Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

IntroductionLarge variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways.MethodsGenome Research at Fundacio ACE ([email protected]) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, [email protected] series were meta-analyzed with additional genome-wide association study data sets.ResultsWe classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444.DiscussionThe regulation of vasculature is a prominent causal component of probable AD. [email protected] meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.     

Determination of Chemical Antioxidants and Phenolic Compounds in the Brazilian Mushroom Agaricus sylvaticus

Agaricus sylvaticus mushroom has been widely studied because of its high nutritional value and medicinal properties. The objective of this study was to evaluate the antioxidant potential of both alcoholic and aqueous extracts of Agaricus sylvaticus and quantify their total polyphenol content. The antioxidant activity was performed by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity and total polyphenol content was assessed by colorimetric method. Observation also noted the great antioxidant potential of aqueous, alcoholic and ethereal extracts (14.6%, 75.6% and 14.6%, respectively) of the Agaricus sylvaticus mushroom, highlighting the alcoholic extract, which demonstrates the extraordinary benefits of this mushroom in the diet, since antioxidants prevent premature ageing and various types of cancer.     

Diaphragmatic Hernia Masquerading as a Pulmonary Metastasis

Iatrogenic injury accounts for the second most common cause of acquired diaphragmatic hernias after penetrating trauma. An increased incidence of these hernias has been observed with the widespread use of laparoscopic surgery. We present the case of a 65-year-old woman who initially underwent sigmoid resection for an adenocarcinoma and a subsequent liver resection for metastasis. She was noted to have a left lower lobe pulmonary nodule on surveillance computed tomography, for which she underwent a mini-thoracotomy for a planned resection. At the time of surgery, the pulmonary nodule was discovered to be a diaphragmatic hernia, most probably of iatrogenic origin. We discuss the difficulty in diagnosis given her history and the location of such a lesion.     

Bond strength of dual-cured resin cements to human teeth

PURPOSE: This study evaluated the bond strength of four commercial resin luting cements to enamel and superficial dentin, using a second-generation laboratory composite. MATERIALS AND METHODS: Forty teeth were embedded in acrylic: 20 had superficial dentin exposed; 20 had enamel exposed. Each group was divided into four subgroups (n = 5) to be bonded with Variolink II, Dual Cement, 2-bond-2, and Permalute System, using an inverted, truncated cone of pre-cured Artglass that was placed over the resin cement with a load of 2 N for 2 seconds. Specimens were stored at 37 degrees C in 100% relative humidity for 24 hours before being tested for tensile bond strength (MPa). Data were analyzed using a two-way analysis of variance. Tukey-Kramer intervals for comparisons among resin cements and bonding substrates were calculated at a .05 significance level. RESULTS: Significant differences were found among resin cements. Variolink II had statistically higher bond strength values for both substrates than the rest of the cements evaluated. When bonding was to enamel, all failures were cohesive in the composite, and when bonding was to dentin, some adhesive failures occurred at the resin cement-dentin interface. Permalute System had higher bond strengths than 2-bond-2 and Dual Cement when bonded to enamel. CONCLUSIONS: Variolink II and Permalute had statistically different bond strengths to enamel and dentin. Variolink II showed statistically higher values for dentin bonding than the other cements. Use of Variolink II and Permalute resulted in statistically higher bond strengths than the other two cements.     

巨大下颌骨囊性病变分期治疗效果评价

目的:探讨对巨大下颌骨囊性病变进行分期治疗的效果。方法:选择2005—2009年在本院收治的下颌骨范围大于5cm的囊性病变18例,其中伴牙列不齐者6例,一期局麻下行减压术,待范围减小至小于原来的1/2后,行二期全麻下囊性病变摘除术,即刻Bio-oss骨粉植入,术后每月定期拍摄口腔全景片观察骨密度变化,伴牙列不齐的6例患者手术后2个月开始以常规正畸加力牵引。结果:一期术后4~6个月,病变减小至原来的1/2左右,二期术后6~12个月,骨粉与周围正常骨密度基本一致,2~3a后无一例复发。6例牙列不齐的患者,经1~2a正畸治疗后,错畸形得以矫正。结论:分期治疗既彻底摘除了病变,又保存了下颌骨的连续性及自体牙,还可同时结合正畸治疗,改善错畸形,提高美学效果。     

Comparison between superficial femoral artery stenting and bypass surgery in severe lower-limb ischaemia: a retrospective study

