Trends in the use of laboratory tests for the diagnosis of Clostridium difficile infection and association with incidence rates in Quebec, Canada, 2010-2014.

BACKGROUND: Several Clostridium difficile infection (CDI) surveillance programs do not specify laboratory strategies to use. We investigated the evolution in testing strategies used across Quebec, Canada, and its association with incidence rates. METHODS: Cross-sectional study of 95 hospitals by surveys conducted in 2010 and in 2013-2014. The association between testing strategies and institutional CDI incidence rates was analyzed via multivariate Poisson regressions. RESULTS: The most common assays in 2014 were toxin A/B enzyme immunoassays (EIAs) (61 institutions, 64%), glutamate dehydrogenase (GDH) EIAs (51 institutions, 53.7%), and nucleic acid amplification tests (NAATs) (34 institutions, 35.8%). The most frequent algorithm was a single-step NAAT (20 institutions, 21%). Between 2010 and 2014, 35 institutions (37%) modified their algorithm. Institutions detecting toxigenic C difficile instead of C difficile toxin increased from 14 to 37 (P < .001). Institutions detecting toxigenic C difficile had higher CDI rates (7.9 vs 6.6 per 10,000 patient days; P = .01). Institutions using single-step NAATs, GDH plus toxigenic cultures, and GDH plus cytotoxicity assays had higher CDI rates than those using an EIA-based algorithm (P < .05). CONCLUSIONS: Laboratory detection of CDI has changed since 2010. There is an association between diagnostic algorithms and CDI incidence. Mitigation strategies are warranted.

The hormone-sensitive lipase gene and body composition: the HERITAGE Family Study.

OBJECTIVE: To investigate whether the C-60G polymorphism and other markers in the hormone-sensitive lipase (LIPE) gene are associated with baseline body composition and free-fatty acid (FFA) concentrations measured at rest and during low-intensity exercise in white and black subjects participating in the HERITAGE Family Study. SUBJECTS: Adult sedentary white (245 men and 258 women) and black (91 men and 185 women) subjects. MEASUREMENTS: body mass index (BMI); fat mass (FAT); percentage body fat (%FAT); fat-free mass (FATFR); sum of eight skinfolds (SF8); subcutaneous (ASF), visceral (AVF) and total (ATF) abdominal fat areas assessed by CT scan; plasma FFA concentrations measured at rest (FFAR), at a power output of 50 W (FFA50) and at a relative power output of 60% of VO(2max) (FFA60%); and fasting insulin (INS). STATISTICAL ANALYSIS: Association between the C-60G polymorphism of the LIPE gene and each phenotype was tested separately in men and women using ANCOVA with the effects of age and race as covariates and with further adjustment for FAT for ASF, AVF, ATF, FFAR, FFA50 and FFA60%. Secondly, owing to significant gene-by-race interaction, associations were investigated separately in each of the two race groups. Linkage was tested with the C-60G polymorphism, a dinucleotide repeat polymorphism in the intron 7 of the LIPE gene and two microsatellites markers (D19S178 and D19S903) flanking the LIPE gene. RESULTS: There were no race differences in the allele frequencies of the C-60G polymorphism of the LIPE gene. No association or gene-by-race interaction was observed in men. However, in women, strong gene-by-race interactions were observed for BMI (P=0.0005), FAT (P=0.0007), %FAT (P=0.0003), SF8 (P=0.0001), ASF (P=0.03) and ATF (P=0.01). When the analysis was performed separately in each race, white women carriers of the -60G allele exhibited lower %FAT (P=0.005) and SF8 (P=0.01) than non-carriers, while in black women, the -60G allele was associated with higher BMI (P=0.004), FAT (P=0.009), %FAT (P=0.01) and SF8 (P=0.0009). These associations were no longer significant after adjusting for INS. Evidence of linkage was observed in whites with ATF, FFAR, FFA50 and FFA60%. CONCLUSION: These results suggest that the C-60G polymorphism in the LIPE gene plays a role in determining body composition and that its effect is sex-, race- and insulin-dependent.

Genetic variation at the lipoprotein lipase locus and plasma lipoprotein and insulin levels in the Québec Family Study.

