title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Antithrombotic medicines following intracerebral haemorrhage: where's the evidence? | The use of antithrombotic medicines in patients who have a history of intracerebral haemorrhage is widely perceived as being contraindicated. However, many patients with intracerebral haemorrhage may suffer from conditions for which antithrombotic medicines are indicated. Such scenarios represent a therapeutic dilemma whereby treating infers an increased risk of recurrent intracerebral haemorrhage, but not treating infers an increase of thrombotic complications. Despite the importance of this dilemma, there is very little guidance for prescribers. This perspective review considered previous systematic reviews that addressed this issue, together with recently published research findings from the Tayside Stroke Cohort. Systematic reviews of experimental and observational studies have concluded that there is a marked lack of data on which to judge the safety of oral anticoagulant agents following intracerebral haemorrhage. In addition, the limited data available regarding the use of antiplatelet medicines following intracerebral haemorrhage provide no evidence that they are harmful, and again further data are required. In the absence of such data, a decision analysis approach has been proposed. This considers the findings of other studies to infer the likely impact of using antithrombotic agents in patients with intracerebral haemorrhage. The success of this approach is contingent on the availability of reliable data that describe the rate of recurrent intracerebral haemorrhage; however, published data on this varies widely. There are a number of factors that conspire against researchers addressing this issue. The current paucity of evidence to guide prescribers faced with this therapeutic dilemma seems likely to remain for some time. | 25,083,213 | [
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Statins and their interactions with other lipid-modifying medications: safety issues in the elderly. | Inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, commonly known as statins, are widely used in both primary and secondary prevention of occlusive cardiovascular disease. Statins are effective not only in improving total and low-density lipoprotein cholesterol concentrations in blood but also in decreasing morbidity and mortality associated with cardiovascular diseases resulting from underlying atheroma. There is, however, evidence that statins are underutilized in elderly patients, possibly due to concerns about safety/tolerability issues or potential drug interactions, including interactions with other lipid-modifying medications, or both. In this review, we summarize the major adverse events associated with statin use, with particular reference to the elderly patient, including factors which might increase the risk of adverse effects. Potential drug interactions between statins and other lipid-modifying medications including fibrates, ezetimibe, nicotinic acid, bile acid sequestrants and omega-3-acid ethyl esters (fish oils) are specifically discussed. Clinical management strategies to avoid these drug interactions are outlined. | 25,083,224 | [
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Risks associated with tiotropium in chronic obstructive pulmonary disease: overview of the evidence to date. | Tiotropium is a long-acting inhaled anticholinergic agent that is widely used in the treatment of chronic obstructive pulmonary disease (COPD). It was initially launched as the tiotropium HandiHaler formulation, but this was followed by a newer version based on a potentially more efficient drug delivery device, known as Respimat. This Respimat formulation is available worldwide but has not yet succeeded in gaining regulatory approval in the USA. In the past few years, the adverse effects profile of tiotropium has come under close scrutiny owing to concerns about the possibility of urinary and cardiovascular adverse effects. These concerns appeared to have been alleviated following the publication of data from the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, which was a large trial of 4 years' duration. This trial did not show any excess myocardial infarction, renal or urinary adverse events with tiotropium compared with placebo. However, the risk of urinary retention has been in the spotlight again following publication of two observational studies reporting a significantly increased risk of urinary retention in men recently started on inhaled anticholinergics, especially when prostatic hyperplasia coexists. More recently, a meta-analysis of mortality data for the tiotropium Respimat formulation raised the possibility of an increased risk of death, including death from cardiovascular causes. It is unclear if the more efficient drug delivery offered by the Respimat device is hitting a different part of the dose-toxicity curve. In the absence of any evidence of superior clinical efficacy with tiotropium Respimat compared with tiotropium HandiHaler, some experts have argued that there is no compelling reason to choose the Respimat formulation given the new uncertainties about its safety profile. | 25,083,231 | [
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Risk of acute urinary retention associated with inhaled anticholinergics in patients with chronic obstructive lung disease: systematic review. | Inhaled anticholinergics (ipratropium bromide and tiotropium bromide) are widely used as maintenance treatment in chronic obstructive pulmonary disease. Previous studies have reported on their cardiovascular effects but relatively little is known about their effects on the bladder. Acute urinary retention is a medical emergency which can be associated with serious complications. Our objective was to evaluate the existing literature regarding the effects of inhaled anticholinergics on urinary retention among patients with chronic obstructive pulmonary disease. We searched PubMed and the United States Food and Drug Administration (FDA) adverse events database for case reports, observational studies, randomized controlled trials (or meta-analyses of such trials) that reported on the outcome of urinary retention with inhaled anticholinergics (ipratropium or tiotropium). We checked 27 published articles and identified relevant papers including two case reports, three pooled analyses, two observational studies and one randomized controlled trial. Two of the observational studies and a pooled analysis of randomized controlled trials reported a significant increase in the risk of acute urinary retention with inhaled anticholinergics. Older patients with benign prostatic hyperplasia seem to be at the highest risk of this adverse effect which tends to occur soon after treatment initiation. Although all the links in the chain have yet to be fully elucidated, the preponderance of evidence suggests the possibility of a causal relationship between inhaled anticholinergics and urinary retention. Clinicians should carefully balance these and other adverse effects of inhaled anticholinergics against their known symptomatic benefits on exacerbations, after eliciting patient preferences for various outcomes in a shared decision-making context. | 25,083,248 | [
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Systems that prevent unwanted represcription of drugs withdrawn because of adverse drug events: a systematic review. | Represcription of medication that was withdrawn after the occurrence of an adverse drug event (including allergy), is a recognized medication safety issue on a patient level. We performed a systematic review to identify systems (electronic and nonelectronic) that can prevent the represcription of drugs withdrawn because of an adverse drug event and the effects of these systems. The review was performed using PRISMA and Cochrane guidelines. PubMed and Embase were searched for articles describing systems that can prevent represcription of drugs that had been withdrawn for causing an adverse drug event. Information on the characteristics of the studies, systems, and if present results achieved with such systems, was extracted. The results showed that of 6793 articles screened, 137 full-text articles were assessed for eligibility. A total of 45 studies describing 33 systems (28 electronic) were included. The five nonelectronic systems used allergy bracelets or allergy labels on hospital medical records or on drug orders. Systems differed in the way adverse drug events were documented and how users were alerted to drug represcription. Most systems functioned within a specific healthcare setting. Of 12 studies that compared pre- and post-intervention periods or wards with and without intervention, 7 showed a reduction in represcription after adverse drug event. In conclusion, several systems have been developed that can prevent the represcription of drugs that elicited an adverse drug event, but the evidence that these systems are effective is limited. | 25,083,253 | [
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The reproductive season of Acropora in Socotra, Yemen. | Determining when corals reproduce has clear management and economic implications. Here we document the reproductive condition of corals in the genus Acropora on the island of Socotra in Yemen during February 2014. Twenty percent of colonies (n = 143) contained mature gametes and 28% had immature gametes indicating that spawning will occur in both February and March in 2014, confirming previous anecdotal reports of coral spawning at this time in Socotra. Acropora typically reproduce in synchrony with many other broadcast spawning scleractinian corals, and we therefore predict that many other species are reproductively active at this time of year. | 25,075,295 | [
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Case Report: Severe form of hemolytic-uremic syndrome with multiple organ failure in a child: a case report. | Hemolytic-uremic syndrome (HUS) is a leading cause of acute renal failure in infants and young children. It is traditionally defined as a triad of acute renal failure, hemolytic anemia and thrombocytopenia that occur within a week after prodromal hemorrhagic enterocolitis. Severe cases can also be presented by acute respiratory distress syndrome (ARDS), toxic megacolon with ileus, pancreatitis, central nervous system (CNS) disorders and multiple organ failure (MOF). A previously healthy 4-year old Caucasian girl developed acute renal failure, thrombocytopenia and hemolytic anemia following a short episode of abdominal pain and bloody diarrhea. By the end of the first week the diagnosis of the typical HUS was established. During the second week the disease progressed into MOF that included ileus, pancreatitis, hepatitis, coma and ARDS, accompanied by hemodynamic instability and extreme leukocytosis. Nonetheless, the girl made a complete recovery after one month of the disease. She was successfully treated in the intensive care unit and significant improvement was noticed after plasmapheresis and continuous veno-venous hemodialysis. Early start of plasmapheresis and meticulous supportive treatment in the intensive care unit, including renal placement therapy, may be the therapy of choice in severe cases of HUS presented by MOF. Monitoring of prognostic factors is important for early performance of appropriate diagnostic and therapeutical interventions. | 25,075,296 | [
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Sensitivity and specificity of an abbreviated (13)C-mixed triglyceride breath test for measurement of pancreatic exocrine function. | A modified (13)C-mixed triglyceride breath test ((13)C -MTGT) detects moderate pancreatic exocrine insufficiency noninvasively and reliably, but it requires prolonged breath sampling (6 hours (hr)). We aimed to investigate whether (13)C -MTGT can be abbreviated, to optimize clinical usability. We analyzed the (13)C-MTGT of 200 consecutive patients, retrospectively. Cumulative 1-5 hr (13)C-exhalation values were compared with the standard parameter (6-hr cumulative (13)C-exhalation). We determined the sensitivity and specificity of shortened breath sampling periods, by comparison with the normal values from 10 healthy volunteers, whom also underwent a secretin test to quantitate pancreatic secretion. Moreover, we evaluated the influence of gastric emptying (GE), using a (13)C-octanoic acid breath test in a subset (N = 117). The 1-5 hr cumulative (13)C-exhalation tests correlated highly and significantly with the standard parameter (p < 0.0001). Sensitivity for detection of impaired lipolysis was high (≥77%), but the specificity was low (≥38%) for the early measurements. Both parameters were high after 4 hrs (88% and 94%, respectively) and 5 hrs (98% and 91%, respectively). Multivariate linear correlation analysis confirmed that GE strongly influenced early postprandial (13)C-exhalation during the (13)C-MTGT. Shortening of the (13)C -MTGT from 6 to 4 hrs of duration was associated with similar diagnostic accuracy, yet increased clinical usability. The influence of GE on early postprandial results of the (13)C-MTGT precluded further abbreviation of the test. | 25,083,286 | [
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Outcomes of patients treated with capecitabine and temozolamide for advanced pancreatic neuroendocrine tumors (PNETs) and non-PNETs. | Retrospective studies have demonstrated high response rates among patients with advanced pancreatic neuroendocrine tumors (PNETs) treated with capecitabine and temozolamide (CapTem), while responses are infrequently seen among non-PNETs. The objective of the study was to describe progression free survival (PFS) among neuroendocrine tumor (NET) patients treated with CapTem, and to identify factors associated with better activity. Patients who were referred to one of five provincial cancer treatment centers between 2009 and 2013 for advanced NETs and initiated CapTem were included. Patients received Cap 1,500 mg/m(2) on days 1-14 and TMZ 200 mg/m(2) on days 10-14 every 28 days. Their characteristics and outcomes were retrospectively analyzed. In our cohort, 29 patients (16 males) with a median age of 59 (range 26-76) received palliative CapTem, 15 of them as first-line chemotherapy. Primary tumors included pancreas (48.3%), small bowel (20.7%), lung (10.3%), unknown (10.3%), rectum (6.9%) and appendix (3.4%). Median number of cycles was three. Fifteen patients (51.7%) received CapTem as first-line chemotherapy and 14 (48.3%) as subsequent lines. Median PFS for the entire cohort was 4.7 months. PNETs had a median PFS of 4.9 months compared to 2.8 months for non-PNETs (P=0.178). Patients with PNETs who received CapTem in the first-line setting had a median PFS of 15.9 months as compared to only 3.1 months for the remainder [P=0.047, hazard ratios (HR) 0.342]. Patients with Ki67 above 5% and ≤5% had median PFS of 4.0 and 4.7 months, respectively (P=0.260). CapTem showed good activity among PNETs, but its broader role in the treatment of carcinoid tumors remains unclear. | 25,083,296 | [
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KRAS mutation profile differences between rectosigmoid localized adenocarcinomas and colon adenocarcinomas. | Colorectal cancer has a heterogeneous nature that is influenced by the tumour site. Many improvements have been made in identifying and characterizing the genetic alterations between colon and rectal cancers. However, there is not enough information about KRAS mutational differences between rectosigmoid and colon cancers arising elsewhere in the large bowel. The aim of this study was to determine the differences in the frequency of KRAS genetic alterations between rectosigmoid cancers and colon cancers. Eighty-four patients diagnosed with colorectal cancer were included in this study. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumour tissue sections. KRAS mutation analysis which was designed to detect the seven most common KRAS gene mutations (Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp) was performed. Chi-square test was used to test the association between mutation status and other variables. This study represents the first KRAS mutational results from Turkish rectosigmoid cancer patients. The KRAS mutation frequency of rectosigmoid tumours is higher (34.3%, 12/35) than that of colon-localized tumours (30.6%, 15/49). However, there is no significant correlation between the KRAS mutation status and tumour location (rectosigmoid and colon). KRAS mutation analysis has a predictive and prognostic value in identifying tumours that may be resistant to treatment. Our study shows that differences in the biological behaviour of rectosigmoid and colon cancers should be considered. This finding highlights the importance of personalized cancer management, which could be assisted by cancer genotyping tools. | 25,083,299 | [
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Mucinous adenocarcinoma of the rectum: a poor candidate for neo-adjuvant chemoradiation? | Mucinous adenocarcinoma (MA) is a distinct pathological entity associated with poor outcome. Due to different biological behavior, the response to neoadjuvant chemo-radiation (NACRT) may be inferior compared to non-mucinous tumours. In this study we compare the pathological response of mucinous tumours after NACRT. A total of 183 patients who underwent NACRT for rectal cancer were classified as mucinous and non-MAs. The dose of radiation was 45 Gy (at 1.8 Gy per fraction) delivered over five weeks with weekly 5-flourouracil (5-FU) (325 mg/m(2)) and leucovorin (20 mg/m(2)). After surgery, the pathological specimens were evaluated and staged. The data are reported as descriptive statistics and chi-square test used to determine difference in proportions. The two varieties were comparable on the basis of the computed tomography (CT) scan in terms of tumour size and lymph node metastasis. However in terms of pathological response, it was seen that there was a higher incidence of pT4 tumours (73.5% vs. 10.7%), margin positivity (11.7% vs. 2.3%) and advanced nodal disease pN2 (29.4% vs. 9.3%) in mucinous and non-mucinous tumours respectively. MA of the rectum show a poor response to NACRT as seen in terms of larger residual tumours, higher incidence of margin positivity, and greater residual nodal disease. Also they showed higher incidence of peritoneal and distant dissemination during NACRT. The role of NACRT in mucinous carcinoma of the rectum is of questionable benefit and needs to be examined in prospective trials. | 25,083,301 | [
