Work life of persons with asthma, rhinitis, and COPD: A study using a national, population-based sample

Objective  

To estimate the duration of work life among persons reporting a physician's diagnosis of COPD, asthma, or rhinitis compared to those with select non-respiratory conditions or none and to delineate the factors associated with continuance of employment.     

Classification and selection of biomarkers in genomic data using LASSO

High-throughput gene expression technologies such as microarrays have been utilized in a variety of scientific applications. Most of the work has been done on assessing univariate associations between gene expression profiles with clinical outcome (variable selection) or on developing classification procedures with gene expression data (supervised learning). We consider a hybrid variable selection/classification approach that is based on linear combinations of the gene expression profiles that maximize an accuracy measure summarized using the receiver operating characteristic curve. Under a specific probability model, this leads to the consideration of linear discriminant functions. We incorporate an automated variable selection approach using LASSO. An equivalence between LASSO estimation with support vector machines allows for model fitting using standard software. We apply the proposed method to simulated data as well as data from a recently published prostate cancer study.     

Biotinylated GHK peptide incorporated collagenous matrix: A novel biomaterial for dermal wound healing in rats

Matrikines are small peptide fragments of extracellular matrix proteins that display potent tissue repair activities. Difficulties in achieving sustained delivery of bioactive concentration of matrikines in the affected area limits their therapeutic use. The present study evaluates the effects biotinylated matrikine peptide (bio-glycyl-histidyl-lysine) incorporated collagen membrane for dermal wound healing processes in rats. Biotinylated peptide incorporated collagen matrix (PIC) showed better healing when compared to wounds treated with collagen matrix [CF (collagen film)] and without collagen [CR (control)]. Binding studies indicate that biotinylated GHK (Bio-GHK) binds effectively to the collagen matrix and red blood cell (RBC) membrane when compared with t-butyloxycarbonyl substituted GHK (Boc-GHK). Wound contraction, increased cell proliferation, and high expression of antioxidant enzymes in PIC treated group indicate enhanced wound healing activity when compared to CF and CR groups. Interestingly Bio-GHK incorporated collagen increases the copper concentration by ninefold at the wound site indicating the wound healing property of Bio-GHK can also be linked with both copper localization and matrikine activities. These results demonstrate the possibility of using Bio-GHK incorporated collagen film as a therapeutic agent in the wound healing process.     

Circadian clock and cell cycle gene expression in mouse mammary epithelial cells and in the developing mouse mammary gland.

Mouse mammary epithelial cells (HC-11) and mammary tissues were analyzed for developmental changes in circadian clock, cellular proliferation, and differentiation marker genes. Expression of the clock genes Per1 and Bmal1 were elevated in differentiated HC-11 cells, whereas Per2 mRNA levels were higher in undifferentiated cells. This differentiation-dependent profile of clock gene expression was consistent with that observed in mouse mammary glands, as Per1 and Bmal1 mRNA levels were elevated in late pregnant and lactating mammary tissues, whereas Per2 expression was higher in proliferating virgin and early pregnant glands. In both HC-11 cells and mammary glands, elevated Per2 expression was positively correlated with c-Myc and Cyclin D1 mRNA levels, whereas Per1 and Bmal1 expression changed in conjunction with beta-casein mRNA levels. Interestingly, developmental stage had differential effects on rhythms of clock gene expression in the mammary gland. These data suggest that circadian clock genes may play a role in mouse mammary gland development and differentiation.     

Effect of oral creatine ingestion on parameters of the work rate-time relationship and time to exhaustion in high-intensity cycling

The relationship between work rate (W˙) and time to exhaustion (t) during intense exercise is commonly described by either a hyperbolic function (NLin), t=W ^′/(W˙?W˙ _cp), or by its linear equivalent (LinW) W _lim =W ^′+W˙ _cp(t). The parameter W˙<INF _cp (critical power) has been described as an inherent characteristic of the aerobic energy system, while W?′ has been shown to be a ralid estimate of anaerobic work capacity. Recent studies have demonstrated that oral supplementation of creatine monohydrate (CrH₂O) increases total muscle creatine stores, and have linked these increases to improved performances in intense intermittent exercise. This study was conducted to determine the effect of CrH₂O supplementation on estimates of W?′ and W˙<INF _cp derived from the NLin and LinW equations, and to determine the effect of CrH₂O on t in exhaustive constant power exercise of different intensities. Fifteen active but untrained university students completed three phases of testing on a cycle ergometer: (1) familiarization, three learning trials, (2) baseline determination of W?′ and W˙<INF _cp, four bouts performed at a W˙ selected to elicit fatigue in 90–600?s, and (3) experimental determination of W?′ and W˙ _cp, four bouts performed at the same W˙ as baseline, but performed after 5 days of ingesting either a placebo (4?×?6?g of glucose/day) or CrH₂O (4?×?5?g of CrH₂O and 1?g glucose/day). Testing was administered in a double-blind manner. Analyses of covariance revealed a significant effect for CrH₂O on both estimates of W?′ (NLin, P=0.04; LinW, P<0.01), but not on estimates of W˙ _cp (NLin, P=0.37; LinW; P=0.30). Within groups, t was significantly different for only CrH₂O at the two highest W˙s (P=0.04). It is concluded that oral ingestion of CrH₂O increases estimates of W?′ due to an improved t at the shorter, more intense exercise bouts.

