title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Inhaled hydrogen gas therapy for prevention of noise-induced hearing loss through reducing reactive oxygen species. | Reactive oxygen species (ROS) that form in the inner ear play an important role in noise-induced hearing loss (NIHL). Recent studies have revealed that molecular hydrogen (H2) has great potential for reducing ROS. In this study, we examined the potential of hydrogen gas to protect against NIHL. We tested this hypothesis in guinea pigs with 0.5%, 1.0% and 1.5% H2 inhalation in air for 5h a day after noise exposure, for five consecutive days. All animals underwent measurements for auditory brainstem response after the noise exposure; the results revealed that there was a better improvement in the threshold shift for the 1.0% and 1.5% H2-treated groups than the non-treated group. Furthermore, outer hair cell (OHC) loss was examined 7 days after noise exposure. A significantly higher survival rate of OHCs was observed in the 1.0% and 1.5% H2-treated group as compared to that of the non-treated group in the basal turn. Immunohistochemical analyses for 8-hydroxy-2'-deoxyguanosine (8-OHdG) were performed to examine the amount of oxidative DNA damage. While strong immunoreactivities against 8-OHdG were observed of the non-treated group, the H2-treated group showed decreased immunoreactivity for 8-OHdG. These findings strongly suggest that inhaled hydrogen gas protects against NIHL. | 25,196,919 | [
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Can gerontology be a science? | During the last half-century, research on aging has become more scientific in its self-representations. Paradoxically, however, it is not at all self-evident that gerontology can flourish as a comprehensive science. Highlighting major trends in the internal and external history of the field's evolution reveals why this is so. And yet, retrospective analysis also provides a vehicle for creating a science of gerontology driven by cumulative, synthetic theory-building. | 25,196,923 | [
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mRNA-based dendritic cell vaccines. | Cancer immunotherapy has been proposed as a powerful treatment modality. Active immunotherapy aspires to stimulate the patient's immune system, particularly T cells. These cells can recognize and kill cancer cells and can form an immunological memory. Dendritic cells (DCs) are the professional antigen-presenting cells of our immune system. They take up and process antigens to present them to T cells. Consequently, DCs have been investigated as a means to stimulate cancer-specific T-cell responses. An efficient strategy to program DCs is the use of mRNA, a well-defined and safe molecule that can be easily generated at high purity. Importantly, vaccines consisting of mRNA-modified DCs showed promising results in clinical trials. Therefore, we will introduce cancer immunotherapy and DCs and give a detailed overview on the application of mRNA to generate cancer-fighting DC vaccines. | 25,196,947 | [
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Interlayer cation exchange stabilizes polar perovskite surfaces. | Global optimization is used to study the structure of the polar KTaO3 (001) surface. It is found that cation exchange near the surface leads to the most stable structure. This mechanism is likely to be general to metal oxides containing cations of differing charge. | 25,196,987 | [
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A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. | Sclerostin, a SOST protein secreted by osteocytes, negatively regulates formation of mineralized bone matrix and bone mass. We report the results of a randomized, double-blind, placebo-controlled multicenter phase 2 clinical trial of blosozumab, a humanized monoclonal antibody targeted against sclerostin, in postmenopausal women with low bone mineral density (BMD). Postmenopausal women with a lumbar spine T-score -2.0 to -3.5, inclusive, were randomized to subcutaneous blosozumab 180 mg every 4 weeks (Q4W), 180 mg every 2 weeks (Q2W), 270 mg Q2W, or matching placebo for 1 year, with calcium and vitamin D. Serial measurements of spine and hip BMD and biochemical markers of bone turnover were performed. Overall, 120 women were enrolled in the study (mean age 65.8 years, mean lumbar spine T-score -2.8). Blosozumab treatment resulted in statistically significant dose-related increases in spine, femoral neck, and total hip BMD as compared with placebo. In the highest dose group, BMD increases from baseline reached 17.7% at the spine, and 6.2% at the total hip. Biochemical markers of bone formation increased rapidly during blosozumab treatment, and trended toward pretreatment levels by study end. However, bone specific alkaline phosphatase remained higher than placebo at study end in the highest-dose group. CTx, a biochemical marker of bone resorption, decreased early in blosozumab treatment to a concentration less than that of the placebo group by 2 weeks, and remained reduced throughout blosozumab treatment. Mild injection site reactions were reported more frequently with blosozumab than placebo. In conclusion, treatment of postmenopausal women with an antibody targeted against sclerostin resulted in substantial increases in spine and hip BMD. These results support further study of blosozumab as a potential anabolic therapy for osteoporosis. | 25,196,993 | [
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Catalytic enantioselective addition of thioacids to trisubstituted nitroalkenes. | The first example of a catalytic enantioselective addition to and nitronate protonation of trisubstituted nitroalkenes to produce highly enantioenriched products with a tetrasubstituted carbon is reported. Thioacids added in excellent yields and with high enantioselectivities to both activated and unactivated nitroalkenes. The 1,2-nitrothioacetate products can be readily converted in two steps to biomedically relevant 1,2-aminosulfonic acids without loss of enantiopurity. | 25,196,997 | [
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Daily variation in lung function in COPD patients with combined albuterol and ipratropium: results from a 4-week, randomized, crossover study. | The bronchodilator response to short-acting β2-agonist and short-acting muscarinic antagonist monotherapies varies on a day-to-day basis within individual patients. The objective of this study was to compare daily variation in bronchodilator response to the combined use of albuterol and ipratropium with monotherapies in patients with chronic obstructive pulmonary disease (COPD). This was a 4-week, randomized, open-label, two-period crossover study in patients with COPD. Patients were randomized 1:1 to receive albuterol via metered dose inhaler followed by ipratropium or vice versa during treatment Period 1 (10-14 days). The order of treatments was then reversed during treatment Period 2 (10-14 days). Pre-defined efficacy endpoints were: forced expiratory volume in 1 s (FEV1), derived FEV1, inspiratory capacity (IC) and daily variability of FEV1 and IC as measured by coefficient of variation (CV). Albuterol and ipratropium improved FEV1 when administered as the first bronchodilator, compared with pre-dose values (0.269 and 0.243 L, respectively). Administration of the second bronchodilator provided further improvements in lung function, but to a lesser magnitude than the first bronchodilator (0.094 L for both treatments). A statistically significant reduction in daily variability in FEV1 was observed for dual bronchodilator therapy compared with monotherapy (difference in CV = 0.007; p = 0.019) and pre-dose values (no treatment; difference in CV = 0.022; p < 0.001). The free combination of albuterol and ipratropium resulted in greater improvements and lower day-to-day variability in FEV1 compared with either monotherapy or no bronchodilator therapy. The reduced daily variability may be an important therapeutic advantage of using different classes of bronchodilators in COPD. NCT01691482. | 25,197,005 | [
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HPV-related oropharyngeal cancer: Risk factors for treatment failure in patients managed with primary transoral robotic surgery. | The purpose of this study was to determine clinical factors that predict locoregional recurrence or distant metastasis in patients with human papillomavirus (HPV)-positive oropharyngeal cancer treated with surgery and guideline-indicated adjuvant therapy. We identified all presumed HPV-positive patients with oropharyngeal cancer in our health system from January 2010 to August 2012 treated with surgery and guideline-indicated adjuvant therapy. Statistical analysis was performed to identify clinical predictors associated with treatment failure. One hundred fourteen p16+ oropharyngeal cancers managed with initial surgical resection were identified. Median follow-up was 17 months. Two-year locoregional failure was 3.3% and distant failure was 8.4%. Statistical analysis found that conventional poor prognostic features did not predict treatment failure. Locoregional recurrence and development of distant metastatic disease are uncommon in patients who are appropriately selected for surgical management of p16+ oropharyngeal cancer regardless of the presence or absence of conventional poor prognostic features. | 25,197,014 | [
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Induction of potential protective immunity against enterotoxemia in calves by single or multiple recombinant Clostridium perfringens toxoids. | Cattle enterotoxemia caused by Clostridium perfringens toxins is a noncontagious, sporadic, and fatal disease characterized by sudden death. Strategies for controlling and preventing cattle enterotoxemia are based on systematic vaccination of herds with toxoids. Because the process of producing conventional clostridial vaccines is dangerous, expensive, and time-consuming, the prospect of recombinant toxoid vaccines against diseases caused by C. perfringens toxins is promising. In this study, nontoxic recombinant toxoids derived from α-, β- and ε-toxins of C. perfringens, namely, rCPA247-370 , rCPB and rEtxHP, respectively, were expressed in Escherichia coli. High levels of specific IgG antibodies and neutralizing antibodies against the toxins were detected in sera from calves vaccinated with either a single recombinant toxoid or a mixed cocktail of all three recombinant toxoids, indicating the potential of these recombinant toxoids to provide calves with protective immunity against enterotoxemia caused by C. perfringens. | 25,197,030 | [
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Chemoenzymatic synthesis of heparan sulfate and heparin. | Heparan sulfate is a polysaccharide that plays essential physiological functions in the animal kingdom. Heparin, a highly sulfated form of heparan sulfate, is a widely prescribed anticoagulant drug worldwide. The heparan sulfate and heparin isolated from natural sources are highly heterogeneous mixtures differing in their polysaccharide chain lengths and sulfation patterns. The access to structurally defined heparan sulfate and heparin is critical to probe the contribution of specific sulfated saccharide structures to the biological functions as well as for the development of the next generation of heparin-based anticoagulant drugs. The synthesis of heparan sulfate and heparin, using a purely chemical approach, has proven extremely difficult, especially for targets larger than octasaccharides having a high degree of site-specific sulfation. A new chemoenzymatic method has emerged as an effective alternative approach. This method uses recombinant heparan sulfate biosynthetic enzymes combined with unnatural uridine diphosphate-monosaccharide donors. Recent examples demonstrate the successful synthesis of ultra-low molecular weight heparin, low-molecular weight heparin and bioengineered heparin with unprecedented efficiency. The new method provides an opportunity to develop improved heparin-based therapeutics. | 25,197,032 | [
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Cell cycle-dependent adaptor complex for ClpXP-mediated proteolysis directly integrates phosphorylation and second messenger signals. | The cell-division cycle of Caulobacter crescentus depends on periodic activation and deactivation of the essential response regulator CtrA. Although CtrA is critical for transcription during some parts of the cell cycle, its activity must be eliminated before chromosome replication because CtrA also blocks the initiation of DNA replication. CtrA activity is down-regulated both by dephosphorylation and by proteolysis, mediated by the ubiquitous ATP-dependent protease ClpXP. Here we demonstrate that proteins needed for rapid CtrA proteolysis in vivo form a phosphorylation-dependent and cyclic diguanylate (cdG)-dependent adaptor complex that accelerates CtrA degradation in vitro by ClpXP. The adaptor complex includes CpdR, a single-domain response regulator; PopA, a cdG-binding protein; and RcdA, a protein whose activity cannot be predicted. When CpdR is unphosphorylated and when PopA is bound to cdG, they work together with RcdA in an all-or-none manner to reduce the Km of CtrA proteolysis 10-fold. We further identified a set of amino acids in the receiver domain of CtrA that modulate its adaptor-mediated degradation in vitro and in vivo. Complex formation between PopA and CtrA depends on these amino acids, which reside on alpha-helix 1 of the CtrA receiver domain, and on cdG binding by PopA. These results reveal that each accessory factor plays an essential biochemical role in the regulated proteolysis of CtrA and demonstrate, to our knowledge, the first example of a multiprotein, cdG-dependent proteolytic adaptor. | 25,197,043 | [
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Quantifying the benefits of vehicle pooling with shareability networks. | Taxi services are a vital part of urban transportation, and a considerable contributor to traffic congestion and air pollution causing substantial adverse effects on human health. Sharing taxi trips is a possible way of reducing the negative impact of taxi services on cities, but this comes at the expense of passenger discomfort quantifiable in terms of a longer travel time. Due to computational challenges, taxi sharing has traditionally been approached on small scales, such as within airport perimeters, or with dynamical ad hoc heuristics. However, a mathematical framework for the systematic understanding of the tradeoff between collective benefits of sharing and individual passenger discomfort is lacking. Here we introduce the notion of shareability network, which allows us to model the collective benefits of sharing as a function of passenger inconvenience, and to efficiently compute optimal sharing strategies on massive datasets. We apply this framework to a dataset of millions of taxi trips taken in New York City, showing that with increasing but still relatively low passenger discomfort, cumulative trip length can be cut by 40% or more. This benefit comes with reductions in service cost, emissions, and with split fares, hinting toward a wide passenger acceptance of such a shared service. Simulation of a realistic online system demonstrates the feasibility of a shareable taxi service in New York City. Shareability as a function of trip density saturates fast, suggesting effectiveness of the taxi sharing system also in cities with much sparser taxi fleets or when willingness to share is low. | 25,197,046 | [
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Ebf2 is a selective marker of brown and beige adipogenic precursor cells. | Brown adipocytes and muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to platelet-derived growth factor α(+), myogenic factor 5(Cre)-lineage-marked cells. RNA-sequence analysis identified early B-cell factor 2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2(GFP) embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2 expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells. | 25,197,048 | [
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Human oxygen sensing may have origins in prokaryotic elongation factor Tu prolyl-hydroxylation. | The roles of 2-oxoglutarate (2OG)-dependent prolyl-hydroxylases in eukaryotes include collagen stabilization, hypoxia sensing, and translational regulation. The hypoxia-inducible factor (HIF) sensing system is conserved in animals, but not in other organisms. However, bioinformatics imply that 2OG-dependent prolyl-hydroxylases (PHDs) homologous to those acting as sensing components for the HIF system in animals occur in prokaryotes. We report cellular, biochemical, and crystallographic analyses revealing that Pseudomonas prolyl-hydroxylase domain containing protein (PPHD) contain a 2OG oxygenase related in structure and function to the animal PHDs. A Pseudomonas aeruginosa PPHD knockout mutant displays impaired growth in the presence of iron chelators and increased production of the virulence factor pyocyanin. We identify elongation factor Tu (EF-Tu) as a PPHD substrate, which undergoes prolyl-4-hydroxylation on its switch I loop. A crystal structure of PPHD reveals striking similarity to human PHD2 and a Chlamydomonas reinhardtii prolyl-4-hydroxylase. A crystal structure of PPHD complexed with intact EF-Tu reveals that major conformational changes occur in both PPHD and EF-Tu, including a >20-Å movement of the EF-Tu switch I loop. Comparison of the PPHD structures with those of HIF and collagen PHDs reveals conservation in substrate recognition despite diverse biological roles and origins. The observed changes will be useful in designing new types of 2OG oxygenase inhibitors based on various conformational states, rather than active site iron chelators, which make up most reported 2OG oxygenase inhibitors. Structurally informed phylogenetic analyses suggest that the role of prolyl-hydroxylation in human hypoxia sensing has ancient origins. | 25,197,067 | [
