CpG Methylation, a Parent-of-Origin Effect for Maternal-Biased Transmission of Congenital Myotonic Dystrophy.

CTG repeat expansions in DMPK cause myotonic dystrophy (DM1) with a continuum of severity and ages of onset. Congenital DM1 (CDM1), the most severe form, presents distinct clinical features, large expansions, and almost exclusive maternal transmission. The correlation between CDM1 and expansion size is not absolute, suggesting contributions of other factors. We determined CpG methylation flanking the CTG repeat in 79 blood samples from 20 CDM1-affected individuals; 21, 27, and 11 individuals with DM1 but not CDM1 (henceforth non-CDM1) with maternal, paternal, and unknown inheritance; and collections of maternally and paternally derived chorionic villus samples (7 CVSs) and human embryonic stem cells (4 hESCs). All but two CDM1-affected individuals showed high levels of methylation upstream and downstream of the repeat, greater than non-CDM1 individuals (p = 7.04958 × 10-12). Most non-CDM1 individuals were devoid of methylation, where one in six showed downstream methylation. Only two non-CDM1 individuals showed upstream methylation, and these were maternally derived childhood onset, suggesting a continuum of methylation with age of onset. Only maternally derived hESCs and CVSs showed upstream methylation. In contrast, paternally derived samples (27 blood samples, 3 CVSs, and 2 hESCs) never showed upstream methylation. CTG tract length did not strictly correlate with CDM1 or methylation. Thus, methylation patterns flanking the CTG repeat are stronger indicators of CDM1 than repeat size. Spermatogonia with upstream methylation may not survive due to methylation-induced reduced expression of the adjacent SIX5, thereby protecting DM1-affected fathers from having CDM1-affected children. Thus, DMPK methylation may account for the maternal bias for CDM1 transmission, larger maternal CTG expansions, age of onset, and clinical continuum, and may serve as a diagnostic indicator.

Multipronged intervention strategy to control an outbreak of Clostridium difficile infection (CDI) and its impact on the rates of CDI from 2002 to 2007.

OBJECTIVE: At the end of 2002, a new, more virulent strain of Clostridium difficile, designated BI/NAP1, was the cause of a massive outbreak of infection in the province of Quebec. This particular strain was associated with a dramatic increase in morbidity and mortality among affected patients in 2003-2004. We tested and implemented a multipronged infection control approach to curtail the rate of C. difficile infection (CDI). DESIGN: Five-year observational study. SETTING: A 554-bed, acute care tertiary hospital, the largest single medical center in Quebec, Canada. METHODS: To curtail the magnitude of the outbreak, we implemented a global strategy consisting of rapid C. difficile testing for all hospitalized patients who had at least 1 occurrence of liquid stool, the rapid isolation of patients infected with C. difficile in a dedicated ward with a specially trained housekeeping team, a global hand hygiene program, and the hiring of infection control practitioners. Antibiotic consumption at the institutional level was also monitored during the 5-year surveillance period. Cases of hospital-acquired CDI per 1,000 admissions were continuously monitored on a monthly basis during the entire surveillance period. RESULTS: The highest recorded CDI rate was 42 cases per 1,000 admissions in January 2004. Once additional infection control resources were put in place, the rate decreased significantly during the period from April 2005 to March 2007. During the 2003-2004 period, there were 762 cases of CDI (mean annual rate, 37.28 cases per 1,000 admissions) recorded in our study, compared with 292 cases of CDI (14.48 cases per 1,000 admissions) during the 2006-2007 period (OR, 0.379 [95% CI, 0.331-0.435]; p< .001), a 61% reduction. In March 2007, the equivalent of 4 full-time equivalent infection control practitioners were in place, which gave a ratio of 0.96 infection control practitioners per 133 beds in use, compared with the ratio of 0.24 infection control practitioners per 133 beds in use in 2003, and the total number of hours dedicated to cleaning and housekeeping increased by 26.2%. The total amount of antibiotics used in the hospital did not vary significantly from 2002 to 2007, although there were changes in the classes antibiotic used. CONCLUSION: The implementation of a multipronged intervention strategy to control the outbreak of CDI significantly improved the overall situation at the hospital and underlined the importance of investing in stringent infection control practices.

Tactile perception and manual dexterity in computer users.

Recent studies suggest that sensory input generated during highly repetitive tasks can degrade the sensory representation of the hand and eventually lead to sensory and motor problems. In this study, we investigated whether early changes in tactile perception and manual dexterity could be detected in persons exposed to computer tasks. Performance in tests designed to assess tactile perception (grating orientation task for spatial acuity and roughness discrimination) and manual dexterity (grooved pegboard test) was compared between two groups of healthy individuals, matched for age, gender, and experience, who differed in terms of computer habits. One group consisted of frequent users (FU, > 2 h/day, n = 36) and the other of non or occasional users (OU, < 2 h/day, n = 28). Comparison of performance between groups with subjects sorted by gender revealed significant differences (t-test, p < 0.05) in female, but not male, participants. Grating resolution thresholds at the tip on the second and fifth digits were, on average, 40% higher in female FU (n = 13) than in female OU (n = 10) and performance scores on the dexterity test were significantly higher for the left hand. The results of this study indicate that early signs of deterioration in hand function can be present in persons constantly exposed to computer tasks and that these signs are more readily apparent in women than in men. The loss of tactile spatial acuity found in female FU possibly reflect an early consequence of the degraded sensory representation of the hand resulting from constant repetitions of fine motor tasks.