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Rapidly progressive subcutaneous metastases from gallbladder cancer: insight into a rare presentation in gastrointestinal malignancies. | Gallbladder cancer (GBCA) is the most common malignancy of the biliary tract. It has an aggressive biology that results in the ability to spread, seed and grow in disparate environments. It can metastasize via lymphatic, hematogenous, and peritoneal seeding. However, GBCA metastasis to distant subcutaneous sites is extremely rare. This case report describes the presentation of metastatic GBCA with rapidly progressive subcutaneous metastases. A 58-year-old woman presented with acute onset right upper quadrant abdominal pain. Computed tomography (CT) revealed a calcified and thickened gallbladder with cholelithiasis and presumed cholecystitis. Diagnostic laparoscopy revealed a gallbladder mass. Biopsies were consistent with GBCA. The patient was referred to our cancer center for further surgical management. However, she was found to have rapidly growing subcutaneous nodules in the shoulders, chest, abdomen, and buttocks. Positron emission tomography (PET) demonstrated that these were fluorodeoxyglucose (FDG)-avid. A core needle biopsy of a chest wall lesion was consistent with metastatic GBCA. Therefore, the patient was diagnosed with stage IVB GBCA and was initiated on systemic chemotherapy. GBCA is known to have an incredible propensity to grow within the peritoneal cavity, as well as along needle biopsy tracts and at laparoscopic port sites. Several case reports have demonstrated that GBCA also has the potential to metastasize to distant subcutaneous sites, most often including breast metastases, while the current cases represents a more diffuse pattern of spread. GBCA belongs to the short list of solid visceral malignancies that have the potential to develop remote subcutaneous metastases. | 25,083,307 | [
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Pancreatic head carcinoma and right hepatic artery: embolization management-A case report. | A replaced right hepatic artery (RHA) is the most common anatomical variation in pancreatic surgery. The RHA is frequently encountered and can be problematic in pancreatic carcinoma. The preservation of the RHA is necessary to avoid ischemic complications but can impact margins resection in pancreaticoduodenectomy (PD). We report a case of a 53-year-old man with a head pancreatic carcinoma. There was a close contact between the tumor and the RHA arising from superior mesenteric artery (SMA). Preoperative embolization of the RHA was performed prior to PD. | 25,083,312 | [
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"Alien Health": A Nutrition Instruction Exergame Using the Kinect Sensor. | <b<iObjective:</i</b A feasibility study was run on an embodied exergame designed to teach 4th-12th grade students about nutrition and several U.S. Department of Agriculture (USDA) <iMyPlate</i guidelines. The study assessed efficacy on a new version of a game that was first implemented on an immersive platform and published in this journal in 2013. The earlier "Alien Health" game was redesigned for use with the Microsoft<sup®</sup (Redmond, WA) Kinect<sup®</sup sensor. Players learned about the amount of nutrients and optimizers in common food items and practiced making food choices while engaging in short cardio exercises. <b<iSubjects and Methods:</i</b Twenty 6th and 7th graders were randomly assigned to either the "Alien Health" game or a treated control condition. All engaged in "front of the classroom" performative activities. The "Alien Health" experimental group experienced the full game narrative of feeding the Alien and automated feedback on the quality of performed exercises. The control group experienced the same performative food choices at the interactive whiteboard but did no exercises. Two-week follow-up data were collected. <b<iResults:</i</b Both groups displayed statistically significant learning gains on the immediate nutrition knowledge posttest. The effect sizes from pretest to 2-week follow-up were 0.83 for the control group and 1.14 for the experimental group. Of interest is the crossover interaction from posttest to follow-up that approached significance (<iF</i<sub19</sub=3.96, <iP</i<0.058). Here, the experimental group outperformed the control group for knowledge retention. <b<iConclusions:</i</b Results suggest acceptability, feasibility, and limited efficacy in a Kinect-based game to instruct in nutrition and the USDA <iMyPlate</i icon. The follow-up test revealed that nutrition knowledge continued to increase for the experimental group that performed short cardio exercises, suggesting that short exercises and perhaps a game narrative may have helped to consolidate content memory. | 25,083,315 | [
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Trial watch: Immunostimulatory cytokines in cancer therapy. | Tumor-targeting immune responses provide a significant contribution to (when they do not entirely account for) the clinical activity of diverse antineoplastic regimens, encompassing not only a large panel of immunotherapeutic strategies but also conventional cytotoxic molecules, targeted anticancer agents and irradiation. In line with this notion, several approaches have been devised to elicit novel or boost existing anticancer immune responses, including the administration of immunomodulatory cytokines. Such a relatively unspecific intervention suffices to mediate clinical effects in (at least a subset of) patients bearing particularly immunogenic tumors, like melanoma and renal cell carcinoma. More often, however, immunostimulatory cytokines are administered to boost the immunogenic potential of other agents, including (but not limited to) immune checkpoint-blocking antibodies, anticancer vaccines, oncolytic viruses and immunogenic chemotherapeutics. Here, we summarize the latest advances in the clinical development of recombinant cytokines as an immunomodulatory intervention for cancer therapy. | 25,083,328 | [
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Automatic large-scale classification of bird sounds is strongly improved by unsupervised feature learning. | Automatic species classification of birds from their sound is a computational tool of increasing importance in ecology, conservation monitoring and vocal communication studies. To make classification useful in practice, it is crucial to improve its accuracy while ensuring that it can run at big data scales. Many approaches use acoustic measures based on spectrogram-type data, such as the Mel-frequency cepstral coefficient (MFCC) features which represent a manually-designed summary of spectral information. However, recent work in machine learning has demonstrated that features learnt automatically from data can often outperform manually-designed feature transforms. Feature learning can be performed at large scale and "unsupervised", meaning it requires no manual data labelling, yet it can improve performance on "supervised" tasks such as classification. In this work we introduce a technique for feature learning from large volumes of bird sound recordings, inspired by techniques that have proven useful in other domains. We experimentally compare twelve different feature representations derived from the Mel spectrum (of which six use this technique), using four large and diverse databases of bird vocalisations, classified using a random forest classifier. We demonstrate that in our classification tasks, MFCCs can often lead to worse performance than the raw Mel spectral data from which they are derived. Conversely, we demonstrate that unsupervised feature learning provides a substantial boost over MFCCs and Mel spectra without adding computational complexity after the model has been trained. The boost is particularly notable for single-label classification tasks at large scale. The spectro-temporal activations learned through our procedure resemble spectro-temporal receptive fields calculated from avian primary auditory forebrain. However, for one of our datasets, which contains substantial audio data but few annotations, increased performance is not discernible. We study the interaction between dataset characteristics and choice of feature representation through further empirical analysis. | 25,083,350 | [
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Resource availability and repeated defoliation mediate compensatory growth in trembling aspen (Populus tremuloides) seedlings. | Plant ecologists have debated the mechanisms used by plants to cope with the impact of herbivore damage. While plant resistance mechanisms have received much attention, plant compensatory growth as a type of plant tolerance mechanisms has been less studied. We conducted a greenhouse experiment to evaluate compensatory growth for trembling aspen (Populus tremuloides) seedlings under varying intensities and frequencies of simulated defoliation, with or without nutrient enriched media. For the purpose of this study, changes in biomass production and non-structural carbohydrate concentrations (NSC) of roots and leaves were considered compensatory responses. All defoliated seedlings showed biomass accumulation under low defoliation intensity and frequency, regardless of resource availability; however, as defoliation intensity and frequency increased, compensatory growth of seedlings was altered depending on resource availability. Seedlings in a resource-rich environment showed complete compensation, in contrast responses ranged from undercompensation to complete compensation in a resource-limited environment. Furthermore, at the highest defoliation intensity and frequency, NSC concentrations in leaves and roots were similar between defoliated and non-defoliated seedlings in a resource-rich environment; in contrast, defoliated seedlings with limited resources sustained the most biomass loss, had lower amounts of stored NSC. Using these results, we developed a new predictive framework incorporating the interactions between frequency and intensity of defoliation and resource availability as modulators of plant compensatory responses. | 25,083,352 | [
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Delayed Presentation of a Congenital Cholesteatoma in a 64-year-old Man: Case Report and Review of the Literature. | Introduction Congenital cholesteatomas of the temporal bone are epidermoid cysts of embryologic origin that result in progressive desquamation and trapping of squamous epithelium behind an intact tympanic membrane. They are benign, slowly progressive lesions that can be found in various areas of the temporal bone. We report a case of a patient with a massive cholesteatoma first detected at the age of 64 years, causing significant destruction of the mastoid and petrous temporal bones, and adjacent occipital bone. Methods We reviewed the literature and a case report of a patient seen in our institution recently. The Medline database was used to search multiple terms including "congenital" and "cholesteatoma." Results The patient's congenital cholesteatoma was detected incidentally on a computed tomography scan when the patient's only symptoms were unilateral conductive hearing loss with a family history of hearing loss. It was subsequently successfully operated on with minimal postoperative complications. Conclusions Congenital cholesteatomas of mastoid origin can often exist for many years in a subclinical state and develop into a massive size before causing symptoms. A high index of suspicion is necessary to detect congenital cholesteatomas in patients with unilateral conductive hearing loss who are otherwise asymptomatic and have a normal tympanic membrane. | 25,083,369 | [
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Atypical presentation of sinonasal cellular schwannoma: a nonsolitary mass with osseous, orbital, and intracranial invasion. | Objective Sinonasal cellular schwannoma represents < 4% of head and neck schwannomas. These benign tumors are typically confined to the nasal cavity or ethmoid sinus. We describe an atypical case of sinonasal cellular schwannoma with diffuse paranasal sinus involvement and both intraorbital and intracranial extension. Results A 62-year-old woman presented with a 6-month history of right orbital proptosis and right-sided headache. Subsequent imaging revealed an invasive paranasal sinus mass extending through the skull base and displacing the right orbit. Preoperative biopsies were not diagnostic but revealed a spindle cell lesion suspicious for malignancy based on lack of encapsulation, infiltration of the sinonasal submucosa, and osseous invasion. The patient underwent open skull base surgery, and pathology confirmed a S100-positive nonencapsulated cellular schwannoma. Conclusion An atypical case of sinonasal cellular schwannoma with intracranial extension is reported. Its presentation is contrary to the common view that these are isolated solitary lesions of the nasoethmoid region. We suggest that sinonasal cellular schwannoma be considered in the differential diagnosis of a poorly defined invasive paranasal sinus mass, particularly following biopsy. | 25,083,375 | [
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Perioperative management of catecholamine-secreting glomus jugulare tumors. | To treat patients with a catecholamine-secreting glomus jugulare tumor, perioperative management is important. Perioperative catecholamine hypersecretion causes severe problems in the treatment of a catecholamine-secreting glomus tumor. Therefore, a precise therapeutic strategy and perioperative management are required through collaboration of the endocrinology, anesthesiology, and endocrine surgery departments . We describe our perioperative management for catecholamine-secreting glomus jugulare tumor. The patient was a 31-year-old woman with a 50-mm glomus jugulare tumor and a significantly elevated plasma noradrenaline level of 21,165 pg/ml. Before the surgery, oral α - blocker administration was initiated for ∼ 3 months, and her body weight increased from 52 kg at the time of examination to 54.2 kg. Coil embolization of the tumor vessel was performed 1 week before surgery, and the intense tumor stain was reduced by 90%. The patient underwent almost total removal of the tumor via mastoidectomy with high cervical exposure via the transsigmoid approach. Postoperatively, plasma noradrenaline decreased markedly. Preoperative pharmacologic stabilization and peri- and postoperative anesthetic management are essential for the treatment of a catecholamine-secreting glomus jugulare tumor. | 25,083,379 | [
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Expressions of D2-40, CK19, galectin-3, VEGF and EGFR in papillary thyroid carcinoma. | To investigate the expressions of D2-40, CK19, galectin-3, VEGF, and EGFR in papillary thyroid carcinoma and their clinical significances. The expressions of D2-40, CK19, galectin-3, VEGF, and EGFR in 38 cases of papillary thyroid carcinoma and 12 cases of thyroid papillary hyperplasia were detected by immunohistochemical staining. The positive expression rates of D2-40, CK19, Galectin-3, VEGF and EGFR in patients with papillary thyroid carcinoma were all significantly higher than those in patients with thyroid papillary hyperplasia (all P<0.05). The expressions of D2-40, VEGF, and EGFR in papillary thyroid carcinoma with lymph node metastasis were significantly higher than those without lymph node metastasis (P<0.05). The expressions of GK19 and galectin-3 showed no significant differences between the papillary thyroid carcinomas with and without lymph node metastasis (P>0.05). The detection of D2-40, CK19, galectin-3, VEGF, and EGFR is helpful for the diagnosis and differential diagnosis of papillary thyroid carcinoma and thyroid papillary hyperplasia. | 25,083,424 | [
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Cryosurgery of breast cancer. | With recent improvements in breast imaging, the ability to identify small breast tumors is markedly improved, prompting significant interest in the use of cryoablation without surgical excision to treat early-stage breast cancer. The cryoablation is often performed using ultrasound-guided tabletop argon-gas-based cryoablation system with a double freeze/thaw cycle. Recent studies have demonstrated that, as a primary therapy for small breast cancer, cryoablation is safe and effective with durable results, and can successfully destroy all cancers <1.0 cm and tumors between 1.0 and 1.5 cm without a significant ductal carcinoma-in-situ (DCIS) component. Presence of noncalcified DCIS is the cause of most cryoablation failures. At this time, cryoablation should be limited to patients with invasive ductal carcinoma <1.5 cm and with <25% DCIS in the core biopsy. For unresectable advanced breast cancer, cryoablation is a palliation modality and may be used as complementary for subsequent resection or other therapies. | 25,083,433 | [
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Lipofilling in breast cancer surgery. | Recently, lipofilling is being performed either as a part of oncoplastic technique or alone by itself for correction of defects and asymmetry after oncologic breast cancer surgery. Its efficacy, safety and technical procedures are varying among institutions and individual surgeon's experiences. We provide a literature review and view point focus on this novel technique which emphasize on the application on breast cancer reconstruction. | 25,083,450 | [
