had the lowest EF levels among CHD patients. EF measurement could be an important and useful test in detecting the presence of an iron deficiency erythropoiesis in CHD patients.     

Immunolocalization of Alk8 during replacement tooth development in zebrafish

The novel type I transforming growth factor-beta (TGF-beta) family member receptor Alk8 was previously identified in a degenerate RT-PCR screen for zebrafish type I and II TGF-beta family member receptors. Functional analyses revealed that Alk8 acts through Bmp signaling pathways in early embryonic dorsoventral patterning, in neural crest cell specification, and in patterning and differentiation of neural crest cell-derived pharyngeal arch cartilages. In addition, Alk8 forms active signaling complexes with TGF-beta1 and the TGF-beta RII receptor, suggesting that Alk8 mediates cross talk between Bmp and TGF-beta subfamily members. In this study, immunohistochemical analysis was performed on zebrafish aged 2 days postfertilization to 1 year, revealing immunolocalization of Alk8 to tissues of the tooth-bearing ceratobranchial 5 (cb5) arch including dental epithelial and mesenchymal tooth tissues of developing primary and replacement teeth, mucous-producing crypt epithelium, keratinized bite plate, and developing taste buds. These results suggest roles for Alk8 in patterning tooth-bearing pharyngeal epithelium, in the initiation of tooth development, in odontoblast and ameloblast differentiation, and in osteoblast maturation. The ability for zebrafish to continuously form teeth throughout their lives allows for the comparison of Alk8 expression in both primary and replacement tooth development, revealing identical Alk8 expression profiles. This study advances our current understanding of the functions of Alk8, particularly with respect to primary and replacement tooth formation, reveals additional roles for Alk8 in dental epithelial patterning and in odontoblast, ameloblast and osteoblast differentiation, and demonstrates the utility of the zebrafish as a model for primary and replacement tooth development.     

Short bowel syndrome: experimental approach to increase intestinal surface in rats by gastric homologous acellular matrix

BACKGROUND/PURPOSE: In this preliminary work the authors used homologous acellular matrix obtained by the gastric wall to increase the small bowel surface in Sprague-Downey rats; through this experimental model the authors verified that homologous acellular matrix can support cell migration and the reconstruction of the intestinal wall. METHODS: A tract of about 2 cm of tubular gastric acellular matrix was inserted with bilateral anastomosis in an isolated ileal loop, which was located in endoabdominal position through a short subcutaneous tunnel. Twelve animals were analyzed at each of the time-points ranging from 1 to 6 weeks after surgery. RESULTS: Histologic evaluation showed that the implanted matrix can be reintegrated in the normal small bowel in a period ranging between 3 and 6 weeks from surgery. The implanted matrix was organized with 4 different tonacae from the third week after the surgery, without interruption at the site of the anastomosis. CONCLUSIONS: To date, the authors do not have a demonstration of the function of the ileal loop reconstructed with this technique; based on these results the authors are engaged in an experimental trial of restoration of intestinal viability with the ileal prosthesis after 3 weeks to study its function.     

Impaired contractile responses and altered expression and phosphorylation of Ca2+ sensitization proteins in gastric antrum smooth muscles from ob/ob mice

Diabetic gastroparesis is a common complication of diabetes, adversely affecting quality of life with symptoms of abdominal discomfort, nausea, and vomiting. The pathogenesis of this complex disorder is not well understood, involving abnormalities in the extrinsic and enteric nervous systems, interstitial cells of Cajal (ICCs), smooth muscles and immune cells. The ob/ob mouse model of obesity and diabetes develops delayed gastric emptying, providing an animal model for investigating how gastric smooth muscle dysfunction contributes to the pathophysiology of diabetic gastroparesis. Although ROCK2, MYPT1, and CPI-17 activities are reduced in intestinal motility disorders, their functioning has not been investigated in diabetic gastroparesis. We hypothesized that reduced expression and phosphorylation of the myosin light chain phosphatase (MLCP) inhibitory proteins MYPT1 and CPI-17 in ob/ob gastric antrum smooth muscles could contribute to the impaired antrum smooth muscle function of diabetic gastroparesis. Spontaneous and carbachol- and high K⁺-evoked contractions of gastric antrum smooth muscles from 7 to 12 week old male ob/ob mice were reduced compared to age- and strain-matched controls. There were no differences in spontaneous and agonist-evoked intracellular Ca²⁺ transients and myosin light chain kinase expression. The F-actin:G-actin ratios were similar. Rho kinase 2 (ROCK2) expression was decreased at both ages. Basal and agonist-evoked MYPT1 and myosin light chain 20 phosphorylation, but not CPI-17 phosphorylation, was reduced compared to age-matched controls. These findings suggest that reduced MLCP inhibition due to decreased ROCK2 phosphorylation of MYPT1 in gastric antrum smooth muscles contributes to the antral dysmotility of diabetic gastroparesis.     

Synonymous Mutations in RNASEH2A Create Cryptic Splice Sites Impairing RNase H2 Enzyme Function in Aicardi–Goutières Syndrome

Aicardi–Goutières syndrome is an inflammatory disorder resulting from mutations in TREX1, RNASEH2A/2B/2C, SAMHD1, or ADAR1. Here, we provide molecular, biochemical, and cellular evidence for the pathogenicity of two synonymous variants in RNASEH2A. Firstly, the c.69G>A (p.Val23Val) mutation causes the formation of a splice donor site within exon 1, resulting in an out of frame deletion at the end of exon 1, leading to reduced RNase H2 protein levels. The second mutation, c.75C>T (p.Arg25Arg), also introduces a splice donor site within exon 1, and the internal deletion of 18 amino acids. The truncated protein still forms a heterotrimeric RNase H2 complex, but lacks catalytic activity. However, as a likely result of leaky splicing, a small amount of full‐length active protein is apparently produced in an individual homozygous for this mutation. Recognition of the disease causing status of these variants allows for diagnostic testing in relevant families.     

Programs for Preventing Depression in Adolescence: Who Benefits and Who Does Not? An Introduction to the Supplemental Issue

We introduce this supplemental issue of Prevention Science, which brings together a set of papers from leading investigators who have conducted trials testing whether intervention programs prevent adolescent depression. Using data from these trials, these papers explore a series of factors that might account for variation in intervention benefit, employing several novel methods for assessing effect heterogeneity. These studies follow two general paradigms: three papers report findings from single randomized preventive intervention trials, while the remaining papers develop and apply new methods for combining data from multiple studies to evaluate effect heterogeneity more broadly. Colleagues from NIMH and SAMHSA also provide commentaries on these studies. They conclude that synthesis of findings from multiple trials holds great promise for advancing the field, and progress will be accelerated if collaborative data sharing becomes the norm rather than the exception.