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Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia. | The promise of cell therapy for repair and restoration of damaged tissues or organs relies on administration of large dose of cells whose healing benefits are still limited and sometimes irreproducible due to uncontrollable cell loss and death at lesion sites. Using a large amount of therapeutic cells increases the costs for cell processing and the risks of side effects. Optimal cell delivery strategies are therefore in urgent need to enhance the specificity, efficacy, and reproducibility of cell therapy leading to minimized cell dosage and side effects. Here, we addressed this unmet need by developing injectable 3D microscale cellular niches (microniches) based on biodegradable gelatin microcryogels (GMs). The microniches are constituted by in vitro priming human adipose-derived mesenchymal stem cells (hMSCs) seeded within GMs resulting in tissue-like ensembles with enriched extracellular matrices and enhanced cell-cell interactions. The primed 3D microniches facilitated cell protection from mechanical insults during injection and in vivo cell retention, survival, and ultimate therapeutic functions in treatment of critical limb ischemia (CLI) in mouse models compared with free cell-based therapy. In particular, 3D microniche-based therapy with 10(5) hMSCs realized better ischemic limb salvage than treatment with 10(6) free-injected hMSCs, the minimum dosage with therapeutic effects for treating CLI in literature. To the best of our knowledge, this is the first convincing demonstration of injectable and primed cell delivery strategy realizing superior therapeutic efficacy for treating CLI with the lowest cell dosage in mouse models. This study offers a widely applicable cell delivery platform technology to boost the healing power of cell regenerative therapy. | 25,197,069 | [
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Multiscale digital Arabidopsis predicts individual organ and whole-organism growth. | Understanding how dynamic molecular networks affect whole-organism physiology, analogous to mapping genotype to phenotype, remains a key challenge in biology. Quantitative models that represent processes at multiple scales and link understanding from several research domains can help to tackle this problem. Such integrated models are more common in crop science and ecophysiology than in the research communities that elucidate molecular networks. Several laboratories have modeled particular aspects of growth in Arabidopsis thaliana, but it was unclear whether these existing models could productively be combined. We test this approach by constructing a multiscale model of Arabidopsis rosette growth. Four existing models were integrated with minimal parameter modification (leaf water content and one flowering parameter used measured data). The resulting framework model links genetic regulation and biochemical dynamics to events at the organ and whole-plant levels, helping to understand the combined effects of endogenous and environmental regulators on Arabidopsis growth. The framework model was validated and tested with metabolic, physiological, and biomass data from two laboratories, for five photoperiods, three accessions, and a transgenic line, highlighting the plasticity of plant growth strategies. The model was extended to include stochastic development. Model simulations gave insight into the developmental control of leaf production and provided a quantitative explanation for the pleiotropic developmental phenotype caused by overexpression of miR156, which was an open question. Modular, multiscale models, assembling knowledge from systems biology to ecophysiology, will help to understand and to engineer plant behavior from the genome to the field. | 25,197,087 | [
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Transcriptome profiling reveals mosaic genomic origins of modern cultivated barley. | The domestication of cultivated barley has been used as a model system for studying the origins and early spread of agrarian culture. Our previous results indicated that the Tibetan Plateau and its vicinity is one of the centers of domestication of cultivated barley. Here we reveal multiple origins of domesticated barley using transcriptome profiling of cultivated and wild-barley genotypes. Approximately 48-Gb of clean transcript sequences in 12 Hordeum spontaneum and 9 Hordeum vulgare accessions were generated. We reported 12,530 de novo assembled transcripts in all of the 21 samples. Population structure analysis showed that Tibetan hulless barley (qingke) might have existed in the early stage of domestication. Based on the large number of unique genomic regions showing the similarity between cultivated and wild-barley groups, we propose that the genomic origin of modern cultivated barley is derived from wild-barley genotypes in the Fertile Crescent (mainly in chromosomes 1H, 2H, and 3H) and Tibet (mainly in chromosomes 4H, 5H, 6H, and 7H). This study indicates that the domestication of barley may have occurred over time in geographically distinct regions. | 25,197,090 | [
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Epigenetic role for the conserved Fe-S cluster biogenesis protein AtDRE2 in Arabidopsis thaliana. | On fertilization in Arabidopsis thaliana, one maternal gamete, the central cell, forms a placenta-like tissue, the endosperm. The DNA glycosylase DEMETER (DME) excises 5-methylcytosine via the base excision repair pathway in the central cell before fertilization, creating patterns of asymmetric DNA methylation and maternal gene expression across DNA replications in the endosperm lineage (EDL). Active DNA demethylation in the central cell is essential for transcriptional activity in the EDL of a set of genes, including FLOWERING WAGENINGEN (FWA). A DME-binding motif for iron-sulfur (Fe-S) cluster cofactors is indispensable for its catalytic activity. We used an FWA-GFP reporter to find mutants defective in maternal activation of FWA-GFP in the EDL, and isolated an allele of the yeast Dre2/human antiapoptotic factor CIAPIN1 homolog, encoding an enzyme previously implicated in the cytosolic Fe-S biogenesis pathway (CIA), which we named atdre2-2. We found that AtDRE2 acts in the central cell to regulate genes maternally activated in the EDL by DME. Furthermore, the FWA-GFP expression defect in atdre2-2 was partially suppressed genetically by a mutation in the maintenance DNA methyltransferase MET1; the DNA methylation levels at four DME targets increased in atdre2-2 seeds relative to WT. Although atdre2-2 shares zygotic seed defects with CIA mutants, it also uniquely manifests dme phenotypic hallmarks. These results demonstrate a previously unidentified epigenetic function of AtDRE2 that may be separate from the CIA pathway. | 25,197,096 | [
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Role of transcutaneous electrical nerve stimulation in post-operative analgesia. | The use of transcutaneous electrical nerve stimulation (TENS) as non-pharmacological therapeutic modality is increasing. The types of TENS used clinically are conventional TENS, acupuncture TENS and intense TENS. Their working is believed to be based on gate control theory of pain and activation of endogenous opioids. TENS has been used in anaesthesia for treatment of post-operative analgesia, post-operative nausea vomiting and labour analgesia. Evidence to support analgesic efficacy of TENS is ambiguous. A systematic search of literature on PubMed and Cochrane Library from July 2012 to January 2014 identified a total of eight clinical trials investigating post-operative analgesic effects of TENS including a total of 442 patients. Most of the studies have demonstrated clinically significant reduction in pain intensity and supplemental analgesic requirement. However, these trials vary in TENS parameters used that is, duration, intensity, frequency of stimulation and location of electrodes. Further studies with adequate sample size and good methodological design are warranted to establish general recommendation for use of TENS for post-operative pain. | 25,197,104 | [
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Undetected hypoparathyroidism: An unusual cause of perioperative morbidity. | Routine investigation of serum calcium is not recommended in ASA one and two patients unless abnormalities of calcium metabolism are clinically suspected. The clinical features of hypocalcaemia can often be subtle and may manifest in the presence of associated factors. Hypoparathyroidism, an important cause of hypocalcaemia, often presents as soft tissue calcification (ostosis). Ligamentum flavum ostosis can present with compressive myelopathy requiring laminectomy. We report a case of ligamentum flavum ostosis and subclinical hypocalcaemia due to hypoparathyroidism, who went undetected pre-operatively resulting in significant post-operative morbidity. | 25,197,121 | [
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How Much Is Personality Structure Affected If One or More Highest-Level Factors Are First Removed? A Sequential Factors Approach. | Rotations of 1 to 12 factors were compared by Goldberg's "bass-ackward" method, with or without initially holding constant one or more principal components. Two sets of data were employed: ratings by 320 undergraduates using 435 personality-descriptive adjectives, and 512 Oregon community members' responses to 184 scales from 8 personality inventories. Holding constant none or one or three initial factors made relatively little difference to the resulting structure. On the whole, that structure was not strongly hierarchical: allowing an additional dimension usually resulted in a new substantive dimension rather than in the splitting of an old one. | 25,197,156 | [
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Recent Developments in Molecular Simulation Approaches to Study Spherical Virus Capsids. | Viruses are a particularly challenging systems to study via molecular simulation methods. Virus capsids typically consist of over 100 subunit proteins and reach dimensions of over 100 nm; solvated viruses capsid systems can be over 1 million atoms in size. In this review, I will present recent developments which have attempted to overcome the significant computational expense to perform simulations which can inform experimental studies, make useful predictions about biological phenomena and calculate material properties relevant to nanotechnology design efforts. | 25,197,162 | [
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Solid pseudo papillary tumor of pancreas: Presenting as acute abdomen in a female child. | Solid pseudo papillary tumor (SPT) or Frantz's tumor is a slow-growing low-grade malignant tumor, commonly seen in young patients with a female predominance, which is commonly located in the body and tail of the pancreas. We report a case of SPT arising from the body of the pancreas in a 12-year-old girl who presented with acute abdomen and was treated successfully by local excision of the tumor with preservation of head of pancreas and spleen. | 25,197,185 | [
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Acute abdomen secondary to complete tubular colonic duplication. | We report the case of a 6-month-old infant who presented with a complete duplication of the large intestine, debuting clinically with acute abdomen and severe metabolic disorders. We discuss the pathogenesis and morphology of the lesions, diagnostic difficulties and peculiarities of surgical treatment. | 25,197,196 | [
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Three new caespitose species of Senecio (Asteraceae, Senecioneae) from South Peru. | Three new species of the genus Senecio (Asteraceae, Senecioneae) belonging to Senecio ser. Suffruticosi subser. Caespitosi were discovered in the tributaries of the upper Tambo River, Moquegua Department, South Peru. Descriptions, diagnoses and discussions about their distribution, a table with the morphological similarities with other species of Senecio, a distribution map, conservation status assessments, and a key to the caespitose Peruvian species of Senecio subser. Caespitosi are provided. The new species are Senecio moqueguensis Montesinos, sp. nov. (Critically Endangered) which most closely resembles Senecio pucapampaensis Beltrán, Senecio sykorae Montesinos, sp. nov. (Critically Endangered) which most closely resembles Senecio gamolepis Cabrera, and Senecio tassaensis Montesinos, sp. nov. (Critically Endangered) which most closely resembles Senecio moqueguensis Montesinos. | 25,197,221 | [
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Melicope balgooyi Appelhans, W.L. Wagner & K.R. Wood, a new species and new record in Melicope section Melicope (Rutaceae) for the Austral Islands. | Melicope balgooyi, a new species of Melicope (Rutaceae) is described. It is known only from the Austral Islands in the South Pacific (French Polynesia). However, it is not closely related to the other two species previously known from the Austral Islands, which are part of Melicope section Vitiflorae. The new species belongs to Melicope section Melicope and is most closely related to species from New Zealand, the Kermadec Islands, and the Society Islands. The new species has alternate to sub-opposite leaves, which is a very rare arrangement in Melicope and has only been described for two other species of the genus so far. | 25,197,227 | [
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First description of the worker caste of Nylanderiasmythiesii (Hymenoptera: Formicidae). | The hitherto unknown worker caste of Nylanderiasmythiesii (Forel, 1894) is described for the first time. Sexuals are redescribed and photomontage images of all castes are provided. A key is presented to separate the six Indian species of Nylanderia. Previously described Nylanderiaassimilis (Jerdon, 1851) is considered a species inquirenda. | 25,197,237 | [
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Pure rotation of a prism on a ramp. | In this work, we study a prism with a cross section in polygon rolling on a ramp inclined at a small angle. The prism under gravity rolls purely around each individual edge, intermittently interrupted by a sequence of <iface collisions</i between the side face of the prism and the ramp. By limiting the prism in a planar motion, we propose a mathematical model to deal with the events of the impacts. With a pair of laser-Doppler vibrometers, experiments are also conducted to measure the motions of various prisms made of different materials and with different edge number. Not only are good agreements achieved between our numerical and experimental results, but also an intriguing physical phenomenon is discovered: the purely rolling motion is nearly independent of the prism's materials, yet it is closely related to the prism's geometry. Imagine that an ideal circular section can be approximately equivalent to a polygon with a large enough edge number <iN</i, the finding presented in this paper may help discover the physical mechanism of rolling friction. | 25,197,242 | [
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An elastica arm scale. | The concept of a 'deformable arm scale' (completely different from a traditional rigid arm balance) is theoretically introduced and experimentally validated. The idea is not intuitive, but is the result of nonlinear equilibrium kinematics of rods inducing configurational forces, so that deflection of the arms becomes necessary for equilibrium, which would be impossible for a rigid system. In particular, the rigid arms of usual scales are replaced by a flexible elastic lamina, free to slide in a frictionless and inclined sliding sleeve, which can reach a unique equilibrium configuration when two vertical dead loads are applied. Prototypes designed to demonstrate the feasibility of the system show a high accuracy in the measurement of load within a certain range of use. Finally, we show that the presented results are strongly related to snaking of confined beams, with implications for locomotion of serpents, plumbing and smart oil drilling. | 25,197,248 | [
