title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Catalytic asymmetric functionalization of aromatic C-H bonds by electrophilic trapping of metal-carbene-induced zwitterionic intermediates. | Asymmetric functionalization of aromatic C-H bonds of N,N-disubstituted anilines with diazo compounds and imines is reported for the efficient construction of α,α-diaryl benzylic quaternary stereocenters in good yields with high diastereoselectivities and excellent enantioselectivities. This Rh(II)/chiral phosphoric acid cocatalyzed transformation is proposed to proceed through a metal-carbene-induced zwitterionic intermediate which undergoes electrophilic trapping. To the best of our knowledge, this is the first asymmetric example of metal carbene-induced intermolecular functionalization of aryl C-H bonds. | 25,195,569 | [
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Renal parenchymal histopathology predicts life-threatening chronic kidney disease as a result of radical nephrectomy. | The preoperative prediction of post-radical nephrectomy renal insufficiency plays an important role in the decision-making process regarding renal surgery options. Furthermore, the prediction of both postoperative renal insufficiency and postoperative cardiovascular disease occurrence, which is suggested to be an adverse consequence caused by renal insufficiency, contributes to the preoperative policy decision as well as the precise informed consent for a renal cell carcinoma patient. Preoperative nomograms for the prediction of post-radical nephrectomy renal insufficiency, calculated using patient backgrounds, are advocated. The use of these nomograms together with other types of nomograms predicting oncological outcome is beneficial. Post-radical nephrectomy attending physicians can predict renal insufficiency based on the normal renal parenchymal pathology in addition to preoperative patient characteristics. It is suggested that a high level of global glomerulosclerosis in nephrectomized normal renal parenchyma is closely associated with severe renal insufficiency. Some studies showed that post-radical nephrectomy severe renal insufficiency might have an association with increased mortality as a result of cardiovascular disease. Therefore, such pathophysiology should be recognized as life-threatening, surgically-related chronic kidney disease. On the contrary, the investigation of the prediction of mild post-radical nephrectomy renal insufficiency, which is not related to adverse consequences in the postoperative long-term period, is also promising because the prediction of mild renal insufficiency might be the basis for the substitution of radical nephrectomy for nephron-sparing surgery in technically difficult or compromised cases. The deterioration of quality of life caused by post-radical nephrectomy renal insufficiency should be investigated in conjunction with life-threatening matters. | 25,195,572 | [
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Stereoscopic visualization and quantification of auricular cartilage regeneration in rabbits using multiphoton microscopy. | Multiphoton microscopy (MPM) was applied for imaging and quantifying the elastic cartilage regeneration tissue in a rabbit ear model without using labeling agents. Morphology of cells and collagen matrix were analysis, showing significant difference between regenerated and intact cartilage in cellular size and collagen distribution. The results demonstrate that high resolution images provide by MPM are consistent with the histological results, and show additional biological behavior which is not visible in standard histology. Advantages in instrumentation may lead to the application of MPM for intravital detection and treatment. | 25,195,587 | [
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Polymer sieving matrices in microanalytical electrophoresis. | Microfluidic design has advanced existing protein separation capabilities and supported novel assays. Key metrics for successful protein separations include fast, robust, and sensitive analysis of complex mixtures of bio-macromolecules. Attaining high separation resolution is a chief concern. Here we review recent advances in polymer-based electrophoresis sieving materials that are impacting microfluidic bioanalytical applications. Looking forward, we comment on unmet needs for advanced separation media in micro-to-nanoscale devices. | 25,195,612 | [
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Facile synthesis of one-dimensional Mn₃O₄/Zn₂SnO₄ hybrid composites and their high performance as anodes for LIBs. | One-dimensional (1D) Mn₃O₄ nanorod/Zn2SnO4 nanoneedle hierarchical composites were conveniently synthesized via a simple hydrothermal process at 180 °C for 24 h. It was found that the reaction time and an appropriate amount of ammonia play vital roles during their formation process, and their formation is likely driven by the lattice match of the cubic Zn₂SnO₄ nanoneedles and cubic Mn₃O₄ nanorods. The as-obtained composites deliver a high initial discharge capacity of 1370.9 mA h g(-1) at 100 mA g(-1) in the range of 0.01-3.0 V, and a reversible specific capacity of 577.4 mA h g(-1) could be retained after 50 cycles. It is noteworthy that 441.5 mA h g(-1) could be maintained after 50 cycles even if the current density was set as high as 1000 mA h g(-1), and the rate performance of nanocomposites (200, 500, 1000 mA g(-1)) also shows excellent reversible character. The high specific capacity, good cycling stability and high rate performance of the as-obtained composites enable them to be promising and competitive high-performance anodes in lithium-ion batteries (LIBs). It is worth noting that the fabrication method reported here can be easily extended to prepare other 1D metal oxide hybrid materials including Mn₃O₄/ZnFe₂O₄, Mn₂O₃/CoFe₂O₄ and Mn₂O₃/NiFe₂O₄ composites via a similar hydrothermal process with/without subsequent calcination, which hold great promise for their wide potential applications in energy, catalysis and environmental science and technology. | 25,195,654 | [
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Synthesis of Pt-Ni alloy nanocrystals with high-index facets and enhanced electrocatalytic properties. | The shape-controlled synthesis of multicomponent metal nanocrystals (NCs) bounded by high-index facets (HIFs) is of significant importance in the design and synthesis of high-activity catalysts. We report herein the preparation of Pt-Ni alloy NCs by tuning their shape from concave-nanocubic (CNC) to nanocubic and hexoctahedral (HOH). Owing to the synergy of the HIFs and the electronic effect of the Pt-Ni alloy, the as-prepared CNC and HOH Pt-Ni alloy NCs exhibited excellent catalytic properties for the electrooxidation of methanol and formic acid, as well as for the oxygen reduction reaction (ORR). | 25,195,668 | [
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Curcumin inhibits the proliferation and invasiveness of MHCC97-H cells via p38 signaling pathway. | Curcumin has been reported to be effective as a cancer therapy. However, the anti-metastatic effect and molecular mechanism(s) of curcumin in hepatocellular carcinoma (HCC) remain poorly understood. The purpose of this study was to test the effects of curcumin on HCC and its putative mechanism(s). Curcumin inhibited the proliferation of HCC cells and inhibited the migration and invasion of these cells at sub-cytotoxic concentrations. Curcumin also decreased the expression and activity of matrix metalloproteinases (MMP)-2 and MMP-9, and reduced p38 phosphorylation. Combination treatment of HCC cells with curcumin and SB203580 (a p38 signaling pathway inhibitor), generated a synergistic effect on the expression of MMP-2 and MMP-9, suggesting that the anti-metastatic effect of curcumin on HCC may involve a p38 signaling pathway. | 25,195,681 | [
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Coeliac-like duodenal pathology in orthotopic liver transplant patients on mycophenolic acid therapy. | Diarrhoea following orthotopic liver transplantation (OLT) is a significant clinical problem associated with mycophenolic acid (MPA). The histological injury pattern associated with MPA in the large bowel is well documented in the literature; however, that in the duodenum is less extensively documented. The aim of this study was to investigate the histological spectrum of duodenal injury specifically in symptomatic OLT patients on MPA, and to compare this with the spectrum in patients with coeliac disease and in normal controls. We reviewed our pathology database for all duodenal biopsies from patients on the OLT list over a period of 19 years. Medical records, anti-tissue transglutaminase IgA serology and histology were reviewed. Of the 667 patients who underwent endoscopy, 127 had duodenal biopsies (152 biopsies). Of these, 87.5% were normal. Sixteen showed abnormal histology, and seven (43.8%) of these were on MPA at the time of biopsy. Significant features included coeliac-like changes (shortened villi and increased intraepithelial lymphocyte counts), and novel findings included increased endocrine cell counts, apoptotic counts and lamina propria eosinophil counts in comparison with normal duodenal biopsies. Pathologists should be aware of the features of MPA-associated duodenal injury, including coeliac-like changes and increased apoptotic counts. In those with abnormal histology, discontinuation or a reduction in the dose of MPA should be discussed. | 25,195,696 | [
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Synaptic Pathophysiology and Treatment of Lambert-Eaton Myasthenic Syndrome. | Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that disrupts the normally reliable neurotransmission at the neuromuscular junction (NMJ). This disruption is thought to result from an autoantibody-mediated removal of a subset of the P/Q-type Ca(2+) channels involved with neurotransmitter release. With less neurotransmitter release at the NMJ, LEMS patients experience debilitating muscle weakness. The underlying cause of LEMS in slightly more than half of all patients is small cell lung cancer, and cancer therapy is the priority for these patients. In the remaining cases, the cause of LEMS is unknown, and these patients often rely on symptomatic treatment options, as there is no cure. However, current symptomatic treatment options, such as 3,4-diaminopyridine (3,4-DAP), can have significant dose-limiting side effects; thus, additional treatment approaches would benefit LEMS patients. Recent studies introduced a novel Ca(2+) channel agonist (GV-58) as a potential therapeutic alternative for LEMS. Additionally, this work has shown that GV-58 and 3,4-DAP interact in a supra-additive manner to completely restore the magnitude of neurotransmitter release at the NMJs of a LEMS mouse model. In this review, we discuss synaptic mechanisms for reliability at the NMJ and how these mechanisms are disrupted in LEMS. We then discuss the current treatment options for LEMS patients, while also considering recent work demonstrating the therapeutic potential of GV-58 alone and in combination with 3,4-DAP. | 25,195,700 | [
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Effects of green tea and physical exercise on memory impairments associated with aging. | We investigated the effects of physical exercise and green tea supplementation (associated or not) on biochemical and behavioral parameters in the time course of normal aging. Male Wistar rats aged 9 months were divided into groups: control, physical exercise (treadmill running), and supplemented with green tea while either performing physical exercise or not. A young control group was also studied. Physical exercise and green tea supplementation lasted 3 months. Afterwards, behavioral and biochemical tests were performed. Biochemical measurements revealed differences in antioxidant and oxidant responses in hippocampus, prefrontal cortex and striatum. Behavioral testing showed age-related memory impairments reversed by physical exercise. The association of green tea supplementation and physical exercise did not provide aged rats with additional improvements in memory or brain oxidative markers. Green tea per se significantly decreased reactive oxygen species levels and improved antioxidant defenses although it did not reverse memory deficits associated with normal aging. | 25,195,719 | [
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Measurement and the interpretation of burden in the Alzheimer's disease experience. | Three components of the Alzheimer's disease care equation are considered : impairment, felt burden, and the institutionalization decision. Measurement and the results of existing studies are compared with field data on the descriptive organization of the caregiving experience. It is suggested that measurement is an inappropriate language for depicting the experience, empirically distorting what is otherwise a practical process of definition and interpretive transformation, shaped in, and constrained by, caregivers' continuing attention to the meaning of their burden. | 25,195,724 | [
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Virulence and genotypic characterization of Listeria monocytogenes isolated from vegetable and soil samples. | Listeria monocytogenes, a foodborne pathogen is ubiquitous to different environments including the agroecosystem. The organism poses serious public health problem. Therefore, an attempt has been made to gain further insight to their antibiotic susceptibility, serotypes and the virulence genes. Out of the 10 vegetables selected, 6 (brinjal, cauliflower, dolichos-bean, tomato, chappan-kaddu and chilli), 20 isolates (10%) tested positive for L. monocytogenes. The prevalence of the pathogen in the respective rhizosphere soil samples was 5%. Noticeably, L. monocytogenes was absent from only cabbage, broccoli, palak and cowpea, and also the respective rhizospheric soils. The 30 isolates + ve for pathogenicity, belonged to serogroup 4b, 4d or 4e, and all were positive for inlA, inlC, inlJ, plcA, prfA, actA, hlyA and iap gene except one (VC3) among the vegetable isolates that lacked the plcA gene. ERIC- and REP-PCR collectively revealed that isolates from vegetables and their respective rhizospheric soils had distinct PCR fingerprints. The study demonstrates the prevalence of pathogenic L. monocytogenes in the selected agricultural farm samples. The increase in the number of strains resistant to ciprofloxacin and/or cefoxitin seems to pose serious public health consequences. | 25,195,727 | [
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Priming IKKβ kinase for action. | IKKβ (IκB kinase β) is a core component of signalling pathways that control the activation of NF-κB (nuclear factor κB) transcription factors, which regulate many physiological processes, including cell survival, immunity and DNA-damage responses. Like many kinases, activation of IKKβ requires phosphorylation of the activation loop of its kinase domain. Different upstream protein kinases, and IKKβ itself, have been reported to directly phosphorylate and activate IKKβ in vitro, but the exact molecular mechanism of IKKβ activation in cells has remained unclear. In a recent article in the Biochemical Journal, Zhang and co-workers showed that IKKβ is activated by two sequential phosphorylations of its activation loop in response to TNF (tumour necrosis factor), IL-1 (interleukin-1) and TLR (Toll-like receptor) ligands. Using a combination of biochemical and genetic approaches, they demonstrate that IKKβ is first phosphorylated by the upstream kinase TAK1 [TGFβ (transforming growth factor β)-activated kinase-1] at Ser177, which then serves as a priming signal for subsequent IKKβ autophosphorylation at Ser181. This study resolves two apparently conflicting earlier models of IKKβ activation into a single unified model, and suggests that the IKKβ activation loop may integrate distinct 'upsteam' signals to activate NF-κB. | 25,195,736 | [
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Satellite tobacco mosaic virus refined to 1.4 Å resolution. | Satellite tobacco mosaic virus (STMV) is among the smallest viruses, having 60 identical subunits arranged with T = 1 icosahedral symmetry. Its crystal structure was solved at 290 K and was refined using, in part, crystals grown in microgravity. Electron-density maps revealed nearly 57% of the genomic ssRNA. Using six flash-cooled crystals, diffraction data were recorded to 1.4 Å resolution and independent refinements of the STMV model were carried out versus the previous 1.8 Å resolution data representing merged data from 21 crystals (271,689 unique reflections), data consisting of corresponding reflections to 1.8 Å resolution from the cooled crystals and 1.4 Å resolution data from the cooled crystals comprised of 570,721 unique reflections. Models were independently refined with full NCS constraints using the program CNS and in restrained mode using the programs CNS, REFMAC5 and SHELX-97, with the latter two procedures including anisotropic temperature factors. Significant additional structural detail emerged from the analyses, including a unique cation and anion arrangement on fivefold axes and a precise assessment of icosahedral symmetry exactness in the crystal lattice. STMV represents the highest resolution native virus structure currently known by a substantial margin, and it permits the evaluation of a precise atomic model of a spherical virus at near-atomic resolution for the first time. | 25,195,746 | [
