Development of nitric oxide synthase-defined neurons in the sea urchin larval ciliary band and evidence for a chemosensory function during metamorphosis.

We previously reported that initiation of metamorphosis of larvae of Lytechinus pictus is negatively regulated by nitric oxide (NO) and cGMP. We have examined the expression of nitric oxide synthase (NOS) and cGMP in cells of the developing larva. A section of the post-oral ciliary band of feeding larvae includes neural cells defined by their expression of both NOS and the echinoderm neural-specific antibody 1E11. These neurons project processes to the pre-oral neuropile during larval development. Larvae regenerated this section of the ciliary band after its excision, complete with NOS-defined neurons that projected again to the pre-oral neuropile. Excision of ectoderm containing the post-oral ciliary band prevented a behavioral and morphogenetic response of competent larvae to biofilm, and delayed initiation of metamorphosis. Elevated cGMP levels were detected in several larval and juvenile cell types prior to metamorphosis. Treatment of larvae with ODQ, an inhibitor of soluble guanylate cyclase, decreased cGMP levels and induced metamorphosis while a generator of NO counteracted this effect, indicating inhibition of metamorphosis by NO operates via interaction with soluble guanylate cyclase. We discuss these observations, proposing that the NOS-defined neurons in the post-oral ciliary band have a chemosensory function during settlement and metamorphosis that involves morphologically specialized ectoderm and manipulation of fluid flow. We provide a tentative cellular model of how environmental signals may be transduced into a metamorphic response.     

PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival

Human T-cell leukemia virus type-1 (HTLV-1) is a tumorigenic retrovirus responsible for development of adult T-cell leukemia/lymphoma (ATLL). This disease manifests after a long clinical latency period of up to 2–3 decades. Two viral gene products, Tax and HBZ, have transforming properties and play a role in the pathogenic process. Genetic and epigenetic cellular changes also occur in HTLV-1-infected cells, which contribute to transformation and disease development. However, the role of cellular factors in transformation is not completely understood. Herein, we examined the role of protein arginine methyltransferase 5 (PRMT5) on HTLV-1-mediated cellular transformation and viral gene expression. We found PRMT5 expression was upregulated during HTLV-1-mediated T-cell transformation, as well as in established lymphocytic leukemia/lymphoma cell lines and ATLL patient PBMCs. shRNA-mediated reduction in PRMT5 protein levels or its inhibition by a small molecule inhibitor (PRMT5i) in HTLV-1-infected lymphocytes resulted in increased viral gene expression and decreased cellular proliferation. PRMT5i also had selective toxicity in HTLV-1-transformed T-cells. Finally, we demonstrated that PRMT5 and the HTLV-1 p30 protein had an additive inhibitory effect on HTLV-1 gene expression. Our study provides evidence for PRMT5 as a host cell factor important in HTLV-1-mediated T-cell transformation, and a potential target for ATLL treatment.     

Uptake of technetium 99m MDP by hepatoblastoma

Focal uptake of ^99mTc-MDP was seen in a case of hepatoblastoma. The focal uptake corresponded to an area of calcification on CT, which was shown histologically to consist of osteoid with mineralization. The mechanism of uptake by the tumor in this case is likely to be the same as for skeletal uptake.     

Zinc Gluconate Lozenges for Treating the Common Cold in Children: A Randomized Controlled Trial