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On the initial value problem for the wave equation in Friedmann-Robertson-Walker space-times. | The propagator <iW</i(<it</i<sub0</sub,<it</i<sub1</sub)(<ig</i,<ih</i) for the wave equation in a given space-time takes initial data (<ig</i(<ix</i),<ih</i(<ix</i)) on a Cauchy surface {(<it</i,<ix</i) : <it</i=<it</i<sub0</sub} and evaluates the solution (<iu</i(<it</i<sub1</sub,<ix</i),∂ <sub<it</i</sub<iu</i(<it</i<sub1</sub,<ix</i)) at other times <it</i<sub1</sub. The Friedmann-Robertson-Walker space-times are defined for <it</i<sub0</sub,<it</i<sub1</sub>0, whereas for <it</i<sub0</sub→0, there is a metric singularity. There is a spherical means representation for the general solution of the wave equation with the Friedmann-Robertson-Walker background metric in the three spatial dimensional cases of curvature <iK</i=0 and <iK</i=-1 given by S. Klainerman and P. Sarnak. We derive from the expression of their representation three results about the wave propagator for the Cauchy problem in these space-times. First, we give an elementary proof of the sharp rate of time decay of solutions with compactly supported data. Second, we observe that the sharp Huygens principle is not satisfied by solutions, unlike in the case of three-dimensional Minkowski space-time (the usual Huygens principle of finite propagation speed is satisfied, of course). Third, we show that for 0<<it</i<sub0</sub<<it</i the limit, [Formula: see text] exists, it is independent of <ih</i(<ix</i), and for all reasonable initial data <ig</i(<ix</i), it gives rise to a well-defined solution for all <it</i>0 emanating from the space-time singularity at <it</i=0. Under reflection <it</i→-<it</i, the Friedmann-Robertson-Walker metric gives a space-time metric for <it</i<0 with a singular future at <it</i=0, and the same solution formulae hold. We thus have constructed solutions <iu</i(<it</i,<ix</i) of the wave equation in Friedmann-Robertson-Walker space-times which exist for all [Formula: see text] and [Formula: see text], where in conformally regularized coordinates, these solutions are continuous through the singularity <it</i=0 of space-time, taking on specified data <iu</i(0,⋅)=<ig</i(⋅) at the singular time. | 25,197,255 | [
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Thermal conductivity of group-IV semiconductors from a kinetic-collective model. | The thermal conductivity of group-IV semiconductors (silicon, germanium, diamond and grey tin) with several isotopic compositions has been calculated from a kinetic-collective model. From this approach, significantly different to Callaway-like models in its physical interpretation, the thermal conductivity expression accounts for a transition from a kinetic (individual phonon transport) to a collective (hydrodynamic phonon transport) behaviour of the phonon field. Within the model, we confirm the theoretical proportionality between the phonon-phonon relaxation times of the group-IV semiconductors. This proportionality depends on some materials properties and it allows us to predict the thermal conductivity of the whole group of materials without the need to fit each material individually. The predictions on thermal conductivities are in good agreement with experimental data over a wide temperature range. | 25,197,256 | [
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Effectiveness of multiple daily injections or continuous subcutaneous insulin infusion for children with type 1 diabetes mellitus in clinical practice. | Aims. To determine whether multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII) contributes to better glucose control in children with different type 1 diabetes duration. Methods. Subjects were grouped according to early (≤1 year after disease onset; 1A) or late (1-3 years after onset; 2A) MDIs/CSII treatment initiation. Corresponding control groups (1B, 2B) received insulin injections twice daily. Results. HbA1c levels were consistently lower in group 1A than in group 1B (6 months (T2): 7.37% versus 8.21%; 12 months (T3): 7.61% versus 8.41%; 24/36 months (T4/T5): 7.61% versus 8.72%; all P < 0.05), but were lower in group 2A than in group 2B only at T2 (8.36% versus 9.19%; P = 0.04). Levels were lower in group 1A than in group 2A when disease duration was matched (7.61% versus 8.49%; P < 0.05). Logistic regression revealed no correlation between HbA1c level and MDIs/CSII therapy. HbA1c levels were only negatively related to insulin dosage. Conclusions. Blood glucose control was better in patients receiving MDIs/CSII than in those receiving conventional treatment. Early MDIs/CSII initiation resulted in prolonged maintenance of low HbA1c levels compared with late initiation. MDIs/CSII therapy should be combined with comprehensive management. | 25,197,275 | [
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Relationship between the Prevalence of Thyroid Nodules and Metabolic Syndrome in the Iodine-Adequate Area of Hangzhou, China: A Cross-Sectional and Cohort Study. | Objective. The association between thyroid nodule (TN) prevalence and metabolic syndrome (MetS) has only rarely been examined in iodine-adequate areas and needs further clarification. We investigated correlations between MetS and TN prevalence in the iodine-adequate area of Hangzhou, China. Material and Method. A cross-sectional study that screened and recruited individuals for cohort research 3 years later. The 13522 subjects (8926 men, 4596 women) were screened in 2009 for all MetS components, thyroid ultrasound (US), and thyroid function. Cohort research recruited 1610 subjects who were screened in both 2009 and 2012, of whom 1061 underwent follow-up research. Results. The prevalence of TN was higher in the MetS (+) group than in the MetS (-) group (χ (2) = 69.63, P < 0.001) and higher in women than in men (χ (2) = 11.65, P = 0.001). Waist circumference (WC) was positively related to the prevalence of TN (OR = 1.022, P < 0.001). Individuals with greater WC in 2009 were more likely to suffer from TN in 2012 (RR = 1.434, P = 0.024). Elevated triglyceride level was a risk factor for developing new TN (RR = 1.001, P = 0.035). Conclusion. Both greater WC and elevated triglycerides are risk factors for new TN in this iodine-adequate area in China. | 25,197,276 | [
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Differentiation of Xanthomonas spp. Causing Bacterial Spot in Bulgaria Based on Biolog System. | During the last 20 years, the causative agents of bacterial spot of tomato and pepper have been subjected to many studies and reclassifications. According to the current data, the species are four (X. euvesicatoria, X. vesicatoria, X. gardneri, and X. perforans) and cause similar symptoms in plants but possess different phenotypic properties. This work provides the full metabolic characteristics obtained by Biolog system of bacterial spot's xanthomonads based on a large selection of strains from different vegetable-producing regions of Bulgaria with accent on their major differentiating properties which could be used for species differentiation by metabolic profiles. The results are compared to the data available in the literature in order to clarify the strong features of each species and distinguish the variable ones. Simple characteristics like amylase activity and utilization of cis-aconitate cannot serve alone for differentiation. | 25,197,281 | [
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Diagnostic evaluation of uterine artery Doppler sonography for the prediction of adverse pregnancy outcomes. | Increased impedance to flow in the uterine arteries assessed by value of the Doppler is associated with adverse pregnancy outcomes, especially pre-eclampsia. We investigated the predictive value of a uterine artery Doppler in the identification of adverse pregnancy outcomes such as 'pre-eclampsia' and 'small fetus for gestational age' (SGA). Three hundred and seventy-nine women, with singleton pregnancy, between 18 and 40 years of age, without risk factors, randomly underwent Doppler interrogation of the uterine arteries, between 16-22 weeks of gestation. Those who had a mean pulsatility index (PI) of >1.45 were considered to have an abnormal result, and were evaluated and compared with those who had normal results for adverse pregnancy outcomes, including pre-eclampsia and small for gestational age. The relationship between the variables was assessed with the use of the chi-square test. There were 17 cases (4.5%) of abnormal uterine artery Doppler results and 15 of them (88.2%) developed pre-eclampsia and four cases (23.5%) had neonates small for gestational age. For predicting pre-eclampsia, the mean uterine artery PI had to be >1.45, had to have a specificity of 95.5% (95% CI, 70-92%), a sensitivity of 79% (95% CI, 43-82%), a negative predictive value (NPV) of 98.9% (95% CI, 72-96%), and a positive predictive value (PPV) of 88.2% (95% CI, 68-98%). In the case of 'small for gestational age' it had to have a specificity of 96.5% (95% CI, 42-68%), a sensitivity of 57% (95% CI, 53-76%), an NPV of 99.2% (95% CI, 70-92%), and a PPV of 23.5% (95% CI, 30-72%). Uterine artery Doppler evaluation at 16-22 weeks of gestation might be an appropriate tool for identifying pregnancies that may be at an increased risk for development of pre-eclampsia and small fetus for gestational age. | 25,197,292 | [
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Memantine add on to citalopram in elderly patients with depression: A double-blind placebo-controlled study. | Proper management of depression in elderly population would improve the outcome of the disease and reduce its related disability and mortality. Use of memantine with minimal side effects and drug interaction seems reasonable in the elderly but its antidepressant activity is controversial. The aim of the current research is to investigate the effects of add-on memantine during citalopram therapy in elderly patients with depression, in Isfahan. In this double-blind, placebo controlled trial study; elderly patients aged more than 60 years who were recently diagnosed with depression, were enrolled. The selected patients were randomlysplit into two groups, viz. intervention and placebo groups. The intervention was memantine (20 mg daily) or identical placebo plus citalopram for 8 weeks. The severity of depression and quality of life was evaluated using Geriatric Depression Scale (GDS-15), Hamilton Rating Scale for depression (HRSD) and World Health Organization Quality of Life WHOQOL-BREF respectively. The mentioned scores were evaluated at baseline, 4 weeks and 8 weeks, after initiating the trial in two studied groups and compared with each other. 28 and 29 patients were studied in the intervention and placebo groups, respectively. Score of GDS-15, HRSD and WHO-QOL-BREF scales at baseline, 4 weeks and 8 weeks, after initiating trial did not change significantly after use of memantine (P > 0.05). There was no significant difference in mean +/- SD of GDS-15, HRSD and WHO-QOL-BREF scales among intervention and placebo groups (P > 0.05). The outcome of this clinical trial did not support the antidepressant effect of add-on memantine in elderly patients with depression receiving citalopram. It is recommended to design further studies considering the limitations of the current study mentioned herein and the effect of memantine with other anti-depressant agents. | 25,197,294 | [
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Potential therapeutic effects of meditation for treating affective dysregulation. | Affective dysregulation is at the root of many psychopathologies, including stress induced disorders, anxiety disorders, and depression. The root of these disorders appears to be an attenuated, top-down cognitive control from the prefrontal cortices over the maladaptive subcortical emotional processing. A form of mental training, long-term meditation practice can trigger meditation-specific neuroplastic changes in the brain regions underlying cognitive control and affective regulation, suggesting that meditation can act as a kind of mental exercise to foster affective regulation and possibly a cost-effective intervention in mood disorders. Increasing research has suggested that the cultivation of awareness and acceptance along with a nonjudgmental attitude via meditation promotes adaptive affective regulation. This review examined the concepts of affective regulation and meditation and discussed behavioral and neural evidence of the potential clinical application of meditation. Lately, there has been a growing trend toward incorporating the "mindfulness" component into existing psychotherapeutic treatment. Promising results have been observed thus far. Future studies may consider exploring the possibility of integrating the element of "compassion" into current psychotherapeutic approaches. | 25,197,309 | [
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Understanding hypoglycemia in hospitalized patients. | Controlling blood glucose in hospitalized patients is important as both hyperglycemia and hypoglycemia are associated with increased cost, length of stay, morbidity and mortality. A limiting factor in stringent control is the concern of iatrogenic hypoglycemia. The association of hypoglycemia with mortality has led to clinical guideline changes recommending more conservative glycemic control than had previously been suggested, with the use of patient specific approaches when appropriate. Healthier, stable patients may be managed with stricter control while the elderly and severely ill may be managed less aggressively. While the avoidance of hypoglycemia is essential in clinical practice, recent studies suggest that a higher mortality rate occurs in spontaneous rather than iatrogenic hypoglycemia. Therefore, inpatient hypoglycemia may be viewed more as a biomarker of disease rather than a true cause of fatality. | 25,197,322 | [
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A guide to histomorphological evaluation of intestinal inflammation in mouse models. | Histomorphology remains a powerful routine evaluating intestinal inflammation in animal models. Emphasizing the focus of a given animal study, histopathology can overstate differences between established models. We aimed to systematize histopathological evaluation of intestinal inflammation in mouse models facilitating inter-study comparisons. Samples of all parts of the intestinal tract from well-established mouse models of intestinal inflammation were evaluated from hematoxylin/eosin-stained sections and specific observations confirmed by subsequent immunohistochemistry. Three main categories sufficiently reflected the severity of histopathology independent of the localization and the overall extent of an inflammation: (i) quality and dimension of inflammatory cell infiltrates, (ii) epithelial changes and (iii) overall mucosal architecture. Scoring schemata were defined along specified criteria for each of the three categories. The direction of the initial hit proved crucial for the comparability of histological changes. Chemical noxes, infection with intestinal parasites or other models where the barrier was disturbed from outside, the luminal side, showed high levels of similarity and distinct differences to changes in the intestinal balance resulting from inside events like altered cytokine responses or disruption of the immune cell homeostasis. With a high degree of generalisation and maximum scores from 4-8 suitable scoring schemata accounted specific histopathological hallmarks. Truly integrating demands and experiences of gastroenterologists, mouse researchers, microbiologists and pathologists we provide an easy-to-use guideline evaluating histomorphology in mouse models of intestinal inflammation. Standard criteria and definitions facilitate classification and rating of new relevant models, allow comparison in animal studies and transfer of functional findings to comparable histopathologies in human disease. | 25,197,329 | [
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Concordant podoplanin expression in cancer-associated fibroblasts and tumor cells is an adverse prognostic factor in esophageal squamous cell carcinoma. | There is growing evidence that cancer-associated fibroblasts (CAFs) interact with tumor cells and play important roles in tumor progression and invasion. Podoplanin is a type-1 transmembrane glycoprotein expressed in a variety of normal human tissues, including lymphatic endothelium. Tumor cell expression of podoplanin correlates with nodal metastasis and poor prognosis in squamous cell carcinoma (SCC) of oral cavity and esophagus. Recently, podoplanin-positive CAFs have been shown to exert adverse or beneficial prognostic effect on different cancer types. However, the significance of podoplanin-positive CAFs in esophageal SCC has not been investigated. This is the first study to investigate podoplanin expression in CAFs and tumor cells by immunohistochemistry in 59 cases of surgically resected esophageal SCC. We found significant association of podoplanin expression between CAFs and tumor cells (P = 0.031). Although the abundance of podoplanin-positive CAFs per se had no prognostic effect, concordant podoplanin expression in CAFs and tumor cells (both high or both low) was strongly associated with short survival (P = 0.00088). Multivariate analysis showed that concordant podoplanin expression was the strongest independent adverse prognostic factor (hazard ratio: 3.62; 95% confidence interval: 1.69-7.77; P = 0.00094). Our data suggest that interaction between podoplanin-positive CAFs and tumor cells is important in tumor biology of esophageal SCC. | 25,197,355 | [