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Space-group and origin ambiguity in macromolecular structures with pseudo-symmetry and its treatment with the program Zanuda. | The presence of pseudo-symmetry in a macromolecular crystal and its interplay with twinning may lead to an incorrect space-group (SG) assignment. Moreover, if the pseudo-symmetry is very close to an exact crystallographic symmetry, the structure can be solved and partially refined in the wrong SG. Typically, in such incorrectly determined structures all or some of the pseudo-symmetry operations are, in effect, taken for crystallographic symmetry operations and vice versa. A mistake only becomes apparent when the R(free) ceases to decrease below 0.39 and further model rebuilding and refinement cannot improve the refinement statistics. If pseudo-symmetry includes pseudo-translation, the uncertainty in SG assignment may be associated with an incorrect choice of origin, as demonstrated by the series of examples provided here. The program Zanuda presented in this article was developed for the automation of SG validation. Zanuda runs a series of refinements in SGs compatible with the observed unit-cell parameters and chooses the model with the highest symmetry SG from a subset of models that have the best refinement statistics. | 25,195,756 | [
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Post-traumatic stress disorder among Syrian refugees in Turkey: a cross-sectional study. | Refugees have had major challenges to meet their health care needs throughout history especially in war zones and natural disaster times. The health care needs of Syrian refugees have been becoming an increasingly important issue. We aimed to examine the prevalence of post-traumatic stress disorder (PTSD) and explore its relation with various socioeconomic variables among Syrian refugees, who sought asylum in Turkey. This cross-sectional study was conducted in a tent city. Sample size calculation yielded 352 and the participants of the study were determined randomly. Experienced and native Arabic speaking, psychiatrist evaluated the participants. The frequency of PTSD was 33.5%. Through the binary logistic regression analysis, we calculated that the probability of having PTSD among Syrian refugees in our sample was 71%, if they had the following features: with female gender; being diagnosed with psychiatric disorder in the past; having a family history of psychiatric disorder; and experiencing 2 or more traumas. The findings of our study suggest that PTSD among Syrian refugees in Turkey might be an important mental health issue in refugee camps especially among female refugees, who were exposed to 2 or more traumatic events and had a personal or family history of psychiatric disorder. | 25,195,765 | [
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T cell-based targeted immunotherapies for patients with multiple myeloma. | Despite high-dose chemotherapy followed by autologs stem-cell transplantation as well as novel therapeutic agents, multiple myeloma (MM) remains incurable. Following the general trend towards personalized therapy, targeted immunotherapy as a new approach in the therapy of MM has emerged. Better progression-free survival and overall survival after tandem autologs/allogeneic stem cell transplantation suggest a graft versus myeloma effect strongly supporting the usefulness of immunological therapies for MM patients. How to induce a powerful antimyeloma effect is the key issue in this field. Pivotal is the definition of appropriate tumor antigen targets and effective methods for expansion of T cells with clinical activity. Besides a comprehensive list of tumor antigens for T cell-based approaches, eight promising antigens, CS1, Dickkopf-1, HM1.24, Human telomerase reverse transcriptase, MAGE-A3, New York Esophageal-1, Receptor of hyaluronic acid mediated motility and Wilms' tumor gene 1, are described in detail to provide a background for potential clinical use. Results from both closed and on-going clinical trials are summarized in this review. On the basis of the preclinical and clinical data, we elaborate on three encouraging therapeutic options, vaccine-enhanced donor lymphocyte infusion, chimeric antigen receptors-transfected T cells as well as vaccines with multiple antigen peptides, to pave the way towards clinically significant immune responses against MM. | 25,195,787 | [
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Stimulus-responsive ultrasound contrast agents for clinical imaging: motivations, demonstrations, and future directions. | Microbubble ultrasound contrast agents allow imaging of the vasculature with excellent resolution and signal-to-noise ratios. Contrast in microbubbles derives from their interaction with an ultrasound wave to generate signal at harmonic frequencies of the stimulating pulse; subtracting the elastic echo caused by the surrounding tissue can enhance the specificity of these harmonic signals significantly. The nonlinear acoustic emission is caused by pressure-driven microbubble size fluctuations, which in both theoretical descriptions and empirical measurements was found to depend on the mechanical properties of the shell that encapsulates the microbubble as well as stabilizes it against the surrounding aqueous environment. Thus biochemically induced switching between a rigid 'off' state and a flexible 'on' state provides a mechanism for sensing chemical markers for disease. In our research, we coupled DNA oligonucleotides to a stabilizing lipid monolayer to modulate stiffness of the shell and thereby induce stimulus-responsive behavior. In initial proof-of-principle studies, it was found that signal modulation came primarily from DNA crosslinks preventing the microbubble size oscillations rather than merely damping the signal. Next, these microbubbles were redesigned to include an aptamer sequence in the crosslinking strand, which not only allowed the sensing of the clotting enzyme thrombin but also provided a general strategy for sensing other soluble biomarkers in the bloodstream. Finally, the thrombin-sensitive microbubbles were validated in a rabbit model, presenting the first example of an ultrasound contrast agent that could differentiate between active and inactive clots for the diagnosis of deep venous thrombosis. | 25,195,785 | [
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Microbial community composition and in silico predicted metabolic potential reflect biogeochemical gradients between distinct peatland types. | It is not well understood how the ecological status and microbial community composition of spruce swamp forests (SSF) relate to those found in bogs and fens. To clarify this, we investigated biogeochemical parameters and microbial community composition in a bog, a fen and two SSF using high throughput barcoded sequencing of the small ribosomal subunit (SSU) variable region V4. The results demonstrated that the microbial community of SSF is positioned between those of bogs and fens, and this was confirmed by in silico predicted metabolic potentials. This corresponds well with the position of SSF on the trophic gradient and reflects distinct responses of microbial communities to environmental variables. Species richness and microbial diversity increased significantly from bog to fen, with SSF in between, reflecting the variation in pH, nutrient availability and peat decomposability. The archaeal community, dominated by hydrogenotrophic methanogens, was more similar in SSF and the bog compared with the fen. The composition of the bacterial community of SSF was intermediate between those of bog and fen. However, the production of CO2 (an indicator of peat decomposability) did not differ between SSF and bog, suggesting the limiting effect of low pH and poor litter quality on the functioning of the bacterial community in SSF. These results help to clarify the transitional position of SSF between bogs and fens and showed the strong effect of environmental conditions on microbial community composition and functioning. | 25,195,805 | [
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The hexosamine biosynthetic pathway induces gene promoter activity of acetyl-CoA carboxylase beta. | The cardiac isoform of acetyl-CoA carboxylase (ACCβ) produces malonyl-CoA, a potent inhibitor of mitochondrial fatty acid (FA) uptake. Higher ACCβ activity decreases FA utilization, potentially leading to intracellular myocardial lipid accumulation and insulin resistance (IR). Since increased hexosamine biosynthetic pathway (HBP) flux is linked to IR onset, we hypothesized that HBP activation leads to the induction of ACCβ gene promoter activity. Rat H9c2 cardio-myoblasts were transiently transfected with a 1317bp human ACCβ promoter-luciferase construct (pPIIβ-1317)±an expression construct encoding the HBP rate-limiting step, i.e., glutamine:fructose 6-phosphate amidotransferase (GFAT)±various HBP modulators. The administration of l-glutamine (HBP substrate) dose-dependently increased, while HBP inhibitors attenuated pPIIβ-1317 activity. Co-transfections with dominant-negative GFAT constructs diminished pPIIβ-1317 activity. To explore underlying transcriptional mechanisms, we co-transfected with upstream stimulatory factor (USF) expression constructs and found that USF2 induced pPIIβ-1317 activity vs. controls. Moreover, co-transfection of a GFAT expression construct+USF reporter-promoter construct (with consensus USF binding elements) led to induction of pPIIβ-1317 activity vs. controls. We next performed transfections with GFAT±full length ACCβ and seven truncated promoter-luciferase constructs, respectively. Here GFAT-mediated ACCβ promoter induction was blunted when co-transfected with the pPIIβ-38/+65 deletion construct indicating that USF2 binds to the proximal ACCβ promoter region (near start codon). Our study demonstrates that HBP activation induces ACCβ gene promoter activity in H9c2 cells via USF2. We propose that such ACCβ induction may elicit serious downstream effects, e.g. the inhibition of FA β-oxidation and the onset of IR. | 25,195,817 | [
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Ceramide modulates pre-mRNA splicing to restore the expression of wild-type tumor suppressor p53 in deletion-mutant cancer cells. | Mutants of tumor suppressor p53 not only lose the activity in genome stabilizing and in tumor suppression, but also exhibit oncogenic function in cancer cells. Most efforts in restoring p53 biological activity focus on either altering mutant-protein conformation or introducing an exogenous p53 gene into cells to eliminate p53-mutant cancer cells. Being different from these, we report that ceramide can restore the expression of wild-type p53 and induce p53-dependent apoptosis in deletion-mutant cancer cells. We show that endogenous long-carbon chain ceramide species (C16- to C24-ceramides) and exogenous C6-ceramide, rather than other sphingolipids, restore wild-type mRNA (intact exon-5), phosphorylated protein (Ser15 in exon-5) of p53, and p53-responsive proteins, including p21 and Bax, in ovarian cancer cells, which predominantly express a deleted exon-5 of p53 mutant before treatments. Consequently, the restored p53 sensitizes these p53-mutant cancer cells to DNA damage-induced growth arrest and apoptosis. Furthermore, we elucidate that ceramide activates protein phosphatase-1, and then the dephosphorylated serine/arginine-rich splicing-factor 1 (SRSF1) is translocated to the nucleus, thus promoting pre-mRNA splicing preferentially to wild-type p53 expression. These findings disclose an unrecognized mechanism that pre-mRNA splicing dysfunction can result in p53 deletion-mutants. Ceramide through SRSF1 restores wild-type p53 expression versus deletion-mutant and leads cancer cells to apoptosis. This suggests that heterozygous deletion-mutants of p53 can be restored in posttranscriptional level by using epigenetic approaches. | 25,195,822 | [
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Support for aging policy: Self-interest, social justice, and political symbols. | This article explores and evaluates theoretical assumptions implied by the familiar hypothesis that anti-elderly scapegoating rhetoric is producing attitude change with respect to citizen support for aging policy. An explanation-the self-interest model-that is consistent with both this hypothesis and existing attitude theory is presented. It is contrasted with a second hypothesis emphasizing the role played by symbolic political attitudes in the formation of citizen policy positions. Survey data from the state of Kansas indicate no support for either the self-interest explanation of aging policy attitudes or for the hypothesized impact of anti-elderly rhetoric. | 25,195,846 | [
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Optimization of a cell counting algorithm for mobile point-of-care testing platforms. | In a point-of-care (POC) setting, it is critically important to reliably count the number of specific cells in a blood sample. Software-based cell counting, which is far faster than manual counting, while much cheaper than hardware-based counting, has emerged as an attractive solution potentially applicable to mobile POC testing. However, the existing software-based algorithm based on the normalized cross-correlation (NCC) method is too time- and, thus, energy-consuming to be deployed for battery-powered mobile POC testing platforms. In this paper, we identify inefficiencies in the NCC-based algorithm and propose two synergistic optimization techniques that can considerably reduce the runtime and, thus, energy consumption of the original algorithm with negligible impact on counting accuracy. We demonstrate that an AndroidTM smart phone running the optimized algorithm consumes 11.5× less runtime than the original algorithm. | 25,195,851 | [
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Particle swarm inspired underwater sensor self-deployment. | Underwater sensor networks (UWSNs) can be applied in sea resource reconnaissance, pollution monitoring and assistant navigation, etc., and have become a hot research field in wireless sensor networks. In open and complicated underwater environments, targets (events) tend to be highly dynamic and uncertain. It is important to deploy sensors to cover potential events in an optimal manner. In this paper, the underwater sensor deployment problem and its performance evaluation metrics are introduced. Furthermore, a particle swarm inspired sensor self-deployment algorithm is presented. By simulating the flying behavior of particles and introducing crowd control, the proposed algorithm can drive sensors to cover almost all the events, and make the distribution of sensors match that of events. Through extensive simulations, we demonstrate that it can solve the underwater sensor deployment problem effectively, with fast convergence rate, and amiable to distributed implementation. | 25,195,852 | [
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Prevalence and cost of epilepsy in Sweden--a register-based approach. | To estimate the prevalence of epilepsy, costs associated with in- and outpatient care, drug utilization and productivity losses due to epilepsy in Sweden for the years 2005 and 2011. Cost components were calculated using registry data on inpatient- and outpatient-care utilization, drug sales and early pensions granted due to permanent disability and mortality. Moreover, by cross-identification of information in healthcare and pharmaceutical registries, we were able to distinguish between pharmaceuticals prescribed for epilepsy and non-epilepsy indications. The prevalence of epilepsy was estimated at 0.62% in 2005 and 0.88% in 2011. The total cost of epilepsy increased during the same period, while the per-patient cost decreased from €2929 to €1729. Direct medical costs accounted for about 36% of the estimated total cost in 2005 and 60% in 2011. The estimated healthcare cost due to epilepsy as a share of total healthcare costs for all illnesses was about the same in 2005 as in 2011 (0.2%), while the corresponding pharmaceutical cost increased from about 0.5% in 2005 to almost 1% in 2011. The per-patient cost of epilepsy is substantial, implying a significant aggregated cost incurred on society (despite a prevalence < 1%). Our results suggest that the per-patient pharmaceutical utilization increased, while the per-patient physician visits and hospitalizations decreased, between 2005 and 2011. Moreover, we demonstrate that the 2005 prevalence measure was underestimated the true prevalence in 2005. | 25,195,857 | [
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The role of pericyte detachment in vascular rarefaction. | Pericytes surround endothelial cells at the perivascular interface. Signaling between endothelial cells and pericytes is crucial for capillary homeostasis, as pericytes stabilize vessels and regulate many microvascular functions. Recently it has been shown that pericytes are able to detach from the vascular wall and contribute to fibrosis by becoming scar-forming myofibroblasts in many organs including the kidney. At the same time, the loss of pericytes within the perivascular compartment results in vulnerable capillaries which are prone to instability, pathological angiogenesis, and, ultimately, rarefaction. This review will give an overview of pericyte-endothelial cell interactions, summarize the signaling pathways that have been identified to be involved in pericyte detachment from the vascular wall, and present pathological endothelial responses in the context of disease of the kidney. | 25,195,856 | [
