Maximally efficient two-stage screening: Determining intellectual disability in Taiwanese military conscripts

Chia-Chang Chien1, Shu-Fen Huang1,2,3,4, For-Wey Lung1,2,3,41Department of Psychiatry, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; 2Graduate Institute of Behavioral Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan; 4Calo Psychiatric Center, Pingtung County, TaiwanObjective: The purpose of this study was to apply a two-stage screening method for the large-scale intelligence screening of military conscripts.Methods: We collected 99 conscripted soldiers whose educational levels were senior high school level or lower to be the participants. Every participant was required to take the Wisconsin Card Sorting Test (WCST) and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) assessments.Results: Logistic regression analysis showed the conceptual level responses (CLR) index of the WCST was the most significant index for determining intellectual disability (ID; FIQ ≤ 84). We used the receiver operating characteristic curve to determine the optimum cut-off point of CLR. The optimum one cut-off point of CLR was 66; the two cut-off points were 49 and 66. Comparing the two-stage window screening with the two-stage positive screening, the area under the curve and the positive predictive value increased. Moreover, the cost of the two-stage window screening decreased by 59%.Conclusion: The two-stage window screening is more accurate and economical than the two-stage positive screening. Our results provide an example for the use of two-stage screening and the possibility of the WCST to replace WAIS-R in large-scale screenings for ID in the future.Keywords: intellectual disability, intelligence screening, two-stage positive screening, Wisconsin Card Sorting Test, Wechsler Adult Intelligence Scale-Revise

Fever Screening at Airports and Imported Dengue

Airport fever screening in Taiwan, July 2003–June 2004, identified 40 confirmed dengue cases. Results obtained by capture immunoglobulin (Ig) M and IgG enzyme-linked immunoassay, real time 1-step polymerase chain reaction, and virus isolation showed that 33 (82.5%) of 40 patients were viremic. Airport fever screening can thus quickly identify imported dengue cases

Moderate glucose control results in less negative nitrogen balances in medical intensive care unit patients: a randomized, controlled study

INTRODUCTION: Hyperglycemia and protein loss are common in critically ill patients. Insulin can be used to lower blood glucose and inhibit proteolysis. The impact of moderate insulin therapy on protein metabolism in critically ill patients has not been evaluated. We compared urinary nitrogen excretion, nitrogen balance, serum albumin concentrations, prealbumin concentrations, and clinical outcomes between patients receiving moderate insulin therapy (MIT) and conventional insulin therapy (CIT) in a medical ICU. METHODS: Patients were randomly divided into groups and treated with MIT (glucose target 120 to 140 mg/dl) or CIT (glucose target 180 to 200 mg/dl). Calories and protein intake were recorded each day. On days 3, 7 and 14, the 24-hour urinary nitrogen excretion, nitrogen balance, and serum albumin and prealbumin concentrations were measured. Clinical outcomes data were collected. RESULTS: A total of 112 medical ICU patients were included, with 55 patients randomized to the MIT group and 57 patients randomized to the CIT group. Patients treated with MIT showed a trend towards increased nitrogen balance (P = 0.070), significantly lower urinary nitrogen excretion (P = 0.027), and higher serum albumin (P = 0.047) and prealbumin (P = 0.001) concentrations than patients treated with CIT. The differences between the two groups were most significant on day 3, when all factors showed significant differences (P < 0.05). CONCLUSIONS: Moderate glucose control results in less negative nitrogen balances in medical ICU patients. Differences are more significant in the early stages compared with the late stages of critical illness. TRIAL REGISTRATION: ClinicalTrial.Gov NCT 0122714

Efficient Prodrug Activator Gene Therapy by Retroviral Replicating Vectors Prolongs Survival in an Immune-Competent Intracerebral Glioma Model.

Prodrug activator gene therapy mediated by murine leukemia virus (MLV)-based retroviral replicating vectors (RRV) was previously shown to be highly effective in killing glioma cells both in culture and in vivo. To avoid receptor interference and enable dual vector co-infection with MLV-RRV, we have developed another RRV based on gibbon ape leukemia virus (GALV) that also shows robust replicative spread in a wide variety of tumor cells. We evaluated the potential of GALV-based RRV as a cancer therapeutic agent by incorporating yeast cytosine deaminase (CD) and E. coli nitroreductase (NTR) prodrug activator genes into the vector. The expression of CD and NTR genes from GALV-RRV achieved highly efficient delivery of these prodrug activator genes to RG-2 glioma cells, resulting in enhanced cytotoxicity after administering their respective prodrugs 5-fluorocytosine and CB1954 in vitro. In an immune-competent intracerebral RG-2 glioma model, GALV-mediated CD and NTR gene therapy both significantly suppressed tumor growth with CB1954 administration after a single injection of vector supernatant. However, NTR showed greater potency than CD, with control animals receiving GALV-NTR vector alone (i.e., without CB1954 prodrug) showing extensive tumor growth with a median survival time of 17.5 days, while animals receiving GALV-NTR and CB1954 showed significantly prolonged survival with a median survival time of 30 days. In conclusion, GALV-RRV enabled high-efficiency gene transfer and persistent expression of NTR, resulting in efficient cell killing, suppression of tumor growth, and prolonged survival upon CB1954 administration. This validates the use of therapeutic strategies employing this prodrug activator gene to arm GALV-RRV, and opens the door to the possibility of future combination gene therapy with CD-armed MLV-RRV, as the latter vector is currently being evaluated in clinical trials

Hypermethylation of the TGF-β target, ABCA1 is associated with poor prognosis in ovarian cancer patients

Background The dysregulation of transforming growth factor-β (TGF-β) signaling plays a crucial role in ovarian carcinogenesis and in maintaining cancer stem cell properties. Classified as a member of the ATP-binding cassette (ABC) family, ABCA1 was previously identified by methylated DNA immunoprecipitation microarray (mDIP-Chip) to be methylated in ovarian cancer cell lines, A2780 and CP70. By microarray, it was also found to be upregulated in immortalized ovarian surface epithelial (IOSE) cells following TGF-β treatment. Thus, we hypothesized that ABCA1 may be involved in ovarian cancer and its initiation. Results We first compared the expression level of ABCA1 in IOSE cells and a panel of ovarian cancer cell lines and found that ABCA1 was expressed in HeyC2, SKOV3, MCP3, and MCP2 ovarian cancer cell lines but downregulated in A2780 and CP70 ovarian cancer cell lines. The reduced expression of ABCA1 in A2780 and CP70 cells was associated with promoter hypermethylation, as demonstrated by bisulfite pyro-sequencing. We also found that knockdown of ABCA1 increased the cholesterol level and promoted cell growth in vitro and in vivo. Further analysis of ABCA1 methylation in 76 ovarian cancer patient samples demonstrated that patients with higher ABCA1 methylation are associated with high stage (P = 0.0131) and grade (P = 0.0137). Kaplan-Meier analysis also found that patients with higher levels of methylation of ABCA1 have shorter overall survival (P = 0.019). Furthermore, tissue microarray using 55 ovarian cancer patient samples revealed that patients with a lower level of ABCA1 expression are associated with shorter progress-free survival (P = 0.038). Conclusions ABCA1 may be a tumor suppressor and is hypermethylated in a subset of ovarian cancer patients. Hypermethylation of ABCA1 is associated with poor prognosis in these patients