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Autophagy may promote carcinoma cell invasion and correlate with poor prognosis in cholangiocarcinoma. | The role of autophagy in cholangiocarcinoma is poorly understood. This study investigated its involvement in cholangiocarcinoma, focusing on carcinoma cell invasion and prognostic significance using cholangiocarcinoma cell lines, CCKS1 and HuCCT1, and human tissues of hilar and extrahepatic cholangiocarcinoma. Nutrient starvation induced the expression of LC3-II and the formation of LC3 puncta in both CCKS1 and HuCCT1, suggesting the occurrence of autophagy. The induction of autophagy was accompanied by the increased expression of an autophagy-related protein, Ambra1, in the cells. Under starvation conditions, the invasive activity of both cells was significantly increased, and a lysosomal inhibitor, chloroquine, attenuated this increased invasive activity. Transforming growth factor-β1 (TGF-β1), known as an inducer of epithelial-mesenchymal transition (EMT), increased the invasive activity of both cells, and chloroquine also significantly reduced TGF-β1-induced cell invasion. Immunohistochemical staining using cholangiocarcinoma tissues showed that the expression of Ambra1 positively correlated with the expression of Snail, one of the major transcriptional factors of EMT. In addition, overexpression of Ambra1 significantly correlated with lymph node metastasis and poor survival rate of the patients. These results suggest that the occurrence of autophagy may be associated with a malignant phenotype and poor prognosis in cholangiocarcinoma, and autophagy is possibly involved in EMT-related cholangiocarcinoma cell invasion. | 25,197,362 | [
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Upregulation of miR-137 protects anesthesia-induced hippocampal neurodegeneration. | Ketamine is commonly used in pediatric anesthesia but may cause neurodegeneration in young brains. The aim of the study is to use an animal model to characterize the role of microRNA 137 (miR-137) in ketamine-induced neurodegeneration in neonatal hippocampus. Young Sprague-Dawley Rats (1 month old) was systemically administrated with ketamine (75 mg/kg) for 3 days. TUNEL assay was used to assess the ketamine-induced neurodegeneration of hippocampal CA1 neurons, quantitative real-time PCR (qRT-PCR) to assess the expression of miR-137 and Morris water maze test (MWM) to assess the damaged memory function. Alternatively, lentivirus over-expressing miR-137 was injected into hippocampus before ketamine administration, and the subsequent effects of miR-137 upregulation on ketamine-induced hippocampal neurodegeneration and memory dysfunction were investigated. Furthermore, the direct downstream target of miR-137, CDC42, was down-regulated by siRNA injection into hippocampus. The effects of CDC42 inhibition on hippocampal apoptosis and memory function were also investigated. Excessive ketamine treatment resulted in severe apoptosis in hippocampal CA1 neurons, downregulation of miR-137 in hippocampus and significant long-term memory dysfunction. Conversely, pre-treatment of overexpressing miR-137 protected hippocampal neurodegeneration and memory loss. The molecular target of miR-137, CDC42 was down-regulated by ketamine in hippocampus. Knocking down hippocampal CDC42 exerted an apoptotic effect on hippocampal neurons and memory loss, similar to the effect of ketamine treatment. Our results demonstrated that miR-137 played an important role in regulating ketamine induced hippocampal neurodegeneration, possibly through CDC42. | 25,197,371 | [
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Lycopene ameliorates renal function in rats with streptozotocin-induced diabetes. | To study the effect of lycopene on ameliorating renal function of diabetic nephropathy. Sixty male SD rats were divided into four groups: normal untreated (NC-U), normal treatment (NC-L), diabetes untreated (DM-U) and diabetes treatment (DM-L). DM was prepared by a single injection of STZ (70 mg/kg, intraperitoneally) dissolved in 0.1 M citrate buffer (pH 4.5). DM-U and NC-U rats received control diet; DM-L and NC-L rats received lycopene. After treated with lycopene for 8 weeks, blood was obtained for analyzing plasma lipid profiles, glucose and renal function. The kidneys were used to determine SOD activity, malondialdehyde (MDA) level, processed for histological examination and western blot. Treatment of diabetic rats with lycopene decreased the values of blood urea nitrogen, 24 h urea protein and creatinine. The serum lipids like TC, TG, and LDL were decreased and HDL was increased in DM-L rats when compared with those of diabetic rats. Administration of lycopene decreased the levels of MDA content and expression of CTGF, increased Akt/PKB phosphorylation and SOD activity in diabetic renal tissues. Lycopene protects against development of diabetic nephropathy and ameliorates renal function via improving oxidative status and regulating p-Akt and CTGF. | 25,197,372 | [
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Antepartum or immediate postpartum renal biopsies in preeclampsia/eclampsia of pregnancy: new morphologic and clinical findings. | Preeclampsia (PE) and eclampsia remain leading causes of maternal and fetal mortality worldwide. The kidney is considered the first and most severely affected organ in women with PE/eclampsia. In this study, we analyzed new morphologic features of kidney biopsies and clinical findings in patients with PE or eclampsia at our hospital. Eight patients with PE/eclampsia underwent renal biopsies during the antepartum (3/8) or postpartum (5/8) period. Maternal clinical findings, major serological indices, neonatal outcomes, and renal histopathologic and immunofluorescent characteristics were reviewed for each case. Most patients had abnormal serum cholesterol (8/8), triglyceride (6/8), albumin (7/8), and uric acid (5/8). The ratio of blood urea nitrogen (BUN) to serum creatinine (SCr) was elevated in all patients. Five of eight newborns survived. Various degrees of morphologic change were present in the renal glomeruli, and were associated with proteinuria. All patients had deposition of complement factor 4 (C4) in the renal glomeruli and seven had deposition of immunoglobulin M (IgM). Endotheliosis, vacuolation of podocytes, proliferation of mesangial cells, and protein casts in the tubule lumens were found in the kidneys of women with PE/eclampsia. Immune depositions of C4 and IgM are major contributors to renal lesions in preeclamptic patients, whose neonates can generally survive. Eclampsia can occur without increased blood pressure. | 25,197,387 | [
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Synchronous gastric and sebaceous cancers, a rare manifestation of MLH1-related Muir-Torre syndrome. | Muir-Torre syndrome (MTS), a rare variant of the hereditary non polyposis colorectal cancer syndrome, is an autosomal dominant genodermatosis characterised by coincidence of sebaceous gland neoplasms (sebaceous adenoma, epithelioma, or carcinoma) and at least one internal malignancy. The underlying cause of MTS is a germline mutation in DNA mismatch repair genes MSH2, MLH1 and MSH6. We report the case of a 52-year-old caucasian woman with the development of metachronous colon cancer at the age of 38 years, uterine cancer at the age of 43 years, and unique occurrence of synchronous gastric and sebaceous carcinomas related to germline point mutation c. 2194A>T in the last exon of MLH1 gene, resulting in truncated protein in C-terminal region p. Lys732X due to premature stop codon. This mutation, not previously reported in MTS, disrupts the function of MutL complexes presumably by preventing the interaction with PMS1/PMS2 and impairing the endonuclease active site. This case points out the importance of sebaceous neoplasia, especially sebaceous adenocarcinoma, as cutaneous markers of MTS for timely implementation of cancer screening programs. | 25,197,397 | [
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A case of chronic hepatitis C patient of myocardial ischemia accompanied with interstitial pneumonia induced by pegylated interferon alpha-2a. | After 3 months of combination treatment using interferon α-2a and Ribavirin, a case of 59-year-old female patient with chronic viral hepatitis C demonstrated symptoms such as headache, dizziness accompanied by nausea, vomiting, dry cough, breathing difficulty, and shortness of breath. Dynamic electrocardiogram showed occasional atrial premature beats, paroxysmal tachycardia, and abnormal ST-T (T wave inversion and prolongation of the QT interval). Ambulatory blood pressure indicated that mean blood pressure was elevated than before. Myocardial radionuclide scan showed focal myocardial ischemia in left ventricular inferior wall. Pulmonary function tests showed that pulmonary diffusion function was decreased, indicating the possibility of interstitial pneumonia. The patient had no history of coronary heart disease or chest X-ray abnormalities before medication, but had hypertensive medical history for 8 years with good blood pressure control. After withdrawal of antiviral drugs, symptoms such as dry cough, breathing difficulty and T wave inversion were gradually relieved. This case indicated that myocardial ischemia and pulmonary lesions were associated with the application of pegylated interferon α-2a. | 25,197,402 | [
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Unclassified mixed germ cell-sex cord-stromal tumor with multiple malignant cellular elements in a young woman: a case report and review of the literature. | Unclassified mixed germ cell-sex cord-stromal tumor composed of germ cells and sex cord derivatives is a rare neoplasm. Approximately 10% of such tumors have malignant germ cell components. We report the case of a 28 year-old female with a right adnexal mass measuring 8 cm in greatest dimension, containing areas with both germ cell and sex cord components. The germ cell portion contained multiple growth patterns with a malignant appearance, while the sex cord element consisted mainly of annular tubules. Within the malignant germ cell elements was a dysgerminoma that accounted for approximately 75% of the tumor volume. Other malignant germ cell elements included yolk sac tumor, embryonal carcinoma, and choriocarcinoma, which comprised about 15% of the tumor volume. The annular tubule structures comprised about 10% of the total tumor volume. To our knowledge, this is the first case reported in the literature of an unclassified mixed germ cell-sex cord-stromal tumor associated with embryonal carcinoma components. The patient had a 46XX karyotype, regular menstrual periods, and no evidence of gross abnormalities in the contralateral ovary. The patient remained clinically well and disease-free 2 years after surgery. In addition to a thorough case description, the literature concerning this entity is reviewed and discussed. | 25,197,407 | [
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Retrograde tracing of medial vestibular nuclei connections to the kidney in mice. | Vestibular nuclei have been identified as a uniform multifunctional structure in order to maintain physiological homeostasis, including the participation of renal sympathetic activity. In this study, the medial vestibular nuclei (MVe) of 10 adult male C57BL/6J strain mice were mapped retrograde using injections of pseudorabies virus (PRV)-614. The virus, injected into the kidney, was specifically transported to the medial vestibular nuclei (MVe). We used a fluorescence immunohistochemistry to characterize the chemical neuroanatomical substrate of MVe innervating the kidney in the mouse. At five days after PRV-614 injection in the kidney, PRV-614 infected neurons were retrogradely labeled in MVeMC and MVePC; PRV-614/tyrosine hydroxylase (TH) double-labeled neurons located predominantly in MVeMC and not in MVePC, whereas PRV-614/tryptophan hydroxylase (TPH) neurons were not localized in MVeMC and MVePC. Our results revealed direct neuroanatomical evidence to identify catecholaminergic projections from the MVeMC to the kidney, suggesting that medial vestibulo-renal pathway may be catecholaminergic. | 25,197,422 | [
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Genome sequence of the squalene-degrading bacterium Corynebacterium terpenotabidum type strain Y-11(T) (= DSM 44721(T)). | Corynebacterium terpenotabidum Takeuchi et. al 1999 is a member of the genus Corynebacterium, which contains Gram-positive and non-spore forming bacteria with a high G+C content. C. terpenotabidum was isolated from soil based on its ability to degrade squalene and belongs to the aerobic and non-hemolytic Corynebacteria. It displays tolerance to salts (up to 8%) and is related to Corynebacterium variabile involved in cheese ripening. As this is a type strain of Corynebacterium, this project describing the 2.75 Mbp long chromosome with its 2,369 protein-coding and 72 RNA genes will aid the G enomic E ncyclopedia of Bacteria and Archaea project. | 25,197,436 | [
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Complete genome sequence of Anabaena variabilis ATCC 29413. | Anabaena variabilis ATCC 29413 is a filamentous, heterocyst-forming cyanobacterium that has served as a model organism, with an extensive literature extending over 40 years. The strain has three distinct nitrogenases that function under different environmental conditions and is capable of photoautotrophic growth in the light and true heterotrophic growth in the dark using fructose as both carbon and energy source. While this strain was first isolated in 1964 in Mississippi and named Anabaena flos-aquae MSU A-37, it clusters phylogenetically with cyanobacteria of the genus Nostoc. The strain is a moderate thermophile, growing well at approximately 40(°) C. Here we provide some additional characteristics of the strain, and an analysis of the complete genome sequence. | 25,197,444 | [
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Non-contiguous finished genome sequence of Anoxybacillus flavithermus subsp. yunnanensis type strain (E13(T)), a strictly thermophilic and organic solvent-tolerant bacterium. | Anoxybacillus flavithermus subsp. yunnanensis is the only strictly thermophilic bacterium that is able to tolerate a broad range of toxic solvents at its optimal temperature of 55-60°C. The type strain E13(T) was isolated from water-sediment slurries collected from a hot spring. This study presents the draft genome sequence of A. flavithermus subsp. yunnanensis E13(T) and its annotation. The 2,838,393bp long genome (67 contigs) contains 3,035 protein-coding genes and 85 RNA genes, including 10 rRNA genes, and no plasmids. The genome information has been used to compare with the genomes from A. flavithermus subsp. flavithermus strains. | 25,197,458 | [
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High quality draft genome sequence of Staphylococcus cohnii subsp. cohnii strain hu-01. | Staphylococcus cohnii subsp. cohnii belongs to the family Staphylococcaceae in the order Bacillales, class Bacilli and phylum Firmicutes. The increasing relevance of S. cohnii to human health prompted us to determine the genomic sequence of Staphylococcus cohnii subsp. cohnii strain hu-01, a multidrug-resistant isolate from a hospital in China. Here we describe the features of S. cohnii subsp. cohnii strain hu-01, together with the genome sequence and its annotation. This is the first genome sequence of the species Staphylococcus cohnii. | 25,197,460 | [
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Complete genome sequence of invertebrate iridovirus IIV22A, a variant of IIV22, isolated originally from a blackfly larva. | Members of the family Iridoviridae are animal viruses that infect only invertebrates and poikilothermic vertebrates. The invertebrate iridoviruses 22 (IIV22) and 25 (IIV25) were originally isolated from a single sample of blackfly larva (Simulium spp., order Diptera) collected from the Ystwyth river near Aberystwyth, Wales. Recently, the genomes of IIV22 (197.7 kbp) and IIV25 (204.8 kbp) were sequenced and reported. Here, we describe the complete genome sequence of IIV22A, a variant that was isolated from the same pool of virions collected from the blackfly larva from which the IIV22 virion genome originated. The IIV22A genome, 196.5 kbp, is smaller than IIV22. Nevertheless, it contains 7 supplementary putative ORFs. Its analysis enables evaluation of the degree of genomic polymorphisms within an IIV isolate. Despite the occurrence of this IIV variant with IIV22 and IIV25 in a single blackfly larva and the features of their DNA polymerase, we found no evidence of lateral genetic transfers between the genomes of these two IIV species. | 25,197,475 | [