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Controlling sulphur precursor addition for large single crystal domains of WS2. | We show that controlling the introduction time and the amount of sulphur (S) vapour relative to the WO3 precursor during the chemical vapour deposition (CVD) growth of WS2 is critical to achieving large crystal domains on the surface of silicon wafers with a 300 nm oxide layer. We use a two furnace system that enables the S precursor to be separately heated from the WO3 precursor and growth substrate. Accurate control of the S introduction time enabled the formation of triangular WS2 domains with edges up to 370 μm which are visible to the naked eye. The WS2 domains exhibit room-temperature photoluminescence with a peak value around ∼635 nm and a full-width at half-maximum (FWHM) of ∼12 nm. Selected area electron diffraction from different regions of the triangular WS2 domains showed that they are single crystal structures. | 25,195,869 | [
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High-resolution crystal structures of alternate forms of the human CD44 hyaluronan-binding domain reveal a site for protein interaction. | Two new crystal structures of the extracellular hyaluronan-binding domain of human CD44 are described at high resolution. A hexagonal crystal form at 1.60 Å resolution and a monoclinic form at 1.08 Å resolution both have two molecules in the asymmetric unit arranged about a similar noncrystallographic twofold axis of symmetry. These structures are compared with those previously reported at 2.20 Å resolution to show that the fold is quite resistant to structural deformation in different crystal environments. Unexpectedly, a short peptide is found in the monoclinic crystals at a site remote from the known hyaluronan-binding groove. The peptide with a valine at the carboxy-terminus must have co-purified from the bacterial expression host and binds on the opposite side of the domain from the known hyaluronan-binding groove. This opportunistic binding may identify a site of interaction used as CD44 assembles with other proteins to accomplish effective signaling regarding changes to the extracellular environment. | 25,195,884 | [
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Crystallization and preliminary X-ray diffraction analysis of the periplasmic domain of the Escherichia coli aspartate receptor Tar and its complex with aspartate. | The cell-surface receptor Tar mediates bacterial chemotaxis toward an attractant, aspartate (Asp), and away from a repellent, Ni(2+). To understand the molecular mechanisms underlying the induction of Tar activity by its ligands, the Escherichia coli Tar periplasmic domain with and without bound aspartate (Asp-Tar and apo-Tar, respectively) were each crystallized in two different forms. Using ammonium sulfate as a precipitant, crystals of apo-Tar1 and Asp-Tar1 were grown and diffracted to resolutions of 2.10 and 2.40 Å, respectively. Alternatively, using sodium chloride as a precipitant, crystals of apo-Tar2 and Asp-Tar2 were grown and diffracted to resolutions of 1.95 and 1.58 Å, respectively. Crystals of apo-Tar1 and Asp-Tar1 adopted space group P41212, while those of apo-Tar2 and Asp-Tar2 adopted space groups P212121 and C2, respectively. | 25,195,895 | [
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The mediating effect of prefrontal asymmetry on the relationship between the COMT Val(158)Met SNP and trait consummatory positive affect. | The Val(158)Met rs4680 polymorphism in the COMT gene regulates dopamine catabolism in the prefrontal cortex (PFC). Dopamine's involvement in reward experience suggests those with the methionine (Met) variant may exhibit trait-level sensitivity to reward due to more post-synaptic dopamine in the PFC. A physiological mediator of this association may be greater relative left asymmetry in the PFC, a putative biomarker for trait positive emotionality. Electroencephalograms of 120 participants were measured during a task that assesses two aspects of reward processing: pre-reward anticipation and post-reward consummatory affect. Participants provided genetics samples and completed the Temporal Experience of Pleasure Scale (TEPS), which assesses trait-level anticipatory and consummatory positive affect. Met carriers had higher TEPS-Consummatory scores. This effect was mediated by greater relative left activation in the post-reward phase of the task. No effects were observed for the pre-reward phase. Results suggest that frontal asymmetry is an endophenotype between COMT genotype and trait reward responsivity. | 25,195,915 | [
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A sleep bruxism detection system based on sensors in a splint - pilot clinical data. | It is difficult in a dental setting to accurately diagnose sleep bruxism and to objectively assess the severity, frequency or natural history of the condition in an individual patient. Yet this information is essential for the management of sleep bruxism and to plan appropriate dental treatment. The objective of this study was to clinically test a device that could be used to record bruxism events in a home environment. Pressure sensors were developed for use under the surface of an occlusal splint, and circuitry was designed to facilitate the recording and wireless transmission of the pressure sensor signal to a computer. Controlled mandibular movements were carried out in vivo to simulate bruxism and non-bruxism patterns. These patterns of force application were graphically presented to two examiners who were asked to identify the type of activity represented by the force curves. Examiners were largely able to distinguish bruxism from non-bruxism activity; the sensitivity ranged from 80% to 100% and the specificity from 75% to 100%. Using sensors in an occlusal splint, it is possible to recognise the typical tooth contact patterns seen in sleep bruxism. Such a device may be useful for monitoring sleep bruxism over an extended period at home. | 25,195,920 | [
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Averaging techniques for reaction barriers in QM/MM simulations. | Herein, we test and compare different techniques to obtain averaged reaction barriers from quantum mechanics/molecular mechanics (QM/MM) simulations based on snapshots taken from molecular dynamics. Reasonable values can be obtained from a fairly small sample of well-chosen snapshots if an exponential averaging, also called Boltzmann averaging, is used. Snapshots with geometries close to the expected transition state are to be picked preferentially. Exponential averaging, arithmetic averaging, and simply taking the minimum barrier are compared to free-energy calculations from umbrella sampling. Three reactions within a protein in a water environment are used as test cases. | 25,195,924 | [
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Self-replication and amplification of enantiomeric excess of chiral multifunctionalized large molecules by asymmetric autocatalysis. | Self-replication of large chiral molecular architectures is one of the great challenges and interests in synthetic, systems, and prebiotic chemistry. Described herein is a new chemical system in which large chiral multifunctionalized molecules possess asymmetric autocatalytic self-replicating and self-improving abilities, that is, improvement of their enantioenrichment in addition to the diastereomeric ratio. The large chiral multifunctionalized molecules catalyze the production of themselves with the same structure, including the chirality of newly formed asymmetric carbon atoms, in the reaction of the corresponding achiral aldehydes and reagent. The chirality of the large multifunctionalized molecules controlled the enantioselectivity of the reaction in a highly selective manner to construct multiple asymmetric stereogenic centers in a single reaction. | 25,195,925 | [
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Examining convergence of retrospective and ecological momentary assessment measures of negative affect and eating disorder behaviors. | Data gathered via retrospective forms of assessment are subject to various recall biases. Ecological momentary assessment (EMA) is an alternative approach involving repeated momentary assessments within a participant's natural environment, thus reducing recall biases and improving ecological validity. EMA has been used in numerous prior studies examining various constructs of theoretical relevance to eating disorders. This investigation includes data from three previously published studies with distinct clinical samples: (a) women with anorexia nervosa (N = 118), (b) women with bulimia nervosa (N = 133), and (c) obese men and women (N = 50; 9 with current binge eating disorder). Each study assessed negative affective states and eating disorder behaviors using traditional retrospective assessments and EMA. Spearman rho correlations were used to evaluate the concordance of retrospective versus EMA measures of affective and/or behavioral constructs in each sample. Bland-Altman plots were also used to further evaluate concordance in the assessment of eating disorder behaviors. There was moderate to strong concordance for the measures of negative affective states across all three studies. Moderate to strong concordance was also found for the measures of binge eating and exercise frequency. The strongest evidence of concordance across measurement approaches was found for purging behaviors. Overall, these preliminary findings support the convergence of retrospective and EMA assessments of both negative affective states and various eating disorder behaviors. Given the advantages and disadvantages associated with each of these assessment approaches, the specific questions being studied in future empirical studies should inform decisions regarding selection of the most appropriate method. | 25,195,932 | [
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Psychotropic drugs and bruxism. | Sleep and awake bruxism is defined as 'a parafunctional activity including clenching, bracing, gnashing, and grinding of the teeth'. Some evidence suggests that bruxism may be caused by, or associated with, alterations in the CNS neurotransmission. Several classes of psychotropic drugs interfering with CNS activity may potentially contribute to bruxism. Thus, the purpose of this study was to examine relevant peer-reviewed papers to identify and describe the various classes of psychotropic substances that may cause, exacerbate or reduce bruxism as the result of their pharmacological action in CNS neurons. A literature search from 1980 to the present was performed using PubMed database. The term 'bruxism' was used in association with 'psychotropic', 'dopamine (DA)', 'serotonin', 'histamine', 'antipsychotics', 'antidepressants', 'antihistaminergics' and 'stimulants'. Studies on the effects of DA agonists (Levo-DOPA, psychostimulants) and antagonists (antipsychotics) identified a central role of DA in the pathogenesis of pharmacologically induced bruxism. Important information from studies on drugs acting on serotonin neurotransmission (antidepressants) was recognized. Other mechanisms involving different neurotransmitters are emerging. This is the case of antihistaminergic drugs which may induce bruxism as a consequence of their disinhibitory effect on the serotonergic system. | 25,195,948 | [
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Adherence to insulin treatment in diabetes: can it be improved? | Insulin is used in all subjects with Type 1 diabetes, and when Type 2 diabetes is not controlled by oral anti-diabetic medicines, insulin is also used in Type 2 diabetes. However, despite this use, there is still increased mortality and morbidity in subjects with diabetes, compared to subjects without diabetes. One of the factors, which may be involved in this increased mortality and morbidity in subjects with diabetes, is nonadherence to insulin. Nonadherence rates to insulin are in the range of 20-38%, and many factors contribute to the nonadherence. The major aim of the review was to determine whether interventions to improve adherence to insulin do actually improve adherence to insulin. Most studies have shown that adherence to insulin was improved by changing from the vial-and-syringe approach to prefilled insulin pens, but not all studies have shown that this translated into better glycemic control and clinical outcomes. The results of studies using automatic telephone messages to improve adherence to insulin to date are inconclusive. There is limited and variable evidence that an intervention by a nurse/educator, which discusses adherence to medicines, does improve adherence to insulin. In contrast, there is little or no evidence that an extra intervention by a doctor or an intervention by a pharmacist, which discusses adherence to insulin, does actually improve the measured adherence to insulin. In conclusion, rather than assuming that an intervention by a health professional discussing adherence to insulin actually improves adherence to insulin, long-term studies investigating this are required. | 25,195,971 | [
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Maintenance of bowel, bladder, and motor functions after sacrectomy. | Repeated cohort studies have consistently demonstrated a survival advantage after en bloc resection for locally aggressive primary tumors in the sacrum. A sacrectomy is often required to remove the tumor en bloc, which may necessitate the sacrifice of sacral nerves. This can potentially result in functional complications, including the impairment of gait, bowel function, or bladder function. To assess the bladder, bowel, and motor functions of patients after resection of a primary sacral tumor. This was a retrospective cohort study at a single academic institution. Consecutive patients who underwent an en bloc sacral tumor resection at a single institution between December 2002 and June 2012 were included. The study population comprised 73 patients. Patients were classified as having had a low, middle, high, or total sacrectomy based on the level of sacral nerves sacrificed, if applicable. Patient data were collected from clinic notes and hospital records that included operative notes, lab studies, and rehabilitation notes. Across all patients, there was no change in bowel function after sacrectomy, whereas bladder and motor functions returned to preoperative (pre-op) levels at 3 and 6 months, respectively. Higher level sacrectomies were associated with worse bowel (p<.001), bladder (p<.001), and motor (p=.027) functions 12 months postoperatively (post-op). At 1 year, none of the six patients with a high or total sacrectomy had intact bladder function and 14.3% (N=7) had intact bowel function. Of patients with a middle sacrectomy, 62.5% (N=8) had intact bladder function and 71.4% (N=7) had intact bowel function at 1 year. Of patients with a low sacrectomy, 91.7% (N=12) had intact bladder function and 91.7% (N=12) had intact bowel function. Preoperative bladder, bowel, and motor functions, level of sacral tumor involvement, and corresponding level of sacrectomy were the greatest predictors of long-term bladder, bowel, and motor functions. There were no statistically significant changes in bladder, bowel, or motor functions from pre-op to 6 months post-op, and therefore, pre-op functional status was predictive of long-term function. | 25,195,977 | [
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Age disparity in palliative radiation therapy among patients with advanced cancer. | Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population. We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy. The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001). Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end of life. | 25,195,994 | [
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The rhetoric of racism: revisiting the creation of the Psychological Institute of the Republic of South Africa (1956-1962). | This paper revisits the 1962 splitting of the South African Psychological Association (SAPA), when disaffected Afrikaner psychologists broke away to form the whites-only Psychological Institute of the Republic of South Africa (PIRSA). It presents an analysis of the rhetorical justification for forming a new professional association on principles at odds with prevailing international norms, demonstrating how the episode involved more than the question of admitting black psychologists to the association. In particular, the paper argues that the SAPA-PIRSA separation resulted from an Afrikaner nationalist reading of the goals of psychological science. PIRSA, that is, insisted on promoting a discipline committed to the ethnic-national vision of the apartheid state. For its part, SAPA's racial integration was of a nominal order only, ostensibly to protect itself from international sanction. The paper concludes that, in a racist society, it is difficult to produce anything other than a racist psychology. | 25,196,057 | [
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EpsinR, a target for pyrenocine B, role in endogenous MHC-II-restricted antigen presentation. | While the presentation mechanism of antigenic peptides derived from exogenous proteins by MHC class II molecules is well understood, relatively little is known about the presentation mechanism of endogenous MHC class II-restricted antigens. We therefore screened a chemical library of 200 compounds derived from natural products to identify inhibitors of the presentation of endogenous MHC class II-restricted antigens. We found that pyrenocine B, a compound derived from the fungus Pyrenochaeta terrestris, inhibits presentation of endogenous MHC class II-restricted minor histocompatibility antigen IL-4 inducible gene 1 (IL4I1) by primary dendritic cells (DCs). Phage display screening and surface plasmon resonance (SPR) analysis were used to investigate the mechanism of suppressive action by pyrenocine B. EpsinR, a target molecule for pyrenocine B, mediates endosomal trafficking through binding of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Lentiviral-mediated short hairpin (sh) RNA downregulation of EpsinR expression in DCs resulted in a decrease in the responsiveness of CD4+ T cells. Our data thus suggest that EpsinR plays a role in antigen presentation, which provides insight into the mechanism of presentation pathway of endogenous MHC class II-restricted antigen. | 25,196,058 | [