The associations between the S447X, BamHI, HindIII and PvuII DNA variants of the lipoprotein lipase (LPL) gene and indicators of body fat, fat distribution and plasma lipids and insulin were studied in the Québec Family Study cohort. Strong linkage disequilibrium among all the markers was observed. For the S447X polymorphism, plasma very low density lipoprotein (VLDL)-cholesterol (chol) (P<0.001), total triglyceride (TG) (P=0.033) and VLDL-TG (P<0.001) levels were lower and high density lipoprotein (HDL)-chol level higher (P<0.001) in the subjects homozygous or heterozygous for X447 (X447+, n=160) compared to the homozygotes for the S447 allele (X447-, n=576). The BamHI, PvuII and HindIII polymorphisms were not associated with the plasma lipid values when all X447 allele carriers were removed. In addition, the HindIII polymorphism as well as the HindIII and S447X markers combination influenced the insulin area under the curve during an oral glucose tolerance test. We conclude that DNA sequence variation in the LPL gene contributes significantly to the variability in the levels of VLDL-chol, total- and VLDL-TG as well as HDL-chol. The effects of the other polymorphisms considered here are most likely mediated by their linkage disequilibrium with the S447X mutation. In addition, genetic variation at the LPL locus may, by an unknown mechanism, influence insulin metabolism but not body fat variability.

Evidence of LPL gene-exercise interaction for body fat and LPL activity: the HERITAGE Family Study.

Evidence of a gene-exercise interaction for traits related to body composition is limited. Here, the association between the lipoprotein lipase (LPL) S447X polymorphism and changes in body mass index, fat mass, percent body fat, abdominal visceral fat measured by computed tomography, and post-heparin plasma LPL activity in response to 20 wk of endurance training was investigated in 741 adult white and black subjects. Changes were compared between carriers and noncarriers of the X447 allele after adjustment for the effects of age and pretraining values. No evidence of association was observed in men. However, white women carrying the X447 allele exhibited greater reductions of body mass index (P = 0.01), fat mass (P = 0.01), and percent body fat (P = 0.03); in black women, the carriers exhibited a greater reduction of abdominal visceral fat (P = 0.05) and a greater increase in post-heparin LPL activity (P = 0.02). These results suggest that the LPL S447X polymorphism influences the training-induced changes in body fat and post-heparin LPL activity in women but not in men.

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not associated with training-induced changes in body composition: The HERITAGE Family Study.

OBJECTIVE: To investigate the association between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and changes in body composition in response to endurance training. RESEARCH METHODS AND PROCEDURES: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat-free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre- and post-training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. RESULTS: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training-induced changes for any of the body composition phenotypes in both men and women. DISCUSSION: These results suggest that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not related to changes in body composition in response to exercise training.

Linkage and association studies of the lipoprotein lipase gene with postheparin plasma lipase activities, body fat, and plasma lipid and lipoprotein concentrations: the HERITAGE Family Study.

Lipoprotein lipase (LPL) is responsible for the hydrolysis of triglyceride (TG)-rich lipoproteins. The aims of the present study were (1) to test for potential linkages (sib-pair method) between postheparin plasma lipase (lipoprotein and hepatic lipase) activities, body fatness, plasma lipid concentrations, and LPL polymorphisms (Ser447Ter and a tetranucleotide repeat) and microsatellite markers flanking the LPL locus (D8S261 and D8S258); and (2) to investigate associations between the LPL Ser447Ter (S447X) polymorphism and these phenotypes. Data on 190 parents and 312 adult offspring from 99 Caucasian families participating in the HERITAGE Family Study were available for this study. Data were adjusted for the effects of age within sex, and lipases, lipid variables, and abdominal visceral fat were further adjusted for fat mass. A suggestive linkage was observed only between the S447X polymorphism and very-low-density (VLDL)-apolipoprotein B (apo B) (332 sib-pairs, P = .013). The S447X polymorphism was not associated with body fat phenotypes or postheparin plasma LPL (PH-LPL) activity (men, P = .19; women, P = .47). In contrast, the X447 allele carriers had lower plasma TG (men and women, P = .01), VLDL-TG (men and women, P = .01), and VLDL-apo B (men and women, P = .009). The relationships between the X447 allele and plasma TG, VLDL-TG, and VLDL-apo B in both genders were observed in obese (body mass index [BMI] > or = 30 kg/m2) but not in normal-weight (BMI < 25 kg/m2) subjects. Thus, the S447X polymorphism of the LPL gene is not associated with body fatness and postheparin plasma lipase activities. However, the obese carriers of the X447 allele have plasma TG, VLDL-TG, and plasma cholesterol/high-density lipoprotein cholesterol (HDL-C) levels equivalent to those of normal-weight sedentary adults.

A note on the distribution of dendritic spines.

Some previously published data concerning the spatial distributions of dendritic spines are re-examined. It appears that such distributions are not completely random, but show a tendency towards repulsion, that is to say a deficiency of short inter-spine distances and an excess of long distances when compared to a totally random model. While this lack of total randomness contradicts an assumption underlying a previously published technique for estimating total spine number, it does not appear to seriously interfere with this technique.