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Siliconoma of the breasts. | Despite prohibiting of the foreign material injection for aesthetic breast augmentation in many countries. Its late complications still bring patients back for corrective and reconstructive surgery. There is no clinical management consensus or international guideline. Most of the literatures recommend surgical removal with immediate reconstruction with autologous tissue. We report a case of bilateral breast siliconoma which was treated by total mastectomy with two stage tissue expander-prosthesis reconstruction. | 25,083,456 | [
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Differential protein expressions in breast cancer between drug sensitive tissues and drug resistant tissues. | To investigate the differential expression of the sensitive and resistant relative proteins in human breast cancer tissue. A drug sensitive group and a drug resistant group for chemotherapy in patients with breast cancer were selected through neoadjuvant therapy. The differential protein expression in 2 groups was detected by proteomic techniques, and parts of differential proteins were identified by Western blotting. There were 13 differential proteins in the 2 groups, in which the expression of 3 proteins was up-regulated and 10 down-regulated. Seven proteins were identified by Western blotting. The expressions of keratin type I cytoskeletal 19 (KIC19) and thymidine phosphorylase (TYPH) were up-regulated, and the expressions of heat shock protein 27 (HSP27), keratin type I cytoskeletal 9 (KIC9), collagen alpha-2(VI) (CO6A2), vimentin (VIME), and actin cytoplasmic 1 (ACTB) were down-regulated in the drug resistant group. There were significant differences between these 2 groups (P<0.01). The expressions of KIC19 and TYPH may be correlated with drug resistance in patients with breast cancer, and HSP27, KIC9, CO6A2, VIME, and ACTB may be correlated with drug sensitivity. | 25,083,461 | [
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Efficacy of prophylactic antibiotic administration for breast cancer surgery in overweight or obese patients: research highlight. | The rate of surgical site infection (SSI) after breast surgery is higher than expected for a 'clean procedure'. There is currently no consensus on the use of antibiotics, and as a result there is variation in use. An infection may compromise cosmesis and delay the start of adjuvant therapy. This research highlight reviews a recent paper by Gulluoglu and colleagues investigating the use of antibiotics in overweight and obese patients undergoing breast cancer surgery and also reviews the current literature on this important topic. | 25,083,467 | [
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Oncoplastic breast surgery: indications, techniques and perspectives. | Breast-conservation surgery (BCS) is established as a safe option for most women with early breast cancer. Recently, advances in oncoplastic techniques have reduced surgical trauma and thus are capable of preserving the breast form and quality of life. In spite of the most BCS defects can be managed with primary closure, the aesthetic outcome may be unpredictable. Oncoplastic reconstruction may begin at the time of BCS (immediate), weeks (delayed-immediate) or months to years afterwards (delayed). With immediate reconstruction, the surgical process is smooth, since both procedures can be associated in one operative setting. Additionally, it permits wider excision of the tumor, with a superior mean volume of the specimen and potentially reducing the incidence of margin involvement. The oncoplastic techniques are related to volume displacement or replacement procedures including local flaps, latissimus dorsi myocutaneous flap and reduction mammaplasty/masthopexy. Regardless of the fact that there is no consensus concerning the best approach, the criteria are determined by the surgeon's experience and the size of the defect in relation to the size of the remaining breast. On the basis of our 15-year experience, it is possible to identify trends in types of breast defects and to develop an algorithm for immediate BCS reconstruction on the basis of the initial breast volume, the extent/location of glandular tissue ressection and the remaining available breast tissue. The main advantages of the technique utilized should include reproducibility, low interference with the oncologic treatment and long-term results. Surgical planning should include the patients's preferences, and chiefly addressing individual reconstructive requirements, enabling each patient to receive an individual "custom-made" reconstruction. | 25,083,476 | [
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Oncoplastic breast surgery in Australia and New Zealand-2014 and beyond. | Oncoplastic breast surgery (OBS) is an established field of surgery bringing together oncological and reconstructive principles to the surgical management of breast disease, which is yet to make inroads into some areas of Australia and New Zealand (A&NZ). Both patients and medical fraternity are supportive of these approaches and improved quality of life and aesthetic outcomes resulting from their application. Oncological outcomes have been shown to be no different when these oncoplastic approaches are utilised. There is a broad interest amongst breast surgeons regarding OBS and development of their own skills. However a new and improved method of training the current and the next generation of breast surgeons is required. This has already begun in some countries such as the UK, but is slower in A&NZ region. Some of the obstacles in training of OBS to the next generation of surgeons are discussed and highlighted.This year first steps in formalised training approaches are being made. The future of breast surgery is likely to involve OBS as part of mainstream surgical management of breast disease. | 25,083,499 | [
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Radiofrequency ablation and breast cancer: a review. | Radiofrequency ablation (RFA) use in breast cancer is a developing area of research. There have been a number of published studies over the last decade, which explores the feasibility of minimally invasive techniques in breast cancer treatment. In this review, we will discuss the most recent data on radiofrequency ablation and examine the current methods, outcomes, complications, and limitations of RFA in breast cancer therapy. Pub Med search for English Language articles on RFA in breast cancer. More than 25 studies were reviewed and we searched for number of tumors, average size, electrode used, if they successfully ablated the tumor, when the tumor was then resected and if the patients experienced any complication from the ablation. Radiofrequency ablation is an emerging minimally invasive therapy in small, localized breast cancer. Currently, no clinical trials have been published to directly compare RFA to the current standard of surgical resection. Ultimately, RFA will need clinical trials to evaluate oncologic outcomes involving long interval follow-up to determine survival, local control and disease progression before it becomes a reasonable alternative to surgical resection. | 25,083,506 | [
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Counting cell number in situ by quantification of dimethyl sulphide in culture headspace. | A novel, non-invasive technique is reported for determining the numbers of cells in a culture by quantifying dimethyl sulphide (DMS) in the culture headspace as produced by the cellular enzymatic reduction of dissolved dimethyl sulphoxide (DMSO). Measured DMS concentrations, as performed using selected ion flow tube mass spectrometry (SIFT-MS), in the headspace of 2D and 3D cultures of four cell lines, viz. HEK293 (kidney), MG63 (bone), hepG2 (liver) and CALU-1 (lung), linearly correlate with starting cell number. Clear differences in the rates of production of DMS by the four cell types in both the 2D and 3D situations are seen. This novel analytical technique for cell enumeration offers a significant contribution to quality assessment across cell-based research and industry, including analysis of large scale culture systems, and for routine cell biology research. | 25,083,513 | [
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Coordination polymer submicrospheres: fast microwave synthesis and their conversion under different atmospheres. | Rare earth (RE) based coordination polymer (CP) submicrospheres have been prepared from pyridine-2,5-dicarboxylic acid and RE(NO3)3 via a facile microwave heating method in 5 min, with N,N-dimethylformamide (DMF) as solvent. The submicrospheres have diameters of 100-400 nm. Furthermore, the surface of the microspheres is smooth and the microspheres are solid. Several CP submicrospheres (RE = La, Gd, Y) were selected and calcined under different atmospheres (including air, N2, and NH3). After calcination in air at 550 °C for 4 h, rare earth oxide (RE2O3) submicrospheres were obtained. On calcination under an N2 atmosphere, LaN/La2O3/C composite spheres were obtained for La-based CPs. For Gd(Y)-based CPs, Gd2O3(Y2O3)/C composite spheres were obtained. Porous carbon submicrospheres were obtained after the removal of RE2O3 and REN from the composite spheres. Interestingly, under an NH3 atmosphere, La2O2CN2 submicrospheres were produced from the La-based CPs. In addition, the Gd-based and Y-based CPs submicrospheres gave Gd2O3/GdN/C and Y2O3/C submicrospheres, respectively. As examples of their potential applications, their upconversion properties and electrochemical properties of the as-prepared products were investigated. This facile microwave synthesis method may offer an attractive approach for the preparation of other RE-CP micro-/nanostructures, and many interesting materials may be derived. | 25,083,590 | [
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Multiple chiral doublet bands of identical configuration in 103Rh. | Three sets of chiral doublet band structures have been identified in the ^{103}Rh nucleus. The properties of the observed chiral doublet bands are in good agreement with theoretical results obtained using constrained covariant density functional theory and particle rotor model calculations. Two of them belong to an identical configuration and provide the first experimental evidence for a novel type of multiple chiral doublets, where an "excited" chiral doublet of a configuration is seen together with the "yrast" one. This observation shows that the chiral geometry in nuclei can be robust against the increase of the intrinsic excitation energy. | 25,083,635 | [
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Universality of returning electron wave packet in high-order harmonic generation with midinfrared laser pulses. | We show that a returning electron wave packet in high-order harmonic generation (HHG) with midinfrared laser pulses converges to a universal limit for a laser wavelength above about 3 μm. The results are consistent among the different methods: a numerical solution of the time-dependent Schrödinger equation, the strong-field approximation, and the quantum orbits theory. We further analyze how the contribution from different electron "trajectories" survives the macroscopic propagation in the medium. Our result thus provides a new framework for investigating the wavelength scaling law for the HHG yields. | 25,083,641 | [
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Characterization of the hemocytes in Larvae of Protaetia brevitarsis seulensis: involvement of granulocyte-mediated phagocytosis. | Hemocytes are key players in the immune response against pathogens in insects. However, the hemocyte types and their functions in the white-spotted flower chafers, Protaetia brevitarsis seulensis (Kolbe), are not known. In this study, we used various microscopes, molecular probes, and flow cytometric analyses to characterize the hemocytes in P. brevitarsis seulensis. The circulating hemocytes were classified based on their size, morphology, and dye-staining properties into six types, including granulocytes, plasmatocytes, oenocytoids, spherulocytes, prohemocytes, and adipohemocytes. The percentages of circulating hemocyte types were as follows: 13% granulocytes, 20% plasmatocytes, 1% oenocytoids, 5% spherulocytes, 17% prohemocytes, and 44% adipohemocytes. Next, we identified the professional phagocytes, granulocytes, which mediate encapsulation and phagocytosis of pathogens. The granulocytes were immunologically or morphologically activated and phagocytosed potentially hazardous substances in vivo. In addition, we showed that the phagocytosis by granulocytes is associated with autophagy, and that the activation of autophagy could be an efficient way to eliminate pathogens in this system. We also observed a high accumulation of autophagic vacuoles in activated granulocytes, which altered their shape and led to autophagic cell death. Finally, the granulocytes underwent mitotic division thus maintaining their number in vivo. | 25,083,702 | [
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Spectral characteristics of phase sensitivity and discharge rate of neurons in the ascending tectofugal visual system. | Drifting gratings can modulate the activity of visual neurons at the temporal frequency of the stimulus. In order to characterize the temporal frequency modulation in the cat's ascending tectofugal visual system, we recorded the activity of single neurons in the superior colliculus, the suprageniculate nucleus, and the anterior ectosylvian cortex during visual stimulation with drifting sine-wave gratings. In response to such stimuli, neurons in each structure showed an increase in firing rate and/or oscillatory modulated firing at the temporal frequency of the stimulus (phase sensitivity). To obtain a more complete characterization of the neural responses in spatiotemporal frequency domain, we analyzed the mean firing rate and the strength of the oscillatory modulations measured by the standardized Fourier component of the response at the temporal frequency of the stimulus. We show that the spatiotemporal stimulus parameters that elicit maximal oscillations often differ from those that elicit a maximal discharge rate. Furthermore, the temporal modulation and discharge-rate spectral receptive fields often do not overlap, suggesting that the detection range for visual stimuli provided jointly by modulated and unmodulated response components is larger than the range provided by a one response component. | 25,083,715 | [
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Community outbreak of legionellosis and an environmental investigation into a community water system. | During two legionellosis outbreak investigations, one at a geriatric centre and the other in high-rise housing for seniors, it was observed that additional cases of legionellosis occurred in nearby smaller residential settings. This apparent geographical cluster of legionellosis occurred in the same general area of a community water storage tank. No potential airborne sources in or near the area could be identified, but a community water system storage tank that was centrally located among case residences spurred an investigation of water-quality factors in the identified investigation area. Conditions conducive for Legionella growth, particularly low chlorine residuals, were found. The rate of legionellosis among residents aged ⩾50 years in the investigation areas (61·0 and 64·1/100 000) was eight times higher than in the rest of the service area (9·0/100 000) and almost 20 times higher than the statewide annual average incidence rate (3·2/100 000). A water mains flushing programme in the area was launched by the water utility, and water samples taken before and during flushing found L. pneumophila. | 25,083,716 | [
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Developing a mouse model of chronic ankle instability. | Ankle sprains are the most common orthopedic pathology experienced during sport and physical activity and often result in chronic ankle instability (CAI). Understanding how to prevent CAI is difficult because of the costs and logistics associated with clinical trials aimed at preventing the heterogeneous symptoms associated with CAI. Thus, a need exists to develop an animal model that presents similar long-term consequences as CAI to assess preclinical data. Thus, the purpose was to determine whether surgically transecting the lateral ligaments of a mouse hind limb results in the development of CAI-like symptoms 12 months after injury. Thirty male mice (CBA/J) were randomly placed into a SHAM (control), CFL (calcaneofibular ligament; mild ankle sprain), or ATFL/CFL (anterior talofibular ligament/CFL; severe) ankle sprain group and housed individually. Three days after surgically transecting the respective lateral ligaments, mice were given a solid surface running wheel and daily running wheel measurements were recorded. Outcome measures of balance and gait were obtained before and at 4, 48, 54, and 60 wk after injury. The ATFL/CFL group had significantly more hind foot slips than the CFL and SHAM groups (P < 0.05). The CFL also had more hind foot slips relative to the SHAM group (P < 0.05). The ATFL/CFL group was significantly less physically active relative to the SHAM and CFL groups (P < 0.05). A cut score of 4.75 foot slips had a sensitivity of 0.68 and specificity of 1.00 and indicates that 70% (14/20) of mice with an ankle sprain had developed CAI. The results of this study indicate that an acute ankle sprain in mice can result in the development of CAI-like symptoms 12 months after injury. | 25,083,728 | [