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Determining the major Bt refuge crops for cotton bollworm in North China. | Evaluation of the effectiveness of refuge strategies involved in cotton bollworm Bt resistance management would be aided by technologies that allow monitoring and quantification of key factors that affect the process under field conditions. We hypothesized that characterization of stable carbon and nitrogen isotopes in adult bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) moths may aid in determining the larval host that they developed upon. We found moths reared from larvae fed on peanut, soybean or cotton, respectively, could be differentiated using isotopic analyses that also corresponded to their respective larval host origins. These techniques were then used to classify feral second-generation bollworm moths caught in Bt cotton (Gossypium hirsutum) fields into different populations based on their isotopic signatures. In 2006-2007 feral moths captured in Bt cotton fields predominantly correlated with the peanut (Arachis hypogea) having served as their larval host, indicating this is the most important refuge crop for Bt-susceptible bollworm individuals (providing 58%-64% individuals) during independent moth peaks for the second generation in North China. The remaining feral moths correlated with soybean (Glycine max) (0-10%); other C3 plant (20%-22%) and non-C3 plant (12%-14%) host types also provided some Bt-sensitive moths. Field observations showed that peanut constitutes the primary refuge crop contributing to sustaining Bt-susceptible moths dispersing into cotton in North China. These results suggest that peanut may be a more effective refuge to sustain Bt-susceptible bollworm individuals and reduce the risk of development of a Bt-resistant biotype. | 25,196,072 | [
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Spectroscopic signatures for interlayer coupling in MoS2-WSe2 van der Waals stacking. | Stacking of MoS2 and WSe2 monolayers is conducted by transferring triangular MoS2 monolayers on top of WSe2 monolayers, all grown by chemical vapor deposition (CVD). Raman spectroscopy and photoluminescence (PL) studies reveal that these mechanically stacked monolayers are not closely coupled, but after a thermal treatment at 300 °C, it is possible to produce van der Waals solids consisting of two interacting transition metal dichalcogenide (TMD) monolayers. The layer-number sensitive Raman out-of-plane mode A(2)1g for WSe2 (309 cm(-1)) is found sensitive to the coupling between two TMD monolayers. The presence of interlayer excitonic emissions and the changes in other intrinsic Raman modes such as E″ for MoS2 at 286 cm(-1) and A(2)1g for MoS2 at around 463 cm(-1) confirm the enhancement of the interlayer coupling. | 25,196,077 | [
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Hydrogen sulfide acts as a pro-inflammatory mediator in rheumatic disease. | Hydrogen sulfide (H<sub2</sub S) is a gaseous mediator produced in the body. In experimental models, endogenously produced H<sub2</sub S has been shown to have pro-inflammatory effects. The aim of this study was to investigate whether H<sub2</sub S is present in three common rheumatic diseases, rheumatoid arthritis (RA), gout and osteoarthritis (OA) and to determine if H<sub2</sub S levels correlate with disease activity. Patients with RA, gout, OA, and healthy controls (n = 30 each) were recruited. Plasma and where possible, synovial fluid (SF), were obtained. Levels of H<sub2</sub S and interleukin-6 (IL-6) (a known inflammatory marker as a positive control) were determined and assessed for their relationship with disease activity. SF-H<sub2</sub S levels were significantly elevated in both RA and gout when compared to respective plasma levels. Plasma levels of H<sub2</sub S were not different from those in healthy controls in patients with either RA or gout. In OA, plasma levels of H<sub2</sub S were significantly elevated compared to healthy controls. In RA, SF-H<sub2</sub S levels correlated with Disease Activity Score (DAS)-28 and tender joint count. H<sub2</sub S is present in the joint and acts as a pro-inflammatory mediator in rheumatic diseases. H<sub2</sub S may be a novel therapeutic target for these conditions. | 25,196,086 | [
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Tenascin-C is required for normal Wnt/β-catenin signaling in the whisker follicle stem cell niche. | Whisker follicles have multiple stem cell niches, including epidermal stem cells in the bulge as well as neural crest-derived stem cells and mast cell progenitors in the trabecular region. The neural crest-derived stem cells are a pool of melanocyte precursors. Previously, we found that the extracellular matrix glycoproteins tenascin-C and tenascin-W are expressed near CD34-positive cells in the trabecular stem cell niche of mouse whisker follicles. Here, we analyzed whiskers from tenascin-C knockout mice and found intrafollicular adipocytes and supernumerary mast cells. As Wnt/β-catenin signaling promotes melanogenesis and suppresses the differentiation of adipocytes and mast cells, we analyzed β-catenin subcellular localization in the trabecular niche. We found cytoplasmic and nuclear β-catenin in wild-type mice reflecting active Wnt/β-catenin signaling, whereas β-catenin in tenascin-C knockout mice was mostly cell membrane-associated and thus transcriptionally inactive. Furthermore, cells expressing the Wnt/β-catenin target gene cyclin D1 were enriched in the CD34-positive niches of wild-type compared to tenascin-C knockout mice. We then tested the effects of tenascins on this signaling pathway. We found that tenascin-C and tenascin-W can be co-precipitated with Wnt3a. In vitro, substrate bound tenascins promoted β-catenin-mediated transcription in the presence of Wnt3a, presumably due to the sequestration and concentration of Wnt3a near the cell surface. We conclude that the presence of tenascin-C in whiskers assures active Wnt/β-catenin signaling in the niche thereby maintaining the stem cell pool and suppressing aberrant differentiation, while in the knockout mice with reduced Wnt/β-catenin signaling, stem cells from the trabecular niche can differentiate into ectopic adipocytes and mast cells. | 25,196,097 | [
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Montelukast-induced adverse drug reactions: a review of case reports in the literature. | Montelukast, a leucotriene receptor antagonist, binds the cysteinyl leucotriene type 1 receptor. Montelukast is commonly prescribed to asthma patients as add-on therapy to inhaled corticosteroids. Several clinical trials emphasized that montelukast can be considered a safe drug. However, recent evidence reconsidered the benefit/risk ratio of the use of montelukast for both paediatric and adult patients. The present review analyzed the previous published case reports regarding montelukast-induced adverse drug reactions (ADRs). They included agitation, anxiety, depression, sleep disturbance, hallucinations, suicidal thinking and suicidality, tremor, dizziness, drowsiness, neuropathies and seizures. The immune system can be involved, in particular, cases of Churg-Strauss syndrome have been published. Furthermore, it can induce hypersensitivity reactions, including anaphylaxis and eosinophilic infiltration. In addition, hepatobiliary, pancreatic and uropoietic disorders have been observed. Some of these cases are characterized by severe prognosis (i.e. neurological deficit and fatal hepatotoxicity). Key Message: The use of montelukast can be burdened by several ADRs, of which physicians should be aware in their clinical practice. A better understanding of the mechanisms causing ADRs after using montelukast could help researchers and clinicians in defining a risk-reduction strategy aimed to lessen montelukast toxicity. More accurate epidemiological studies, in order to discover risk factors favouring montelukast-associated ADRs, are demanded. | 25,196,099 | [
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Automated detection and recognition of wildlife using thermal cameras. | In agricultural mowing operations, thousands of animals are injured or killed each year, due to the increased working widths and speeds of agricultural machinery. Detection and recognition of wildlife within the agricultural fields is important to reduce wildlife mortality and, thereby, promote wildlife-friendly farming. The work presented in this paper contributes to the automated detection and classification of animals in thermal imaging. The methods and results are based on top-view images taken manually from a lift to motivate work towards unmanned aerial vehicle-based detection and recognition. Hot objects are detected based on a threshold dynamically adjusted to each frame. For the classification of animals, we propose a novel thermal feature extraction algorithm. For each detected object, a thermal signature is calculated using morphological operations. The thermal signature describes heat characteristics of objects and is partly invariant to translation, rotation, scale and posture. The discrete cosine transform (DCT) is used to parameterize the thermal signature and, thereby, calculate a feature vector, which is used for subsequent classification. Using a k-nearest-neighbor (kNN) classifier, animals are discriminated from non-animals with a balanced classification accuracy of 84.7% in an altitude range of 3-10 m and an accuracy of 75.2% for an altitude range of 10-20 m. To incorporate temporal information in the classification, a tracking algorithm is proposed. Using temporal information improves the balanced classification accuracy to 93.3% in an altitude range 3-10 of meters and 77.7% in an altitude range of 10-20 m. | 25,196,105 | [
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Open reduction and internal fixation of extracapsular mandibular condyle fractures: a long-term clinical and radiological follow-up of 25 patients. | During the last 2 decades, many studies on the treatment of mandibular condyle fracture have been published. The incidence of mandibular condyle fractures is variable, ranging from 17.5% to 52% of all mandibular fractures. This retrospective study evaluated the long-term clinical and radiological outcomes after surgical treatment of 25 patients with a total of 26 extracapsular condyle fractures. We used 2 types of surgical approaches, the retromandibular retroparotid or preauricular approach. Three kinds of rigid internal fixation plates were used-single plate, double plate, and trapezoidal plate. The following post-operative clinical parameters were evaluated: dental occlusion, facial nerve functionality, skin scarring, and temporomandibular joint functionality. All patients underwent post-operative orthopanoramic radiography and computed tomography. The patients were also monitored for complications such as Frey's syndrome, infection, salivary fistula, plate fracture, and permanent paralysis of the facial nerve; the patient's satisfaction was also recorded. Of the 25 patients, 80% showed occlusion recovery, 88% had no facial nerve injury, and 88% presented good surgical skin scarring. The patients showed early complete recovery of temporomandibular joint functionality and 72% of them were found to be asymptomatic. The postoperative radiographs of all patients indicated good recovery of the anatomical condylar region, and 80% of them had no postoperative complications. The average degree of patient satisfaction was 8.32 out of 10. Our results confirm that the technique of open reduction and internal fixation in association with postoperative functional rehabilitation therapy should be considered for treating patients with extracapsular condylar fractures. The topic of condylar injury has generated more discussion and controversy than any other topic in the field of maxillofacial trauma. We confirm that open reduction and internal fixation is the treatment of choice for patients with neck and sub-condylar mandibular fractures. | 25,196,114 | [
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Extension and validation of the GROMOS 53A6(GLYC) parameter set for glycoproteins. | An extension of the GROMOS 53A6GLYC force field for carbohydrates to encompass glycoprotein linkages is presented. The set includes new atomic charges and incorporates adequate torsional potential parameters for N-, S-, C-, P-, and O-glycosydic linkages, offering compatibility with the GROMOS force field family for proteins. Validation included the description of glycosydic linkage geometries between amino acid and monosaccharide residues, comparison of NMR-derived protein-carbohydrate and carbohydrate-carbohydrate nuclear overhauser effect (NOE) signals for glycoproteins and the effects of glycosylation on protein flexibility and dynamics. | 25,196,137 | [
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Long-term type 1 diabetes alters the deposition of collagens and proteoglycans in the early pregnant myometrium of mice. | We have previously shown that long-term type 1 diabetes affects the structural organization, contractile apparatus and extracellular matrix (ECM) of the myometrium during early pregnancy in mice. This study aimed to identify which myometrial ECM components are affected by diabetes, including fibril-forming collagen types I, III and V, as well as proteoglycans, decorin, lumican, fibromodulin and biglycan. Alloxan-induced type 1 diabetic female mice were divided into subgroups D1 and D2, formed by females that bred 90-100 and 100-110 days after diabetes induction, respectively. The deposition of ECM components in the myometrium was evaluated by immunohistochemistry/immunofluorescence. The subgroup D1 showed decreased deposition of collagen types I and III in the external muscle layer (EML) and decreased collagen types III and V in the internal muscle layer (IML). Collagen types I and III were decreased in both muscle layers of the subgroup D2. In addition, increased deposition of collagen types I and III and lumican as well as decreased collagen type V were observed in the connective tissue between muscle layers of D2. Lumican was decreased in the EML of the subgroups D1 and D2. Fibromodulin was repressed in the IML and EML of both D1 and D2. In contrast, decorin deposition diminished only in muscle layers of D2. No changes were noticed for biglycan. Subgroups D1 and D2 showed distinct stages of progression of diabetic complications in the myometrium, characterized by both common and specific sets of changes in the ECM composition. | 25,196,145 | [
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Redox interactions between Cr(VI) and Fe(II) in bioreduced biotite and chlorite. | Contamination of the environment with Cr as chromate (Cr(VI)) from industrial activities is of significant concern as Cr(VI) is a known carcinogen, and is mobile in the subsurface. The capacity of Fe(II)-containing phyllosilicates including biotite and chlorite to alter the speciation, and thus the mobility, of redox-sensitive contaminants including Cr(VI) is of great interest since these minerals are common in soils and sediments. Here, the capacity of bacteria, ubiquitous in the surface and near-surface environment, to reduce Fe(III) in phyllosilicate minerals and, thus, alter their redox reactivity was investigated in two-step anaerobic batch experiments. The model Fe(III)-reducing bacterium Geobacter sulfurreducens was used to reduce Fe(III) in the minerals, leading to a significant transformation of structural Fe(III) to Fe(II) of 0.16 mmol/g (∼ 40%) in biotite and 0.15 mmol/g (∼ 20%) in chlorite. The unaltered minerals could not remove Cr(VI) from solution despite containing a larger excess of Fe(II) than would be required to reduce all the added Cr(VI), unless they were supplied in a very high concentration (a 1:10 solid to solution ratio). By contrast, even at very low concentrations, the addition of bioreduced biotite and chlorite caused removal of Cr(VI) from solution, and surface and near surface X-ray absorption spectroscopy confirmed that this immobilization was through reductive transformation to Cr(III). We provide empirical evidence that the amount of Fe(II) generated by microbial Fe(III) reduction is sufficient to reduce the Cr(VI) removed and, in the absence of reduction by the unaltered minerals, suggest that only the microbially reduced fraction of the iron in the minerals is redox-active against the Cr(VI). | 25,196,156 | [
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Effectiveness of a television advertisement campaign on giving cigarettes in a chinese population. | Anti-tobacco television advertisement campaigns may convey messages on smoking-related health consequences and create norms against giving cigarettes. Altogether, 156 and 112 slots of a television advertisement "Giving cigarettes is giving harm" were aired on Suzhou and Yizheng, respectively, over one month in 2010. Participants were recruited from 15 locations in Suzhou and 8 locations in Yizheng using a street intercept method. Overall 2306 residents aged 18-45 years completed questionnaires, including 1142 before the campaign and 1164 after, with respective response rates of 79.1% and 79.7%. Chi square tests were used to compare the difference between categorical variables. After the campaign, 36.0% of subjects recalled that they had seen the advertisement. Residents of Suzhou had a higher recall rate than those of Yizheng (47.6% vs. 20.6%, P < 0.001). The rate of not giving cigarettes dropped from 32.1% before the campaign to 28.5% after (P = 0.05). In the post-campaign evaluation, participants who reported seeing the advertisement were more likely not to give cigarettes in the future than those who reported not seeing the advertisement (38.7% vs. 27.5%, P < 0.001). Our study showed that an anti-tobacco television advertisements helped change societal norms and improve health behavior. Continuous and adequate funding of anti-tobacco media campaigns targeted at different levels of the general population is needed, in conjunction with a comprehensive tobacco control effort. | 25,196,169 | [
