Introduction
We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development.
Aims: To assess the effects of a Pilates exercise program compared to conventional pelvic floor muscle training (PFMT) protocol on pelvic floor muscle strength (PFMS) in patients with post-prostatectomy urinary incontinence. Methods: Patients were randomized into three treatment groups (G1: Pilates, G2: electrical stimulation combined with PFMT, and G3: control group). Duration of therapy was 10 weeks. Baseline assessment included the 24 h pad-test and the ICI-Q questionnaire. PFMS was measured using a manometric perineometry device at baseline and 4 months after radical prostatectomy (RP). The level of significance was P < 0.05. Results: One hundred twenty three patients were randomized and 104 patients completed the study protocol (G1: n = 34; G2: n = 35; G3: n = 35). Post-treatment assessment showed statistically significant improvements in maximum strength in G2, increased endurance in G1 and G2, and increment of muscle power in all three groups (P < 0.05). However, there were no significant differences in the mean changes of maximum strength, endurance, and muscle power between groups after treatment (P > 0.05). G1 and G2 achieved a higher number of fully continent patients than G3 (P < 0.05). At the end of treatment, 59% of patients in G1, 54% in G2, and 26% in G3 were continent (no pads/day). Conclusions: Improvements in PFMS parameters were distinct among active treatment groups versus controls, but did not predict recovery of urinary continence at final assessment. The Pilates method promoted similar outcomes in the proportion of fully continent patients when compared to conventional PFMT 4 months after RP.
K E Y W O R D Spelvic floor muscle strength, Pilates protocol, radical prostatectomy, urinary incontinence Hashim Hashim led the peer-review process as the Associate Editor responsible for the paper.346 |
The objective of this study was to determine factors associated with vegetable contamination with zoonotic protozoan. Samples of water, soil and vegetables were collected from July/2014 to May/2016, totaling 83 samples, 21 properties of Londrina region, Paraná, Brazil. DNA amplification of Toxoplasma gondii, Cryptosporidium spp. and Giardia intestinalis in the samples was conducted using polymerase chain reaction (PCR). The PCR results were positive for T. gondii in 12.9% (8/62), Cryptosporidium spp. in 11.3% (7/62) and G. intestinalis in 25.8% (16/62) of the samples. DNA sequencing identified C. parvum in five samples and G. intestinalis Assemblage E in three. The statistical associations demonstrated greater probability of positive samples for T. gondii and for at least one of the three protozoa when the source of irrigation water was the river; a greater chance of positive samples for Cryptosporidium spp. when deer were present on the property; and a smaller chance of positive samples for at least one of the three etiologic agents when soil was supplemented with limestone. The results expose some critical contamination points, providing support for training farmers on good management practices during the production process.
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