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Reduced miR-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting RANK.

Osteoblasts and osteoclasts are responsible for the formation and resorption of bone, respectively. An imbalance between these two processes results in a disease called osteoporosis, in which a decreased level of bone strength increases the risk of a bone fracture. MicroRNAs (miRNAs) are small non-coding RNA molecules of 18-25 nucleotides that have been previously shown to control bone metabolism by regulating osteoblast and osteoclast differentiation. In the present study, we detected the expression pattern of 10 miRNAs in patient serum samples, and identified six miRNAs altered expression in patients with osteoporosis relative to non-osteoporosis. We selected miR-144-3p for further investigation, and showed that it regulates osteoclastogenesis by targeting RANK and that it is conserved amongst vertebrates. Disrupted expression of miR-144-3p in CD14+ PBMCs changed TRAP activity and the osteoclast-specific genes TRAP, cathepsin K (CTSK), and NFATC. TRAP staining,CCK-8 and flow cytometry analyses revealed that miR-144-3p also affects osteoclast formation, proliferation and apoptosis. Together, these results indicate that miR-144-3p critically mediates bone homeostasis, and thus, represents a promising novel therapeutic candidate for the treatment of this disease.

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Gender- and Muscle-Specific Responses During Fatiguing Exercise.

The purpose of the present investigation was to examine potential gender-related differences in electromyographic (EMG) and mechanomyographic (MMG) responses during submaximal, concentric, isokinetic, forearm flexion muscle contractions. Twelve men and twelve women performed concentric peak torque trials prior to (pretest) and following (posttest) a fatiguing exercise bout that consisted of 50 submaximal (65% of concentric peak torque), concentric, isokinetic (60°·s), forearm flexion muscle contractions. Surface EMG and MMG signals were simultaneously recorded from the biceps brachii and brachioradialis muscles. There was a gender-related difference in the decline in absolute concentric peak torque for the men (23.8%) versus women (18.5%) that was eliminated when covaried for differences in pretest concentric peak torque values. During the fatiguing exercise bout, EMG amplitude (AMP) increased and EMG mean power frequency (MPF) decreased for both genders and muscles. There were, however, muscle- and gender-specific increases, decreases, and no changes for MMG AMP and MMG MPF. The gender-related difference for the posttest decline in concentric peak torque was associated with differences in muscle strength which may have resulted in greater blood flow occlusion in the men than the women. The muscles with the most pronounced fatigue-induced neuromuscular responses were the biceps brachii in men and the brachioradialis in women. These findings may be related to gender differences in the usage patterns of synergistic muscles during a fatiguing task.

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Evaluation of recombinant factor VIIa, tranexamic acid and desmopressin to reduce prasugrel-related bleeding: A randomised, placebo-controlled study in a rabbit model.

Prasugrel is a thienopyridine that inhibits platelet aggregation more rapidly and effectively than clopidogrel, with an increased bleeding risk.

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Oxygen in the critically ill: friend or foe?

To examine the potential harmful effects of hyperoxia and summarize the results of most recent clinical studies evaluating oxygen therapy in critically ill patients.

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A Novel Hinged Scleral Patch Graft for the Repair of Overfiltration and Bleb Leaks.

The repair of the scleral flap is often needed in cases of severe hypotony or bleb leaks with over filtration. We present a simple novel technique to restore the hinged flap using a scleral patch graft.

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Improvement of endothelial function by pitavastatin: a meta-analysis.

Dyslipidemia is commonly associated with endothelial dysfunction and increased cardiovascular risk. Pitavastatin has been shown to reduce total and low-density lipoprotein cholesterol, to increase high-density lipoprotein (HDL)-cholesterol and improve HDL function. Furthermore, several trials explored its effects on flow-mediated dilation (FMD), as an index of endothelial function. The authors evaluated the effect of pitavastatin therapy on FMD.

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Activation state of circulating eosinophils in nasal polyposis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease with an uncertain pathophysiology. It is characterized by polyps rich in eosinophils, with an activation status already investigated at the tissue level. In a group of CRSwNP patients, we assessed the activation status of circulating eosinophils in the blood before migration into tissues.

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Combining allele frequency and tree-based approaches improves phylogeographic inference from natural history collections.