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Shifting chemical equilibria in flow--efficient decarbonylation driven by annular flow regimes. | To efficiently drive chemical reactions, it is often necessary to influence an equilibrium by removing one or more components from the reaction space. Such manipulation is straightforward in open systems, for example, by distillation of a volatile product from the reaction mixture. Herein we describe a unique high-temperature/high-pressure gas/liquid continuous-flow process for the rhodium-catalyzed decarbonylation of aldehydes. The carbon monoxide released during the reaction is carried with a stream of an inert gas through the center of the tubing, whereas the liquid feed travels as an annular film along the wall of the channel. As a consequence, carbon monoxide is effectively vaporized from the liquid phase into the gas phase and stripped from the reaction mixture, thus driving the equilibrium to the product and preventing poisoning of the catalyst. This approach enables the catalytic decarbonylation of a variety of aldehydes with unprecedented efficiency with a standard coil-based flow device. | 25,196,172 | [
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In vitro and in vivo evaluations of three-dimensional hydroxyapatite/silk fibroin nanocomposite scaffolds. | In this study, three-dimensional hydroxyapatite/silk fibroin (HAp/SF) nanocomposite scaffolds were successfully prepared through layer solvent casting combined with the freeze-drying technique for tissue engineering applications. Various SF aqueous concentrations, ranging from 2.5% to 10%, were used to control the physicochemical properties of the prepared scaffolds. Biologic responses of the rat bone marrow stromal cells (rBMSCs) to the HAp/SF scaffolds were examined by culturing the cells within them. In addition, biodegradation and biocompatibility of the scaffolds were evaluated in vitro and in vivo, respectively. Among the prepared scaffolds, HAp/SF-2.5% was the most brittle sample and showed porous structure with lowest mechanical properties. The average pore diameters were 350 ± 67 and 112 ± 89 µm and decreased with the increase in the SF concentration from 5% to 10%, respectively. The pores formed in the scaffolds, made up of the 5% SF, were more uniform and regular than those of the scaffolds made up of 5% and 10% SF. The HAp/SF scaffolds did not change the rBMSCs viability and were not cytotoxic compared with the control sample. The scanning electron microscopy micrographs showed that the cells migrated into the pores and well attached to the scaffolds and their cytoplasm was extended in all directions, indicating a promising cell adhesion, high biocompatibility, and no cytotoxicity of the HAp/SF-5% nanocomposite scaffolds. Subcutaneous implantation of the HAp/SF-5% scaffolds in rat models suggested an excellent biocompatibility. All data obtained from this study suggest the potential use of the HAp/SF-5% for hard tissue engineering. | 25,196,187 | [
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Quality of life in non-melanoma skin cancer. | Basal cell carcinoma and squamous cell carcinoma are the most common malignancies and are classified under the umbrella of non-melanoma skin cancer (NMSC). NMSC exerts a small but appreciable decrement in quality of life (QOL). The impact posed may arise from the tumour itself or as a result of treatment, and through symptoms, functional limitations, cosmetic burden and auxiliary considerations such as cost and disturbance to the activities of daily living. Researchers have evaluated this burden using a variety of outcome measures including generic, dermatology-specific and disease-specific instruments. The skin cancer index represents a promising disease-specific patient-reported outcome measure in this setting. To overcome some of the constraints inherent to disease-specific instruments, and to allow comparisons with other diseases, utility weightings have been developed. Utility weightings represent a cardinal measure for a specific health status and are established through methods such as the standard gamble, willingness-to-pay and time trade-off, and have also been employed to generate utility weightings for NMSC. Utilities are becoming increasingly important as a means of comparing health states across medicine and are of particular importance from a health-care policy perspective as they are used for resource allocation. The small but definite impact on the individual's QOL posed by NMSC should be a clinical consideration for physicians and it should be recognised by researchers as a potential outcome measure. | 25,196,191 | [
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Caregivers of Children with Congenital Heart Disease: Does Socioeconomic Class Have Any Effect on Their Perceptions? | Studies from other parts of the world have documented knowledge gaps in parents of children with congenital heart disease (CHD). The authors are not aware of any study in the Nigerian population assessing the effect of socioeconomic class on the perceptions of caregivers of children with CHD. The study aimed to evaluate the effect of socioeconomic class on the perceptions of caregivers of children with CHD. A descriptive and cross-sectional questionnaire survey was conducted in a tertiary pediatric cardiac center involving 300 caregivers of children with CHD, recruited at the outpatient clinic from April 2008 to March 2012. Age range of the respondents was 16 to 72 years with a mean of 34.7 ± 8.1 years. Forty percent (119) of the caregivers had not heard about CHD; those in the upper socioeconomic class had better awareness (P = .02). Ninety percent of all the respondents knew that the cause of CHD is unknown. Only seven of the respondents (2.3%) had a good knowledge of the indicators, while 9.6% had a fair knowledge, almost 60% of the respondent had a poor knowledge, and up to 30% had no knowledge of the pointers. Nearly one-fifth (19.3%) of the respondents were not aware of any treatment options for children with CHD. Only 12.7% of the respondents knew the best mode of treatment, and only 43% of the respondents believed CHD could be prevented. Further analysis revealed that there was no statistically significant difference between the various socioeconomic classes with regard to knowledge of the indicators of CHD, awareness of the best mode of treatment, and perception of preventability (P = .06, .74, and .13, respectively). More parents in the upper socioeconomic class had heard about CHD. However, most parents of children with CHD had poor knowledge of CHD, its indicators, its best mode of treatment, and its preventability, irrespective of their socioeconomic class. Our findings suggest an urgent need to develop an educational program to promote better understanding of CHD among caregivers. | 25,196,209 | [
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A straightforward approach towards cyclic photoactivatable tubulysin derivatives. | The development of a new photolabile protecting group containing an additional allyl functionality allows the synthesis of cyclic photoactivatable natural products. Cyclization occurs between the allyl moiety in the protecting group and a second double bond in the target molecule by means of ring-closing metathesis. Cyclization should increase the metabolic stability towards proteases. On the other hand, the conformational change should cause diminished biological activity. As illustrated for tubulysin derivatives, cyclic and photoactivatable drug candidates can easily be obtained in only two steps from simple building blocks through Ugi reaction and ring-closing metathesis. The photolabile protecting group is introduced by means of the isocyanide component during the Ugi reaction. | 25,196,233 | [
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Changes in secondary organic aerosol composition and mass due to photolysis: relative humidity dependence. | This study is focused on the relative humidity (RH) dependence of water-soluble secondary organic aerosol (SOA) aging by photolysis. Particles containing α-pinene SOA and ammonium sulfate, generated by atomization, were exposed to UV radiation in an environmental chamber at three RH conditions (5, 45, and 85%), and changes in chemical composition and mass were monitored using an aerosol mass spectrometer (AMS). Under all RH conditions, photolysis leads to substantial loss of SOA mass, where the rate of mass loss decreased with decreasing RH. For all RH conditions, the less oxidized components of SOA (e.g., carbonyls) exhibited the fastest photodegradation rates, which resulted in a more oxidized SOA after photolytic aging. The photolytic reactivity of SOA material exhibited a dependence on RH likely due to moisture-induced changes in SOA morphology or phase. The results suggest that the atmospheric lifetime of SOA with respect to photolysis is dependent on its RH cycle, and that photolysis may be an important sink for some SOA components occurring on an initial time scale of a few hours under ambient conditions. | 25,196,234 | [
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Global health and development in early childhood. | Health and nutritional risks co-occur in the lives of children under the age of 2 years who live in developing countries. We review evidence showing how these risks, in addition to inadequate psychosocial stimulation, prevent children from developing expected cognitive and language abilities. A systematic review and meta-analysis of 21 interventions aimed at enhancing stimulation and 18 interventions that provided better nutrition--all conducted since 2000--revealed that stimulation had a medium effect size of 0.42 and 0.47 on cognitive and language development, respectively, whereas nutrition by itself had a small effect size of 0.09. The implementation processes of these interventions are described and compared. A number of unresolved issues are outlined and discussed, including ways to maximize parental health behavior change, assess mediators that account for intervention effects, and expand the assessment of young children's brain functions that underlie language and cognition and are affected by nutrition and stimulation. | 25,196,276 | [
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Regional comparisons of porcine menisci. | The purpose of this study was to analyze histologic, biochemical, and biomechanical differences between zonal, regional, and anatomic locations of porcine menisci. We evaluated six menisci removed from pigs. Medial and lateral menisci were divided into three regions: anterior, middle, and posterior. In each portion, the central zone (CZ) and peripheral zone (PZ) were examined histologically (hematoxylin & eosin, safranin O/Fast green, and picrosiriusred staining), using scanning electron microscopy, biochemically (hydroxyproline assay for collagen content and dimethylmethylene blue assay for glycosaminoglycan [GAG] content), and biomechanically (compression testing). Collagen content in the CZ was lower than that in the PZ. GAG content in the CZ was higher than that in the PZ. GAG content in the PZ of the posterior portion was significantly higher than that in the anterior and middle portions. Compression strength in the CZ was higher than that in the PZ. The differences in cellular phenotype, vascular penetration, and ECM not only between CZ and PZ but also among the anterior, middle, and posterior portions were clarified in the immature porcine meniscus. This result helps further our understanding of the biological characteristic of the meniscus. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1602-1611, 2014. | 25,196,310 | [
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Water-splitting electrocatalysis in acid conditions using ruthenate-iridate pyrochlores. | The pyrochlore solid solution (Na(0.33)Ce(0.67))2(Ir(1-x)Ru(x))2O7 (0≤x≤1), containing B-site Ru(IV) and Ir(IV) is prepared by hydrothermal synthesis and used as a catalyst layer for electrochemical oxygen evolution from water at pH<7. The materials have atomically mixed Ru and Ir and their nanocrystalline form allows effective fabrication of electrode coatings with improved charge densities over a typical (Ru,Ir)O2 catalyst. An in situ study of the catalyst layers using XANES spectroscopy at the Ir L(III) and Ru K edges shows that both Ru and Ir participate in redox chemistry at oxygen evolution conditions and that Ru is more active than Ir, being oxidized by almost one oxidation state at maximum applied potential, with no evidence for ruthenate or iridate in +6 or higher oxidation states. | 25,196,322 | [
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Changing tracks as situations change: humanitarian and health response along the Liberia-Côte d'Ivoire border. | In recent years, protracted crises and fragile post-conflict settings have challenged the co-existence, and even the linear continuum, of relief and development aid. Forced migration has tested humanitarian and development paradigms where sudden-onset emergencies, violence and displacement arise alongside ongoing development work. Drawing on Médecins Sans Frontières interventions in the region from December 2010 to May 2011, this paper examines aid and healthcare responses to displacement in Côte d'Ivoire and Liberia; it focuses on challenges to the maintenance of preparedness for such foreseeable emergencies and to adaptation in response to changing situations of displacement and insecurity. This 'backsliding' from development to emergency remains a substantial challenge to aid; yet, in exactly such cases, it also presents the opportunity to ensure access to medical care that is much more urgently needed in times of crisis, including the suspension of user fees for medical care. | 25,196,331 | [
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The self-built ecovillage in L'Aquila, Italy: community resilience as a grassroots response to environmental shock. | The paper applies the community resilience approach to the post-disaster case of Pescomaggiore, an Italian village affected by the L'Aquila earthquake in 2009. A group of residents refused to accept the housing recovery solutions proposed by the government, opting for autonomous recovery. They developed a housing project in the form of a self-built ecovillage, characterised by earthquake-proof buildings made of straw and wood. The project is a paradigmatic example of a community-based response to an external shock. It illustrates the concept of 'community resilience', which is widely explored in the scientific debate but still vaguely defined. Based on qualitative methodologies, the paper seeks to understand how the community resilience process can be enacted in alternative social practices such as ecovillages. The goal is to see under which conditions natural disasters can be considered windows of opportunity for sustainability. | 25,196,333 | [
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Improved Thin-Film Transistor Performance Through a Melt of Poly(para-phenyleneethynylene). | The performance of polymer field-effect transistors (PFETs) based on short rigid rod semiconducting poly(2,5-didodecyloxy-p-phenyleneethynylene) (D-OPPE) is highlighted. The controlled heating and cooling of thin films of D-OPPE allows for a recrystallization from the melt, boosting the performance of D-OPPE-based transistors. The improved film properties induced by controlled annealing lead to a hole field-effect mobility around 0.014 cm<sup2</sup V<sup-1</sup s<sup-1</sup , an on/off ratio of 10<sup6</sup , a sub-threshold swing of 3 V dec<sup-1</sup and a threshold voltage of -35 V, employing a poly(methyl methacrylate) (PMMA) gate dielectric. Thus, PFETs out of D-OPPE compete now with spin-coated, polycrystalline poly(3-hexylthiophene)-based PFETs. | 25,196,352 | [
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Heterozygous DLX5 nonsense mutation associated with isolated split-hand/foot malformation with reduced penetrance and variable expressivity in two unrelated families. | Split-hand/foot malformation (SHFM) is a clinically and genetically heterogeneous limb abnormality characterized by the absence or hypoplasia of the central rays of the autopod. SHFM1, which is one out of seven known SHFM loci, maps to 7q21.2-q21.3. SHFM1 is usually inherited as an autosomal dominant trait with reduced penetrance, although recessive inheritance has been described for a single family carrying a homozygous DLX5 missense variant. In most cases, SHFM1 results from heterozygous deletions encompassing DLX5/DLX6 genes or from inversions and translocations separating the genes from their limb specific enhancers. Recently, a single Chinese family with dominant SHFM1 was shown to result from a heterozygous DLX5 missense mutation. In this study, we report on four male individuals from two unrelated Polish families (one sporadic and one familial case) presenting with isolated SHFM. We tested both probands for known molecular causes of SHFM, including TP63, WNT10B, DLX5 mutations and copy number changes using 1.4 M array CGH. Sanger sequencing of DLX5 revealed a novel heterozygous nonsense mutation c.G115T(p.E39X) in both index patients. Segregation studies demonstrated that the variant was present in all affected family members but also in three apparently healthy relatives (two females and one male). This is the first report of a heterozygous DLX5 nonsense mutation resulting in incompletely penetrant autosomal dominant isolated SHFM1. Data shown here provides further evidence for the contribution of DLX5 point mutations to the development of ectrodactyly and suggest the possibility of sex-related segregation distortion with an excess of affected males. | 25,196,357 | [