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High quality draft genome sequence of the slightly halophilic bacterium Halomonas zhanjiangensis type strain JSM 078169(T) (DSM 21076(T)) from a sea urchin in southern China. | Halomonas zhanjiangensis Chen et al. 2009 is a member of the genus Halomonas, family Halomonadaceae, class Gammaproteobacteria. Representatives of the genus Halomonas are a group of halophilic bacteria often isolated from salty environments. The type strain H. zhanjiangensis JSM 078169(T) was isolated from a sea urchin (Hemicentrotus pulcherrimus) collected from the South China Sea. The genome of strain JSM 078169(T) is the fourteenth sequenced genome in the genus Halomonas and the fifteenth in the family Halomonadaceae. The other thirteen genomes from the genus Halomonas are H. halocynthiae, H. venusta, H. alkaliphila, H. lutea, H. anticariensis, H. jeotgali, H. titanicae, H. desiderata, H. smyrnensis, H. salifodinae, H. boliviensis, H. elongata and H stevensii. Here, we describe the features of strain JSM 078169(T), together with the complete genome sequence and annotation from a culture of DSM 21076(T). The 4,060,520 bp long draft genome consists of 17 scaffolds with the 3,659 protein-coding and 80 RNA genes and is a part of Genomic Encyclopedia of Type Strains, Phase I: the one thousand microbial genomes (KMG) project. | 25,197,480 | [
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Non-contiguous finished genome sequence and description of Bacillus massilioalgeriensis sp. nov. | Strain EB01(T) sp. nov. is the type strain of Bacillus massilioalgeriensis, a new species within the genus Bacillus. This strain, whose genome is described here, was isolated from sediment sample of the hypersaline lake Ezzemoul sabkha in northeastern Algeria. B. massilioalgeriensis is a facultative anaerobic Gram-positive bacillus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 5,269,577 bp long genome contains 5,098 protein-coding and 95 RNA genes, including 12 rRNA genes. | 25,197,482 | [
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Non-contiguous finished genome sequence and description of Anaerococcus provenciensis sp. nov. | Anaerococcus provenciensis strain 9402080(T) sp. nov. is the type strain of A. provenciensis sp. nov., a new species within the genus Anaerococcus. This strain was isolated from a cervical abscess sample. A. provenciensis is a Gram-positive anaerobic cocci. Here, we describe the features of this organism, together with the complete genome sequence and annotation. The 2.26 Mbp long genome contains 2099 protein-coding and 57 RNA genes including 8 rRNA genes and exhibits a G+C content of 33.48%. | 25,197,492 | [
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Genome sequence of the exopolysaccharide-producing Salipiger mucosus type strain (DSM 16094(T)), a moderately halophilic member of the Roseobacter clade. | Salipiger mucosus Martínez-Cànovas et al. 2004 is the type species of the genus Salipiger, a moderately halophilic and exopolysaccharide-producing representative of the Roseobacter lineage within the alphaproteobacterial family Rhodobacteraceae. Members of this family were shown to be the most abundant bacteria especially in coastal and polar waters, but were also found in microbial mats and sediments. Here we describe the features of the S. mucosus strain DSM 16094(T) together with its genome sequence and annotation. The 5,689,389-bp genome sequence consists of one chromosome and several extrachromosomal elements. It contains 5,650 protein-coding genes and 95 RNA genes. The genome of S. mucosus DSM 16094(T) was sequenced as part of the activities of the Transregional Collaborative Research Center 51 (TRR51) funded by the German Research Foundation (DFG). | 25,197,501 | [
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The effect of weight reduction on ultrasonographic findings of nonalcoholic Fatty liver. | BACKGROUND Non-alcoholic fatty liver (NAFL) includes a spectrum of diseases ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFL is typically seen in association with obesity, diabetes and hypertriglyceridaemia. In order to seek the role of diet therapy in treatment of NAFL, we compared the ultrasonographic findings of patients with fatty liver disease before and after standard diet therapy. METHODS Twenty-three overweight or obese subjects with incidental fatty liver discovered during ultrasonography were included. Subjects underwent 3 months of diet therapy, and anthropometric data including weight, height, BMI, waist circumference, and hip circumference were measured. Ultrasonographic findings were graded from 0 to 3. Changes in ultrasonographic findings and anthropometric data were studied. RESULTS After three months of dieting, the ultrasonographic grade of all patients decreased by one or two grades. Fifteen patients decreased one grade while 8 others decreased by 2 grades. We observed a significant correlation between the decrease in ultrasonographic grade and the decrease in weight and BMI. CONCLUSION Our study indicates that standard diet therapy could be used as an effective treatment for NAFL patients. | 25,197,505 | [
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Comparison of electrotherapy, rubber band ligation and hemorrhoidectomy in the treatment of hemorrhoids: a clinical and manometric study. | BACKGROUND Treatment of hemorrhoid disease is one of the most challenging fields in general surgery in which different methods are used to treat this condition. In this study, we compared the manometric and clinical results of three treatment methods for hemorrhoids. METHODS A total of 150 patients with symptomatic grades II or III internal hemorrhoids were randomly assigned to three groups. Group A underwent Ferguson hemorrhoidectomy, group B were treated with rubber band ligation (RBL) and group C were treated with direct current electrotherapy. RESULTS Preoperatively, grade III hemorrhoids had significantly higher mean resting pressure and mean squeezing pressure in comparison to grade II hemorrhoids. After hemorrhoidectomy, patients in group A had a significant decrease in the maximum resting pressure (90.8 to 77.7 mmHg) and maximum squeezing pressure (130.6 to 114.8 mmHg) with a significant raise in the volume of the first sensation. However there was no significant change in manometric indexes after RBL and electrotherapy. Group A patients had more postoperative pain and itching compared to groups B and C. CONCLUSION We conclude that electrotherapy is a safe, effective and simple method of treating grades II and III uncomplicated internal hemorrhoids. This procedure is associated with little postoperative pain and complications, and has the least changes in anorectal manometric characteristics. Therefore electrotherapy may be recommended as a treatment of choice for grades II and III uncomplicated internal hemorrhoids. | 25,197,506 | [
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Prevalence of dyspepsia and its correlation with demographic factors and lifestyle in shiraz, southern iran. | BACKGROUND Dyspepsia is a common disorder that can present many clinical dilemmas in patient management. Although not life-threatening, the symptoms are long-lasting, interfere with daily activities and have a significant impact upon quality of life. The aim of this study was to determine prevalence of dyspepsia and its relationship with demographic and socioeconomic factors, and lifestyle in an apparently healthy population in Shiraz, southern Iran. METHODS In a population-based study, 1978 subjects aged 35 years or older were interviewed from April to September 2004. A questionnaire consisting of demographic factors, lifestyle data and gastrointestinal symptoms was completed for each participant. The validity and reliability of the questionnaire were determined. RESULTS The prevalence of dyspepsia was 29.9%. The dyspeptic patients were classified as having ulcer-like (27.9%), dysmotility-like (26.2%) or unspecified dyspepsia (45.9%). The prevalence was higher in females, water-pipe smokers, NSAIDs users, and in those with psychological distress, recurrent headache, anxiety, nightmares and past history of gastrointestinal disease. Dyspepsia had an inverse relationship with consumption of pickles, fruits and vegetables, and with duration of meal ingestion. Subjects with dyspepsia symptoms were more likely to restrict their diet, take herbal medicine, use over-the-counter drugs, consult with physicians and consume medication advised by their friends. CONCLUSION This study reveals that dyspepsia has a high prevalence in Shiraz, southern Iran and is associated with several demographic factors, lifestyle and health-seeking behavior. | 25,197,509 | [
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Hepatocellular carcinoma in the world and the middle East. | Hepatocellular carcinoma (HCC) is a major worldwide public health concern. Despite recent advances, there has been little success in improving the survival of HCC patients. Due to advances in diagnostic modalities and the increasing incidence of chronic viral hepatitis and nonalcoholic fatty liver disease (NAFLD), both of which are well known risk factors of HCC, the prevalence of HCC is increasing in developed countries and it is expected that this trend will continue in the future. In Middle Eastern countries the prevalence of this cancer is lower compared to sub-Saharan Africa and some Far East countries; however it is documented that the prevalence of this cancer in some parts of the Middle East is also increasing. In the current review, the prevalence and burden of this disease worldwide, particularly in Middle Eastern countries, and risk factors for HCC are discussed. | 25,197,510 | [
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Time Trends of Gastro-esophageal Reflux Disease (GERD) and Peptic Ulcer Disease (PUD) in Iran. | BACKGROUND Epidemiology of diseases changes over time with changes in socio-economic status, culture and health care systems. Gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD) are among the diseases whose epidemiology has changed over the past few decades in the west. Studies addressing the trend of GERD and PUD occurrence in Iran are lacking. We aimed to look at the time trends of GERD and PUD in a referral endoscopy clinic in Tehran, Iran. METHODS All patients with dyspeptic symptoms who underwent upper GI endoscopy from 1993 to 2005 (inclusive) in a tertiary outpatient GI referral center in Tehran were enrolled. Erosive esophagitis (EE, used as a proxy for GERD as a whole), PUD, rapid urease test (RUT) status and demographic characteristics were recorded from the endoscopy reports according to the year the endoscopy was performed. RESULTS Over a period of 13 years, 8,029 endoscopic examinations were performed. The most common endoscopic diagnosis was EE that occurred in 4,808 patients (59.8%) followed by duodenal ulcer in 2,188 (27.3%) and gastric ulcer in 88 (1.1%). Over 13 years (1995-2005), the proportion of EE increased from 14.1% in 1993 to 75.1% in 2005 among dyspeptic patients in this referral clinic. The proportion of each grade of GERD according to the Los Angeles classification was as follows: GERD-A 76.0%, GERD-B 20.9%, GERD-C 2.8% and GERD-D 0.3%. RUT positivity decreased from 71.4% to 9.5% during the study period. CONCLUSION This study shows a remarkable increase in EE with a concomitant decrease in PUD and RUT positivity among dyspeptic patients in Tehran over a decade. This change in trend is important for future health care planning. | 25,197,517 | [
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Repair of iatrogenic large colon perforation using laparoscopic methods. Case report and review of the literature. | Iatrogenic perforation of the colon during elective colonoscopy is a serious complication. Surgical treatment remains the standard of care. We report a patient with a large colonic perforation that occurred during a screening colonoscopy, successfully repaired with laparoscopic methods. Although the safety and efficacy of this approach is not entirely established, laparoscopy can be used to treat iatrogenic colonic perforation when the defect is readily recognized, easily accessible for closure and the bowel preparation is excellent. A laparoscopic approach to treat iatrogenic colon perforation results in decreased morbidity and hospital stay, in addition to a shorter incision length compared to an open method. In those cases where it is feasible and the surgical skill exists, a laparoscopic attempt at colon repair should probably be the initial clinical approach.. | 25,197,522 | [
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Assessment of propofol usefulness as an anesthetic agent during colonoscopy. | BACKGROUND Propofol is used as a sedative drug during colonoscopy. In this study we analyzed the adverse effects of propofol (i.e., hemodynamic and respiratory) on patients who underwent colonoscopies. METHODS This study was performed in Qom Province, Iran. In this study, 125 patients (63 females, 62 males) were enrolled. Study patients were administered (0.5-1.5 mg/kg) intravenous propofol by an anesthesiologist. Oxygen saturation and blood pressure were recorded at three minute intervals. We used the American Society of Anesthesiology (ASA) classification to stratify patients by risk prior to the procedure. For statistical analysis, the chi-square and paired t-tests were used. A p -value less than 0.05 was considered significant. RESULTS Patients' mean age was 45.36 ± 16.19 years. ASA-I comprised 25.6% of study patients and 74.4% were categorized as ASA-II. Hypopnea occurred in 56.8% of patients and was prolonged in 32.4%. Of the study patients, 5.6% developed hypoxemia which was successfully controlled by the administration of nasal oxygen and no need for mechanical ventilation. The mean arterial blood pressure (p < 0.0001), oxygen saturation (p < 0.0001) and heart rate (p < 0.0001) significantly decreased during colonoscopy. The occurrence of hypopnea significantly increased in patients with pre-procedure oxygen saturation levels ≤ 95% (p < 0.02), age <50 years (p < 0.0001) and ASA class II (p < 0.0001) Agitation, hypotension and cough were seen in 1.6%, 1.6% and 0.8% of patients, respectively. CONCLUSION Propofol has a short half life that enables faster recovery of normal neurologic and social functions we recommend the use of propofol under supervision of anesthesiologist or a trained gastroenterologist. | 25,197,531 | [
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Pegaferon in hepatitis C: Results of a Multicenter Study. | BACKGROUND Chronic hepatitis C (CHC) is a major contributor to cirrhosis and hepatocellular carcinoma and major global public health problem that causes mortality in both developed and developing countries.For the past decade, treatment with pegylated interferon (peg interferon α) and ribavirin (RBV) has been associated with rates of sustained virologic response of ≤ 66% among patients with hepatitis C virus (HCV) infection. In this study, we report the response rate of Iranian treatment-naïve CHC patients to Pegaferon, a locally developed pegylated interferon-α2a (PEG-IFNα2a). METHODS Patients diagnosed with CHC who referred to two university based outpatient clinics in Tehran from December 2007 to May 2011 were enrolled in a single-group, open-labeled experimental design. Eligible patients were above 15 years of age and had HCV infection with evidence of chronic hepatitis. Exclusion criteria included the presence of a debilitating disease, decompensated cirrhosis or refusal to participate in the study. Patients were treated with 180μg Pegaferon weekly in addition to 800-1200 mg daily, weight-based RBV for 24 or 48 weeks depending on genotype. Viral response and adverse effects were recorded. RESULTS A total of 216 patients were enrolled in the study of which 83.3% were male and 16.7% were female. In 93 (43.1%) patients, the HCV RNA viral load was ≥ 800,000 IU/ml before starting treatment. "As-treated analysis" indicated that a total of 168 (77.8%) patients achieved sustained viral response (SVR, undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment). CONCLUSION This study, with a larger number of participants, confirms the results of a previous study by the authors that Pegaferon, a PEG-IFNα 2a locally produced in Iran, is effective in treatment-naïve CHC patients. | 25,197,541 | [
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Chronic myeloid leukemia with an e1a3 BCR-ABL fusion protein: transformation to lymphoid blast crisis. | Chronic myelogenous leukemia (CML) results from the neoplastic transformation of a hematopoietic stem cell. CML is cytogenetically characterized by the presence of the Philadelphia chromosome (Ph'). Most patients with CML express e13a2 or e14a2 mRNAs that result from a rearrangement of the major breakpoint cluster regions (M-BCR) generating the 210-kDa (p210BCR-ABL) fusion proteins b2a2 or b3a2 respectively. The e1a3 CML-related atypical translocation has been reported with an indolent clinical course, low leukocyte count, long chronic phase even without treatment and good response to therapy. We report the case of a patient initially diagnosed as CML in chronic phase whose cells expressed the e1a3 variant. The patient readily responded to imatinib 400 mg with the achievement of a rapid complete cytogenetic response and the normalization of the blood count values, but after 5 months transformed into lymphoid blast crisis. | 25,197,554 | [