     

Modified milk fat reduces plasma triacylglycerol concentrations in normolipidemic men compared with regular milk fat and nonhydrogenated margarine

BACKGROUND: A modified milk fat with reduced cholesterol was developed by fractionation technology. OBJECTIVE: The effect of this modified milk fat on the lipoprotein profile of 21 normolipidemic men was compared with that of regular milk fat and nonhydrogenated margarine. DESIGN: A crossover design was used for the administration of the 3 experimental diets, which provided 13240 kJ as 16% protein, 51% carbohydrates, 33-34% lipids, and 21 g fiber/d. The ratio of polyunsaturated to saturated fat was 1.3:1 for the margarine diet and 0.3:1 for the milk-fat diets. The cholesterol content of the modified milk-fat and margarine diets was similar (248 and 254 mg/d, respectively), but was significantly higher (428 mg/d) for the regular milk-fat diet. RESULTS: Modified and regular milk fats did not change plasma total and LDL cholesterol significantly, but margarine did (P < 0.01). Furthermore, modified milk fat maintained initial HDL(2)-cholesterol concentrations, but margarine reduced this variable significantly (P < 0.05). These results can be explained by the lower ratio of polyunsaturated to saturated fat in the modified and regular milk-fat diets than in the margarine diet. Men who ingested modified milk fat had significantly (P < 0.05) lower total and VLDL-triacylglycerol and VLDL-cholesterol concentrations than did those who ingested either regular milk fat or margarine. This may have been, in part, because of the lower intestinal fat absorption with modified milk fat than with regular milk fat and margarine arising from changes in the melting properties of milk fat with fractionation. CONCLUSION: A reduction in plasma triacylglycerol concentrations after the consumption of modified milk fat may prevent the onset of hypertriacylglycerolemia.     

Chemosensitization of murine fibrosarcoma cells to drugs affected by the multidrug resistance phenotype by the antidepressant trazodone - an experimental-model for the reversal of intrinsic drug-resistance

A variety of resistance phenotypes to cytotoxic agents in bacteria, protozoa parasites and mammalian cells are mediated by evolutionarily conserved proteins of the mdr family. The finding that chloroquine resistance in the malarial parasite, Plasmodium falciparum, that is mediated by an mdr-1 gene product can be circumvented by tricyclic antidepressant drugs has stimulated the present study to assess whether this class of agents might also modulate the multidrug resistance (MDR) phenotype(s) in mammalian tumor cells. The possible chemosensitizing effects of nine antidepressant drugs have been tested against the UV-2237M murine fibrosarcoma line and its MDR variant. At nontoxic concentrations all nine antidepressants markedly enhanced the cytotoxicity of ADR against the parental cells but were much less effective against the MDR cells. The most active antidepressant, trazodone, also enhanced the cytotoxicities of vinblastine and vincristine, but not those of actinomycin D, mitomycin C, or 5-fluorouracil. The parental cells treated with trazodone exhibited an increased accumulation of intracellular ADR, but lacked detectable alterations in the expression and drug-binding activity of plasma membrane P-glycoprotein, and trazodone did not affect the activities of isolated protein kinase C and calmodulin. These data suggest that the antidepressant drug trazodone may be useful in the reversal of the intrinsic drug resistance of tumor cells that express low levels of P-glycoprotein.     

Mental retardation and sentences for murder: comparison of two recent court cases

Several states and the United States have laws that exempt persons who have mental retardation from the death penalty and other severe sentences. Two recent murder cases in Indiana, which has such a law, illustrate some of the problems in applying it. The characteristics of the two defendants were quite similar, but one defendant was found to have mental retardation and was exempted from the death penalty and the other was not. The disparity was attributed to differences in the assessment of adaptive behavior and to general stereotypes of people who have mental retardation. Equal application of sentencing limitation laws requires greater involvement of professionals with specialized training and experience in mental retardation.