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Challenges in mucosal HIV vaccine development: lessons from non-human primate models. | An efficacious HIV vaccine is urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trial in Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosal surfaces, development of immunity at these sites is critical, but few clinical vaccine trials have targeted these sites or assessed vaccine-elicited mucosal immune responses. Pre-clinical studies in non-human primate models have facilitated progress in mucosal vaccine development by evaluating candidate vaccine approaches, developing methodologies for collecting and assessing mucosal samples, and providing clues to immune correlates of protective immunity for further investigation. In this review we have focused on non-human primate studies which have provided important information for future design of vaccine strategies, targeting of mucosal inductive sites, and assessment of mucosal immunity. Knowledge gained in these studies will inform mucosal vaccine design and evaluation in human clinical trials. | 25,196,380 | [
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The use of propranolol in the treatment of infantile haemangiomas: an update on potential mechanisms of action. | Currently, propranolol is the preferred treatment for problematic proliferating infantile haemangiomas (IHs). The rapid action of propranolol has been shown to be especially dramatic in IHs involving dyspnoea, haemodynamic compromise, palpebral occlusion or ulceration. Another remarkable aspect of propranolol treatment revealed that the growth of the IHs was not only stabilized, but also that the improvement continued until complete involution was achieved, leading to a considerable shortening of the natural course of IH. However, the mechanisms underlying the effects of propranolol have not been fully elucidated. Recent studies have offered evidence of a variety of mechanisms. These include the promotion of pericyte-mediated vasoconstriction, the inhibition of vasculogenesis and catecholamine-induced angiogenesis, the disruption of haemodynamic force-induced cell survival, and the inactivation of the renin-angiotensin system. This review summarizes these mechanisms and the new concepts that are emerging in this area of research. Moreover, several molecular mechanisms by which propranolol may modify neovascularization in IH have also been proposed. The antihaemangioma effect of propranolol may not be attributable to a single mechanism, but rather to a combination of events that have not yet been elucidated or understood. Further studies are needed to evaluate and verify these mechanisms to gain a greater understanding of the effects of the intake of propranolol on haemangioma involution. | 25,196,392 | [
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Introduction to the special issue on achieving healthy weight in black American communities. | The prevalence of obesity is high in the United States, and highest among racial and ethnic minority groups. This special issue of Obesity Reviews is based upon evidence reviews prepared for and presented at a national invited workshop convened by the African American Collaborative Obesity Research Network (AACORN) in August of 2012. A set of potential topics was developed, a priori, and AACORN network members and colleagues with relevant expertise were invited to lead evidence reviews. The result is 10 articles focused on providing a comprehensive picture of what is known and unknown about interventions to prevent and treat obesity or improve weight-related behaviours in African American adults and children. Evidence reviews included in this special issue focus on children and adolescents (n=2); adults from various perspectives (n=5); eHealth interventions (n=1); interventions within faith organizations (n=1); and environmental and policy change interventions (n=1). Overall, the reviews show a small evidence base for research on African Americans and call for additional prioritization of funding to include studies that can inform action and bring progress in obesity prevention and treatment in African Americans on par with the scope and seriousness of the problem. | 25,196,403 | [
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Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus. | Approximately 5% of newborns were infected by hepatitis B virus (HBV) via intrauterine transmission and this is the main reason for high prevalence of HBV in endemic regions. However, the mechanisms by which intrauterine transmission is avoided in most cases remain elusive and placental natural anti-microbial factors may play a role in the prevention of HBV intrauterine transmission. The expression levels of human β-defensin-3 (HBD-3), apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G (A3G) and mannose binding lectin (MBL) were determined in the placenta of 30 HBV-seronegative pregnant women (controls), 7 HBV-seropositive pregnant women with infants infected via intrauterine transmission (infected group) and 30 HBV-seropositive pregnant women with non-infected infants (non-infected group). The expression of HBD-3, A3G, and MBL of placental trophoblast cell line Swan71 was determined after exposed to HBV. There were significant differences in placental HBD-3 and A3G levels among three groups, but the expression of MBL did not significantly differ. The expressions of HBD-3 and A3G were higher in non-infected group than controls and infected group, but not significantly different between infected group and controls. The exposure to HBV increased significantly the expression of HBD-3, A3G, and MBL by Swan 71. It may be concluded HBV up-regulates HBD-3 and A3G expression in vivo and in vitro in placental trophoblast and lack of this up-regulation is possibly associated with intrauterine transmission of HBV. | 25,196,417 | [
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Priorities in the communication needs of adolescents with psychosocial problems and their parents. | In patient-centred care, professionals should recognize their patient's needs and adapt their communication accordingly. Studies into patients' communication needs suggest priorities vary depending on sociodemographic characteristics, and type and severity of the complaints. However, evidence lacks on priorities in the communication needs of adolescents in psychosocial care and their parents. To assess adolescents' and parents' importance ratings concerning affective communication, information provision, shared decision-making, interprofessional communication and the degree to which client and care characteristics determine these. Adolescents aged 12-18 (n = 403) and one of their parents (n = 403) rated the importance of communication before the psychosocial care process started. Multivariable logistic regression analysis was applied to determine which characteristics were associated with the 25% lowest importance ratings for communication aspects. Adolescents and parents considered affective communication to be the most important, with shared decision-making the least important. For adolescents, lower importance ratings were associated with dissatisfaction with prior care (OR 1.8), negative expectations (ORs 1.9-2.4), emotional problems (ORs 0.2-0.5) and low prosocial behaviour skills (ORs 2.0). For parents, low education (ORs 1.7-1.8), negative expectations (OR 0.4), adolescent's hyperactivity/inattention (ORs 0.4-0.5) and low prosocial behaviour skills (ORs 1.8-2.6) determined lower importance ratings. Affective communication has highest priority for adolescents and their parents. Client and care characteristics are associated with client priorities in communication. Being attentive to clients' educational level, previous care experiences, current expectations and specific problem types might help professionals to adapt better to their clients' communication needs. | 25,196,418 | [
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A critique of a World Health Organization-commissioned report and associated paper on electronic cigarettes. | The World Health Organization (WHO) recently commissioned a report reviewing evidence on electronic cigarettes and making policy recommendations. A version of it was subsequently published as an academic paper. We identify important errors in the description and interpretation of the studies reviewed, and find many of its key conclusions misleading. | 25,196,419 | [
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Functional nanovalves on protein-coated nanoparticles for in vitro and in vivo controlled drug delivery. | A multifunctional mesoporous drug delivery system that contains fluorescent imaging molecules, targeting proteins, and pH-sensitive nanovalves is developed and tested. Three nanovalve-mesoporous silica nanoparticle (NV-MSN) systems with varied quantities of nanovalves on the surface are synthesized. These systems are characterized and tested to optimize the trade-off between the coverage of nanovalves on the MSNs to effectively trap and deliver cargo, and the remaining underivatized silanol groups that can be used for protein attachments. The NV-MSN system that has satisfactory coverage for high loading and spare silanols is chosen, and transferrin (Tf) is integrated into the system. Abiotic studies are performed to test the operation of the nanovalve in the presence of the protein. In vitro studies are carried out to demonstrate the autonomous activation and function of the nanovalves in the system under biological conditions. Enhanced cellular uptake of the Tf-modified MSNs is seen using fluorescence microscopy and flow cytometry in MiaPaCa-2 cells. The MSNs are then tested using SCID mice, which show that both targeted and untargeted NV-MSN systems are fully functional to effectively deliver cargo. These new multifunctional nanoparticles serve proof of concept of nanovalve functionality in the presence of large proteins and demonstrate another dimension of MSN-based theranostic platforms. | 25,196,485 | [
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Qualitative and quantitative analysis of fibrosis in the kidney. | Renal fibrosis results from an excess accumulation of connective tissue, primarily collagen, in response to tissue injury-associated aberrant wound healing, which is over-expressed in the renal vascular, glomerular and tubulointerstitial compartments. Despite being the final common pathway of end stage kidney disease, there is a lack of consensus on standardized approaches to measure fibrosis. In this article we therefore describe how a combination of immunohistochemical staining and biochemical measurement of hydroxyproline can be used to qualitatively and quantitatively examine the different forms of fibrosis. These techniques provide measures of both the composition of fibrosis, and a means of evaluating interventions in this significant process. | 25,196,487 | [
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Influence of smoking dosage and chronic obstructive lung disease on the incidence of appropriate therapies and mortality in patients with structural heart disease and an implantable cardioverter defibrillator. | Smoking is known as a relevant risk factor for severe cardiac morbidities and mortality. This study was initiated to explore the influence of smoking dosage and presence of chronic obstructive lung disease (COPD) on the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions and on mortality. Prior studies on patients equipped with an ICD suggested that nicotine consumption increases the risk of experiencing an appropriate ICD therapy. There is no substantial data regarding the influence of cigarette smoking dosage on overall mortality in such endangered patients. A total of 349 patients with structural heart disease, either coronary artery disease or nonischemic cardiomyopathy equipped with an ICD, were included. Every patient answered a questionnaire regarding his smoking status and performed a spirometry and body plethysmography. A total of 104 patients (30%) suffered from COPD. Fifty-eight patients (17%) were "current smokers," 196 patients (56%) were revealed as "former smokers," while 93 (27%) patients were registered as "never smokers." A total of 163 patients (47%) received at least one appropriate ICD intervention during follow-up (median 48 ± 8 months). Twenty-three patients died during this study (6.6%). There was no association of COPD with the incidence of appropriate ICD therapies or mortality. Smoking dosage revealed as a significant risk factor for both appropriate ICD interventions (hazard ratio [HR] 1.5 for 60 pack years [PY] P = 0.04) and mortality (HR 2.3 for 60 PY P = 0.02). This study demonstrates a dose-related increased risk of smokers for appropriate ICD interventions and mortality. The results of this trail urge a strict nicotine abstinence, especially in patients with a structural heart disease undergoing ICD therapy. | 25,196,490 | [
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Metal coordination, and metal-ligand redox non-innocence, modulates allosteric C-N bond homolysis in an N-benzyl tetrazine. | Remote coordination of a Ru(hfac)2 moiety to a chelating N-benzyl tetrazine lowers the C-N homolytic bond dissociation enthalpy by approximately 20 kJ mol(-1). The significant bond strength perturbation is believed to arise as a consequence of metal-ligand redox non-innocence. | 25,196,495 | [
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Bone marrow-derived progenitor cells attenuate inflammation in lipopolysaccharide-induced acute respiratory distress syndrome. | Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill patients. Novel treatment strategies are required to address this common clinical problem. The application of exogenous adult stem cells was associated with a beneficial outcome in various pre-clinical models of ARDS. In the present study we evaluated the functional capacity and homing ability of bone marrow-derived progenitor cells (BMDPC) in vitro and investigated their potential as a treatment strategy in lipopolysaccharide (LPS)-induced ARDS. Evaluation of the BMDPC showed functional capacity to form endothelial outgrowth cell colonies, which stained positive for CD133 and CD31. Furthermore, DiI-stained BMDPC were demonstrated to home to injured lung tissue. Rats treated with BMDPC showed significantly reduced histopathological changes, a reduced expression of ICAM-1 and VCAM-1 by the lung tissue, an inhibition of proinflammatory cytokine synthesis, a reduced weight loss and a reduced mortality (p < 0.03) compared to rats treated with LPS alone. These findings suggest that the application of exogenous BMDPC can attenuate inflammation in LPS-induced ARDS and thereby reduce the severity of septic organ damage. Cell therapy strategies using adult stem cells might therefore become a novel and alternative option in ARDS therapy. | 25,196,505 | [
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Single nucleotide polymorphisms generated by genotyping by sequencing to characterize genome-wide diversity, linkage disequilibrium, and selective sweeps in cultivated watermelon. | A large single nucleotide polymorphism (SNP) dataset was used to analyze genome-wide diversity in a diverse collection of watermelon cultivars representing globally cultivated, watermelon genetic diversity. The marker density required for conducting successful association mapping depends on the extent of linkage disequilibrium (LD) within a population. Use of genotyping by sequencing reveals large numbers of SNPs that in turn generate opportunities in genome-wide association mapping and marker-assisted selection, even in crops such as watermelon for which few genomic resources are available. In this paper, we used genome-wide genetic diversity to study LD, selective sweeps, and pairwise FST distributions among worldwide cultivated watermelons to track signals of domestication. We examined 183 Citrullus lanatus var. lanatus accessions representing domesticated watermelon and generated a set of 11,485 SNP markers using genotyping by sequencing. With a diverse panel of worldwide cultivated watermelons, we identified a set of 5,254 SNPs with a minor allele frequency of ≥ 0.05, distributed across the genome. All ancestries were traced to Africa and an admixture of various ancestries constituted secondary gene pools across various continents. A sliding window analysis using pairwise FST values was used to resolve selective sweeps. We identified strong selection on chromosomes 3 and 9 that might have contributed to the domestication process. Pairwise analysis of adjacent SNPs within a chromosome as well as within a haplotype allowed us to estimate genome-wide LD decay. LD was also detected within individual genes on various chromosomes. Principal component and ancestry analyses were used to account for population structure in a genome-wide association study. We further mapped important genes for soluble solid content using a mixed linear model. Information concerning the SNP resources, population structure, and LD developed in this study will help in identifying agronomically important candidate genes from the genomic regions underlying selection and for mapping quantitative trait loci using a genome-wide association study in sweet watermelon. | 25,196,513 | [