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An analysis of patient presentations at a 2-day mass-participation cycling event: the Ride to Conquer Cancer Case Series, 2010-2012. | To analyze the unique factors involved in providing medical support for a long-distance, cross-border, cycling event, and to describe patient presentations and event characteristics for the British Columbia (BC) Ride to Conquer Cancer from 2010 through 2012. This study was a 3-year, descriptive case series report. Medical encounters were documented, prospectively, from 2010-2012 using an online registry. Data for event-related variables also were reported. Providing medical support for participants during the 2-day ride was complicated by communication challenges, weather conditions, and cross-border issues. The total number of participants for the ride increased from 2,252 in 2010 to 2,879 in 2011, and 3,011 in 2012. Patient presentation rates (PPRs) of 125.66, 155.26, and 198.93 (per 1,000 participants) were documented from 2010 through 2012. Over the course of three years, and not included in the PPR, an additional 3,840 encounters for "self-treatment" were documented. The Ride to Conquer Cancer Series has shown that medical coverage at multi-day, cross-national cycling events must be planned carefully to face a unique set of circumstances, including legislative issues, long-distance communication capabilities, and highly mobile participants. This combination of factors leads to potentially higher PPRs than have been reported for noncycling events. This study also illuminates the additional workload "self-treatment" visits place on the medical team. | 25,083,761 | [
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Urinary sodium excretion and dietary sources of sodium intake in Chinese postmenopausal women with prehypertension. | Reducing salt intake in communities is one of the most effective and affordable public health strategies to prevent hypertension, stroke and renal disease. The present study aimed to determine the sodium intake in Hong Kong Chinese postmenopausal women and identify the major food sources contributing to sodium intake and urine excretion. This was a cross-sectional study among 655 Chinese postmenopausal women with prehypertension who were screened for a randomized controlled trial. Data collection included 24 h urine collection for the measurement of sodium, potassium and creatinine, 3-day dietary records, anthropometric measures and questionnaire survey on demographic data and dietary habits. The average salt intake estimated from urinary excretion was 7.8 ± 3.2 g/d with 82.1% women above WHO recommendation of 5 g/day. Food groups as soup (21.6%), rice and noodles (13.5%), baked cereals (12.3%), salted/preserved foods (10.8%), Chinese dim sum (10.2%) and sea foods (10.1%) were the major contributors of non-discretionary salt. Discretionary salt use in cooking made a modest contribution to overall intake. Vegetable and fruit intake, age, sodium intake from salted foods, sea foods and soup were the independent determinants of urinary sodium excretion. Our data revealed a significant room for reduction of the sodium intake. Efforts to reduce sodium from diets in Hong Kong Chinese postmenopausal women should focus on both processed foods and discretionary salt during cooking. Sodium reduction in soup and increase in fruit intake would be potentially effective strategy for reducing sodium. | 25,083,775 | [
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Assessment of anterior chamber parameters after cataract surgery by Galilei dual Scheimpflug analyzer. | To quantify the difference between anterior chamber parameters determined by the Galilei dual Scheimpflug analyzer after uneventful cataract surgery in normotensive eyes. In this study, 39 eyes of 30 patients (11 men and 19 women) who had uneventful cataract surgery with phacoemulsification were evaluated preoperatively, and at 1 month postoperatively with the Galilei. We investigated the measurements including anterior chamber depth (ACD), anterior chamber angle (ACA), anterior chamber volume (ACV), central corneal thickness (CCT), and the 3-, 5-, and 7-mm corneal thickness (CT) preoperatively and postoperatively. The differences between ACD (P=0.01), ACA (P=0.07), ACV (P=0.01), and 7-mm CT (P=0.01), and intraocular pressure (P=0.03) were statistically significant after the first month of phacoemulsification. However, the differences between CCT (P=0.60), 3-mm CT (P=0.75), and 5-mm (P=0.17) CT were not statistically significant. After the first month of cataract surgery, a significant increase was observed in ACD, ACV, ACA, and 7-mm CT parameters, which were practically determined by a new noncontact Scheimpflug imagining system. | 25,083,777 | [
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Topical cyclosporine a 1% for the treatment of chronic ocular surface inflammation. | To evaluate the use of topical cyclosporine A (CsA) 1% emulsion in the treatment of chronic ocular surface inflammation (OSI). We conducted a retrospective chart review of patients with various forms of OSI treated with topical CsA 1% from 2001 to 2012. Twenty-nine patients (52 eyes) with various forms of OSI, including epidemic keratoconjunctivitis (n=14), chronic follicular conjunctivitis (n=12), Thygeson superficial punctate keratopathy (n=2), and vernal keratoconjunctivitis (n=1), were included. Twenty-seven patients had inflammation refractory to prior therapies. Twenty-four patients received concurrent medications with CsA 1%. Twenty-three of 24 patients on concurrent corticosteroids (CS) were able to taper their use while receiving CsA 1%. Thirteen patients experienced ocular discomfort with CsA 1%; one patient discontinued therapy all together as a result of these side effects; another switched to CsA 0.5% with improvement of adverse symptoms. Inflammation was controlled in 22 (92%) of the 24 patients who received CsA 1% for at least 2 months in duration. Topical CsA 1% helps to control inflammation and spares CS use in patients with chronic OSI. | 25,083,780 | [
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HLA-C -35kb expression SNP is associated with differential control of β-HPV infection in squamous cell carcinoma cases and controls. | A single nucleotide polymorphism (SNP) 35 kb upstream of the HLA-C gene is associated with HLA-C expression, and the high expressing genotype (CC) has been associated with HIV-I control. HLA-C is unique among the classical MHC class I molecules for its role in the control of viral infections and recognition of abnormal or missing self. This immunosurveillance is central to the pathogenesis of non-melanoma skin cancer (NMSC), and of squamous cell carcinoma (SCC) in particular. While sun exposure is a major risk factor for these cancers, cutaneous infections with genus β-HPV have been implicated in the development of SCC. We hypothesized that the high expression HLA-C genotype is associated with β-HPV infections. Therefore, we investigated the association between β-HPV serology and the -35 kb SNP (rs9264942) in a population-based case-control study of 510 SCC cases and 608 controls. Among controls, the high expression -35 kb SNP genotype (CC) reduced the likelihood of positive serology for multiple (≥2) β-HPV infections (OR = 0.49, 95% CI: 0.25-0.97), and β-HPV species 2 infection (OR = 0.43, 95% CI: 0.23-0.79). However, no association with β-HPV status was observed among SCC cases. Our findings suggest that underlying immunogenotype plays an important role in differential control of β-HPV in SCC cases and controls. | 25,083,782 | [
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Greenhouse gas emissions from production chain of a cigarette manufacturing industry in Pakistan. | This study quantified greenhouse gas (GHG) emissions from the Pakistan Tobacco Company (PTC) production using a life cycle approach. The PTC production chain comprises of two phases: agricultural activities (Phase I) and industrial activities (Phase II). Data related to agricultural and industrial activities of PTC production chain were collected through questionnaire survey from tobacco growers and records from PTC manufacturing units. The results showed that total GHG emissions from PTC production chain were 44,965, 42,875, and 43,839 tCO2e respectively in 2009, 2010, and 2011. Among the agricultural activities, firewood burning for tobacco curing accounted for about 3117, 3565, and 3264 tCO2e, fertilizer application accounted for 754, 3251, and 4761 tCO2e in 2009, 2010, and 2011, respectively. Among the industrial activities, fossil fuels consumption in stationary sources accounted for 15,582, 12,733, and 13,203 tCO2e, fossil fuels used in mobile sources contributed to 2693, 3038, and 3260 tCO2e, and purchased electricity consumed resulted in 15,177, 13,556, and 11,380 tCO2e in 2009, 2010, and 2011, respectively. The GHG emissions related to the transportation of raw materials and processed tobacco amounted to 6800, 6301, and 7317 respectively in 2009, 2010, and 2011. GHG emissions from energy use in the industrial activities constituted the largest emissions (i.e., over 80%) of GHG emissions as PTC relies on fossil fuels and fossil fuel based electrical power in industrial processes. The total emissions of carbon footprint (CFP) from PTC production were 0.647 tCO2e per million cigarettes produced in 2009, 0.675 tCO2e per million cigarettes in 2010 and 0.59 tCO2e per million cigarettes in 2011. Potential strategies for GHG emissions reductions for PTC production chain include energy efficiency, reducing reliance on fossil fuels in non-mobile sources, adoption of renewable fuels including solar energy, energy from crop residues, and promotion of organic fertilizers. | 25,083,801 | [
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Lineage selection and plasticity in the intestinal crypt. | We know more about the repertoire of cellular behaviours that define the stem and progenitor cells maintaining the intestinal epithelium than any other renewing tissue. Highly dynamic and stochastic processes define cell renewal. Historically the commitment step in differentiation is viewed as a ratchet, irreversibly promoting a given fate and corresponding to a programme imposed at the point of cell division. However, the emerging view of intestinal self-renewal is one of plasticity in which a stem cell state is easily reacquired. The pathway mediators of lineage selection are largely known but how they interface within highly dynamic populations to promote different lineages and yet permit plasticity is not. Advances in understanding gene regulation in the nervous system suggest possible mechanisms. | 25,083,805 | [
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Novel insights into the metabolic and biochemical underpinnings assisting dry-season survival in female malaria mosquitoes of the Anopheles gambiae complex. | The mechanisms by which Anopheles gambiae mosquitoes survive the desiccating conditions of the dry season in Africa and are able to readily transmit malaria soon after the rains start remain largely unknown. The desiccation tolerance and resistance of female An. gambiae M and S reared in contrasting environmental conditions reflecting the onset of dry season ("ods") and the rainy season ("rs") was determined by monitoring their survival and body water loss in response to low relative humidity. Furthermore, we investigated the degree to which the physiology of 1-h and 24-h-old females is altered at "ods" by examining and comparing their quantitative metabotypes and proteotypes with conspecifics exposed to "rs" conditions. Results showed that distinct biochemical rearrangements occurred soon after emergence in female mosquitoes that enhance survival and limit water loss under dry conditions. In particular, three amino acids (phenylalanine, tyrosine, and valine) playing a pivotal role in cuticle permeability decreased significantly from the 1-h to 24-h-old females, regardless of the experimental conditions. However, these amino acids were present in higher amounts in 1-h-old female An. gambiae M reared under "ods" whereas no such seasonal difference was reported in S ones. Together with the 1.28- to 2.84-fold increased expression of cuticular proteins 70 and 117, our data suggests that cuticle composition, rigidity and permeability were adjusted at "ods". Increased expression of enzymes involved in glycogenolytic and proteolytic processes were found in both forms at "ods". Moreover, 1-h-old S forms were characterised by elevated amounts of glycogen phosphorylase, isocitrate dehydrogenase, and citrate synthase, suggesting an increase of energetic demand in these females at "ods". | 25,083,809 | [
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Molecular neurobiology of addiction: what's all the (Δ)FosB about? | The transcription factor ΔFosB is upregulated in numerous brain regions following repeated drug exposure. This induction is likely to, at least in part, be responsible for the mechanisms underlying addiction, a disorder in which the regulation of gene expression is thought to be essential. In this review, we describe and discuss the proposed role of ΔFosB as well as the implications of recent findings. The expression of ΔFosB displays variability dependent on the administered substance, showing region-specificity for different drug stimuli. This transcription factor is understood to act via interaction with Jun family proteins and the formation of activator protein-1 (AP-1) complexes. Once AP-1 complexes are formed, a multitude of molecular pathways are initiated, causing genetic, molecular and structural alterations. Many of these molecular changes identified are now directly linked to the physiological and behavioral changes observed following chronic drug exposure. In addition, ΔFosB induction is being considered as a biomarker for the evaluation of potential therapeutic interventions for addiction. | 25,083,822 | [
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Sympathectomy versus Sympathicotomy in Palmar Hyperhidrosis Comparing T3 Ablation. | The objective of this study was to evaluate and compare thoracoscopic sympathectomy and sympathicotomy at the third ganglia (T3) level for the treatment of primary palmar hyperhidrosis in terms of initial surgery results, complications, and patient satisfaction. Two groups of patient underwent T3 thoracoscopic sympathectomy and thoracoscopic sympathicotomy under general anesthesia using single-lung ventilation via a double-lumen endotracheal tube by the same surgical team for the treatment of severe primary palmar hyperhidrosis or a combination of levels for multiarea between 2008 and 2013. The groups were homogeneous for relevant demographic, physiological, and clinical data. All patients were examined preoperatively and were followed up at 6 months postoperatively. In both groups, patient's satisfaction was evaluated 6 months after surgery by a detailed interview and scored into three grades (1 = very satisfied, 2 = satisfied, and 3 = dissatisfied). No operative mortality, major intraoperative complication, infections, and Horner syndrome were recorded. There was no treatment failure. The average time of operation was 50 minutes for Group A (sympathectomy) and 36 minutes for Group B (sympathicotomy). Compensatory sweating occurred in 40 patients (89% for Group A and 85.11% for Group B) with a different accumulation of the severity degree. The satisfaction rate was 91.11% for Group A and 93.61% for Group B. There was no significant difference between thoracoscopic sympathectomy and sympathicotomy at the third ganglia (T3) level for the treatment of primary palmar hyperhidrosis in terms of initial surgery results, complications, and patient satisfaction. Neither surgical technique is better than the other one for palmar hyperhidrosis treatment. Development of severe compensatory sweating and postoperative pain are major determinant factors of patient dissatisfaction. Sympathicotomy should be preferred for palmar hyperhidrosis treatment, as it is much technically shorter, simpler to implement, and also easier to learn. | 25,083,833 | [
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Binocular vision of bilaterally pseudophakic eyes with induced astigmatism. | Induced myopic astigmatism improves the monocular near logMAR (logarithm of the minimal angle of resolution) acuity of pseudophakes with monofocal intraocular lens implants but with a small loss in distance acuity. The impact of induced astigmatism on binocular vision of pseudophakes remains unknown. This study determined the impact of bilaterally induced astigmatism on binocular distance and near logMAR and stereoacuity of bilateral pseudophakes with monofocal intraocular lens implants. Distance (3 m) and near (40 cm) logMAR acuity and near (40 cm) stereoacuity were measured in 15 bilateral pseudophakes with 10 different combinations of induced astigmatism. Combinations were chosen such that one eye had no astigmatism or 1 diopter (D) myopic astigmatism at 90 degrees axis or 1 D hyperopic astigmatism at 90 degrees axis. The fellow eye had the same error or that with orthogonal axis (180 degrees) or different magnitude (2.5 D) or opposite polarity. Distance logMAR acuity deteriorated by up to 0.2 logMAR units from median best-corrected values (-0.06 logMAR) only for bilaterally induced (p < 0.01) but not for unilaterally induced (p > 0.9) astigmatism. Near logMAR acuity and stereoacuity improved by up to 0.25 logMAR units and 130 arc sec from their respective median uncorrected values (0.65 logMAR and 225.8 arc sec) for induced myopic astigmatism (p < 0.001). Near acuity was similar or worse than uncorrected values for induced hyperopic astigmatism (p ≥ 0.003). Stereoacuity was better with parallel than with orthogonal axes of induced myopic astigmatism in the two eyes (p = 0.001). LogMAR acuity did not change with axis of astigmatism in the two eyes (p > 0.6). Distance and near logMAR acuity and stereoacuity of bilateral pseudophakes vary with the combination of astigmatism induced before two eyes. Combinations with myopic astigmatism partly benefit binocular near vision, albeit with a loss of distance vision. Near stereoacuity is better with parallel than with orthogonal axes of myopic astigmatism in the two eyes. Visual performance is equal to or worse than uncorrected condition for hyperopic astigmatism. | 25,083,837 | [
