Mass Screening for Severe Problem Behavior among Infants and Toddlers In Peru

INTRODUCTION: Severe behavior problems among people with intellectual and developmental disabilities (IDD) are a major barrier to integration in the community. Recent research suggests that these behaviors often begin very early in life and might be prevented by early identification and intervention (Rojahn, Schroeder, & Hoch, 2008). The current paper presents a method of mass screening for early signs of severe behavior problems among infants and toddlers in Peru. METHODS: A Parental Concerns Questionnaire (PCQ) which asks 15 questions, each related to a risk factor for severe behavior problems, based on past research on IDD, was used by veteran parents to interview 341 new parents who had been solicited by TV, radio, and public service announcements across the country. Of these, 262 were recruited and enrolled in a longitudinal study in which they will be followed for 12 months, to see if at-risk children actually will develop severe behavior problems. An extensive initial interdisciplinary evaluation was given to each child. Consumer satisfaction questionnaires were given to the parents as to their attitude toward the screening method. RESULTS: Data from the Interdisciplinary Evaluations of the sample suggest a very high hit rate (96%) by the screening instrument (PCQ). Consumer satisfaction was 98%, suggesting that the method was tolerated well by parents. DISCUSSION: The PCQ is a brief and efficient method to screen infants and toddlers at risk for severe behavior problems. The data also suggest that parents suspect these problems at a very early age. Early intervention thus seems a feasible strategy to intervene before these problems become deeply ingrained as children develop.     

The XIVth International HIV Drug Resistance Workshop, Quebec City, Canada, June 2005

This report summarizes research advances that further our understanding of the evolution, mechanisms and clinical impact of HIV drug resistance presented at the XIVth International HIV Drug Resistance Workshop held in Quebec City, Canada from June 7-11, 2005. The topics that were discussed included the clinical implications of resistance in mother-to-child transmission, breakthroughs in technologies for studying resistance, resistance to new antiretroviral agents, mechanisms of HIV drug resistance, epidemiological trends, and HIV fitness and pathogenesis.     

A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth

Malignant melanoma is the most aggressive form of skin cancer and its incidence has doubled in the last two decades. It represents only 4% of skin cancer cases per year, but causes as many as 74% of skin cancer deaths. Early detection of malignant melanoma is associated with survival rates of up to 90%, but later detection (stage III to stage IV) is associated with survival rates of only 10%. Dysregulation of microRNA (miRNA) expression has been linked to tumor development and progression by functioning either as a tumor suppressor, an oncogene or a metastasis regulator in multiple cancer types. To understand the role of miRNA in the pathogenesis of malignant melanoma and identify biomarkers of metastasis, miRNA expression profiles in skin punches from 33 metastatic melanoma patients and 14 normal healthy donors were compared. We identified a cluster of 14 miRNAs on the X chromosome, termed the miR-506-514 cluster, which was consistently overexpressed in nearly all melanomas tested (30-60 fold, P<0.001), regardless of mutations in N-ras or B-raf. Inhibition of the expression of this cluster as a whole, or one of its sub-clusters (Sub-cluster A) consisting of six mature miRNAs, led to significant inhibition of cell growth, induction of apoptosis, decreased invasiveness and decreased colony formation in soft agar across multiple melanoma cell lines. Sub-cluster A of the miR-506-514 cluster was critical for maintaining the cancer phenotype, but the overexpression of the full cluster was necessary for melanocyte transformation. Our results provide new insights into the functional role of this miRNA cluster in melanoma, and suggest new approaches to treat or diagnose this disease.     

Properties of a concentrated minipool solvent‐detergent treated cryoprecipitate processed in single‐use bag systems

Summary. Cryoprecipitate is still used to treat factor VIII (FVIII), von Willebrand factor (VWF) and/or fibrinogen deficiency. Recently a solvent‐detergent (S/D) process of minipools of cryoprecipitate performed in a closed bag system has been designed to improve its viral safety. Still, cryoprecipitate has other drawbacks, including low concentration in active proteins, and presence of haemolytic isoagglutinins. We report here the biochemical evaluation of S/D‐treated minipools of cryoprecipitates depleted of cryo‐poor plasma. Cryoprecipitates were solubilized by 8 mL of a sterile glucose/saline solution, pooled in batches of 40 donations and subjected to S/D treatment in a plastic bag system using either 2% TnBP or 1% TnBP‐1%Triton X‐45, followed by oil extractions (n = 10). Mean (±SD) FVIII and fibrinogen content was 8.86 (±1.29) IU mL^?1 and 16.02 (±1.98) mg mL^?1, and 8.92 (±1.05) IU mL^?1 in cryoprecipitate minipools treated with 2% TnBP, and 17.26 (±1.71) mg mL^?1, in those treated by TnBP‐Triton X‐45, respectively. The WWF antigen, ristocetin cofactor and collagen binding activities were close to 10, 7 and 8 IU mL^?1, respectively, and were not affected by either SD treatment. VWF multimeric pattern of SD‐treated cryoprecipitates were similar to that of normal plasma, and the >15 mers and >10 mers content was identical to that of the starting cryoprecipitates. The anti‐A and anti‐B titre was 0–1 and 0–1/8, respectively. Therefore, it is possible to prepare virally inactivated cryoprecipitate minipools depleted of isoagglutinins and enriched in functional FVIII, VWF and clottable fibrinogen.     

Variable phenotypes associated with mutations in DOK7.

Many patients with the limb-girdle variant of congenital myasthenic syndrome (CMS) possess mutations in the human Dok-7 gene (DOK7). We identified six unrelated CMS patients with DOK7 mutations. Two patients, one mildly and the other moderately affected, were homozygous for the previously described 1263insC mutation. The common 1124_1127dupTGCC mutation was detected in the other four patients, whose clinical phenotypes range from mildly to severely affected. This striking phenotypic heterogeneity found both within and between mutational classes is made more compelling by data from our electrophysiological studies and electron microscopy of the neuromuscular junction (NMJ). Indeed, several aspects of the physiological and morphometric data do not correlate with genotype or severity of clinical phenotype. Overall, our study corroborates the findings of others and provides an additional demonstration of the considerable phenotypic variability associated with CMS due to DOK7 mutations.