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Presence and characterisation of anaemia in diabetic foot ulceration. | Introduction. Diabetic foot ulceration (DFU) is the commonest cause of severe limb ischaemia in the western world. In diabetes mellitus, anaemia is frequently unrecognized, yet studies have shown that it is twice as common in diabetics compared with nondiabetics. We aimed to assess the incidence of anaemia and further classify the iron deficiency seen in a high-risk DFU patient group. Methods. An observational study was undertaken in a multidisciplinary diabetic foot clinic setting. All patients with DFU attending over a four-month period were included. Anaemia was defined as haemoglobin (Hb) levels <12 g/dL. Iron deficiency was classified according to definitions of AID (absolute iron deficiency) and FID (functional iron deficiency). Results. 27 patients had DFU; 14 (51.9%) were anaemic; two (7.41%) had severe anaemia (Hb < 10 g/dL). No patient had B12 or Folate deficiency. In patients with anaemia, there was significant spread of indices. Only one patient had "textbook" absolute iron deficiency (AID) defined as low Hb, MCV, MCH, and ferritin. Functional iron deficiency (FID) was seen in a further seven patients (25.5%). Conclusion. Anaemia and iron deficiency are a common problem in patients with DFU. With current clinical markers, it is incredibly difficult to determine causal relationships and further in-depth scientific study is required. | 25,197,565 | [
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How to evaluate adenomyosis in patients affected by endometriosis? | Objective. The aim of the study is to evaluate adenomyosis in patients undergoing surgery for different type of endometriosis. It is an observational study including women with preoperative ultrasound diagnosis of adenomyosis. Demographic data and symptoms were recorded (age, body mass index, parity, history of previous surgery, dysmenorrhea, dyspareunia, dyschezia, dysuria, and abnormal uterine bleeding). Moreover a particular endometrial shape "question mark sign" linked to the presence of adenomyosis was assessed. Results. From 217 patients with ultrasound diagnosis of adenomyosis, we found 73 with ovarian histological confirmation of endometriosis, 92 with deep infiltrating endometriosis, and 52 patients who underwent surgery for infertility. Women with adenomyosis alone represented the oldest group of patients (37.8 ± 5.18 years, P = 0.02). Deep endometriosis patients were nulliparous more frequently (P < 0.0001), had history of previous surgery (P = 0.004), and complained of more intense pain symptoms than other groups. Adenomyosis alone was significantly associated with abnormal uterine bleeding (P < 0.0001). The question mark sign was found to be strongly related to posterior deep infiltrating endometriosis (P = 0.01). Conclusion. Our study confirmed the strong relationship between adenomyosis and endometriosis and evaluated demographic aspects and symptoms in patients affected by different type of endometriosis. | 25,197,569 | [
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Comparison of clinical efficacy of intravenous acetaminophen with intravenous morphine in acute renal colic: a randomized, double-blind, controlled trial. | The aim of this study was to compare the clinical efficacy of intravenous acetaminophen with intravenous morphine in acute renal colic pain management. In this double-blind controlled trial, patients aged 18-55 years, diagnosed with acute renal colic, who met the inclusion and exclusion criteria, were randomized into two groups. First, using the visual analogue scale (VAS), intensity of pain was assessed in both groups. Then, one gram of intravenous acetaminophen or 0.1 mg/kg morphine was infused in 100 mL normal saline to either acetaminophen or morphine group. Intensity of pain was reassessed in 15, 30, 45, and 60 minutes according to VAS criteria. Finally, data from 108 patients were analyzed, 54 patients in each group. No significant difference was observed between the two groups in regard to sex (P = 0.13), mean age (P = 0.54), and baseline visual analogue score (P = 0.21). A repeated measure analysis of variance revealed that the difference between the two treatments was significant (P = 0.0001). The VAS reduction at primary endpoint (30 min after drug administration) was significantly higher in the acetaminophen group than in the morphine group (P = 0.0001). This study demonstrated that intravenous acetaminophen could be more effective than intravenous morphine in acute renal colic patients' pain relief. | 25,197,573 | [
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Melanocyte and melanoma cell activation by calprotectin. | Calprotectin, a heterodimer of S100A8 and S100A9, is a proinflammatory cytokine released from ultraviolet radiation-exposed keratinocytes. Calprotectin binds to Toll-like receptor 4, the receptor for advanced glycation end-products, and extracellular matrix metalloproteinase inducer on target cells to stimulate migration. Melanocytes and melanoma cells produce little if any calprotectin, but they do express receptors for the cytokine. Thus, keratinocyte-derived calprotectin has the potential to activate melanocytes and melanoma cells within the epidermis in a paracrine manner. We examined the ability of calprotectin to stimulate proliferation and migration in normal human melanocytes and melanoma cells in vitro. We first showed, by immunofluorescence and quantitative RT-PCR, that the melanocytic cells employed expressed a calprotectin receptor, the receptor for advanced end-products. We then demonstrated that calprotectin significantly enhanced proliferation, migration, and Matrigel invasion in both normal human melanocytes and melanoma cells. Thus, calprotectin is one of the numerous paracrine factors released by ultraviolet radiation-exposed keratinocytes that may promote melanomagenesis and is a potential target for melanoma prevention or therapy. | 25,197,574 | [
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Growing teratoma syndrome. | Growing teratoma syndrome (GTS) is a rare clinical entity, which presents with enlarging teratomas masses of the retroperitoneum or other locations, occurring during or after systemic chemotherapy for the treatment of nonseminomatous germ cell of the testis (NSGCT), with normalised tumour markers. Awareness of this syndrome is necessary in order to prevent unnecessary chemotherapy and allow optimal management. Prognosis is excellent after the excision of these tumors, but surgery has to be as complete as possible. Surgical resection of bulky GTS lesions is technically challenging; intraoperative complications may occur; that is, why the treatment must not be delayed. Our experience in the surgical management of these lesions is reviewed in the following work. | 25,197,607 | [
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Metastatic prostate adenocarcinoma posing as urothelial carcinoma of the right ureter: a case report and literature review. | This is a case report of a 67-year-old patient with distant metastasis of prostate cancer to the right ureter which caused hydronephrosis. At the beginning, both of the cytology of the morning urine and imaging findings were consistent with urothelial carcinoma. Nephroureterectomy was subsequently performed. Interestingly, the pathological examination of the excised ureter revealed that the malignancy was derived from the prostate. No skeletal metastasis was detected. However, after four months of follow-up, several abnormal signal shadows were reported in skeletal scintigraphy and the prostate specific antigen (PSA) was gradually increasing. We present such a case for its unique presentation. A review of the literature is also provided. | 25,197,608 | [
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<i>Ex vivo</i> Expansion of Human Adult Pancreatic Cells with Properties of Distributed Stem Cells by Suppression of Asymmetric Cell Kinetics. | Transplantation therapy for type I diabetes (T1D) might be improved if pancreatic stem cells were readily available for investigation. Unlike macroscopic islets, pancreatic tissue stem cells could more easily access the retroperitoneal pancreatic environment and thereby might achieve more effective pancreatic regeneration. Unfortunately, whether the adult pancreas actually contains renewing stem cells continues as a controversial issue in diabetes research. We evaluated a new method developed in our lab for expanding renewing distributed stem cells (DSCs) from adult tissues as a means to provide more evidence for adult pancreatic stem cells, and potentially advance their availability for future clinical investigation. The new method was designed to switch DSCs from asymmetric self-renewal to symmetric self-renewal, which promotes their exponential expansion in culture with reduced production of differentiated cells. Called suppression of asymmetric cell kinetics (SACK), the method uses natural purine metabolites to accomplish the self-renewal pattern shift. The SACK purine metabolites xanthine, xanthosine, and hypoxanthine were evaluated for promoting expansion of DSCs from the pancreas of adult human postmortem donors. Xanthine and xanthosine were effective for deriving both pooled and clonal populations of cells with properties indicative of human pancreatic DSCs. The expanded human cell strains had signature SACK agent-suppressible asymmetric cell kinetics, produced Ngn3+ bipotent precursors for α-cells and β-cells, and were non-tumorigenic in immunodeficient mice. Our findings support the existence of pancreatic DSCs in the adult human pancreas and indicate a potential path to increasing their availability for future clinical evaluation. | 25,197,614 | [
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Recombinant factor VIIa use in patients presenting with intracranial hemorrhage. | Recombinant factor VIIa (rFVIIa) can be used for rapid INR normalization in life-threatening hemorrhage in anticoagulated patients. Dosing is unclear and may carry thromboembolic risks. We reviewed the use of rFVIIa at a comprehensive stroke and cerebrovascular center to evaluate dose effectiveness on INR reduction and thromboembolic complications experienced. The primary endpoint was to review the efficacy of rFVIIa in lowering INR. Secondary endpoints included doses used and adverse effects caused by rFVIIa administration. Forty-one percent of patients presented with a subdural hemorrhage. The mean INR prior to rFVIIa administration was 3.5 (0.9-15) and decreased to 1.13 (0.6-2). The mean dose of rFVIIa given was 73 mcg/kg (±24 mcg/kg). Two patients (3%) experienced a thromboembolic event. Recombinant factor VIIa appears to lower INR without significant thromboembolic complications. | 25,197,623 | [
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Parasites as biological tags to assess host population structure: Guidelines, recent genetic advances and comments on a holistic approach. | We review the use of parasites as biological tags of marine fishes and cephalopods in host population structure studies. The majority of the work published has focused on marine fish and either single parasite species or more recently, whole parasite assemblages, as biological tags. There is representation of host organisms and parasites from a diverse range of taxonomic groups, although focus has primarily been on host species of commercial importance. In contrast, few studies have used parasites as tags to assess cephalopod population structure, even though records of parasites infecting cephalopods are well-documented. Squid species are the only cephalopod hosts for which parasites as biological tags have been applied, with anisakid nematode larvae and metacestodes being the parasite taxa most frequently used. Following a brief insight into the importance of accurate parasite identification, the population studies that have used parasites as biological tags for marine fishes and cephalopods are reviewed, including comments on the dicyemid mesozoans. The advancement of molecular genetic techniques is discussed in regards to the new ways parasite genetic data can be incorporated into population structure studies, alongside host population genetic analyses, followed by an update on the guidelines for selecting a parasite species as a reliable tag candidate. As multiple techniques and methods can be used to assess the population structure of marine organisms (e.g. artificial tags, phenotypic characters, biometrics, life history, genetics, otolith microchemistry and parasitological data), we conclude by commenting on a holistic approach to allow for a deeper insight into population structuring. | 25,197,624 | [
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CC chemokine ligand 18 correlates with malignant progression of prostate cancer. | CC chemokine ligand 18 (CCL18) promotes malignant behaviors of various human cancer types. However, its involvement in human prostate cancer has not been fully elucidated. The aim of this study was to investigate the role of CCL18 in PCa. Expression of CCL18 at mRNA and protein levels was detected using real-time qRT-PCR and immunohistochemistry analysis. We analyzed the associations of CCL18 expression with clinical features of human PCa. The effects of PCa cell migration, invasion, and apoptosis were tested. The efficiency of CCL18 on prostate tumor growth was assessed in a subcutaneous xenograft model. CCL18 expression was upregulated (both P < 0.01) in PCa tissues compared with those in noncancerous prostate tissues. CCL18 upregulation was correlated with high Gleason score (P = 0.034) of patients with PCa. rCCL18 stimulation in PCa cells promoted cell migration and invasion but decreased DU145 cells apoptosis rate. Furthermore, subcutaneous homografts models showed the increased tumor growth and tumor vascularization with the CCL18 stimulation, and the expression of Ki67, PCNA, and CD31 in CCL18 stimulation mice was also significantly increased. Our data offer the convincing evidence that the upregulation of CCL18 may be involved in the malignant progression of PCa. | 25,197,632 | [
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Implementation of a computerized decision support system to improve the appropriateness of antibiotic therapy using local microbiologic data. | A prospective quasi-experimental study was undertaken in 218 patients with suspicion of nosocomial infection hospitalized in a polyvalent ICU where a new electronic device (GERB) has been designed for antibiotic prescriptions. Two GERB-based applications were developed to provide local resistance maps (LRMs) and preliminary microbiological reports with therapeutic recommendation (PMRTRs). Both applications used the data in the Laboratory Information System of the Microbiology Department to report on the optimal empiric therapeutic option, based on the most likely susceptibility profile of the microorganisms potentially responsible for infection in patients and taking into account the local epidemiology of the hospital department/unit. LRMs were used for antibiotic prescription in 20.2% of the patients and PMRTRs in 78.2%, and active antibiotics against the finally identified bacteria were prescribed in 80.0% of the former group and 82.4% of the latter. When neither LMRs nor PMRTRs were considered for empiric treatment prescription, only around 40% of the antibiotics prescribed were active. Hence, the percentage appropriateness of the empiric antibiotic treatments was significantly higher when LRM or PMRTR guidelines were followed rather than other criteria. LRMs and PMRTRs applications are dynamic, highly accessible, and readily interpreted instruments that contribute to the appropriateness of empiric antibiotic treatments. | 25,197,643 | [
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LH pretreatment as a novel strategy for poor responders. | Poor response to ovarian stimulation is still a major problem in IVF. The study presents a new stimulation protocol evaluated in a suppopulation of very difficult young poor ovarian responders. The study consists in two sections. The first includes data from a randomized controlled study involving forty-three young patients with a poor ovarian response in at least two previous cycles (intended as cycle cancellation or with ≤3 collected oocytes). Patients were randomized in two groups: group A (control) received FSH (400 IU/day), while group B received the new stimulation protocol consisting in a sequential association of 150 IU r-LH for 4 days followed by 400 IU r-FSH/after downregulation with daily GnRh agonist. The second includes data from the overall results in 65 patients treated with the new protocol compared to their previous performance with conventional cycles (historical control). Both in the RCT and in the historical control study, LH pretreatment was able to decrease the cancellation rate, to improve the in vitro performance, and to significantly increase the live birth rates. LH pretreatment improved oocyte quantity and quality in young repeated poor responders selected in accordance with the Bologna criteria. | 25,197,669 | [