Symptomatic superficial femoral artery (SFA) disease presenting either with severe claudication or critical limb ischaemia is treated with bypass surgery and traditionally has been the ‘goldstandard’ procedure. Surgical bypass using autogenous vein or prosthetic grafts as a conduit is well accepted and there are comparable patencies and limb salvage rates with either conduit.1There have been considerable advances in the last two decades in percutaneous endovascular technology for the treatment of SFA disease. The techniques that have been developed include percutaneous balloon angioplasty and stenting, with variable results.2,3 Despite having three different options, namely surgical bypass, balloon angioplasty and stenting, none is superior to the other.Although the five-year primary patency rate of femoropopliteal above-the-knee bypass with autogenous saphenous vein is 70%, this method of treatment is invasive with long incisions in the lower extremities and a peri-operative complication rate of 12%.4 Vascular surgeons have become more experienced with catheter-based technology and due to the minimal invasiveness of the procedure, both patients and vascular surgeons are increasingly attracted to endovascular procedures. Mwipatayi et al.5 and Nguyen et al.6 found stenting resulted in equivalent outcomes when compared to balloon angioplasty alone, but Laird et al.7 found that self-expanding nitinol stents were associated with better angiographic results and improved patency compared with balloon angioplasty alone.Randomised, controlled trials comparing bypass surgery and balloon angioplasty alone generally showed similar outcomes in terms of amputation-free survival but in the short term, surgery was more expensive than angioplasty.8 Another study comparing surgical bypass with balloon angioplasty and stenting showed better primary patency for the stent group (67%) than the bypass group (49%) and there were higher re-intervention rates in the bypass group.9Since there are conflicting data in the literature regarding the success of different methods of treatment of SFA disease and there is a lack of consensus guidelines on the optimum management of SFA disease, the aim of this study was to compare the results of stenting and surgical bypass in the local environment with regard to limb salvage rates in patients with severe leg ischaemia.     

Functional analysis of gene expression in risperidone treated cells provide new insights in molecular mechanism and new candidate genes for pharmacogenetic studies

Risperidone is a potent antagonist of both dopamine and serotonin receptors. However, little is known about the underlying molecular mechanism by which risperidone acts. Although a number of genetic variants have been observed to correlate with treatment response there are no definitive predictors of response. We performed a genome-wide gene expression analysis (Human Genome U219 Array Plate) of a human neuroblastoma cell line (SK-N-SH) exposed to risperidone to identify molecular mechanisms involved in the cellular response to risperidone and thus identify candidate genes for pharmacogenetic studies. Our results revealed that cellular risperidone treatment is associated with a range of gene expression changes, which are time (6–48 h) and dose related (0.1–10 μM). We found that functional clusters of these changes correspond to Gene Ontology categories related to neural cell development functions, and synaptic structure and functions. We also identified Canonical Pathways related to these functional categories: neurogenesis and axon guidance; synaptic vesicle; and neurotransmitter signaling (dopamine, serotonin and glutamate). Finally, we identified candidate genes for pharmacogenetic studies related to the main risperidone secondary effects: motor disorders, cardiovascular disorders and metabolic disorders. Our results suggest that risperidone treatment affects the neurogenesis and neurotransmission of neuroblastoma cells, which is in agreement with the “initiation and adaptation” model to explain the mechanism of action of psychotropic drugs.     

Phospholipid transfer between plasma and platelets in vitro

Washed rabbit platelets were resuspended in plasma in which all of the major phospholipids had been isotopically labeled by injection of 32PO4 into rabbits. At certain time intervals during a 6-hr incubation at 37 degrees C, aliquots were removed from the incubation mixture and the platelets were isolated and subjected to lipid extraction and phospholipid analysis. A continuous rise in platelet non-lipid-bound and lipid-bound radioactivity was observed through-out the incubation period. Two platelet phospholipids, lecithin and lysolecithin, were significantly labeled, whereas little or no labeling of the other phospholipids was found. There was no detectable change in total or individual platelet phospholipid content. At 6 hr, 4% of total platelet phospholipid, 43% of platelet lysolecithin, and 7% of platelet lecithin were labeled. Platelets incubated in plasma from rabbits with diet- induced hyperlipidemia took up and incorporated significantly more label into their phospholipids than did platelets in normal plasma. Labeling of both platelet lysolecithin and lecithin could be due to uptake and metabolism of plasma lysolecithin by platelets. However, labeling of platelet lecithin could at least in part be the result of direct exchange of this phospholipid with the plasma. Uptake and incorporation of endogenous plasma lysolecithin by platelets and, possibly, direct exchanged of platelet lecithin may be important mechanisms in the modification by plasma lipids of platelet membrane phospholipid fatty acid composition and platelet function.