Importance of measuring pharmacologically active metabolites of edoxaban: development and validation of an ultra-high-performance liquid chromatography coupled with a tandem mass spectrometry method

Journal of Thrombosis and Thrombolysis - Although DOACs do not require regular measurements of their blood concentrations, clinical situations may require an assessment of their concentration....     

Platelet‐Rich Plasma–Assisted Guided Bone Regeneration for Ridge Augmentation: A Randomized,Controlled Clinical Trial

Background: Platelet‐rich plasma (PRP) contains a number of biologically active growth factors, and previous studies have reported conflicting ridge augmentation results. The primary aim of this randomized, controlled, masked, clinical trial was to determine if PRP combined with a rapidly resorbing cancellous allograft would enhance the regenerative result compared with an allograft without PRP. Methods: Thirty‐two patients with an edentulous ridge defect were sequentially entered into the study; four were excluded from data analysis. Fourteen patients received a cancellous allograft (CAN group) and the other 14 received a cancellous allograft mixed with PRP (PRP group). All 28 grafted sites were covered with a resorbable polylactide membrane. After elevation of a full‐thickness flap, horizontal ridge dimensions were measured with a digital caliper at the crest and 5 mm apical to the crest. Vertical ridge dimensions were measured from a tooth‐supported stent. All sites were reentered at 4 months, and a trephine core was obtained for histologic analysis before implant placement. Results: The crestal ridge width for the CAN group had a mean gain of 2.0 ± 1.2 mm, whereas the PRP group gained 2.9 ± 1.0, and the difference was statistically significant between groups (P <0.05). The percent vital bone was 36% ± 14% for the CAN group compared with 51% ± 15% for the PRP group and was statistically significant between groups (P <0.05). Loss of augmented ridge width was 34% ± 17% for the CAN group and 28% ± 17% for the PRP group (P >0.05). Conclusion: These clinical and histologic findings suggest that PRP enhanced bone regeneration and resulted in increased horizontal bone gain and percentage vital bone.     

High Hydrostatic Pressure Processing of Human Milk Increases Apelin and GLP-1 Contents to Modulate Gut Contraction and Glucose Metabolism in Mice Compared to Holder Pasteurization

Background: High hydrostatic pressure (HHP) processing is a non-thermal method proposed as an alternative to Holder pasteurization (HoP) for the sterilization of human breast milk (BM). HHP preserves numerous milk bioactive factors that are degraded by HoP, but no data are available for milk apelin and glucagon-like peptide 1 (GLP-1), two hormones implicated in the control of glucose metabolism directly and via the gut–brain axis. This study aims to determine the effects of HoP and HHP processing on apelin and GLP-1 concentrations in BM and to test the effect of oral treatments with HoP- and HHP-BM on intestinal contractions and glucose metabolism in adult mice. Methods: Mice were treated by daily oral gavages with HoP- or HHP-BM during one week before intestinal contractions, and glucose tolerance was assessed. mRNA expression of enteric neuronal enzymes known to control intestinal contraction was measured. Results: HoP-BM displayed a reduced concentration of apelin and GLP-1, whereas HHP processing preserved these hormones close to their initial levels in raw milk. Chronic HHP-BM administration to mice increased ileal mRNA nNos expression level leading to a decrease in gut contraction associated with improved glucose tolerance. Conclusion: In comparison to HoP, HPP processing of BM preserves both apelin and GLP-1 and improves glucose tolerance by acting on gut contractions. This study reinforces previous findings demonstrating that HHP processing provides BM with a higher biological value than BM treated by HoP.     

Early changes in white matter pathways of the sensorimotor cortex in premanifest Huntington's disease

Objectives: To investigate the function–structure relationship of white matter within different stages of Huntington's disease (HD) using diffusion tensor imaging (DTI). Experimental design: From the TRACK‐HD study, an early stage HD group and a premanifest gene carrier group (PMGC) were age‐matched to two healthy control groups; all underwent 3‐T MRI scanning of the brain. Region of interest (ROI) segmentation of the corpus callosum, caudate nucleus, thalamus, prefrontal cortex, and sensorimotor cortex was applied, and the apparent fiber pathways of these regions were analyzed. Functional measures of motor, oculomotor, cognition, and behavior were correlated to DTI measures. Principle observations: In PMGC versus controls, higher apparent diffusion coefficient (ADC) was seen in white matter pathways of the sensorimotor cortex (P < 0.01) and in the ROI of corpus callosum (P < 0.017). In early HD, fiber tract analysis showed higher ADC in pathways of the corpus callosum, thalamus, sensorimotor, and prefrontal region (P < 0.01). ROI analysis showed higher diffusivity in the corpus callosum and caudate nucleus (P < 0.017). Motor, oculomotor, cognition, and probability of onset within 2 and 5 years, correlated well with ADC measures of the corpus callosum (P < 0.01 – P < 0.005), sensorimotor (P < 0.01 – P < 0.005), and prefrontal region (P < 0.01). Conclusions: Disturbances in the white matter connections of the sensorimotor cortex can be demonstrated not only in manifest HD but also in premanifest gene carriers. Connectivity measures are well related to clinical functioning. DTI measures can be regarded as a potential biomarker for HD, due to their ability to objectify changes in brain structures and their role within brain networks. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Effect of variation in diacylglycerol kinase eta (DGKH) gene on brain function in a cohort at familial risk of bipolar disorder

Several lines of evidence indicate that the diacylglycerol kinase eta (DGKH) gene is implicated in the etiology of bipolar disorder (BD). However, the functional neural mechanisms of DGKH's risk association remain unknown. Therefore, we examined the effects of three haplotype-tagging risk variants in DGKH (single nucleotide polymorphisms rs9315885, rs1012053, and rs1170191) on brain activation using a verbal fluency functional magnetic resonance imaging task. The subject groups consisted of young individuals at high familial risk of BD (n=81) and a comparison group of healthy controls (n=75). Individuals were grouped based on risk haplotypes described in previous studies. There was a significant risk haplotype*group interaction in the left medial frontal gyrus (BA10, involving anterior cingulate BA32), left precuneus, and right parahippocampal gyrus. All regions demonstrated greater activation during the baseline condition than sentence completion. Individuals at high familial risk for BD homozygous for the DGKH risk haplotype demonstrated relatively greater activation (poor suppression) of these regions during the task vs the low-risk haplotype subjects. The reverse pattern was seen for the control subjects. These findings suggest that there are differential effects of the DGKH gene in healthy controls vs the bipolar high-risk group, which manifests as a failure to disengage default-mode regions in those at familial risk carrying the risk haplotype.     

Portal Vein Embolization in the Setting of Staged Hepatectomy with Preservation of Segment IV ± I Only for Bilobar Colorectal Liver Metastases: Safety,Efficacy, and Clinical Outcomes

Purpose

To assess frequency of adverse events, efficacy, and clinical outcomes of percutaneous portal vein embolization (PVE) in patients with bilobar colorectal liver metastases undergoing staged hepatectomy with preservation of segment IV ± I only.