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Pelvic autonomic neuromonitoring: present reality, future prospects. | Currently, the means to assess the autonomic nervous system primarily depend on end organ functional measurement: intravesical pressure, skin resistance, and penile strain gauge tension, for example. None of these measures has been generally accepted in the operating room. Nevertheless, the segmental and peripheral pelvic autonomic nerve supply is placed at risk during both pelvic and lower spine surgery. In this difficult era of suboptimal post-prostatectomy outcomes, the urological literature does reveal the salutary development of safer dissection techniques about the peri-prostatic and cavernous plexus. Means of reliably specific nerve identification remain elusive. The need for actual nerve monitoring (not just identification) has only recently been proposed. Data from the animal lab reinforce an appreciation of the intimate and elegant interconnectedness of autonomic and somatic structures, particularly at the segmental level. Also, the biochemistry of erectile tissue engorgement (in both sexes) is very well understood (the electrophysiology increasingly so). Understanding these principles should permit parallel investigation and implementation of neurophysiological techniques which both identify and monitor pelvic autonomic function. The predicates for these proposed new approaches in the operating room are discussed in this review. | 25,083,841 | [
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Examination of motor unit control properties of the vastus lateralis in an individual that had acute paralytic poliomyelitis. | The purpose of the study was to examine motor unit (MU) recruitment and derecruitment thresholds and firing rates of the vastus lateralis between 2 healthy (HE) individuals (women, ages = 19 and 23 years) and 1 individual (man, age = 22 years) who acquired acute poliomyelitis (PO). Each participant performed submaximal isometric trapezoid muscle actions of the leg extensors from 20% to 90% maximal voluntary contraction in 10% increments with a sensor placed on the vastus lateralis to record electromyography. Electromyographic signals were decomposed into the firing events of single MUs. Linear regressions were performed on the firing rates at recruitment and peak firing rates versus the recruitment thresholds and the derecruitment versus recruitment thresholds. In addition, data were pooled together from all contractions to examine differences between PO and HE with independent samples t-tests calculated for firing rates at recruitment, peak firing rates, recruitment thresholds, derecruitment thresholds, and duration of MU activity. The results demonstrated systematic differences in MU control strategies between the PO and HE. There were differences in the recruitment thresholds (P < 0.001; HE = 30.5% ± 22.2% maximal voluntary contraction; PO = 14.5% ± 5.0% maximal voluntary contraction), firing rates at recruitment (P < 0.001; HE = 7.4 ± 2.5 pulses per second; PO = 6.2 ± 1.7 pulses per second) and peak firing rates across the force spectrum (P = 0.001; HE = 22.2 ± 5.8 pulses per second; PO = 20.3 ± 2.3 pulses per second), altered derecruitment versus recruitment relationships (HE slope = 0.82 derec/rec, PO slope = 1.78 derec/rec), and duration of MU activity (P < 0.001) between the PO (18.6 ± 2.4 seconds) and HE (15.3 ± 3.0 seconds). Future research should examine the possible differences in MU behavior between PO and HE as a result of fatigue to further elucidate disease-related changes in MU properties. | 25,083,857 | [
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Detection of rare antigen-presenting cells through T cell-intrinsic meandering motility, mediated by Myo1g. | To mount an immune response, T lymphocytes must successfully search for foreign material bound to the surface of antigen-presenting cells. How T cells optimize their chances of encountering and responding to these antigens is unknown. T cell motility in tissues resembles a random or Levy walk and is regulated in part by external factors including chemokines and lymph-node topology, but motility parameters such as speed and propensity to turn may also be cell intrinsic. Here we found that the unconventional myosin 1g (Myo1g) motor generates membrane tension, enforces cell-intrinsic meandering search, and enhances T-DC interactions during lymph-node surveillance. Increased turning and meandering motility, as opposed to ballistic motility, is enhanced by Myo1g. Myo1g acts as a "turning motor" and generates a form of cellular "flânerie." Modeling and antigen challenges show that these intrinsically programmed elements of motility search are critical for the detection of rare cognate antigen-presenting cells. | 25,083,865 | [
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H3K4me3 breadth is linked to cell identity and transcriptional consistency. | Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly over genes in a given cell type preferentially mark genes that are essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells. Machine learning models reveal that the broadest H3K4me3 domains represent a distinct entity, characterized by increased marks of elongation. The broadest H3K4me3 domains also have more paused polymerase at their promoters, suggesting a unique transcriptional output. Indeed, genes marked by the broadest H3K4me3 domains exhibit enhanced transcriptional consistency and [corrected] increased transcriptional levels, and perturbation of H3K4me3 breadth leads to changes in transcriptional consistency. Thus, H3K4me3 breadth contains information that could ensure transcriptional precision at key cell identity/function genes. | 25,083,876 | [
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Endometriosis is associated with rare copy number variants. | Endometriosis is a complex gynecological condition that affects 6-10% of women in their reproductive years and is defined by the presence of endometrial glands and stroma outside the uterus. Twin, family, and genome-wide association (GWA) studies have confirmed a genetic role, yet only a small part of the genetic risk can be explained by SNP variation. Copy number variants (CNVs) account for a greater portion of human genetic variation than SNPs and include more recent mutations of large effect. CNVs, likely to be prominent in conditions with decreased reproductive fitness, have not previously been examined as a genetic contributor to endometriosis. Here we employ a high-density genotyping microarray in a genome-wide survey of CNVs in a case-control population that includes 2,126 surgically confirmed endometriosis cases and 17,974 population controls of European ancestry. We apply stringent quality filters to reduce the false positive rate common to many CNV-detection algorithms from 77.7% to 7.3% without noticeable reduction in the true positive rate. We detected no differences in the CNV landscape between cases and controls on the global level which showed an average of 1.92 CNVs per individual with an average size of 142.3 kb. On the local level we identify 22 CNV-regions at the nominal significance threshold (P<0.05), which is greater than the 8.15 CNV-regions expected based on permutation analysis (P<0.001). Three CNV's passed a genome-wide P-value threshold of 9.3 × 10(-4); a deletion at SGCZ on 8p22 (P = 7.3 × 10(-4), OR = 8.5, Cl = 2.3-31.7), a deletion in MALRD1 on 10p12.31 (P = 5.6 × 10(-4), OR = 14.1, Cl = 2.7-90.9), and a deletion at 11q14.1 (P = 5.7 × 10(-4), OR = 33.8, Cl = 3.3-1651). Two SNPs within the 22 CNVRs show significant genotypic association with endometriosis after adjusting for multiple testing; rs758316 in DPP6 on 7q36.2 (P = 0.0045) and rs4837864 in ASTN2 on 9q33.1 (P = 0.0002). Together, the CNV-loci are detected in 6.9% of affected women compared to 2.1% in the general population. | 25,083,881 | [
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Global women's health--a global perspective. | The burden of disease and public health issues affecting girls and women throughout their lives is significantly greater in resource-poor settings. These women and girls suffer from high rates of maternal mortality, obstetric fistulas, female genital cutting, HIV/AIDS, malaria in pregnancy, and cervical cancer. Although the Millennium Development Goals (MDGs) are being met in some nations, the majority of the goals will not be reached by 2015. In addition, insufficient attention is given to non-communicable and chronic diseases such as diabetes, hypertension, hypercholesterolemia, cardiovascular diseases, stroke, obesity, and chronic respiratory diseases. A life-course approach that includes improvements in earlier-life factors such as diet and exercise is necessary to improve women's long-term health outcomes. Innovative diagnostic tools and treatment strategies along with cost-effective health service delivery systems are needed to make a significant impact on women's and girls' health worldwide. | 25,083,886 | [
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The regulation and assessment of follicular growth. | Folliculogenesis is the process by which waves of small primordial follicles possessing immature oocytes are recruited to undergo development into large antral follicles, with one then being selected for ovulation of a fully competent oocyte. Folliculogenesis can be divided into three stages: follicle recruitment, selection and ovulation, and has two phases: the initial gonadotrophin-independent phase and the later gonadotrophin-dependent phase. It involves an elaborate array of biochemical signalling factors, both stimulatory and inhibitory, and the regulation of follicle growth relies on these being tightly controlled. Their increasing understanding allows reproductive biologists to attempt manipulation of folliculogenesis, which can be useful in clinical areas such as assisted reproduction and contraception. The rising average age of childbearing in many developed countries is bringing an additional focus on the importance of assessing a woman's non-growing follicular pool; i.e. her ovarian reserve. This review examines the important regulatory players in the different stages of folliculogenesis and describes some of the currently available measures of ovarian reserve. | 25,083,887 | [
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Diagnosis of gestational diabetes. | Abstract Previous approaches to diagnosing gestational diabetes mellitus (GDM) have included 50 g, 75 g and 100 g glucose challenges, lasting 1-3 hours, with 1 or 2 elevations required. Thresholds were validated by their predictive value for subsequent diabetes, or were the same thresholds used in non-pregnant individuals. None were based on their prediction of adverse pregnancy outcomes. Diagnostic paradigms vary throughout the world, making comparisons impossible and severely limiting communication among investigators. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study collected outcome data on > 23,000 pregnancies recruited prospectively in nine countries after a blinded 75 g, 2-hour oral glucose tolerance test (OGTT) at 24-28 weeks gestation. Primary outcomes (LGA, PCS, neonatal hypoglycemia, high cord C-peptide), and most secondary outcomes (e.g. preeclampsia, preterm birth, shoulder dystocia and birth injury), were significantly, directly and continuously related to each of the three plasma glucose measurements. The International Association of Diabetes in Pregnancy Study Groups (IADPSG) developed recommendations for the use of a 75 g, 2-h OGTT, ≥ 1 elevation diagnosing GDM, with thresholds: fasting plasma glucose ≥ 5.1 mmol/L (92 mg/dL) , 1 h ≥ 10 mmol/L (180 mg/dL) and 2 h ≥ 8.5 mmol/L (153 mg/dL). These have generated wide discussion and are currently being considered throughout the world. They are pregnancy outcome-based; the 75 g glucose load will bring consistency to GTTs; universal adoption will lead to consistency of diagnostic criteria worldwide; studies of treatment at similarly mild levels of glycemia have demonstrated improvement in outcomes; use of a single abnormal value will obviate the confusion arising when one elevated value is encountered. The primary argument against the recommendations is that prevalence of GDM will rise to 16-18 %, increasing health care costs. Balanced against this is the world-wide epidemic of obesity, prediabetes and diabetes. | 25,083,890 | [
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Xanthomonas axonopodis virulence is promoted by a transcription activator-like effector-mediated induction of a SWEET sugar transporter in cassava. | The gene-for-gene concept has historically been applied to describe a specific resistance interaction wherein single genes from the host and the pathogen dictate the outcome. These interactions have been observed across the plant kingdom and all known plant microbial pathogens. In recent years, this concept has been extended to susceptibility phenotypes in the context of transcription activator-like (TAL) effectors that target SWEET sugar transporters. However, because this interaction has only been observed in rice, it was not clear whether the gene-for-gene susceptibility was unique to that system. Here, we show, through a combined systematic analysis of the TAL effector complement of Xanthomonas axonopodis pv. manihotis and RNA sequencing to identify targets in cassava, that TAL20Xam668 specifically induces the sugar transporter MeSWEET10a to promote virulence. Designer TAL effectors (dTALE) complement TAL20Xam668 mutant phenotypes, demonstrating that MeSWEET10a is a susceptibility gene in cassava. Sucrose uptake-deficient X. axonopodis pv. manihotis bacteria do not lose virulence, indicating that sucrose may be cleaved extracellularly and taken up as hexoses into X. axonopodis pv. manihotis. Together, our data suggest that pathogen hijacking of plant nutrients is not unique to rice blight but also plays a role in bacterial blight of the dicot cassava. | 25,083,909 | [
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Division of labour and terminal differentiation in a novel Bacillus thuringiensis strain. | A major challenge in bacterial developmental biology has been to understand the mechanisms underlying cell fate decisions. Some differentiated cell types display cooperative behaviour. Cooperation is one of the greatest mysteries of evolutionary biology and microbes have been considered as an excellent system for experimentally testing evolution theories. Bacillus thuringiensis (Bt) is a spore-forming bacterium, which is genetically closely related to B. anthracis, the agent of anthrax, and to B. cereus, an opportunistic human pathogen. The defining feature that distinguishes Bt from its relatives is its ability to produce crystal inclusions in the sporulating cells. These toxins are solubilized after ingestion and are cooperative public goods in insect hosts. In this study, we describe a Bt strain LM1212 that presents the unique ability to terminally differentiate into crystal producers and spore formers. Transcriptional analysis based on lacZ and gfp reporter genes suggested that this phenotype is the consequence of a new type of cell differentiation associated with a novel regulation mode of cry gene expression. The differentiating crystal-producer phenotype has higher spore productivity than a typical Bt strain and is better able to compete with Cry toxin null 'cheaters'. Potentially, this division of labour provides additional fitness benefits in terms of spore viability or durability of Cry toxin. | 25,083,932 | [
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False-negative chest radiographs in emergency department diagnosis of pneumonia. | Emergency department (ED) patients frequently undergo chest x-ray (CXR) to evaluate for pneumonia. The rate of false-negative CXR in patients with pneumonia is unclear. Identify patients admitted with pneumonia who were diagnosed by CT despite nondiagnostic CXR. Retrospective analysis of quality improvement data on adult ED patients admitted with pneumonia over 21 months. Primary outcome was percent of patients diagnosed by CT despite normal CXR. Patients were classified as CXR-diagnosed if they had CXR and no CT, or if antibiotics were ordered after CXR and before CT. CT-based diagnosis was indicated by administration of antibiotics only after CT was completed. 49 patients (11.4%) were diagnosed by CT (p<0.001). These patients were younger (p<0.001) and more often complained of chest pain (p<0.001). Patients with pneumonia may present with normal or nondiagnostic CXR, although false negatives may be less common than previously reported. | 25,083,953 | [
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Evaluation of the fallopian tubes after neoadjuvant chemotherapy: persistence of serous tubal intraepithelial carcinoma. | The origin of pelvic serous carcinoma continues to be controversial. Recent studies of patients undergoing primary surgery for ovarian, primary peritoneal, and uterine serous carcinomas have indicated the value of complete fimbrial sampling for detecting occult serous tubal intraepithelial carcinoma (STIC). Evidence suggests that a significant proportion of pelvic serous carcinomas may arise from in situ lesions on the distal fallopian tube. In this study, 14 consecutive cases of interval debulking surgery after neoadjuvant chemotherapy were reviewed, using both hematoxylin and eosin staining and, as needed, immunohistochemistry for p53 and MIB-1. The degree of fimbrial sampling was evaluated, and cases were examined for tumor involvement in the endosalpinx and the presence of STIC. Tumor treatment response was classified using a semiquantitative 4-tier scale. The results indicate that STIC can persist despite chemotherapy and can be readily identified during microscopic examination. These results are expected to improve the quality of the pathology evaluation by providing data-driven recommendations for sampling in interval surgery cases and showing the value of a systematic approach to evaluating the fallopian tube (sectioning and extensively examining the fimbria protocol). These results demonstrate that a tubal primary can still be assigned in these situations. Finally, this study raises interesting biologic questions about the sensitivity of cells originating from serous cancer tumor to chemotherapy. The presence or absence of STIC in specimens from interval surgery after neoadjuvant treatment has not previously, to our knowledge, been addressed. | 25,083,961 | [
