Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance).

BACKGROUND: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown. PATIENTS AND METHODS: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards. RESULTS: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status. CONCLUSION: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT00003835.

A new air-stable zinc complex based on a 1,2-phenylene-diimino-2-cyanoacrylate ligand as an efficient catalyst of the epoxide-CO2 coupling.

A novel zinc complex based on a diethyl 1,2-phenylene-diimino-2-cyanoacrylate ligand is a very efficient catalyst in the conversion of epoxides with CO2 to organic carbonates, in the case of propylene carbonate also under mild reaction conditions. Using cyclohexene oxide leads to the formation of alternating aliphatic polycarbonates in good yields.

Synthesis of cyclic carbonates from epoxides and carbon dioxide catalyzed by an easy-to-handle ionic iron(III) complex.

We report the successful utilization of monometallic, ionic iron(II)- and iron(III)-N2O2-ligand-systems as highly active homogeneous catalysts for the conversion of CO2 with different epoxides to cyclic carbonates. The catalytic tests were performed using propylene oxide (PO) and a range of nine substituted epoxides. Terminal monosubstituted oxides react quantitatively.

The role of peptide modules in protein evolution.

Protein evolution shows interesting strategies to be used in protein design. During evolution the creation of new proteins has been accomplished by combining different peptide modules, i.e. evolutionary successful stable folding units. Thereby, the evolution of proteins has been greatly enhanced. Today this mechanism of recombining optimized building blocks to design new proteins has been introduced into applied molecular evolution.

Tuberculosis infection-control practices in United States emergency departments.

STUDY OBJECTIVE: To determine the frequency with which patients with suspected tuberculosis (TB) or TB risk factors present to US emergency departments and to describe current ED TB infection-control facilities and practices. DESIGN: Mailed survey of a sample of EDs in US acute care facilities. PARTICIPANTS: A random sample (n = 446) of subjects who responded to a 1992 survey of all US municipal, Veterans Affairs, and university-affiliated hospitals and a 20% random sample of all private hospitals with more than 100 beds conducted by the Centers for Disease Control and Prevention (CDC). RESULTS: We collected data on patient demographics and general ED characteristics, TB isolation facilities and policies, and employee tuberculin skin-testing policies and results. Of 446 facilities surveyed, 305 surveys (68.4%) were returned. The proportions of facilities reporting that patients suspected of having TB are seen daily, weekly, monthly, and less frequently were, respectively, 12.6%, 17.2%, 23.3%, and 46.9%. The proportion of EDs in which indigent patients are cared for on a daily basis was 89%; the homeless, 57.5%; the HIV-infected, 35.9%; i.v. drug users, 45.4%; and recent immigrants, 30%. Written criteria for isolation of patients with suspected TB at triage or in the ED were in place in 56% and 76% of facilities, respectively. TB isolation rooms fulfilling CDC guidelines were available in triage or waiting areas in 1.7% of facilities and in 19.6% of EDs. Air venting directly outside, high-efficiency particulate air filtration of recirculated air, and UV germicidal lights were used in 21%, 17%, and 8% of general patient care areas of EDs, respectively. At least one ED employee had shown tuberculin skin test conversion in 16.1% of EDs in 1991; this figure was 26.9% in 1992. CONCLUSION: Patients with TB or at risk for TB are often treated in US EDs, and the risk for transmission of TB in this setting appears to be increasing. Prolonged waiting times and lack of infection-control facilities in EDs may contribute to this problem. Consideration should be given to implementation of policies and facilities recommended by the CDC.

Identification of molecular defects causing congenital adrenal hyperplasia by cloning and differential hybridization of polymerase chain reaction-amplified 21-hydroxylase (CYP21) genes.

Congenital adrenal hyperplasia (CAH), one of the most common autosomal recessive disorders, is caused primarily by defects in the gene encoding steroid 21-hydroxylase, CYP21B. The molecular diagnosis of CAH, important for prenatal diagnosis, carrier detection, and a better understanding of the various clinical CAH forms, is complicated by the close proximity of a highly similar pseudogene, CYP21A, containing (and probably donating, by gene conversion-like events) most of the defects underlying CAH. In this study, we describe an efficient strategy to identify molecular defects causing CAH: polymerase chain reaction-amplified CYP21 loci are cloned and hybridized to a set of oligonucleotides, allowing rapid and allele-specific identification of all known CYP21B mutations relevant to 21-hydroxylase function. Possible new mutations can be identified by subsequent nucleic acid sequencing provided they reside within the cloned CYP21B fragment (from the TATA box to the 8th of the 10 CYP21B gene exons). Using this method, the CYP21B gene mutations of a heterozygous carrier and 25 CAH patients have been identified by oligonucleotide hybridization. All disease haplotypes seem to have been generated by recombinational events involving the CYP21A pseudogene. In 5 individuals, these data were subsequently verified by nucleic acid sequencing. The procedure can be used for diagnostic applications and may facilitate identification of new CYP21B defects.