Model selection approaches in phylogeography have allowed researchers to evaluate the support for competing demographic histories, which provides a mode of inference and a measure of uncertainty in understanding climatic and spatial influences on intraspecific diversity. Here, to rank all models in the comparison set, and determine what proportion of the total support the top-ranked model garners, we conduct model selection using two analytical approaches -allele frequency-based, implemented in fastsimcoal2, and gene tree-based, implemented in PHRAPL. We then expand this model-selection framework by including an assessment of absolute fit of the models to the data. For this, we utilize DNA isolated from existing natural history collections that span the distribution of red alder (Alnus rubra) in the Pacific Northwest of North America to generate genomic data for the evaluation of 13 demographic scenarios. The quality of DNA recovered from herbarium specimen leaf tissue was assessed for its utility and effectiveness in demographic model selection, specifically in the two approaches mentioned. We present strong support for the use of herbarium tissue in the generation of genomic DNA, albeit with the inclusion of additional quality control checks prior to library preparation and analyses with multiple approaches that incorporate various data. Analyses with allele frequency spectra and gene trees predominantly support A. rubra having experienced an ancient vicariance event with intermittent and frequent gene flow between the disjunct populations. Additionally, the data consistently fit the most frequently selected model, corroborating the model selection techniques. Finally, these results suggest that the A. rubra disjunct populations do not represent separate species. This article is protected by copyright. All rights reserved.

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Early Burst in Body Size Evolution is Uncoupled from Species Diversification in Diving Beetles (Dytiscidae).

Changes in morphology are often thought to be linked to changes in species diversification, which is expected to leave a signal of Early Burst (EB) in phenotypic traits. However, such signal is rarely recovered in empirical phylogenies, even for groups with well-known adaptive radiation. Using a comprehensive phylogenetic approach in Dytiscidae, which harbors ~4,300 species with as much as 50-fold variation in body size among them, we ask whether pattern of species diversification correlates with morphological evolution. Additionally, we test if the large variation in body size is linked to habitat preference and if the later influences species turnover. We found, in sharp contrast to most animal groups, that Dytiscidae body size evolution follows an Early Burst model with subsequent high phylogenetic conservatism. However, we found no evidence for associated shifts in species diversification, which point to an uncoupled evolution of morphology and species diversification. We recovered the ancestral habitat of Dytiscidae as lentic (standing water), with many transitions to lotic habitat (running water) that are concomitant to a decrease in body size. Finally, we found no evidence for difference in net diversification rates between habitats nor difference in turnover in lentic and lotic species. This result, together with recent findings in dragonflies, contrasts with some theoretical expectations of the Habitat Stability Hypothesis. Thus, a thorough reassessment of the impact of dispersal, gene flow and range size on the speciation process is needed to fully encompass the evolutionary consequences of the lentic-lotic divide for freshwater fauna. This article is protected by copyright. All rights reserved.

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Towards the continuous production of Pt-based heterogeneous catalysts using microfluidic systems.

The continuous production of Pt-based heterogeneous catalysts based on ultra-small (<2 nm) noble metal nanoparticles deposited on mesoporous ordered silica and their catalytic activity in VOC abatement are here reported. Microfluidic reactors can be used not only to enable the fast and controlled production of ultra-small Pt nanoparticles (NPs), but also alloyed NPs including PtPd, PtRu and PtRh can be formed in short residence times (between 60 s and 5 min). A novel continuous and homogeneous loading of these catalytic NPs on SBA-15 used as a mesoporous support is also here reported. This procedure eases the NP loading and minimizes washing post-treatments. A 12-fold decrease in the synthesis time was obtained when using this microfluidic reactor compared to the traditional batch production of Pt NPs. Microflow and batch type reactors yielded a Pt precursor conversion to generate Pt NPs with a 90% and 85% yield, respectively. Under the same conditions, the productivity of the microfluidic system (27 mg Pt NPs per h) was twice the one achieved in the conventional batch type reactor. The catalytic performance of the supported catalysts separately prepared by microfluidics and by conventional impregnation under the same conditions and with the same noble metal loading was also compared in the n-hexane abatement as a model of VOCs. Both catalysts were active in the VOC oxidation reaction but a 95% reduction in the catalyst synthesis time was obtained when using the catalysts produced in the microfluidic platform. For this reaction a long-term activity test was successfully carried out at 175 °C during 30 h on stream using the heterogeneous catalyst prepared by using the flow reactor.

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