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Lung-targeted RNA interference against angiopoietin-2 ameliorates multiple organ dysfunction and death in sepsis. | Angiopoietin-2, a protein secreted by stimulated endothelium and an antagonist of the endothelium-stabilizing receptor Tie2, contributes to the pathophysiology of septic multiple organ dysfunction. We tested the therapeutic potential of a pulmonary-endothelium-specific RNA interference-based angiopoietin-2 targeting strategy in sepsis. Laboratory and animal research. Research laboratories of the Medical School Hannover, Department of Nephrology and Hypertension, Hannover and Silence Therapeutics GmbH, Berlin. C57Bl/6 mice. Lung-endothelium-specific angiopoietin-2 small interfering RNA was administered both before and after sepsis induction (cecal ligation and puncture or lipopolysaccharides) intravenously. Angiopoietin-2 small interfering RNA was highly specific and reduced angiopoietin-2 expression in the septic murine lungs up to 73.8% (p = 0.01) and enhanced the phosphorylation of Tie2 both in control and septic animals. Angiopoietin-2 small interfering RNA reduced pulmonary interleukin-6 transcription, intercellular adhesion molecule expression, neutrophil infiltration, and vascular leakage. Manifestations of sepsis were also attenuated in distant organs, including the kidney, where renal function was improved without affecting local angiopoietin-2 production. Finally, angiopoietin-2 small interfering RNA ameliorated the severity of illness and improved survival in cecal ligation and puncture, both as a pretreatment and as a rescue intervention. The Tie2 antagonist angiopoietin-2 represents a promising target against sepsis-associated multiple organ dysfunction. A novel RNA interference therapeutic approach targeting gene expression in the pulmonary endothelium could be a clinically relevant pharmacological strategy to reduce injurious angiopoietin-2 synthesis. | 25,083,983 | [
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Sexually dimorphic RB inactivation underlies mesenchymal glioblastoma prevalence in males. | The prevalence of brain tumors in males is common but unexplained. While sex differences in disease are typically mediated through acute sex hormone actions, sex-specific differences in brain tumor rates are comparable at all ages, suggesting that factors other than sex hormones underlie this discrepancy. We found that mesenchymal glioblastoma (Mes-GBM) affects more males as the result of cell-intrinsic sexual dimorphism in astrocyte transformation. We used astrocytes from neurofibromin-deficient (Nf1(-/-)) mice expressing a dominant-negative form of the tumor suppressor p53 (DNp53) and treated them with EGF as a Mes-GBM model. Male Mes-GBM astrocytes exhibited greater growth and colony formation compared with female Mes-GBM astrocytes. Moreover, male Mes-GBM astrocytes underwent greater tumorigenesis in vivo, regardless of recipient mouse sex. Male Mes-GBM astrocytes exhibited greater inactivation of the tumor suppressor RB, higher proliferation rates, and greater induction of a clonogenic, stem-like cell population compared with female Mes-GBM astrocytes. Furthermore, complete inactivation of RB and p53 in Mes-GBM astrocytes resulted in equivalent male and female tumorigenic transformation, indicating that intrinsic differences in RB activation are responsible for the predominance of tumorigenic transformation in male astrocytes. Together, these results indicate that cell-intrinsic sex differences in RB regulation and stem-like cell function may underlie the predominance of GBM in males. | 25,083,989 | [
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DEAD-box helicase DP103 defines metastatic potential of human breast cancers. | Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment. | 25,083,991 | [
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Evaluation of complications and feasibility of indwelling epidural catheter use for post-operative pain control in dogs in the home environment. | The objective of this study was to describe the use of indwelling epidural catheters post-operatively in dogs in a home environment, and to report associated complications. Dogs undergoing surgical procedures of the hind limb (n=83) were included in the study and were administered 0.05 or 0.10 mg/kg epidural morphine via an indwelling epidural catheter every 6 hours. Data compiled relating to catheter placement included time of placement, ease of placement and problems encountered, number of attempts of placement, and individual placing the catheter. A client questionnaire was provided to evaluate side effects, complications, pain, and ease of use of the epidural catheter system after discharge from the hospital and catheter removal at home. Side effects were compared between the dogs receiving 0.05 or 0.1 mg/kg epidural morphine. The most common patient complication was abnormal urination patterns (32/82, 39%); specifically dribbling urine where laying, emptying the entire bladder where laying, not urinating for extended periods of time, and taking a longer time to pass urine were reported. There were no significant differences in the number or types of side effects reported in either dosing group. The most common technical issues reported by owners were difficulty getting the needle into the injection port (10/81, 12%) and removing the adhesive covering keeping the epidural catheter system in place (19/78, 24%). There were no reports of inflammation or discharge at the catheter site in any of the dogs. Of the respondents surveyed, 76/79 (97%) found the epidural catheter system easy to use at home in the post-operative period. Indwelling epidural catheters are a feasible method of administration of post-operative analgesia in the immediate post-operative period in the home environment and were associated with only a few minor complications in this population. | 25,084,014 | [
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Drug delivery to paranasal sinuses using pulsating aerosols. | Chronic rhinosinusitis (CRS) is the major disorder of the upper airways, affecting about 10-15% of the total population. Topical treatment regimens show only modest efficacy, because drug delivery to the posterior nose and paranasal sinuses is still a challenge. Therefore, there is a high rate of functional endoscopic sinus surgery in CRS patients. Most nasally administered aerosolized drugs, like nasal pump sprays, are efficiently filtered by the nasal valve and do not reach the posterior nasal cavity and the sinuses, which are poorly ventilated. However, as highlighted in this review, sinus ventilation and paranasal aerosol delivery can be achieved by using pulsating airflow, offering new topical treatment options for nasal disorders. Radioaerosol inhalation and imaging studies in nasal casts and in healthy volunteers have shown 4-6% of the nasally administered dose within the sinuses. In CRS patients, significant aerosol deposition in the sinus cavities was reported before sinus surgery. After surgery, deposition increased to the amount observed in healthy volunteers. In addition, compared with nasal pump sprays, retention kinetics of the radiolabel deposited in the nasal cavity was prolonged, both in healthy volunteers and in CRS patients. These efficiencies may be sufficient for topical aerosol therapies of sinus disorders and, due to the prolonged retention kinetics, may reduce application modes, but have to be proven in future clinical trials. Pulsating aerosols may offer additional new topical treatment options of nasal and sinus disorders before as well as after surgery. | 25,084,017 | [
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STAT3 inhibitor WP1066 as a novel therapeutic agent for bCCI neuropathic pain rats. | Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in the development of chronic pain, but the complex regulation of STAT3-dependent pathway and the functional significance of inhibiting this pathway during the development of neuropathic pain remain elusive. To evaluate the contribution of the JAK2/STAT3 pathway to neuropathic pain and the potentiality of this pathway as a novel therapeutic target, we examined the effects of the STAT3 inhibitor WP1066 by intrathecal administration in a rat model of bilateral chronic constriction injury (bCCI). The pain behavior tests were performed before the surgery and on postoperative day 3, 7, 14 and 21. L4-L6 dorsal spinal cord were harvested at each time point. Both RT-PCR and Western blot were performed to evaluate the activation of JAK2/STAT3 pathway. To observe the influence of WP1066 on neuropathic pain and its molecular mechanism, WP1066 (10 μl, 10 mmol/L in DMSO) or the same capacity of DMSO as the control were applied through the intrathecal tube on the day before bCCI surgery, and on the postoperative day 3 and 5. Behavioral tests were performed to observe the therapeutic effect on mechanical, thermal and cold hyperalgesia. L4-L6 dorsal spinal cord was harvested on postoperative day fourteen, followed by RT-PCR and Western blot evaluation of the JAK2/STAT3 pathway activation. The mechanical, thermal and cold hyperalgesia of the bCCI rats were significantly decreased when compared with the Sham or the Naïve group at each postoperative time point (P<0.05). JAK2 mRNA and STAT3 mRNA were significantly increased in the bCCI rats, accompanied by SOCS3 mRNA with a similar tendency. Western blot analysis showed that JAK2 and phosphorylated STAT3 increased significantly since 3 days after bCCI. JAK2 peaked on postoperative day 14 while phosphorylated STAT3 peaked on postoperative day 7 and gradually decreased thereafter and SOCS3׳s peak level on postoperative day 3. When WP1066 were administered intrathecally, the pain behaviors of the bCCI rats were significantly improved (P<0.05). WP1066 also inhibited the mRNA level of JAK2, STAT3 and SOCS3 in bCCI rats significantly, together with the protein level of JAK2, phosphorylated STAT3 and SOCS3 on postoperative day 14 as well. Our results found that the JAK2/STAT3 pathway in the spinal cord dorsal horn was significantly activated in the bCCI neuropathic pain rats. WP1066, which inhibited the STAT3 pathway specifically, could partially alleviate the pain behavior of the bCCI rats. So it may serve as a novel therapeutic strategy against neuropathic pain. | 25,084,036 | [
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Activation of GABAA and GABAB receptors in the lateral septum increases sucrose intake by differential stimulation of sucrose licking activity. | The present study was aimed to determine how direct injections into the lateral septum (LS) of muscimol and baclofen, GABAA and GABAB receptor agonists, respectively, affect intake of 10% sucrose and sucrose licking activity in rats. The effects of muscimol and baclofen on the 1-h intake of sucrose and sucrose licking activity were tested at low (350pmol), medium (876pmol), and high (1752pmol) doses. The medium and high doses of muscimol and the high dose of baclofen significantly increased 1-h sucrose intake. The total sucrose lick number was significantly increased by the medium dose of muscimol and the high dose of baclofen. An increase in sucrose licking activity induced by muscimol but not baclofen occurred in the first 15min after injections. The medium and high doses of muscimol but not baclofen significantly decreased latency to initiate the first lick of sucrose. The total licking time calculated as the sum of the duration of all sucrose lick clusters showed a significant increase by the high dose of baclofen but not by any dose of muscimol. Therefore, the GABAA and GABAB LS mechanisms appear to be involved in stimulating sucrose intake, but this stimulation occurs by differential regulation of the sucrose licking activity. Muscimol intra-LS administration led to a short-latency rapid increase in sucrose licking. In contrast, baclofen did not decrease latency to initiate licking, but significantly increased total licking duration. | 25,084,040 | [
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Pyrogenic molecular markers: linking PAH with BPCA analysis. | Molecular characterization of pyrogenic organic matter (PyOM) is of great interest to understand the formation and behavior of these increasingly abundant materials in the environment. Two molecular marker methods have often been used to characterize and trace PyOM: polycyclic aromatic hydrocarbon (PAH) and benzenepolycarboxylic acid (BPCA) analysis. Since both methods target pyrogenic polycyclic compounds, we investigated the linkages between the two approaches using chars that were produced under controlled conditions. Rye and maize straws and their analogues charred at 300, 400 and 500 °C, respectively, were thus analyzed with both methods. Moreover, we also measured BPCAs directly on the lipid extracts, on which PAHs were analyzed, and on the respective extraction residues, too. Both methods revealed important features of the chars, in particular the increasing degree of aromatic condensation with increasing highest heating temperature (HTT). The overlap between the two methods was identified in the lipid fraction, where the proportion of benzenetricarboxylic acids (B3CAs) correlated with PAH abundance. The results confirmed the validity and complementarity of the two molecular marker methods, which will likely continue to play a crucial role in PyOM research due to the recent developments of compound-specific PAH and BPCA stable carbon (δ(13)C) and radiocarbon ((14)C) isotope methods. | 25,084,061 | [
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Determination of receptor protein binding site specificity and relative binding strength using a time-resolved competition assay. | Competitive binding assays can be used to decipher not only the binding kinetics of studied ligands but also the binding site preference. Such assays are an essential step in the characterization of radioligands. However, the currently used competition assays require high concentrations of usually expensive ligands and still provide only binding site preference. By employing the time-resolved competition assay presented in this paper, binding characteristics including binding site preference can be obtained using less ligand. To demonstrate the appropriateness of the time-resolved competition assay, we developed an assay in which the ligand binding was interrupted with a competitor. Experiments were performed on human carcinoma cell lines expressing epidermal growth factor receptor (EGFR). The targeting of the receptor was performed with radio-iodinated epidermal growth factor (EGF). The employed competitors involved either natural ligand transforming growth factor alpha (TGF-α) or anti-EGFR antibodies cetuximab and panitumumab targeting the same EGFR domain. Radio-iodinated EGF bound to EGFR was displaced with either low concentrations of cetuximab or high concentrations of panitumumab. In the case of TGF-α, we observed no competitive displacement of bound EGF at either high or low concentrations. When comparing the time-resolved competition assay with a manual competition assay, the resulting data of measured inhibition constants were in agreement. The results summarised in this study confirm the appropriateness of the time-resolved competition assay for assessing ligand binding properties. The assay has the potential to complement or replace conventional competition assays for determining binding site preference in the future. | 25,084,055 | [
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Effect of feeding frequency on the daily rhythms of acidic digestion in a teleost fish (gilthead seabream). | Gilthead seabream is a fish species of great importance in Mediterranean aquaculture, attracting many studies on nutrition and chronobiology, although nothing is known about the effect of feeding frequency on the daily rhythms of the gastric digestion process. In this article, we investigated daily rhythms in stomach fullness, gastric and intestine pH, as well as pepsin activity and expression of pepsinogen and proton pump in juvenile fish under three different feeding protocols: (A) one daily meal at 9:00, (B) two daily meals at 9:00 and 17:00 and (C) continuous feeding during the daytime. The results revealed that feeding protocol affected significantly the rhythm of gastric pH and the pepsin activity pattern. The gastric pH exhibited significant daily rhythms in the three cases with the acrophase located at night in the regimes A and B and during daytime, in the regime C. In the regimes A and B, the pepsin activity peaked few hours after the meals, although the afternoon meal in B produced a higher peak. In the regime C, the peak occurred in the middle of the feeding period. Lowest total pepsin activity was observed in regime A, and the highest activity with the regime C. In contrast, the pepsinogen gene expression remained low along the daily cycle, with an expression peak just before or after the morning meal in regimes A and C, respectively. The proton pump gene expression was also practically constant with a peak right after the morning meal in the regime C. On the other hand, intestinal pH showed a postprandial increase after the first morning meal in all the three treatments, recovering the resting values in the dark period. Two meals and continuous feeding allowed a better and prolonged gastric digestion and consequently the juveniles exhibited better growth with the same daily ration of food. In short, while the gastric digestion pattern is mainly driven by pH changes induced by the time of food ingestion, the regulation of the intestinal digestion seems to be more independent of the feeding protocol. | 25,084,069 | [