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Autophagy, Warburg, and Warburg reverse effects in human cancer. | Autophagy is a highly regulated-cell pathway for degrading long-lived proteins as well as for clearing cytoplasmic organelles. Autophagy is a key contributor to cellular homeostasis and metabolism. Warburg hypothesized that cancer growth is frequently associated with a deviation of a set of energy generation mechanisms to a nonoxidative breakdown of glucose. This cellular phenomenon seems to rely on a respiratory impairment, linked to mitochondrial dysfunction. This mitochondrial dysfunction results in a switch to anaerobic glycolysis. It has been recently suggested that epithelial cancer cells may induce the Warburg effect in neighboring stromal fibroblasts in which autophagy was activated. These series of observations drove to the proposal of a putative reverse Warburg effect of pathophysiological relevance for, at least, some tumor phenotypes. In this review we introduce the autophagy process and its regulation and its selective pathways and role in cancer cell metabolism. We define and describe the Warburg effect and the newly suggested "reverse" hypothesis. We also discuss the potential value of modulating autophagy with several pharmacological agents able to modify the Warburg effect. The association of the Warburg effect in cancer and stromal cells to tumor-related autophagy may be of relevance for further development of experimental therapeutics as well as for cancer prevention. | 25,197,670 | [
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Strut deformation in CFRP-strengthened reinforced concrete deep beams. | Strut-and-tie model (STM) method evolved as one of the most useful designs for shear critical structures and discontinuity regions (D-regions). It provides widespread applications in the design of deep beams as recommended by many codes. The estimation of bottle-shaped strut dimensions, as a main constituent of STM, is essential in design calculations. The application of carbon fibre reinforced polymer (CFRP) as lightweight material with high tensile strength for strengthening D-regions is currently on the increase. However, the CFRP-strengthening of deep beam complicates the dimensions estimation of bottle-shaped strut. Therefore, this research aimed to investigate the effect of CFRP-strengthening on the deformation of RC strut in the design of deep beams. Two groups of specimens comprising six unstrengthened and six CFRP-strengthened RC deep beams with the shear span to the effective depth ratios (a/d) of 0.75, 1.00, 1.25, 1.50, 1.75, and 2.00 were constructed in this research. These beams were tested under four-point bending configuration. The deformation of struts was experimentally evaluated using the values of strain along and perpendicular to the strut centreline. The evaluation was made by the comparisons between unstrengthened and CFRP-strengthened struts regarding the widening and shortening. The key variables were a/d ratio and applied load level. | 25,197,698 | [
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Optimal sixteenth order convergent method based on quasi-Hermite interpolation for computing roots. | We have given a four-step, multipoint iterative method without memory for solving nonlinear equations. The method is constructed by using quasi-Hermite interpolation and has order of convergence sixteen. As this method requires four function evaluations and one derivative evaluation at each step, it is optimal in the sense of the Kung and Traub conjecture. The comparisons are given with some other newly developed sixteenth-order methods. Interval Newton's method is also used for finding the enough accurate initial approximations. Some figures show the enclosure of finitely many zeroes of nonlinear equations in an interval. Basins of attractions show the effectiveness of the method. | 25,197,701 | [
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Development of UHPC mixtures utilizing natural and industrial waste materials as partial replacements of silica fume and sand. | In the exploratory study presented in this paper, an attempt was made to develop different mixtures of ultrahigh performance concrete (UHPC) using various locally available natural and industrial waste materials as partial replacements of silica fume and sand. Materials such as natural pozzolana (NP), fly ash (FA), limestone powder (LSP), cement kiln dust (CKD), and pulverized steel slag (PSS), all of which are abundantly available in Saudi Arabia at little or no cost, were employed in the development of the UHPC mixtures. A base mixture of UHPC without replacement of silica fume or sand was selected and a total of 24 trial mixtures of UHPC were prepared using different percentages of NP, FA, LSP, CKD, and PSS, partially replacing the silica fume and sand. Flow and 28-d compressive strength of each UHPC mixture were determined to finally select those mixtures, which satisfied the minimum flow and strength criteria of UHPC. The test results showed that the utilization of NP, FA, LSP, CKD, and PSS in production of UHPC is possible with acceptable flow and strength. A total of 10 UHPC mixtures were identified with flow and strength equal to or more than the minimum required. | 25,197,709 | [
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Effect of Chocobar Ice Cream Containing Bifidobacterium on Salivary Streptococcus mutans and Lactobacilli: A Randomised Controlled Trial. | To examine the effect of chocobar ice cream containing bifidobacteria on salivary mutans streptococci and lactobacilli. A double-blind, randomised controlled trial was conducted with 30 subjects (18 to 22 years of age) divided into 2 groups, test (chocobar ice cream with probiotics) and control (chocobar ice cream without probiotics). The subjects were instructed to eat the allotted chocobar ice cream once daily for 18 days. Saliva samples collected at intervals were cultured on Mitis Salivarius agar and Rogosa agar and examined for salivary mutans streptococci and lactobacilli, respectively. The Mann-Whitney U-test, Friedman and Wilcoxon signed-rank tests were used for statistical analysis. Postingestion in the test group, a statistically significant reduction (p < 0.05) of salivary mutans streptococci was recorded, but a non-significant trend was seen for lactobacilli. Significant differences were was also observed between follow-ups. Short-term daily ingestion of ice cream containing probiotic bifidobacteria may reduce salivary levels of mutans streptococci in young adults. | 25,197,733 | [
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Overexpression of the Salmonella KdpF membrane peptide modulates expression of kdp genes and intramacrophage growth. | Membrane peptides appear as an emerging class of regulatory molecules in bacteria, which can interact with membrane proteins, including transporters and sensor kinases. The KdpF peptide, which is cotranscribed with kdpABC genes and regulated by the KdpDE two-component system, is supposed to stabilize the KdpABC potassium transporter complex but may also exhibit unsuspected regulatory function(s). The mycobacterial KdpF can interact with the KdpD histidine kinase, and kdpF overexpression has been shown to reduce intramacrophage replication of Mycobacterium bovis BCG. In this study, we investigated whether KdpF displays similar behavior in another intracellular pathogen, Salmonella enterica serovar Typhimurium. We show that Salmonella KdpF can interact with KdpD in a bacterial two-hybrid assay. We have constructed a Salmonella strain overexpressing kdpF, and we have investigated expression of the kdp regulon, as well as intramacrophage survival. We show that kdpF overexpression reduces expression of kdpA and kdpD genes under potassium limitation. Moreover, kdpF overexpression increases intramacrophage multiplication of S. Typhimurium. Hence, our results indicate that KdpF can play a regulatory role in S. Typhimurium, modulating kdp gene expression and intramacrophage survival, but in a way that differs from the one reported for M. bovis BCG. | 25,197,761 | [
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Low Levels of Energy Expenditure in Childhood Cancer Survivors: Implications for Obesity Prevention. | Childhood cancer survivors are at an increased risk of obesity but causes for this elevated risk are uncertain. We evaluated total energy expenditure in childhood cancer survivors using the doubly labeled water method in a cross-sectional study of 17 survivors of pediatric leukemia or lymphoma (median age, 11.5 y). Mean total energy expenditure was 2073 kcal/d, which was nearly 500 kcal/d lower than estimated energy requirements with recommended levels of physical activity. This energy gap is likely to contribute to the risk of obesity in this population and future trials are needed to assess implications and potential treatment strategies. | 25,197,775 | [
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Dental visits time interval since last visit, United States - july 1963-june 1964. | Data collected during the period July 1963 and June 1964 indicate that an estimated 78.1 million persons, or 42.0 percent of the civilian, noninstitutional population, made one or more dental visits within the year prior to interview. Approximately 16.6 percent of the population had never seen a dentist. These data are derived from household interviews conducted in a nation-wide sample of the population for the Division of Health Interview Statistics of the National Center for Health Statistics. The proportion of persons with recent dental visits varied markedly with age. Proportionally fewer persons at the extremes of the age range-under 5 years and 65 years and over-had seen a dentist in the past year than had persons in the other age groups. Persons aged 5-24 had the highest percentages. Population groups with the highest proportion of persons receiving dental care within a year were females 5-14 years (55.8 percent) and 15-24 years (58.3 percent). In all age groups a larger proportion of females than of males had visited a dentist within the yeur prior to interview. An estimated 44.6 percent of white persons and 22,7 percent of nonwhite persons made one or more dental visits in the year prior to interview. This large differential was reduced somewhat when white and nonwhite persons with similar incomes were compared. | 25,197,790 | [
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Electroencephalographic power spectral density profile of the orexin receptor antagonist suvorexant in patients with primary insomnia and healthy subjects. | Suvorexant, an orexin receptor antagonist, improves sleep in healthy subjects (HS) and patients with insomnia. We compared the electroencephalographic (EEG) power spectral density (PSD) profile of suvorexant with placebo using data from a phase 2 trial in patients with insomnia. We also compared suvorexant's PSD profile with the profiles of other insomnia treatments using data from 3 HS studies. Phase 2 trial--randomized, double-blind, two-period (4 w per period) crossover. HS studies--randomized, double-blind, crossover. Sleep laboratories. Insomnia patients (n = 229) or HS (n = 124). Phase 2 trial--suvorexant 10 mg, 20 mg, 40 mg, 80 mg, placebo; HS study 1--suvorexant 10 mg, 50 mg, placebo; HS study 2--gaboxadol 15 mg, zolpidem 10 mg, placebo; HS study 3--trazodone 150 mg, placebo. The PSD of the EEG signal at 1-32 Hz of each PSG recording during nonrapid eye movement (NREM) and rapid eye movement (REM) sleep were calculated. The day 1 and day 28 PSD profiles of suvorexant at all four doses during NREM and REM sleep in patients with insomnia were generally flat and close to 1.0 (placebo) at all frequencies. The day 1 PSD profile of suvorexant in HS was similar to that in insomnia patients. In contrast, the other three drugs had distinct PSD profiles in HS that differed from each other. Suvorexant at clinically effective doses had limited effects on power spectral density compared with placebo in healthy subjects and in patients with insomnia, in contrast to the three comparison insomnia treatments. These findings suggest the possibility that antagonism of the orexin pathway might lead to improvements in sleep without major changes in the patient's neurophysiology as assessed by electroencephalographic. | 25,197,807 | [
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The contribution of bone and cartilage to the near-infrared spectrum of osteochondral tissue. | Near-infrared (NIR) spectroscopy has been used to assess hyaline cartilage quality in human and animal osteochondral tissues. However, due to the lack of NIR signal from bone phosphate and the relatively deep penetration depth of the radiation, the separate contributions of cartilage and bone to the spectral signatures have not been well defined. The objectives of the current study were (1) to improve the understanding of the contributions of bone and cartilage to NIR spectra acquired from osteochondral tissue and (2) to assess the ability of this nondestructive method to predict cartilage thickness and modified Mankin grade of human tibial plateau articular cartilage. Near-infrared spectra were acquired from samples of bovine bone and cartilage with varying thicknesses and from 22 tibial plateaus harvested from patients undergoing knee replacement surgery. The spectra were recorded from regions of the tibial plateaus with varying degrees of degradation, and the cartilage thickness and modified Mankin grade of these regions were assessed histologically. The spectra from bone and cartilage samples of known thicknesses were investigated to identify spectral regions that were distinct for these two tissues. Univariate and multivariate linear regression methods were used to correlate modified Mankin grade and cartilage thickness with NIR spectral changes. The ratio of the NIR absorbances associated with water at 5270 and 7085 cm(-1) was the best differentiator of cartilage and bone spectra. The NIR prediction models for thickness and Mankin grade calculated using partial least squares regression were more accurate than were univariate-based prediction models, with a root mean square errors of cross-validation of 0.42 mm (for thickness) and 1.3 (for modified Mankin grade). We conclude that NIR spectroscopy may be used to simultaneously assess articular cartilage thickness and modified Mankin grade, based in part on differences in spectral contributions from bone and cartilage. | 25,197,817 | [
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A small library of synthetic di-substituted 1, 4-naphthoquinones induces ROS-mediated cell death in murine fibroblasts. | Synthesis of compound libraries and their concurrent assessment as selective reagents for probing and modulating biological function continues to be an active area of chemical biology. Microwave-assisted solid-phase Dötz benzannulation reactions have been used to inexpensively synthesize 2, 3-disubstituted-1, 4-naphthoquinone derivatives. Herein, we report the biological testing of a small library of such compounds using a murine fibroblast cell line (L929). Assessment of cellular viability identified three categories of cytotoxic compounds: no toxicity, low/intermediate toxicity and high toxicity. Increased levels of Annexin-V-positive staining and of caspase 3 activity confirmed that low, intermediate, and highly toxic compounds promote cell death. The compounds varied in their ability to induce mitochondrial depolarization and formation of reactive oxygen species (ROS). Both cytotoxic and non-cytotoxic compounds triggered mitochondrial depolarization, while one highly cytotoxic compound did not. In addition, all cytotoxic compounds promoted increased intracellular ROS but the cells were only partially protected from compound-induced apoptosis when in the presence of superoxide dismutase, catalase, or ascorbic acid suggesting utilization of additional pro-death mechanisms. In summary, nine of twelve (75%) 1, 4-naphthoquinone synthetic compounds were cytotoxic. Although the mitochondria did not appear to be a central target for induction of cell death, all of the cytotoxic compounds induced ROS formation. Thus, the data demonstrate that the synthesis regime effectively created cytotoxic compounds highlighting the potential use of the regime and its products for the identification of biologically relevant reagents. | 25,197,824 | [
