Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

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

The Efficacy of Inositol and N-Acetyl Cysteine Administration (Ovaric HP) in Improving the Ovarian Function in Infertile Women with PCOS with or without Insulin Resistance

Objective. Substances such as inositol and N-acetylcysteine (NAC) have been recently shown to be effective in treatment of PCOS patients. The aim of this prospective trial is to evaluate the efficacy of NAC + Inositol + folic acid on ovulation rate and menstrual regularity in PCOS patients with and without insulin resistance. Methods. Among the 91 PCOS patients treated with NAC + Inositol + folic, insulin resistance was present in 44 subjects (A) and absent in 47 (B). The primary endpoint was the ovulation rate/year, determined by menstrual diary, serum progesterone performed between 21° and 24° days, ultrasound findings of growth follicular or luteal cysts, and luteal ratio. HOMA-index assessment after 6 and 12 months of treatment was evaluated as secondary endpoint. Results. In both groups there was a significant increase in ovulation rate and no significant differences were found in the primary outcome between two groups. In group A, a significant reduction of HOMA-index was observed. Conclusions. The association NAC + Inositol + folic, regardless of insulin-resistance state, seems to improve ovarian function in PCOS patients. Therefore, inositol and NAC may have additional noninsulin-related mechanisms of action that allow achieving benefits also in those patients with negative HOMA-index

Effectiveness of risedronate in osteoporotic postmenopausal women with inflammatory bowel disease: A prospective, parallel, open-label, two-year extension study

Objective: To evaluate long-term efficacy of risedronate in osteoporotic postmenopausal patients with inflammatory bowel disease (IBD).Design: A prospective, parallel, open-label, 2-year extension study of a randomized, double-blind, 1-year clinical trial. Eighty-one osteoporotic postmenopausal women with IBD were treated with risedronate (n = 40) or placebo (n = 41). Bone mineral density (BMD), biochemical bone turnover markers, and vertebral and nonvertebral fractures were assessed throughout the study. Data were analyzed using the intent-to-treat principle.Results: Significant (P &lt; 0.05) differences were observed between risedronate and placebo groups at 1-, 2-, and 3-year follow-up visits in bone turnover markers and in lumbar spine, trochanter, and femoral neck BMD. In partcipants treated with risedronate, the percentage of changes from baseline in bone turnover markers and in lumbar spine, trochanter, and femoral neck BMD were significantly (P &lt; 0.05) higher at 2- and 3-year follow-up in comparison with baseline and 1-year follow-up, with a significant (P &lt; 0.05) difference between the 2- and 3-year follow-up visits. At the end of the study, the cumulative risk of vertebral and nonvertebral fractures was significantly (P &lt; 0.05) lower in the risedronate group than in the placebo group. The relative risk for new vertebral fractures was 0.456 (95% CI: 0.134-1.559, P = 0.211) and 0.296 (95% CI: 0.121-0.721, P = 0.007) and was 0.209 (95% CI: 0.023-1.867, P = 0.161) and 0.137 (95% CI: 0.030-0.620, P = 0.010), respectively, for new nonvertebral fractures after 2 and 3 years of risedronate treatment.Conclusions: In postmenopausal osteoporotic women with IBD, long-term treatment with risedronate is effective in increasing BMD and reducing vertebral and nonvertebral fracture risk

Studio randomizzato controllato sul confronto tra due morcellatori tissutali: Gynecare Morcellex® versus Rotocut G1®

Obiettivo dello studio è quello di comparare la sicurezza e l’efficienza di due morcellatori tissutali, Gynecare Morcellex® e Rotocut G1®, per l’esecuzione di interventi di isterectomia sopracervicale e miomectomia per via laparoscopica. Si tratta di uno studio randomizzato controllato, svolto presso la Cattedra di Ginecologia e Ostetricia dell’Università “Magna Graecia” di Catanzaro. Sono state reclutate 74 donne con fibromi sintomatici e candidate per interventi di isterectomia sopracervicale o miomectomia per via laparoscopica, seguiti da morcellamento tissutale effettuato con Gynecare Morcellex® (gruppo sperimentale) o Rotocut G1® (gruppo controllo). Sono stati registrati per ogni paziente i parametri clinici, biochimici e chirurgici. Non sono state evidenziate differenze statisticamente significative tra i due gruppi di pazienti nel tempo operatorio totale (91.9±30.9 vs. 84.3±27.3, rispettivamente; P=0.264) e nel tempo di morcellamento (5.8±2.9 vs. 5.0±3.0 rispettivamente; P=0.281), mentre una differenza statisticamente significativa (P<0.05) è stata riscontrata nel grado di maneggevolezza del Morcellex® rispetto al Rotocut G1®. Tra i due gruppi non sono state registrate differenze in alcun altro parametro valutato. Concludendo, il Gynecare Morcellex® è uno strumento sicuro ed efficiente che potrebbe essere preferito da chirurghi con un minore grado di esperienza nel morcellamento elettronico di tessuti in corso di interventi laparoscopici