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Results of a pilot multicenter genotype-based randomized placebo-controlled trial of propranolol to reduce pain after major thermal burn injury. | Results of previous studies suggest that β-adrenoreceptor activation may augment pain, and that β-adrenoreceptor antagonists may be effective in reducing pain, particularly in individuals not homozygous for the catechol-O-methyltransferase (COMT) high-activity haplotype. Consenting patients admitted for thermal burn injury at participating burn centers were genotyped; those who were not high-activity COMT homozygotes were randomized to propranolol 240 mg/d or placebo. Primary outcomes were study feasibility (consent rate, protocol completion rate) and pain scores on study days 5 to 19. Secondary outcomes assessed pain and posttraumatic stress disorder symptoms 6 weeks postinjury. Seventy-seven percent (61/79) of eligible patients were consented and genotyped, and 77% (47/61) were genotype eligible and randomized. Ninety-one percent (43/47) tolerated study drug and completed primary outcome assessments. In intention-to-treat and per-protocol analyses, patients randomized to propranolol had worse pain scores on study days 5 to 19. Genotype-specific pain medication interventions are feasible in hospitalized burn patients. Propranolol is unlikely to be a useful analgesic during the first few weeks after burn injury. | 25,084,070 | [
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Arterial stiffness and pulse wave reflection are increased in patients suffering from severe periodontitis. | This single blind cross-sectional study compared the vascular health of subjects suffering from severe chronic periodontitis, severe aggressive periodontitis and periodontal healthy controls by evaluating pulse wave velocity (PWV), augmentation index (AIx) and pulse pressure amplification (PPA). In a total of 158 subjects, 92 suffering from severe periodontitis and 66 matched periodontal healthy controls, PWV, AIx, central and peripheral blood pressure were recorded using an oscillometric device (Arteriograph). Subjects suffering from severe chronic or aggressive periodontitis exhibited significantly higher PWV (p = 0.00004), higher AIx (p = 0.0049) and lower PPA (p = 0.028) than matched periodontal healthy controls. The results of this study confirm the association between periodontal inflammation and increased cardiovascular risk shown by impaired vascular health in case of severe periodontitis. As impaired vascular health is a common finding in patients suffering from severe periodontal disease a concomitant routine cardiovascular evaluation may be advised. | 25,084,111 | [
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The role of melanin concentrating hormone (MCH) in the central chemoreflex: a knockdown study by siRNA in the lateral hypothalamus in rats. | Melanin concentrating hormone (MCH), a neuropeptide produced mainly in neurons localized to the lateral hypothalamic area (LHA), has been implicated in the regulation of food intake, energy balance, sleep state, and the cardiovascular system. Hypothalamic MCH neurons also have multisynaptic connections with diaphragmatic motoneurons and project to many central chemoreceptor sites. However, there are few studies of MCH involvement in central respiratory control. To test the hypothesis that MCH plays a role in the central chemoreflex, we induced a down regulation of MCH in the central nervous system by knocking down the MCH precursor (pMCH) mRNA in the LHA using a pool of small interfering RNA (siRNA), and measured the resultant changes in breathing, metabolic rate, body weight, and blood glucose levels in conscious rats. The injections of pMCH-siRNA into the LHA successfully produced a ∼ 62% reduction of pMCH mRNA expression in the LHA and a ∼ 43% decrease of MCH levels in the cerebrospinal fluid relative to scrambled-siRNA treatment (P = 0.006 and P = 0.02 respectively). Compared to the pretreatment baseline and the scrambled-siRNA treated control rats, knockdown of MCH resulted in: 1) an enhanced hypercapnic chemoreflex (∼ 42 & 47% respectively; P < 0.05) only in wakefulness; 2) a decrease in body weight and basal glucose levels; and 3) an unchanged metabolic rate. Our results indicate that MCH participates not only in the regulation of glucose and sleep-wake homeostasis but also the vigilance-state dependent regulation of the central hypercapnic chemoreflex and respiratory control. | 25,084,113 | [
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The effect of sandblasting and different primers on shear bond strength between yttria-tetragonal zirconia polycrystal ceramic and a self-adhesive resin cement. | To evaluate the effect of zirconia primers, air-abrasion, and tribochemical surface treatment methods on the shear bond strength between yttria-tetragonal zirconia polycrystal (Y-TZP) ceramic and self-adhesive resin cement. Y-TZP ceramic surfaces were ground flat with 600-grit silicon carbide paper and then divided into seven groups of 10 and treated as follows: untreated (control), Monobond Plus, Z-PRIME Plus, ESPE Sil with CoJet, air-abrasion, Monobond Plus with air-abrasion, and Z-PRIME Plus with air-abrasion. Self-adhesive resin cement was placed onto the treated Y-TZP specimens for each group. All specimens were thermocycled and subjected to a shear bond strength test. Scanning electron microscope images of the fractured areas and x-ray diffraction (XRD) analysis of the surface-treated Y-TZP specimens were performed. Data were statistically analyzed using one-way analysis of variance and the Student-Newman-Keuls multiple comparison test (p<0.05). The Z-PRIME Plus treatment in combination with air-abrasion produced the highest bond strength (16.50±2.26 MPa), followed by air-abrasion (10.56±3.32 MPa), and then Monobond Plus combined with air-abrasion (8.93±3.13 MPa), ESPE Sil after CoJet application (8.54±3.98 MPa), and the Z-PRIME Plus group (8.27±2.79 MPa). The control (3.91±0.72 MPa) and Monobond Plus (4.86±1.77 MPa) groups indicated the lowest results (p<0.05). The XRD results showed the peaks of the monoclinic phase for the air-abrasion and CoJet treatment groups compared with the Y-TZP control. Z-PRIME Plus primer application after air-abrasion presented the best results for improving the bond strength between Y-TZP ceramic and self-adhesive resin cement. | 25,084,110 | [
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Treating hypertension in type 2 diabetes. | The co-existence of hypertension and diabetes mellitus is very common. Hypertension remarkably increases the cardiovascular risk in diabetic patients. Lowering blood pressure (BP) in these patients is particularly beneficial. This paper will discuss what the target BP is for diabetic patients and how that target can be reached. Previous guidelines recommended lowering BP < 130/80 mmHg in diabetic patients. However, recent studies did not support this target and accordingly most recent guidelines recommend lowering BP to < 140/90 mmHg in diabetic patients. Non-pharmacological approaches are recommended in all patients. If BP levels are above the target despite non-pharmacological treatment, drug therapy should be initiated. Despite the lack of clear evidence, blockers of the renin-angiotensin-aldosterone system (RAAS) represent the cornerstone of the antihypertensive arsenal; however, in most patients combination therapy is required. Combination of RAAS blocker and a calcium antagonist is the preferred one. In many patients three or four drugs are needed. Treatment should be individualized according to concomitant risk factors and diseases and according hemodynamic and laboratory parameters as well as age. In order to maximally reduce cardiorenal risk, lipid and glycemic control should also be achieved. | 25,084,118 | [
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Atom-economical access to highly substituted indenes and furan-2-ones via tandem reaction of diazo compounds and propargyl alcohols. | A facile synthesis of highly substituted as well as conjugated indene/furanone systems via a BF3·OEt2 catalyzed tandem reaction of α-diazo-esters/-amides and propargyl alcohols has been demonstrated under mild conditions. This method offers great potential for the synthesis of biologically active indene and furanone derivatives and their related polycyclic compounds. | 25,084,140 | [
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Ca3Na4LiBe4B10O24F: a new beryllium borate with a unique beryl borate ∞(2)[Be8B16O40F2] layer intrabridged by [B12O24] groups. | A novel beryllium borate, Ca3Na4LiBe4B10O24F, has been discovered. It possesses a unique ∞(2)[Be8B16O40F2] layer composed of two opposite parallel [Be4B4O12F]∞ layers bridged with [B12O24] polyborates. The linkage of [B12O24] to other structural units is first found in anhydrous borates. In the ∞(2)[Be8B16O40F2] layer, multiple tunnels are arranged along different directions resided by the alkali and alkaline-earth cations. The compound remains stable in an ambient atmosphere from room temperature to the melting point at 830 °C and melts incongruently. | 25,084,149 | [
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Fundus changes in central retinal vein occlusion. | To investigate systematically the retinal and optic disk changes in central retinal vein occlusion (CRVO) and their natural history. This study comprised 562 consecutive patients with CRVO (492 nonischemic [NI-CRVO] and 89 ischemic CRVO [I-CRVO] eyes) seen within 3 months of onset. Ophthalmic evaluation at initial and follow-up visits included recording visual acuity, visual fields, and detailed anterior segment and fundus examinations and fluorescein fundus angiography. Retinal and subinternal limiting membrane hemorrhages and optic disk edema in I-CRVO were initially more marked (P < 0.0001) and took longer to resolve (P < 0.015) than that in NI-CRVO. Initially, macular edema was more marked in I-CRVO than that in NI-CRVO (P < 0.0001) but did not significantly differ in resolution time (P = 0.238). Macular retinal epithelial pigment degeneration, serous macular detachment, and retinal perivenous sheathing developed at a higher rate in I-CRVO than that in NI-CRVO (P < 0.0001). Ischemic CRVO had more retinal venous engorgement than NI-CRVO (P = 0.003). Fluorescein fundus angiography showed significantly more fluorescein leakage, retinal capillary dilatation, capillary obliteration, and broken capillary foveal arcade (P < 0.0001) in I-CRVO than NI-CRVO. Resolution time of CRVO was longer for I-CRVO than NI-CRVO (P < 0.0001). Characteristics and natural history of fundus findings in the two types of CRVO are different. | 25,084,156 | [
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Safety and efficacy of percutaneous renal biopsy by physicians-in-training in an academic teaching setting. | The safety and efficacy of percutaneous renal biopsy (PKB) are relatively little studied in a training setting. We sought to review our recent experience with bedside PKB in our training program. We performed a retrospective cohort review of our consecutive 2.5-year renal biopsy experience (May 2007-November 2009) at the University of Mississippi Nephrology Fellowship. All of the biopsies were performed exclusively by renal fellows using real-time ultrasound (US) visualization within the framework of a structured US-PKB training course. A total of 64 patients underwent PKB during the index period; 50 (78.1%) of these procedures were performed on native kidneys. Participant age was 39.8 ± 13.7 years, blood pressures measured 140.1/85.3 ± 21.5/14.9 mm Hg, serum creatinine was 3.05 ± 3.15 mg/dL, and median random urine protein:creatinine ratio was 2.38 (25%-75% interquartile range 0.49-7.32). The biopsied kidneys measured 11.8 (±1.6) cm. We recovered 18.8 ± 11.5 glomeruli per procedure; two biopsies were unsuccessful. Focal glomerular sclerosis and lupus nephritis (22% and 25%, respectively) predominated among the specimens. Only three specimens returned with no diagnostic changes. There was a close correlation between preceding history and recovered diagnoses of diabetic changes and lupus nephritis (r 0.605 and 0.842; P < 0.0001 for both). Initial hemoglobin of 10.8 ± 1.8 g/dL dropped to 10.2 (1.9) g/dL after the procedure (P < 0.0001). Five (7.8%) patients needed transfusion; one patient experienced persistent urine leakage; however, none of the patients needed surgical or radiological intervention or died. In the setting of a well-structured training environment, US-guided PKB is a reasonably safe and valuable component of renal fellowship training. | 25,084,192 | [
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Role of solute carrier transporters in pancreatic cancer: a review. | Nucleoside analogs such as gemcitabine and 5-fluorouracil are currently the cornerstone of chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). Decreased drug transport into tumor cells that may be caused by low expression of membrane proteins, such as solute carrier transporters, represents one of the principal mechanisms of chemotherapy resistance. Individual diversity of multidrug resistance is the major challenge limiting the success of anticancer treatment. Novel biomarkers and pharmacogenomic approaches could further optimize treatment algorithms leading to better survival and lower treatment toxicity in PDAC patients. In this review, the most promising predictive biomarkers from the solute carrier transporter family of membrane transporters and the potential applications for PDAC therapy with nucleoside analogues are summarized. | 25,084,206 | [
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Rac1 signaling regulates neutrophil-dependent tissue damage in experimental colitis. | Excessive neutrophil recruitment in the colon is a major feature in acute colitis although the signaling mechanisms behind colonic recruitment of neutrophils remain elusive. Herein, we hypothesized that Rac1 activity might play an important role in neutrophil infiltration in the inflamed colon. Female Balb/c mice were treated with the Rac1 inhibitor NSC23766 (0.5 and 5mg/kg) before and daily after administration of 5% dextran sodium sulfate (DSS). Colonic tissue was collected for quantification of neutrophil recruitment, interleukin-6 (IL-6) and CXC chemokine formation as well as histological damage score five days after challenge with DSS. Rac1 activity was determined by western blot and Mac-1 expression by flow cytometry in neutrophils. Administration of NSC23766 decreased DSS-induced neutrophil recruitment and tissue damage in the colon. Rac1 inhibition decreased colonic formation of IL-6 and CXC chemokines in experimental colitis. Chemokine challenge increased Rac1 activity in neutrophils and NSC23766 markedly reduced this neutrophil activity of Rac1. Inhibition of Rac1 abolished CXC chemokine-induced neutrophil chemotaxis and up-regulation of Mac-1 in vitro. Taken together, Rac1 signaling plays a significant role in controlling accumulation of neutrophils and tissue injury in experimental colitis. Thus, our novel results suggest that targeting Rac1 signaling might be a useful way to protect against neutrophil-mediated tissue injury in acute colitis. | 25,084,221 | [
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How to determine the adsorption energy of the surfactant's hydrophilic head? How to estimate easily the surface activity of every simple surfactant? | A definite way to determine the adsorption energy of the surfactant's hydrophilic head on the air water interface is presented. For this purpose, the Davies adsorption theory and the most advanced version of Helfand-Frish-Lebowitz adsorption theory were applied to the surface tension isotherms of homologous series of sodium alkyl sulfate (CnH2n+1SO4Na, n=7-12), thus deriving the equilibrium adsorption constant, the cross-sectional area of the surfactant molecule, the interaction coefficient and the cohesion constant versus the number of the carbon atoms into the alkyl sulfate molecule. Thus, the total adsorption energy of each particular homolog was calculated in line with the latest development of the adsorption theory, thus calculating the dimensionless adsorption energy of the hydrophilic head Ehead/kBT. In our particular case (SO4(-)) we calculated Ehead/kBT=-2.79, which indicates the strong propensity of the SO4(-) to be surrounded by water molecules. The procedure for calculation Ehead/kBT does not depend on the charge of the hydrophilic head. Similarly, we calculated Ehead/kBT of another six well known in the literature hydrophilic heads (COOH, OH, DMPO, DEPO, N(CH3)3(+), and NH3(+)), indicating that the adsorption energy of the CH2 group depends slightly on the type of the hydrophilic head, but it affects substantially the adsorption energy of the whole surfactant molecule. Finally, we defined and validated a parameter called adsorption capacity of surfactants with simple molecular structure, for easy estimation of their surface activity. Linear dependence between the CMC of ionic surfactants and their adsorption capacity was established. | 25,084,231 | [
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Converting a binding protein into a biosensing conformational switch using protein fragment exchange. | Biosensors can be used in applications ranging from identifying disease biomarkers to detecting spatial and temporal distributions of specific molecules in living cells. A major challenge facing biosensor development is how to functionally couple a biological recognition domain to an output module so that the binding event can be transduced to a visible and quantifiable signal [e.g., Förster resonance energy transfer (FRET)]. Most designs achieve coupling by means of a binding protein that changes conformation upon interacting with its target. This approach is limited by the fact that few proteins possess such natural allosteric mechanisms, and for those that do, the conformational change is frequently not extensive enough to produce a large change in distance between FRET donor and acceptor groups. Here, we introduce protein fragment exchange (FREX) to address both problems. FREX employs two components: a folded binding protein and a fragment duplicated from it, the latter of which can be chosen from many possible fragments. The system is rationally tuned so that addition of ligand induces a conformational change in which the fragment exchanges positions with the corresponding segment of the binding protein. Placing fluorescent donor and acceptor groups on the binding protein and fragment reduces the background level of FRET of the unbound sensor, resulting in a ratiometric FRET response that is expected to be strong and reproducible from protein to protein. FREX is demonstrated using fibronectin III, a monobody binding scaffold that has been tailored to recognize multiple targets. Sensors labeled with Alexa FRET pairs exhibit ratiometric FRET changes of up to 8.6-fold and perform equally well in buffer and serum. A genetically encoded variant of this sensor is shown to be functional in cell lysates and in mammalian cell cultures. | 25,084,233 | [
