Genetic Variants in Toll-Like Receptor 2 (TLR2), TLR4, TLR9, and FCγ Receptor II Are Associated with Antibody Response to Quadrivalent Meningococcal Conjugate Vaccine in HIV-Infected Youth

This study examined the association of host genetic variants with the antibody response to the quadrivalent meningococcal conjugate vaccine (MCV4) in HIV-infected youth. Genetic variants associated with severity of meningococcal disease, including the IgG Fc receptor (FCγRII)-A484T, interleukin-10 (IL-10)-A1082G, -C819T, and -C627A, IL-4-C589T, mannose binding lectin-2 (MBL2)-A/O, -H/L, -P/Q, and -X/Y, toll-like receptor 2 (TLR2)-G2408A, TLR4-A12874G and -C13174T, and TLR9-T1237C and -T1486C were determined by real-time PCR (RT-PCR) for 271 HIV-infected subjects (median, 17 years). Response was defined as a ≥4-fold increase from entry in bactericidal antibody titers to each serogroup. Generalized estimating equation (GEE) models were used to evaluate the association of allelic variants with the immunologic response to all serogroups within each subject with and without adjusting for CD4 percentage and HIV viral load. At week 4, but not after, subjects with TLR2-2408-G/A versus -G/G genotypes and the TLR4-12874-A/A genotype were more likely to achieve a ≥4-fold increase overall in the four serogroups (unadjusted P of 0.006 and adjusted P of 0.008 and unadjusted P of 0.008 and adjusted P of 0.019, respectively). At week 28, the TLR9-1237 T allele was associated with enhanced antibody response (T allele versus C/C, unadjusted P of 0.014 and adjusted P of 0.009), which was maintained at week 72 (unadjusted and adjusted P of 0.008). At week 72, the FcγRII-131Arg allotype was associated with a ≥4-fold increase in antibody titer versus those with His/His (unadjusted P of 0.009; adjusted P of <0.001). These findings suggest that for HIV-infected youth, the initial antibody response to MCV4 is associated with variants in TLR2 and TLR4 while the long-term response is associated with genetic polymorphisms in TLR9 and FcγRIIa.     

Head‐pelvis coupling is increased during turning in patients with Parkinson's disease and freezing of gait

Turning is the most important trigger for freezing of gait (FOG). The aim of this study was to investigate the relationship between impaired head‐pelvis rotation during turning and FOG. Head, trunk, and pelvic rotation were measured at onset and throughout a 180‐degree turn in 13 freezers and 14 nonfreezers (OFF medication). We also studied 14 controls at preferred and slow speed to investigate the influence of turn velocity on axial rotation. Location and duration of FOG episodes were defined during the turn. At turning onset, head rotation preceded thorax and pelvic rotation in all groups, but this craniocaudal sequence disappeared when FOG occurred. Maximum head‐pelvis separation was significantly greater in controls, compared to freezers and nonfreezers (35.4 versus 25.7 and 27.3 degrees; P < 0.01), but this finding was speed dependent. Timing of maximum head‐pelvis separation was delayed in freezers, compared to nonfreezers and controls, irrespective of turn velocity. This delay was correlated with increased neck rigidity (R = 0.62; P = 0.02) and worsened during FOG trials. FOG occurred more often at the end of the turn, when difference in rotation velocity between head and pelvis was greatest. Even after controlling for speed and disease severity, turning in freezers was characterized by delayed head rotation and a closer coupling between head and pelvis, especially in turns where FOG occurred. These changes may be attributed to delayed preparation for the change in walking direction and, as such, contribute to FOG. © 2013 Movement Disorder Society     

A randomised comparison of single-incision versus traditional transobturator midurethral sling in women with stress urinary incontinence: results of a 24-month follow-up

Introduction and hypothesis

Midurethral sling procedures have become the principal surgical treatment for women with stress urinary incontinence (SUI). The 1-year results of this international trial comparing the efficacy and morbidity of a single-incision midurethral sling (SIMS; MiniArc) and a transobturator standard midurethral sling (SMUS; Monarc) showed that MiniArc is non-inferior regarding subjective cure and superior with regard to postoperative pain and recovery. The objective was to compare subjective and objective cure, morbidity and surgery-related discomfort following SIMS and transobturator SMUS up to a 24-month follow-up.

Methods

We carried out a non-blinded, randomised, controlled trial. Women with symptomatic SUI were eligible. Primary outcome was subjective cure, defined as an improvement on the Patient Global Impression of Improvement (PGI-I), at 12, 24 and 36 months. Secondary outcomes were objective cure based on the cough stress test, disease-specific quality of life questionnaires, surgical parameters and physical performance during recovery. Analysis was by intent to treat. Differences between the two groups regarding dichotomous variables were Chi-squared tested and presented as relative risks (RR) with corresponding 95 % confidence intervals.

Results

We randomised 97 women to MiniArc and 96 to Monarc. At the 24-month follow-up, subjective cure was 84 % following MiniArc and 89 % following Monarc (RR ?5; 95% CI ?0.17 to 0.06). Objective cure was 93 % following MiniArc and 94 % following Monarc (RR ?1; 95% CI ?0.10 to 0.07). Both procedures have low complication rates.

Conclusions

At the 2-year follow-up, the non-prespecified analysis of this randomised trial showed that the MiniArc, a single-incision sling, had similar subjective and similar objective cure rates, although non-inferiority to Monarc for subjective cure could not be demonstrated.

     

CTX-M beta-lactamase-producing Escherichia coli in French hospitals: prevalence, molecular epidemiology, and risk factors

In 2004, 65 CTX-M-producing Escherichia coli isolates were collected from infected patients in four French hospitals. The blaCTX-M-15 genes were predominant. Pulsed-field gel electrophoresis highlighted a clonal propagation of CTX-M-15-producing strains belonging to phylogenetic group B2, notably in the community. The main risk factors for acquiring these isolates were urinary tract infections or the presence of a urinary catheter in diabetic or renal failure patients.     

Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone levels and behaviour in two strains of laboratory mouse

Behaviour was assessed in 32 C57BL/6JCrl and 32 C3H/HeN male mice 1 h following vasectomy; saline or meloxicam was administered 30 min prior to surgery at 5, 10, or 20 mg kg(-1). Faeces were collected 24 h prior to, and 3, 6, 9, 12, 24 h following, vasectomy for measurement of faecal corticosterone. Peak corticosterone levels were significantly higher in mice that underwent vasectomy and received saline (p<0.001) or meloxicam at 5 or 10 mg kg(-1) (p=0.021, and p<0.001, respectively) compared with normal un-operated controls. Mice that underwent vasectomy and received 20 mg kg(-1) meloxicam had peak corticosterone levels that were not different from normal un-operated mice (p=0.254). Discriminant analysis was used to identify behaviours responsible for group separation; these were summed to create two behaviour scores. Score 2 (the frequency of flinching, writhing, rear leg lift and press 2) was thought to be pain related; mice that underwent vasectomy and received saline exhibited significantly more of these behaviours than the normal controls (p=0.032), and the mice that received meloxicam (at any dose). Strain differences were observed in both the stress response to vasectomy and the behavioural changes; the C3H/HeN mice had higher pain scores (behaviour Score 2) and peak corticosterone responses than the C57BL/6JCrl mice. We have demonstrated that significant changes occur in the behaviour of mice following vasectomy, and these changes are reduced by use of meloxicam. Vasectomy elicits a rise in corticosterone levels that was only reduced by the highest dose of meloxicam.