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The knowledge translation status in selected Eastern-Mediterranean universities and research institutes. | A serious worldwide effort to strengthen research based knowledge translation (KT) has begun in recent years and some countries, particularly developed ones, are trying to incorporate KT in their health and health research systems. Keeping in mind the recent economic depression and the need to perform more efficient research, we aimed to assess and compare the KT status of selected health research institutes in the Eastern Mediterranean Regions' countries, and to identify their strengths and weaknesses in the field. After finding the focal points that would steer the focus group discussions (FGDs) and help complete the 'Self Assessment Tool for Research Institutes' (SATORI) tool, each focal point held two FGDs in which researchers, research authorities and other individuals specified in detail further in the study were held. The scores obtained by each institute were evaluated quantitatively, and the transcriptions were analyzed qualitatively with OpenCode software. For ease of analysis the 50 items of the SATORI were classified into 7 main domains: 'priority setting', 'research quality and timeliness', 'researchers' KT capacities', 'facilities and pre-requisites of KT', 'processes and regulations supporting KT', 'interaction with research users', and 'promoting and evaluating the use of knowledge'. Based on the scoring system, the strongest domain was 'research quality and timeliness'. 'Priority setting' was the weakest domain of all. The remaining domains were more or less equal in strength and were not in a favorable state. The qualitative findings confirmed the quantitative findings. The main problem, it seems, is that a KT climate does not exist in the region. And despite the difference in the contexts, there are many similarities in the region's institutes included in this study. Collaborative efforts can play a role in creating this climate by steering countries towards KT and suggesting regional strategic directions according to their needs. | 25,197,834 | [
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Prognostic impact of renal dysfunction does not differ according to the clinical profiles of patients: insight from the acute decompensated heart failure syndromes (ATTEND) registry. | Renal dysfunction associated with acute decompensated heart failure (ADHF) is associated with impaired outcomes. Its mechanism is attributed to renal arterial hypoperfusion or venous congestion, but its prognostic impact based on each of these clinical profiles requires elucidation. ADHF syndromes registry subjects were evaluated (N = 4,321). Logistic regression modeling calculated adjusted odds ratios (OR) for in-hospital mortality for patients with and without renal dysfunction. Renal dysfunction risk was calculated for subgroups with hypoperfusion-dominant (eg. cold extremities, a low mean blood pressure or a low proportional pulse pressure) or congestion-dominant clinical profiles (eg. peripheral edema, jugular venous distension, or elevated brain natriuretic peptide) to evaluate renal dysfunction's prognostic impact in the context of the two underlying mechanisms. On admission, 2,150 (49.8%) patients aged 73.3 ± 13.6 years had renal dysfunction. Compared with patients without renal dysfunction, those with renal dysfunction were older and had dominant ischemic etiology jugular venous distension, more frequent cold extremities, and higher brain natriuretic peptide levels. Renal dysfunction was associated with in-hospital mortality (OR 2.36; 95% confidence interval 1.75-3.18, p<0.001), and the prognostic impact of renal dysfunction was similar in subgroup of patients with hypoperfusion- or congestion-dominant clinical profiles (p-value for the interaction ranged from 0.104-0.924, and was always >0.05). Baseline renal dysfunction was significantly associated with in-hospital mortality in ADHF patients. The prognostic impact of renal dysfunction was the same, regardless of its underlying etiologic mechanism. | 25,197,833 | [
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The place of mathematical models in psychology and the social sciences. | Comments on the comments made by Brown et al. (see record 2013-24609-001). Brown et al. presented a scathing critique of the work of Fredrickson and Losada (see record 2005-11834-001) on the use of advanced mathematical methods (specifically, nonlinear dynamics) in describing changes in human emotions over time, terming it "entirely unfounded" (p. 802). However, I feel that although their critique serves an important role in identifying potential flaws in the theory, it goes too far by using terms such as "completely illusory 'applications' of mathematics" (p. 812) and may inadvertently discourage junior researchers in pursuing the use of mathematical methods in psychology. | 25,197,849 | [
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G-loading and vibration effects on heart and respiration rates. | Operational environments expose pilots and astronauts to sustained acceleration (G loading) and whole-body vibration, alone and in combination. Separately, the physiological effects of G loading and vibration have been well studied; both have effects similar to mild exercise. The few studies of combined G loading and vibration have not reported an interaction between these factors on physiological responses. We tested the effects of G loading (+1 and +3.8 G(x)) and vibration (0.5 gx at 8, 12, and 16 Hz), alone and in combination, on heart and respiration rate. We observed an effect of G loading on heart rate (average increase of 23 bpm, SD 12) and respiration rate (average increase of 5 breaths per minute, SD 5), an effect of vibration on heart rate, and an interaction on heart rate. With vibration, we observed heart rate increases of 4 bpm (SD: 3) with no increase in respiration rate. In the +1 G(x) condition, the largest heart rate increase occurred during low-frequency (8 Hz) vibration, while at +3.8 G(x), the largest heart rate increase occurred during high-frequency (16 Hz) vibration, demonstrating interaction. Consistent with previous reports, our G-loading and vibration effects are similar to mild exercise. In addition, we observed an interaction between G loading and vibration on heart rate, with maximum heart rates occurring at a higher vibration frequency at +3.8 G(x) compared to +1 G(x). The observed interaction demonstrates that G-loading and vibration effects are not independent and can only be properly assessed during combined exposure. | 25,197,894 | [
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Bilastine as a potential treatment in allergic rhinitis. | Allergic rhinitis is a very frequent disease. H1 antihistamines have been used for treatment of allergic rhinitis for more than 5 decades. They differ in chemical structure, pharmacokinetics, pharmacodynamics, clinical efficacy and adverse effects. We performed a detailed analysis of all available publications concerning the new H1-antihistamine bilasitine. Bilastine, a piperidine derivative, is a novel potent H1 antihistamine. It is at least as potent as cetirizine or fexofenadine in in vitro studies. In animal studies it demonstrates dose-dependent antihistaminic and antiallergic effects. In humans its metabolism is not affected by age, gender or renal function but may be affected by coadministration of P glycoprotein inhibitors. Efficacy of bilastine in therapy of allergic rhinitis patients has been documented in several large controlled clinical trials showing bilastine being at least as effective as cetirizine or desloratadine. No significant suppressive effect on central nervous system could be demonstrated when bilastine was used in the recommended doses. Bilastine is a novel H1 antihistamine with anti-allergic properties which is highly effective in the treatment of symptoms of allergic rhinitis. It has a favorable pharmacokinetic and pharmacodynamic profile and is generally well tolerated. | 25,197,918 | [
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Sinonasal sarcoidosis: A new system of classification acting as a guide to diagnosis and treatment. | The signs and symptoms of sinonasal sarcoidosis are diverse and nonspecific. It easily mimics more common sinonasal disorders such as allergic rhinitis, bacterial sinusitis, and atrophic rhinitis. The purpose of this study was to develop a classification system of sinonasal sarcoidosis that will help serve as a guide for both diagnosis and treatment. A retrospective chart review was performed of all patients diagnosed with sinonasal sarcoidosis from 1974 to 2013. A PubMed literature review of all published case series of sinonasal sarcoidosis was also reviewed. The charts of 14 patients with biopsy-proven sinonasal sarcoidosis were reviewed. Follow-up time ranged from 6 months to 28 years. Presenting signs included hypertrophic mucosa, nasal polyps, crusting, nasal enlargement, and destructive processes. Eight patients underwent medical management alone and six patients underwent endoscopic sinus surgery. Five of the six patients were successfully treated with surgery. On review of the literature, 256 cases of sinonasal sarcoidosis were found, of which 43 patients underwent surgery. Clinical outcomes of the patients who underwent surgery were not consistently reported. Based on critical analysis of the clinical presentation of sinonasal sarcoidosis in our case series and on review of the literature, sinonasal sarcoidosis can be classified into four subgroups: atrophic, hypertrophic, destructive, and nasal enlargement. Each subgroup responds differently to treatment and has its own differential diagnosis. Surgery is only indicated for a select group of patients and the vast majority of patients benefit from medical management alone. | 25,197,919 | [
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Study of leaf metabolome modifications induced by UV-C radiations in representative Vitis, Cissus and Cannabis species by LC-MS based metabolomics and antioxidant assays. | UV-C radiation is known to induce metabolic modifications in plants, particularly to secondary metabolite biosynthesis. To assess these modifications from a global and untargeted perspective, the effects of the UV-C radiation of the leaves of three different model plant species, Cissus antarctica Vent. (Vitaceae), Vitis vinifera L. (Vitaceae) and Cannabis sativa L. (Cannabaceae), were evaluated by an LC-HRMS-based metabolomic approach. The approach enabled the detection of significant metabolite modifications in the three species studied. For all species, clear modifications of phenylpropanoid metabolism were detected that led to an increased level of stilbene derivatives. Interestingly, resveratrol and piceid levels were strongly induced by the UV-C treatment of C. antarctica leaves. In contrast, both flavonoids and stilbene polymers were upregulated in UV-C-treated Vitis leaves. In Cannabis, important changes in cinnamic acid amides and stilbene-related compounds were also detected. Overall, our results highlighted phytoalexin induction upon UV-C radiation. To evaluate whether UV-C stress radiation could enhance the biosynthesis of bioactive compounds, the antioxidant activity of extracts from control and UV-C-treated leaves was measured. The results showed increased antioxidant activity in UV-C-treated V. vinifera extracts. | 25,197,936 | [
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Ginsenoside 20(S)-Rg3 targets HIF-1α to block hypoxia-induced epithelial-mesenchymal transition in ovarian cancer cells. | The prognosis of patients with ovarian cancer has remained poor mainly because of aggressive cancer progression. Since epithelial-mesenchymal transition (EMT) is an important mechanism mediating invasion and metastasis of cancer cells, targeting the EMT process with more efficacious and less toxic compounds to inhibit metastasis is of great therapeutic value for the treatment of ovarian cancer. We have found for the first time that the ginsenoside 20(S)-Rg3, a pharmacologically active component of the traditional Chinese herb Panax ginseng, potently blocks hypoxia-induced EMT of ovarian cancer cells in vitro and in vivo. Mechanistic studies confirm the mode of action of 20(S)-Rg3, which reduces the expression of hypoxia-inducible factor 1α (HIF-1α) by activating the ubiquitin-proteasome pathway to promote HIF-1α degradation. A decrease in HIF-1α in turn leads to up-regulation, via transcriptional suppression of Snail, of the epithelial cell-specific marker E-cadherin and down-regulation of the mesenchymal cell-specific marker vimentin under hypoxic conditions. Importantly, 20(S)-Rg3 effectively inhibits EMT in nude mouse xenograft models of ovarian cancer, promising a novel therapeutic agent for anticancer therapy. | 25,197,976 | [
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ASC spheroid geometry and culture oxygenation differentially impact induction of preangiogenic behaviors in endothelial cells. | Cell-based angiogenic therapies offer potential for the repair of ischemic injuries, while avoiding several of the limitations associated with material-based growth factor delivery strategies. Evidence supports that applying MSCs as spheroids rather than dispersed cells can improve retention and enhance therapeutic effect through increased secretion of angiogenic factors due to hypoxia. However, while spheroid culture appears to modulate MSC behavior, there has been little investigation of how major culture parameters that affect cellular oxygen tension, such as external oxygenation and culture size, impact the angiogenic potential of spheroids. We cultured equal numbers of adipose-derived stem cells (ASCs) as spheroids containing 10,000 (10k) or 60,000 (60k) cells each, in 20% and 2% oxygen. VEGF secretion varied among the sample groups, with 10k, 2% O2 spheroids exhibiting the highest production. Spheroid-conditioned media was applied to HUVEC monolayers, and proliferation was assessed. Spheroids of either size in 2% oxygen induced comparable proliferation compared to a 2 ng/ml VEGF control sample, while spheroids in 20% oxygen induced less proliferation. Spheroids were also applied in coculture with HUVEC monolayers, and induction of migration through a Transwell membrane was evaluated. Sixty thousand, 2% O2 spheroids induced similar levels of migration as VEGF controls, while 10k, 2% O2 spheroids induced significantly more. Ten thousand, 20% spheroids performed no better than VEGF-free controls. We conclude that the therapeutic ability of ASC spheroids to stimulate angiogenesis in endothelial cells is affected by both culture size and oxygenation parameters, suggesting that, while ASC spheroids offer potential in the treatment of injured and ischemic tissues, careful consideration of culture size in respect to in vivo local oxygen tension will be necessary for optimal results. | 25,197,983 | [
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The effect of sodium hypochlorite application on the success of calcium hydroxide and mineral trioxide aggregate pulpotomies in primary teeth. | This study's purpose was to evaluate the success of calcium hydroxide (CH) and mineral trioxide aggregate (MTA) pulpotomies following the use of five percent sodium hypochlorite (NaOCl) as an antibacterial agent to clean the chamber prior to application of the pulpotomy agent. A total of 128 teeth were randomly divided into two pulpotomy groups (CH or MTA). The teeth in each pulpotomy group, CH and MTA, were further randomly divided into subgroups to receive either the NaOCl (experimental) or saline (control) cleaning agent prior to applying the pulpotomy agent. The treatments were followed clinically and radiographically for 12 months. The radiographic success rates were 84 percent for CH NaOCl, 74 percent for CH saline control, 97 percent for MTA NaOCl, and 100 percent for MTA saline control. There were no significant differences between the radiographic success rates in the CH and MTA subgroups (CH NaOCl-CH control and MTA NaOCl-MTA control); no significant differences were observed when comparing the CH NaOCl-MTA NaOCl groups and the CH NaOCl-MTA control groups. Use of sodium hypochlorite as an antibacterial agent prior to application of the pulpotomy agent improved the success of calcium hydroxide pulpotomies to equal the success of mineral trioxide aggregate pulpotomies for observation up to 12 months. | 25,197,997 | [
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Feasibility of frequency-modulated wireless transmission for a multi-purpose MEMS-based accelerometer. | Recent advances in the Micro Electro-Mechanical System (MEMS) technology have made wireless MEMS accelerometers an attractive tool for Structural Health Monitoring (SHM) of civil engineering structures. To date, sensors' low sensitivity and accuracy--especially at very low frequencies--have imposed serious limitations for their application in monitoring large-sized structures. Conventionally, the MEMS sensor's analog signals are converted to digital signals before radio-frequency (RF) wireless transmission. The conversion can cause a low sensitivity to the important low-frequency and low-amplitude signals. To overcome this difficulty, the authors have developed a MEMS accelerometer system, which converts the sensor output voltage to a frequency-modulated signal before RF transmission. This is achieved by using a Voltage to Frequency Conversion (V/F) instead of the conventional Analog to Digital Conversion (ADC). In this paper, a prototype MEMS accelerometer system is presented, which consists of a transmitter and receiver circuit boards. The former is equipped with a MEMS accelerometer, a V/F converter and a wireless RF transmitter, while the latter contains an RF receiver and a F/V converter for demodulating the signal. The efficacy of the MEMS accelerometer system in measuring low-frequency and low-amplitude dynamic responses is demonstrated through extensive laboratory tests and experiments on a flow-loop pipeline. | 25,198,003 | [
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-0.1802372,
0.2276069,
-0.1609392,
-0.18811... |
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