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....     

Mapping vaccine hesitancy—Country-specific characteristics of a global phenomenon

The term vaccine hesitancy refers to delay in acceptance or refusal of vaccines despite the availability of vaccination services. Different factors influence vaccine hesitancy and these are context-specific, varying across time and place and with different vaccines. Factors such as complacency, convenience and confidence are involved. Acceptance of vaccines may be decreasing and several explanations for this trend have been proposed. The WHO Strategic Advisory Group of Experts (SAGE) on Immunization has recognized the global importance of vaccine hesitancy and recommended an interview study with immunization managers (IMs) to better understand the range of vaccine hesitancy determinants that are encountered in different settings. Interviews with IMs in 13 selected countries were conducted between September and December 2013 and various factors that discourage vaccine acceptance were identified. Vaccine hesitancy was not defined consistently by the IMs and most interpreted the term as meaning vaccine refusal. Although vaccine hesitancy existed in all 13 countries, some IMs considered its impact on immunization programmes to be a minor problem. The causes of vaccine hesitancy varied in the different countries and were context-specific, indicating a need to strengthen the capacity of national programmes to identify the locally relevant causal factors and to develop adapted strategies to address them.     

Topological methods reveal high and low functioning neuro‐phenotypes within fragile X syndrome

Fragile X syndrome (FXS), due to mutations of the FMR1 gene, is the most common known inherited cause of developmental disability as well as the most common single‐gene risk factor for autism. Our goal was to examine variation in brain structure in FXS with topological data analysis (TDA), and to assess how such variation is associated with measures of IQ and autism‐related behaviors. To this end, we analyzed imaging and behavioral data from young boys (n = 52; aged 1.57–4.15 years) diagnosed with FXS. Application of topological methods to structural MRI data revealed two large subgroups within the study population. Comparison of these subgroups showed significant between‐subgroup neuroanatomical differences similar to those previously reported to distinguish children with FXS from typically developing controls (e.g., enlarged caudate). In addition to neuroanatomy, the groups showed significant differences in IQ and autism severity scores. These results suggest that despite arising from a single gene mutation, FXS may encompass two biologically, and clinically separable phenotypes. In addition, these findings underscore the potential of TDA as a powerful tool in the search for biological phenotypes of neuropsychiatric disorders. Hum Brain Mapp 35:4904–4915, 2014. © 2014 Wiley Periodicals, Inc.     

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.     

Production of consonants by prelinguistically deaf children with cochlear implants

Consonant production following the sensory restoration of audition was investigated in 22 prelinguistically deaf French children who received cochlear implants. Spontaneous speech productions were recorded at 6, 12, and 18 months post‐surgery and consonant inventories were derived from both glossable and non‐glossable phones using two acquisition criteria. The results showed that children initiated appropriate production of consonants after six months of implant use. Stops and labials were the most frequently produced speech sounds, whereas glides and palatals were still infrequent after 18 months. Speech accuracy also improved throughout the study. Consonant visibility appeared to influence the order of acquisition in the first months following the implantation and, as experience with auditory information increased, patterns of development tended to resemble those seen in children with normal hearing. Finally, a signed mode of communication and oral rehabilitation programs prior to implantation were better outcome predictors than age at implantation.