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Complete proteome of a quinolone-resistant Salmonella Typhimurium phage type DT104B clinical strain. | Salmonellosis is one of the most common and widely distributed foodborne diseases. The emergence of Salmonella strains that are resistant to a variety of antimicrobials is a serious global public health concern. Salmonella enterica serovar Typhimurium definitive phage type 104 (DT104) is one of these emerging epidemic multidrug resistant strains. Here we collate information from the diverse and comprehensive range of experiments on Salmonella proteomes that have been published. We then present a new study of the proteome of the quinolone-resistant Se20 strain (phage type DT104B), recovered after ciprofloxacin treatment and compared it to the proteome of reference strain SL1344. A total of 186 and 219 protein spots were recovered from Se20 and SL1344 protein extracts, respectively, after two-dimensional gel electrophoresis. The signatures of 94% of the protein spots were successfully identified through matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS). Three antimicrobial resistance related proteins, whose genes were previously detected by polymerase chain reaction (PCR), were identified in the clinical strain. The presence of these proteins, dihydropteroate synthase type-2 (sul2 gene), aminoglycoside resistance protein A (strA gene) and aminoglycoside 6'-N-acetyltransferase type Ib-cr4 (aac(6')-Ib-cr4 gene), was confirmed in the DT104B clinical strain. The aac(6')-Ib-cr4 gene is responsible for plasmid-mediated aminoglycoside and quinolone resistance. This is a preliminary analysis of the proteome of these two S. Typhimurium strains and further work is being developed to better understand how antimicrobial resistance is developing in this pathogen. | 25,196,519 | [
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Recent approaches in vaccine development against Streptococcus pneumoniae. | Streptococcus pneumoniae is a major cause of morbidity and mortality among children under 5 years of age worldwide. Vaccines have long been used for protection against pneumococcal infections. Capsular polysaccharides of pneumococci are main antigenic components of these vaccines. However, pneumococcal polysaccharide-based vaccines are not able to elicit appropriate immunological responses in young children and cannot induce the immune memory. Thus, pneumococcal conjugate vaccines were developed through chemical coupling of an immunogenic carrier protein to the capsule. The currently available pneumococcal conjugate vaccines elicited protection against the bacterium efficiently. However, these vaccines are expensive to manufacture and have limited serotype coverage. In this mini-review, therefore, we describe approaches attempted by researchers to circumvent the shortcomings of the conjugate vaccines including specifying appropriate cultivation conditions for the production of S. pneumoniae capsular antigens, development of suitable expression systems for the frequently used carrier protein in the conjugate vaccines (cross-reacting material 197), construction of protein-based vaccines, whole-cell vaccines, DNA vaccines, and using antigen delivery vehicles. Future trends in this field are also discussed. | 25,196,525 | [
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Chronic abdominal pain in a patient with escobar syndrome. | Escobar syndrome is characterized with multiple pterygia or webs of the skin and multiple congenital anomalies. We present a 15-year-old patient with Escobar syndrome who complained of persistent blunt abdominal pain for 1 year. Preoperative evaluation confirmed the diagnosis of imperforate hymen, and the patient underwent hymenectomy under intravenous sedation. The patient's postoperative course was uneventful and her complaints resolved completely. After a 3-month follow-up, she reported having normal menstrual bleeding intervals each month without any complications. Patients with Escobar syndrome may suffer from abdominal pain due to imperforate hymen. Careful evaluation of these patients must include a complete gynaecological assessment and, if indicated, surgical treatment must be performed without delay. | 25,196,531 | [
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Using Web searches to track interest in synthetic cannabinoids (a/k/a 'herbal incense'). | This article reports a content analysis of Internet websites related to an emerging designer drug, synthetic cannabinoids. The number of synthetic cannabinoids searchers in the USA has steadily increased from November 2008 to November 2011. To determine the information available on the Internet in relation to synthetic cannabinoids, sites were identified using the Google search engine and the search term 'herbal incense'. The first 100 consecutive sites were visited and classified by two coders. The websites were evaluated for type of content (retail, information, news, other). US unique monthly visitor data were examined for the top 10 retail sites, and these sites were coded for the quality of information available regarding the legality of synthetic cannabinoids sale and use. The Google search yielded 2,730,000 sites for 'herbal incense' (for comparison of search terms: 'synthetic marijuana', 1,170,000; 'K2 Spice', 247,000; and 'synthetic weed', 122,000). Moreover, in the Google search, 87% of the sites were retail sites, 5% news, 4% informational and 4% non-synthetic cannabinoid sites. Many tools found within Google free services hold promise in providing a technique to identify emerging drug markets. We recommend continued surveillance of the Internet using the online tools presented in this brief report by both drug researchers and policy-makers to identify the emerging trends in synthetic drugs' availability and interest. | 25,196,534 | [
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The strength of aversive and appetitive associations and maladaptive behaviors. | Certain maladaptive behaviors are thought to be acquired through classical Pavlovian conditioning. Exaggerated fear response, which can develop through Pavlovian conditioning, is associated with acquired anxiety disorders such as post-traumatic stress disorders (PTSDs). Inflated reward-seeking behavior, which develops through Pavlovian conditioning, underlies some types of addictive behavior (e.g., addiction to drugs, food, and gambling). These maladaptive behaviors are dependent on associative learning and the development of long-term memory (LTM). In animal models, an aversive reinforcer (fear conditioning) encodes an aversive contextual and cued LTM. On the other hand, an appetitive reinforcer results in conditioned place preference (CPP) that encodes an appetitive contextual LTM. The literature on weak and strong associative learning pertaining to the development of aversive and appetitive LTM is relatively scarce; thus, this review is particularly focused on the strength of associative learning. The strength of associative learning is dependent on the valence of the reinforcer and the salience of the conditioned stimulus that ultimately sways the strength of the memory trace. Our studies suggest that labile (weak) aversive and appetitive LTM may share similar signaling pathways, whereas stable (strong) aversive and appetitive LTM is mediated through different pathways. In addition, we provide some evidence suggesting that extinction of aversive fear memory and appetitive drug memory is likely to be mediated through different signaling molecules. We put forward the importance of studies aimed to investigate the molecular mechanisms underlying the development of weak and strong memories (aversive and appetitive), which would ultimately help in the development of targeted pharmacotherapies for the management of maladaptive behaviors that arise from classical Pavlovian conditioning. | 25,196,552 | [
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The case for treating refractory congestive heart failure with ultrafiltration. | Extracellular fluid retention and congestion is a fundamental manifestation of heart failure (HF) and cardiorenal syndrome (CRS). Patients are normally hospitalized and treated with diuretics, but their outcomes are often poor as severe congestion and diuretics resistance is the primary cause of HF-related hospital admissions and readmissions. Isolated ultrafiltration (UF), which can be considered as a 'mechanical diuretic and natriuretic' tool, offers promise in achieving safe and effective fluid volume removal in HF patients with CRS who are resistant to stepwise guided diuretic therapy. This paper outlines the rationale for machine-driven isolated UF in CRS and the available clinical evidence regarding its use in patients with HF. In addition, this article summarizes some future clinical perspectives for expanding the use of UF therapy in HF patients in order to improve outcomes. | 25,196,568 | [
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Water-soluble manganese inorganic polymers: the role of carborane clusters and producing large structural adjustments from minor molecular changes. | The reaction of two different carboranylcarboxylate ligands, 1-CH3-2-CO2H-1,2-closo-C2B10H10 or 1-CO2H-1,2-closo-C2B10H11, with MnCO3 in water leads to polymeric compounds 1 a and 1 b. Both compounds have been characterized by analytical and spectroscopic techniques. Additionally, electrochemical techniques have also been used for compound 1 a. X-ray analysis revealed substantial differences between both compounds: whereas a six-coordinated Mn(II) compound with water molecules bridging two Mn(II) centers has been observed for 1 a, a square pyramidal geometry around each Mn(II) ion with terminal water molecules coordinated to each Mn(II) center has been found for 1 b. The observed differences have been attributed to the existence of different substituents, -CH3 or -H, on one of the carbon atoms of the carboranylcarboxylate ligand. The reaction of 1 a and 1 b with coordinating solvents, such as ethers or Lewis bases, leads to the formation of new compounds with low (mononuclear 4 a, 4 b; dinuclear 3 a, 3 b; and trinuclear 2 a) or high nuclearity (hybrid polymer, 5 a), due to breakage of the corresponding polymer. X-ray analysis shows that the structural core present in the polymeric materials is not maintained in the resulting compounds, with the exception of trinuclear compound 2 a. The magnetic properties of the compounds studied show weak antiferromagnetic coupling. | 25,196,570 | [
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A highly sensitive ratiometric fluorescent probe for the detection of cytoplasmic and nuclear hydrogen peroxide. | As a marker for oxidative stress and a second messenger in signal transduction, hydrogen peroxide (H2O2) plays an important role in living systems. It is thus critical to monitor the changes in H2O2 in cells and tissues. Here, we developed a highly sensitive and versatile ratiometric H2O2 fluorescent probe (NP1) based on 1,8-naphthalimide and boric acid ester. In response to H2O2, the ratio of its fluorescent intensities at 555 and 403 nm changed 1020-fold within 200 min. The detecting limit of NP1 toward H2O2 is estimated as 0.17 μM. It was capable of imaging endogenous H2O2 generated in live RAW 264.7 macrophages as a cellular inflammation response, and especially, it was able to detect H2O2 produced as a signaling molecule in A431 human epidermoid carcinoma cells through stimulation by epidermal growth factor. This probe contains an azide group and thus has the potential to be linked to various molecules via the click reaction. After binding to a Nuclear Localization Signal peptide, the peptide-based combination probe (pep-NP1) was successfully targeted to nuclei and was capable of ratiometrically detecting nuclear H2O2 in living cells. These results indicated that NP1 was a highly sensitive ratiometric H2O2 dye with promising biological applications. | 25,196,578 | [
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A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. | Growth Arrest-Specific 5 (GAS5) is known to negatively regulate cell survival and is aberrantly expressed in several cancers. The influence of GAS5 on osteoarthritis (OA) has not been determined. To address this, articular chondrocytes were isolated from relatively normal (Non-OA) and clear OA regions (OA) of cartilage in total knee replacement (TKR) patients and biopsied normal cartilage. We found that GAS5 was up-regulated in OA chondrocytes compared with Non-OA and normal chondrocytes. The over-expression of GAS5 increased the expression levels of several MMPs, such as MMP-2, MMP-3, MMP-9, MMP-13, and ADAMTS-4; stimulated apoptosis; and suppressed autophagic responses. Furthermore, we subsequently identified miR-21 as a regulator of GAS5 during OA pathogenesis. The expression level of miR-21 was significantly reduced in OA patients, and the ectopic expression of GAS5 is capable of suppressing miR-21 induction. Consistent with GAS5 experiments, the introduction of miR-21 stimulated the apoptosis of chondrocytes and inhibited the expression levels of autophagic complexes, including LC-3B. In vivo, we found that the introduction of miR-21 into the cartilage of OA mice significantly stimulated cartilage destruction. Together, these results show that GAS5 contributes to the pathogenesis of OA by acting as a negative regulator of miR-21 and thereby regulating cell survival. | 25,196,583 | [
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Olfactory neuroblastoma and olfactory ventricle. A case report. | A case of dumbbell nasal and intracerebral olfactory neuroblastoma (ONB) related to possible seeding through an "olfactory ventricle" in the olfactory bulb and nerve is reported. This anatomic variant was recognized at operation for the first time: it consists of a hollow cavity within the olfactory bulb and nerve which may be connected to the subventricular zone of the frontal horn of the lateral ventricle. Better scrutiny of this structure is necessary in view of its possible interference with the course and diffusion of ONBs. | 25,196,619 | [
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Isolated contralateral sudden sensorineural hearing loss: an unusual manifestation of pontine infarct. | Unilateral, acute onset sensorineural hearing loss ("sudden sensorineural hearing loss" [SSNHL]) as an isolated event without other associated neurological deficits usually results from a lesion of the cochlea. Lesions in the ascending central auditory pathways cranial to the cochlear nucleus seldom result in unilateral hearing loss due to decussation of the central auditory pathways at multiple levels. We describe a patient with a tiny acute infarct in the right pons resulting in isolated acute onset left-sided SSHNL, without any other associated acute neurological deficits. | 25,196,624 | [
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Is It All about the Higher Dose? Why Psychoanalytic Therapy Is an Effective Treatment for Major Depression. | Empirical evidence for the effectiveness of long-term psychodynamic psychotherapy (LTPP) in patients with mood disorders is growing. However, it is unclear whether the effectiveness of LTPP is due to distinctive features of psychodynamic/psychoanalytic techniques or to a higher number of sessions. We tested these rival hypotheses in a quasi-experimental study comparing psychoanalytic therapy (i.e., high-dose LTPP) with psychodynamic therapy (i.e., low-dose LTPP) and cognitive-behavioural therapy (CBT) for depression. Analyses were based on a subsample of 77 subjects, with 27 receiving psychoanalytic therapy, 26 receiving psychodynamic therapy and 24 receiving CBT. Depressive symptoms, interpersonal problems and introject affiliation were assessed prior to treatment, after treatment and at the 1-, 2- and 3-year follow-ups. Psychoanalytic techniques were assessed from three audiotaped middle sessions per treatment using the Psychotherapy Process Q-Set. Subjects receiving psychoanalytic therapy reported having fewer interpersonal problems, treated themselves in a more affiliative way directly after treatment and tended to improve in depressive symptoms and interpersonal problems during follow-up as compared with patients receiving psychodynamic therapy and/or CBT. Multilevel mediation analyses suggested that post-treatment differences in interpersonal problems and introject affiliation were mediated by the higher number of sessions, and follow-up differences in depressive symptoms were mediated by the more pronounced application of psychoanalytic techniques. We also found some evidence for indirect treatment effects via psychoanalytic techniques on changes in introject affiliation during follow-up. These results provide support for the prediction that both a high dose and the application of psychoanalytic techniques facilitate therapeutic change in patients with major depression. Psychoanalytic therapy is an effective treatment for major depression, especially in the long run. The differential effectiveness of psychoanalytic therapy cannot be fully explained by its higher dose. Distinctive features of psychoanalytic technique (e.g., focusing on patients' dreams, fantasies, sexual experiences or childhood memories) may play an important role in establishing sustained therapeutic change. | 25,196,642 | [