Context.— The common cold is one of the most frequently occurring illnesses and is responsible for substantial morbidity and economic loss. Biochemical evidence suggests that zinc may be an effective treatment, and zinc gluconate glycine (ZGG) lozenges have been shown to reduce the duration of cold symptoms in adults. Objective.— To determine the efficacy of ZGG treatment of colds in children and adolescents. Design.— A randomized, double-masked, placebo-controlled study. Setting.— Two suburban school districts in Cleveland, Ohio. Patients.— A total of 249 students in grades 1 through 12 were enrolled within the first 24 hours of experiencing at least 2 of 9 symptoms of the common cold. Intervention.— Zinc lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6) or 6 times a day (in grades 7-12). Main Outcome Measures.— Time to resolution of cold symptoms based on subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and sneezing. Results.— Time to resolution of all cold symptoms did not differ significantly between students receiving zinc (n=124) and those receiving placebo (n=125) (median, 9 days; 95% confidence interval [CI], 8-9 days; median, 9 days, 95% CI, 7-10 days, respectively; P=.71). There were no significant differences in the time to resolution of any of the 9 symptoms studied. Compared with controls, more students in the zinc group reported adverse effects (88.6% vs 79.8%; P=.06); bad taste (60.2% vs 37.9%; P=.001); nausea (29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%; P=.03); and diarrhea (10.6% vs 4.0%; P=.05). Conclusions.— In this community-based, randomized controlled trial, ZGG lozenges were not effective in treating cold symptoms in children and adolescents. Further studies with virologic testing are needed to clarify what role, if any, zinc may play in treating cold symptoms.      

Revision total hip arthroplasty in the United States: national trends and in-hospital outcomes

Purpose

With the increasing number of primary total hip arthroplasties (THA) being performed, the frequency of revision surgery is also expected to increase. We analysed the immediate in-hospital complications and epidemiologic data of 3,469 revision and 18,186 primary THA cases.

Methods

The National Hospital Discharge Survey (NHDS) was evaluated between 2001 and 2010 for patients who underwent revision and primary THA. Patients were identified and included in our retrospective study based on ICD-9 procedure codes.

Results

The number of primary and revision THAs increased steadily from 2001 to 2010. The revision burden decreased for the same studied period (r?=?–0.92) to reach 13.9 % in 2010. The South region had higher revision burden of 17.4 % (p?<?0.001). The primary THA group was more likely to be obese, morbidly obese, and have hypertension (p?<?0.001). The revision THA group had an increased rate of blood transfusions (p?<?0.001), deep venous thrombosis (p?=?0.008), post-operative sepsis (p?<?0.001), and wound complications (p?<?0.001). The in-hospital mortality rate was also higher for the revision THA group (0.6 % versus 0.2 %, p?<?0.001).

Conclusions

The revision burden has undergone a steady decrease over the ten years studied and the reason for this is likely multifactorial. The South region had a significantly higher revision burden when compared to the rest of the United States. Larger hospitals tend to perform relatively more revisions. Revision THA patients are associated with longer hospital stay, higher complications rate, and higher in-hospital mortality rate.

     

KRAS Testing and Its Importance in Colorectal Cancer

Cetuximab and panitumumab are monoclonal antibodies used in the treatment of metastatic colorectal cancer (mCRC) by selectively targeting the epidermal growth factor receptor (EGFR) axis. Studies have shown that mutations in codons 12/13 of exon 2 of the KRAS gene render these therapies ineffective. As a result, the National Comprehensive Cancer Network and American Society of Clinical Oncology recommend KRAS mutation testing in mCRC. Appropriate testing depends on the coordinated efforts of the entire treatment team, including the pathologist, who selects the tumor sample and testing platform as well as interprets and reports results. In addition to describing rationale and methodologies for KRAS mutation testing, the authors also summarize their algorithmic approach and elaborate the potential role of newer molecular biomarkers to predict anti-EGFR resistance in wild-type KRAS tumors.     

Efficacy of magnetic resonance imaging in 139 children with tumors

One hundred thirty-nine children with neoplasms were studied using magnetic resonance imaging (MRI). This procedure was as accurate as computed tomography in predicting tumor histology, except that MRI was unable to detect small areas of tumor calcification. Magnetic resonance imaging could accurately identify the organ of origin of tumor masses and differentiate soft tissue from fat, fluid, or hemorrhage. In addition, MRI was helpful in planning surgery in many cases: It was better than computed tomography in defining the size and extent of soft-tissue tumor masses. It was accurate in defining the extent of the spread of bone sarcomas in the bone marrow. Without requiring the injection of intravenous contrast agents, it accurately defined displacement, encasement, or invasion of major abdominal blood vessels by Wilms' tumors and neuroblastomas. As a means of evaluating pediatric neoplasms, MRI is noninvasive, painless, and well tolerated by children, and it uses no radiation.