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Soft magnets from the self-organization of magnetic nanoparticles in twisted liquid crystals. | Organizing magnetic nanoparticles into long-range and dynamic assemblies would not only provide new insights into physical phenomena but also open opportunities for a wide spectrum of applications. In particular, a major challenge consists of the development of nanoparticle-based materials for which the remnant magnetization and coercive field can be controlled at room temperature. Our approach consists of promoting the self-organization of magnetic nanoparticles in liquid crystals (LCs). Using liquid crystals as organizing templates allows us to envision the design of tunable self-assemblies of magnetic nanoparticles, because liquid crystals are known to reorganize under a variety of external stimuli. Herein, we show that twisted liquid crystals can be used as efficient anisotropic templates for superparamagnetic nanoparticles and demonstrate the formation of hybrid soft magnets at room temperature. | 25,196,652 | [
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Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals. | Increased levels of oxidatively damaged DNA have been documented in studies of metal, metal oxide, carbon-based and ceramic engineered nanomaterials (ENMs). In particular, 8-oxo-7,8-dihydroguanine-2'-deoxyguanosine (8-oxodG) is widely assessed as a DNA nucleobase oxidation product, measured by chromatographic assays, antibody-based methods or the comet assay with DNA repair enzymes. However, spurious oxidation of DNA has been a problem in certain studies applying chromatographic assays, yielding high baseline levels of 8-oxodG. Antibody-based assays detect high 8-oxodG baseline levels, related to cross-reactivity with other molecules in cells. This review provides an overview of efforts to reliably detect oxidatively damaged DNA and a critical assessment of the published studies on DNA damage levels. Animal studies with high baseline levels of oxidatively damaged DNA are more likely to show positive associations between exposure to ENMs and oxidized DNA in tissue than studies showing acceptable baseline levels (odds ratio = 12.1, 95% confidence interval: 1.2-124). Nevertheless, reliable studies indicate that intratracheal instillation of nanosized carbon black is associated with increased levels of oxidatively damaged DNA in lung tissue. Oral exposure to nanosized carbon black, TiO2 , carbon nanotubes and ZnO is associated with elevated levels of oxidatively damaged DNA in tissues. These observations are supported by cell culture studies showing concentration-dependent associations between ENM exposure and oxidatively damaged DNA measured by the comet assay. Cell culture studies show relatively high variation in the ability of ENMs to oxidatively damage DNA; hence, it is currently impossible to group ENMs according to their DNA damaging potential. | 25,196,723 | [
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Oxidation of bioethanol using zeolite-encapsulated gold nanoparticles. | With the ongoing developments in biomass conversion, the oxidation of bioethanol to acetaldehyde may become a favorable and green alternative to the preparation from ethylene. Here, a simple and effective method to encapsulate gold nanoparticles in zeolite silicalite-1 is reported and their high activity and selectivity for the catalytic gas-phase oxidation of ethanol are demonstrated. The zeolites are modified by a recrystallization process, which creates intraparticle voids and mesopores that facilitate the formation of small and disperse nanoparticles upon simple impregnation. The individual zeolite crystals comprise a broad range of mesopores and contain up to several hundred gold nanoparticles with a diameter of 2-3 nm that are distributed inside the zeolites rather than on the outer surface. The encapsulated nanoparticles have good stability and result in 50 % conversion of ethanol with 98 % selectivity toward acetaldehyde at 200 °C, which (under the given reaction conditions) corresponds to 606 mol acetaldehyde/mol Au hour(-1) . | 25,196,739 | [
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Photo-Wolff Rearrangement of 2-Diazo-1,2-naphthoquinone: Stern-Volmer Analysis of the Stepwise Reaction Pathway. | 2-Diazo-1,2-naphthoquinone (1) and its derivatives are the photoactive components in Novolak photoresists. A femtosecond infrared study has established that the photoreaction of 1 proceeds largely by a concerted Wolff rearrangement yielding the ketene 1H-inden-1-ylidene-methanone (3) within 300 fs after excitation, but earlier trapping studies gave evidence for a minor reaction path via a carbene intermediate 1-oxo-2(1H)-naphthalenylidene (2) with a lifetime of about 10 ps. Here, we provide a quantitative assessment of the stepwise pathway by Stern-Volmer analysis of the trapping of 2 by methanol to yield 2-methoxy-1-naphthol (4). We conclude that the lifetime of the carbene 2 is at least 200 ps. Moreover, [3 + 2]cycloaddition of 2 and acetonitrile yielding 2-methylnaphth[2,1-d]oxazole (5) was observed. A comparison of the yields of 5 formed upon photolysis and upon thermolysis of 1 in acetonitrile provides evidence that a substantial part of the hot nascent carbene 2 formed photolytically rearranges to the ketene 3 during its vibrational relaxation (hot ground-state reaction). | 25,196,741 | [
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Physician-reported barriers to referring cancer patients to specialists: prevalence, factors, and association with career satisfaction. | Quality care for patients with cancer often requires access to specialty providers, but little is known about barriers to referring cancer patients for specialized care. Referral barriers may also lessen physician career satisfaction. The study was aimed at determining what factors are associated with these barriers and whether greater barriers are associated with low career satisfaction. This cross-sectional study examined 1562 primary care physicians (PCPs) and 2144 specialists responding to the multiregional Cancer Care Outcomes Research and Surveillance Consortium physician survey. The prevalence of physician-reported barriers to referring cancer patients for more specialized care (restricted provider networks, preauthorization requirements, patient inability to pay, lack of surgical subspecialists, and excessive patient travel time) was assessed. The 5 items were averaged to calculate a barrier score. A multivariate linear regression was used to determine physician and practice setting characteristics associated with the barrier score, and a multivariate logistic regression was used to analyze the association of the barrier score with physician career satisfaction. Three in 5 physicians reported always, usually, or sometimes encountering any barrier to cancer patient specialty referrals. In adjusted analyses of PCPs and specialists, international medical graduates, physicians practicing in solo or government-owned practices, and physicians with <90% of their patients in managed care plans had higher barrier scores than others (P < .05). High barrier scores were associated with lower physician career satisfaction among PCPs and specialists (P < .05). Many physicians experience barriers to specialty referral for cancer patients. Uniform systems for providing and tracking timely referrals may enhance care and promote physician career satisfaction. | 25,196,776 | [
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Does exercise habit strength moderate the relationship between emotional distress and short-term memory in Malaysian primary school children? | We examined the moderating effects of exercise habit strength on the relationship between emotional distress and short-term memory in primary school children. The sample consisted of 165 primary school students (10-12 years old). Participants completed measures of emotional distress, exercise habit strength, and the Digit Span Test. Mid-year exam results were used as an indicator of academic performance. Structural equation modelling (SEM) was used to analyse the data. The results of SEM revealed an acceptable fit for the hypothesised model. Exercise habit was positively associated with short-term memory, and better short-term memory was associated with better academic performance. However, although an inverse relationship was found between emotional distress and short-term memory, a positive association was found between exercise habit strength and emotional distress. The findings indicate that exercise habit is positively associated with cognitive ability and mediates the negative effect of distress. | 25,196,807 | [
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Regulatory Fe(II/III) heme: the reconstruction of a molecule's biography. | More than 20 years of research on heme as a temporary effector molecule of proteins have revealed its widespread impact on virtually all primary functions in the human organism. As our understanding of this influence is still growing, a comprehensive overview of compiled data will give fresh impetus for creativity and developing new strategies in heme-related research. From known data concerning heme-regulated proteins and their involvement in the development of diseases, we provide concise information of Fe(II/III) heme as a regulator and the availability of "regulatory heme". The latter is dependent on the balance between free and bound Fe(II/III) heme, here termed "hemeostasis". Imbalance of this system can lead to the development of diseases that were not always attributed to this small molecule. Diseases such as cancer or Alzheimer's disease highlight the reawakened interest in heme, whose function was previously believed to be completely understood. | 25,196,849 | [
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Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer. | The aim of this study is to identify factors that increase the occurrence of severe neutropenia (SN) and febrile neutropenia (FN) during docetaxel treatment for castration-resistant prostate cancer (CRPC). We retrospectively reviewed 258 courses during the first three cycles among 95 patients. Docetaxel at a dose of 75 mg/m(2) was administered every 3 or 4 weeks. Patient background, laboratory data, and bone scan results were collected to assess predictive factors for SN and FN. We defined SN as an absolute neutrophil count (ANC) of <500/mm(3) and defined FN as an ANC of <1000/mm(3) with a body temperature of >38.3 °C. The mean age of the patients was 72.6 ± 6.4 years and the mean prostate-specific antigen was 135.4 ± 290.9 ng/ml. During the first three courses of treatment, SN occurred in 72.6% of patients and FN occurred in 9.5 % of patients. Univariate analysis demonstrated that age ≥ 75 years (p = 0.002), number of comorbidities ≥ 1.2 (p = 0.008 and p = 0.006) and previous external beam radiation therapy (EBRT) (p = 0.001) were predictive factors for the development of SN or FN. In multivariate analysis, significant predictors of SN or FN were age ≥ 75 years (hazard ratio [HR] 5.77; p = 0.004) and previous EBRT (HR 14.5; p = 0.012). According to the subgroup analysis dividing SN and FN separately, multivariate analysis also revealed that age ≥ 75 years and previous EBRT were also significant predictors for developing SN (HR 5.09; p = 0.023, HR 12.7; p = 0.020, respectively) and for developing FN (HR 5.45; p = 0.042, HR 7.72; p = 0.015, respectively). Patients aged ≥ 75 years and with a history of localized radiation therapy are at higher risk for significant neutropenic events and require closer surveillance. | 25,196,861 | [
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Accompanying artery of sciatic nerve as recipient vessel for free-flap transfer: a computed tomographic angiography study and case reports. | Suitable recipient vessels for free-flap transfer are hard to find in the posterior thigh. To investigate the versatility of accompanying artery of sciatic nerve as a recipient vessel in this region, we performed computed tomographic angiographic study of 20 consecutive healthy thighs in 10 patients. The presence and internal diameter of the accompanying artery were studied. The accompanying artery of the sciatic nerve was present in 11 thighs (55%) and the internal diameter of the artery at the mid-thigh level ranged from 2.1 to 3.2 mm. We used this artery as a recipient vessel for free flaps transferred to reconstruct extensive thigh defects in three patients with sarcomas. In all patients the flaps survived without vascular compromise. No sensory or motor dysfunction in the sciatic nerve distribution occurred in any patients. We believe that the accompanying artery of the sciatic nerve may be a recipient vessel for free-flap transfer in selected patients. | 25,196,891 | [
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Development of a two-step high-resolution melting (HRM) analysis for screening sequence variants associated with resistance to the QoIs, benzimidazoles and dicarboximides in airborne inoculum of Botrytis cinerea. | A rapid, high-resolution melting (HRM) analysis protocol was developed to detect sequence variations associated with resistance to the QoIs, benzimidazoles and dicarboximides in Botrytis cinerea airborne inoculum. HRM analysis was applied directly in fungal DNA collected from air samplers with selective medium. Three and five different genotypes were detected and classified according to their melting profiles in BenA and bos1 genes associated with resistance to benzimidazoles and dicarboximides, respectively. The sensitivity of the methodology was evident in the case of the QoIs, where genotypes varying either by a single nucleotide polymorphism or an additional 1205-bp intron were separated accurately with a single pair of primers. The developed two-step protocol was completed in 82 min and showed reduced variation in the melting curves' formation. HRM analysis rapidly detected the major mutations found in greenhouse strains providing accurate data for successfully controlling grey mould. | 25,196,894 | [
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Switch from intravitreal ranibizumab to bevacizumab for the treatment of neovascular age-related macular degeneration: clinical comparison. | To compare outcomes after switching from intravitreal ranibizumab to bevacizumab in neovascular age-related macular degeneration (AMD). A retrospective review of 110 eyes treated in a 1+PRN (pro re nata) clinical setting with ranibizumab that were switched to bevacizumab. Patients analyzed had at least 3 ranibizumab injections followed by at least 3 bevacizumab injections. Changes in best-corrected visual acuity (BCVA), retinal thickness and frequency of injections were compared. The mean duration of ranibizumab treatment was 18.1 months, followed by 12.2 months of bevacizumab. Mean injection rates per month were similar (0.54 and 0.56 respectively, p = 0.230). There were no significant differences between BCVA at baseline and at the time of the switch (52.4 and 54.8 letters, p = 0.059). After the switch, there was a statistically significant decrease in BCVA to 51.7 letters (p < 0.001). Switching patients to bevacizumab may have a minor negative effect on the initial gain obtained with ranibizumab; however the degenerative history of wet AMD could explain this small variation in visual acuity. | 25,196,907 | [
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Evidence for substrate binding-induced zwitterion formation in the catalytic Cys-His dyad of the SARS-CoV main protease. | The coronavirus main protease (M(pro)) represents an attractive drug target for antiviral therapy of coronavirus (CoV) infections, including severe acute respiratory syndrome (SARS). The SARS-CoV M(pro) and related CoV proteases have several distinct features, such as an uncharged Cys-His catalytic dyad embedded in a chymotrypsin-like protease fold, that clearly separate these enzymes from archetypical cysteine proteases. To further characterize the catalytic system of CoV main proteases and to obtain information about improved inhibitors, we performed comprehensive simulations of the proton-transfer reactions in the SARS-CoV M(pro) active site that lead to the Cys(-)/His(+) zwitterionic state required for efficient proteolytic activity. Our simulations, comprising the free enzyme as well as substrate-enzyme and inhibitor-enzyme complexes, lead us to predict that zwitterion formation is fostered by substrate binding but not inhibitor binding. This indicates that M(pro) employs a substrate-induced catalytic mechanism that further enhances its substrate specificity. Our computational data are in line with available experimental results, such as X-ray geometries, measured pKa values, mutagenesis experiments, and the measured differences between the kinetic parameters of substrates and inhibitors. The data also provide an atomistic picture of the formerly postulated electrostatic trigger involved in SARS-CoV M(pro) activity. Finally, they provide information on how a specific microenvironment may finely tune the activity of M(pro) toward specific viral protein substrates, which is known to be required for efficient viral replication. Our simulations also indicate that the low inhibition potencies of known covalently interacting inhibitors may, at least in part, be attributed to insufficient fostering of the proton-transfer reaction. These findings suggest ways to achieve improved inhibitors. | 25,196,915 | [
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0.08858126,
-0.0005686699,
0.1619292,
0.2377339,
0.09573662,
0.3019712,
0.0323249,
0.03975185,
0.1166106,
0.07659942,
-0.04405431,
-0.3173596,
0.25678,
-0.3204688,
0.1251409,
-0.002336189,
0.08808848,
0.04810691,
-0.1115032,
-0.323516,
... |
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