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NBO, HOMO, LUMO analysis and vibrational spectra (FTIR and FT Raman) of 1-Amino 4-methylpiperazine using ab initio HF and DFT methods. | Experimental FTIR and FT-Raman spectroscopic analysis of 1-Amino-4-methylpiperazine (1A4MP) have been performed. A detailed quantum chemical calculations have been carried out using ab initio HF and density functional theory calculations (B3LYP) with 6-311+G(d,p) basis set. The atomic charges, electronic exchange interaction and charge delocalization of the molecule have been performed by natural bond orbital (NBO) analysis. Electron density distribution and frontier molecular orbitals (FMOs) have been constructed at B3LYP/6-311+G(d,p) level to understand the electronic properties. The charge density distribution and site of chemical reactivity of the molecule have been obtained by mapping electron density isosurface with electrostatic potential surfaces (ESP). The electronic properties, HOMO and LUMO energies were measured by time-dependent TD-DFT approach. The dipole moment (μ), polarizability (α), anisotropy polarizability (Δα) and hyperpolarizability (β) of the molecule have been reported. | 25,084,238 | [
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Synthesis, structure and spectroscopic properties of the trinuclear cobalt(II) and nickel(II) complexes based on 2-hydroxynaphthaldehyde and bis(aminooxy)alkane. | A new Salen-type bisoxime ligand, 2,2'-[ethylenedioxybis(nitrilomethylidyne)]dinaphthol (H2L) and its corresponding cobalt(II) and nickel(II) complexes, [{CoL(DMF)}2(OAC)2Co] and [{NiL(H2O)}2(OAc)2Ni]⋅2C2H5OH have been synthesized, and characterized by elemental analyses, IR spectra, UV-vis spectra, TG-DTA and molar conductance measurements, etc. The X-ray crystal structure studies reveal that the cobalt(II) and nickel(II) complexes are symmetric trinuclear structures. All of the M(II) (Co(II) or Ni(II)) ions for the cobalt(II) or nickel(II) complexes are six-coordinated and have slightly distorted octahedral coordination geometries. | 25,084,240 | [
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Detection of uranium and chemical state analysis of individual radioactive microparticles emitted from the Fukushima nuclear accident using multiple synchrotron radiation X-ray analyses. | Synchrotron radiation (SR) X-ray microbeam analyses revealed the detailed chemical nature of radioactive aerosol microparticles emitted during the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, resulting in better understanding of what occurred in the plant during the early stages of the accident. Three spherical microparticles (∼2 μm, diameter) containing radioactive Cs were found in aerosol samples collected on March 14th and 15th, 2011, in Tsukuba, 172 km southwest of the FDNPP. SR-μ-X-ray fluorescence analysis detected the following 10 heavy elements in all three particles: Fe, Zn, Rb, Zr, Mo, Sn, Sb, Te, Cs, and Ba. In addition, U was found for the first time in two of the particles, further confirmed by U L-edge X-ray absorption near-edge structure (XANES) spectra, implying that U fuel and its fission products were contained in these particles along with radioactive Cs. These results strongly suggest that the FDNPP was damaged sufficiently to emit U fuel and fission products outside the containment vessel as aerosol particles. SR-μ-XANES spectra of Fe, Zn, Mo, and Sn K-edges for the individual particles revealed that they were present at high oxidation states, i.e., Fe(3+), Zn(2+), Mo(6+), and Sn(4+) in the glass matrix, confirmed by SR-μ-X-ray diffraction analysis. These radioactive materials in a glassy state may remain in the environment longer than those emitted as water-soluble radioactive Cs aerosol particles. | 25,084,242 | [
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Silver-catalyzed radical tandem cyclization: an approach to direct synthesis of 3-acyl-4-arylquinolin-2(1H)-ones. | A silver-catalyzed efficient and practical synthesis of 3-acyl-4-arylquinolin-2(1H)-ones or 3-acyl-4-aryldihydroquinolin-2(1H)-ones through intermolecular radical addition/cyclization in aqueous solution is reported. This method provides a novel, highly efficient, and straightforward route to substituted quinolin-2-ones or 3,4-dihydroquinolin-2-ones in one step. A possible mechanism for the formation of quinolin-2-ones is proposed. | 25,084,243 | [
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Sequencing and G-quadruplex folding of the canine proto-oncogene KIT promoter region: might dog be used as a model for human disease? | Downregulation of gene expression by induction of non-canonical DNA structures at promotorial level is a novel attractive anticancer strategy. In human, two guanine-rich sequences (h_kit1 and h_kit2) were identified in the promotorial region of oncogene KIT. Their stabilization into G-quadruplex structures can find applications in the treatment of leukemias, mastocytosis, gastrointestinal stromal tumor, and lung carcinomas which are often associated to c-kit mis-regulation. Also the most common skin cancer in domestic dog, mast cell tumor, is linked to a mutation and/or to an over-expression of c-kit, thus supporting dog as an excellent animal model. In order to assess if the G-quadruplex mediated mechanism of regulation of c-kit expression is conserved among the two species, herein we cloned and sequenced the canine KIT promoter region and we compared it with the human one in terms of sequence and conformational equilibria in physiologically relevant conditions. Our results evidenced a general conserved promotorial sequence between the two species. As experimentally confirmed, this grants that the conformational features of the canine kit1 sequence are substantially shared with the human one. Conversely, two isoforms of the kit2 sequences were identified in the analyzed dog population. In comparison with the human counterpart, both of them showed an altered distribution among several folded conformations. | 25,084,283 | [
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Developmental programming of aging of isolated pancreatic islet glucose-stimulated insulin secretion in female offspring of mothers fed low-protein diets in pregnancy and/or lactation. | Diabetes predisposition is determined by pancreatic islet insulin secretion and insulin resistance. We studied female rat offspring exposed to low-protein maternal diet (50% control protein diet) in pregnancy and/or lactation at postnatal days 36, 110 and 450. Rats were fed either control 20% casein diet (C) or restricted diet (R - 10% casein) during pregnancy. After delivery, mothers received either C or R diet until weaning to provide four offspring groups: CC, RR, CR and RC (first letter denoting maternal pregnancy diet and the second lactation diet). Serum glucose, insulin and homeostatic model assessment (HOMA) were measured. Pancreatic islets were isolated and in vitro insulin secretion quantified in low glucose (5 mM) and high glucose (11 mM). Serum glucose, insulin and HOMA were similar in all groups at 36 and 110 postnatal days. HOMA was only higher in RR at 450 postnatal days. Only CC demonstrated differences in glucose sensitivity of β-cells to high and low doses at the three ages studied. At 36 days, RR, CR and RC and at 450 days RR and RC groups did not show glucose-stimulated insulin secretion differences between low and high glucose. Aging-associated glucose-stimulated insulin secretion loss was affected by maternal dietary history, indicating that developmental programming must be considered a major factor in aging-related development of predisposition to later-life dysfunctional insulin metabolism. Female offspring islets' insulin secretion was higher than previously reported in males. | 25,084,301 | [
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HermiteFit: fast-fitting atomic structures into a low-resolution density map using three-dimensional orthogonal Hermite functions. | HermiteFit, a novel algorithm for fitting a protein structure into a low-resolution electron-density map, is presented. The algorithm accelerates the rotation of the Fourier image of the electron density by using three-dimensional orthogonal Hermite functions. As part of the new method, an algorithm for the rotation of the density in the Hermite basis and an algorithm for the conversion of the expansion coefficients into the Fourier basis are presented. HermiteFit was implemented using the cross-correlation or the Laplacian-filtered cross-correlation as the fitting criterion. It is demonstrated that in the Hermite basis the Laplacian filter has a particularly simple form. To assess the quality of density encoding in the Hermite basis, an analytical way of computing the crystallographic R factor is presented. Finally, the algorithm is validated using two examples and its efficiency is compared with two widely used fitting methods, ADP_EM and colores from the Situs package. HermiteFit will be made available at http://nano-d.inrialpes.fr/software/HermiteFit or upon request from the authors. | 25,084,327 | [
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Domain mobility as probed by small-angle X-ray scattering may account for substrate access to the active site of two copper-dependent amine oxidases. | Amine oxidases are a family of dimeric enzymes that contain one copper(II) ion and one 2,4,5-trihydroxyphenyalanine quinone per subunit. Here, the low-resolution structures of two Cu/TPQ amine oxidases from lentil (Lens esculenta) seedlings and from Euphorbia characias latex have been determined in solution by small-angle X-ray scattering. The active site of these enzymes is highly buried and requires a conformational change to allow substrate access. The study suggests that the funnel-shaped cavity located between the D3 and D4 domains is narrower within the crystal structure, whereas in solution the D3 domain could undergo movement resulting in a protein conformational change that is likely to lead to easier substrate access. | 25,084,330 | [
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Mapping the conformational space accessible to catechol-O-methyltransferase. | Methylation catalysed by catechol-O-methyltransferase (COMT) is the main pathway of catechol neurotransmitter deactivation in the prefrontal cortex. Low levels of this class of neurotransmitters are held to be causative of diseases such as schizophrenia, depression and Parkinson's disease. Inhibition of COMT may increase neurotransmitter levels, thus offering a route for treatment. Structure-based drug design hitherto seems to be based on the closed enzyme conformation. Here, a set of apo, semi-holo, holo and Michaelis form crystal structures are described that define the conformational space available to COMT and that include likely intermediates along the catalytic pathway. Domain swaps and sizeable loop movements around the active site testify to the flexibility of this enzyme, rendering COMT a difficult drug target. The low affinity of the co-substrate S-adenosylmethionine and the large conformational changes involved during catalysis highlight significant energetic investment to achieve the closed conformation. Since each conformation of COMT is a bona fide target for inhibitors, other states than the closed conformation may be promising to address. Crystallographic data for an alternative avenue of COMT inhibition, i.e. locking of the apo state by an inhibitor, are presented. The set of COMT structures may prove to be useful for the development of novel classes of inhibitors. | 25,084,335 | [
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Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid-binding SCP/TAPS protein that lacks the prototypical CAP motifs. | Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen-like proteins (SmVALs) from the SCP/TAPS (sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. The first SmVAL structure, SmVAL4, was refined to a resolution limit of 2.16 Å. SmVAL4 has a unique structure that could not be predicted from homologous structures, with longer loops and an unusual C-terminal extension. SmVAL4 has the characteristic α/β-sandwich and central SCP/TAPS cavity. Furthermore, SmVAL4 has only one of the signature CAP cavity tetrad amino-acid residues and is missing the histidines that coordinate divalent cations such as Zn(2+) in other SCP/TAPS proteins. SmVAL4 has a cavity between α-helices 1 and 4 that was observed to bind lipids in tablysin-15, suggesting the ability to bind lipids. Subsequently, SmVAL4 was shown to bind cholesterol in vitro. Additionally, SmVAL4 was shown to complement the in vivo sterol-export phenotype of yeast mutants lacking their endogenous CAP proteins. Expression of SmVAL4 in yeast cells lacking endogenous CAP function restores the block in sterol export. These studies suggest an evolutionarily conserved lipid-binding function shared by CAP proteins such as SmVAL4 and yeast CAP proteins such as Pry1. | 25,084,337 | [
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Highly efficient hydrophobic titania ceramic membranes for water desalination. | Hydrophobic titania ceramic membranes (300 kD) were prepared by grafting of C6F13C2H4Si(OC2H5)3 and C12F25C2H4Si(OC2H5)3 molecules and thus applied in membrane distillation (MD) process of NaCl solutions. Grafting efficiency and hydrophobicity were evaluated by contact angle measurement, atomic force microscopy, scanning electron microscopy, nitrogen adsorption/desorption, and liquid entry pressure measurement of water. Desalination of NaCl solutions was performed using the modified hydrophobic membranes in air gap MD (AGMD) and direct contact MD (DCMD) processes in various operating conditions. High values of NaCl retention coefficient (>99%) were reached. The permeate fluxes were in the range 231-3692 g·h(-1)·m(-2), depending on applied experimental conditions. AGMD mode appeared to be more efficient showing higher fluxes and selectivity in desalination. Overall mass transfer coefficients (K) for membranes tested in AGMD were constant over the investigated temperature range. However, K values in DCMD increased at elevated temperature. The hydrophobic layer was also stable after 4 years of exposure to open air. | 25,084,346 | [
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0.02003096,
... |
Carriage of Streptococcus pneumoniae and other respiratory bacterial pathogens in low and lower-middle income countries: a systematic review and meta-analysis. | Infection with Streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide, especially in low income countries where pneumococcal conjugate vaccines (PCVs) are still underused. In countries where PCVs have been introduced, much of their efficacy has resulted from their impact on nasopharyngeal carriage in vaccinated children. Understanding the epidemiology of carriage for S. pneumoniae and other common respiratory bacteria in developing countries is crucial for implementing appropriate vaccination strategies and evaluating their impact. We have systematically reviewed published studies reporting nasopharyngeal or oropharyngeal carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Neisseria meningitidis in children and adults in low and lower-middle income countries. Studies reporting pneumococcal carriage for healthy children <5 years of age were selected for a meta-analysis. The prevalences of carriage for S. pneumoniae, H. influenzae, and M. catarrhalis were generally higher in low income than in lower-middle income countries and were higher in young children than in adults. The prevalence of S. aureus was high in neonates. Meta-analysis of data from young children before the introduction of PCVs showed a pooled prevalence estimate of 64.8% (95% confidence interval, 49.8%-76.1%) in low income countries and 47.8% (95% confidence interval, 44.7%-50.8%) in lower-middle income countries. The most frequent serotypes were 6A, 6B, 19A, 19F, and 23F. In low and lower-middle income countries, pneumococcal carriage is frequent, especially in children, and the spectrum of serotypes is wide. However, because data are limited, additional studies are needed to adequately assess the impact of PCV introduction on carriage of respiratory bacteria in these countries. | 25,084,351 | [
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Catecholamine and volume therapy for cardiac surgery in Germany--results from a postal survey. | Management of cardiac surgery patients is a very standardized procedure in respective local institutions. Yet only very limited evidence exists concerning optimal indication, safety and efficacy of hemodynamic monitoring catecholamine and fluid therapy. Between April and May 2013, all 81 German anaesthesia departments involved in cardiac surgery care were asked to participate in a questionnaire addressing the institutional specific current practice in hemodynamic monitoring, catecholamine and volume therapy. 51 (63%) questionnaires were completed and returned. All participating centers used basic hemodynamic monitoring (i.e. invasive arterial blood pressure and central venous pressure), supplemented by transesophageal echocardiography. Pulmonary arterial catheter and calibrated trend monitoring devices were also routinely available. In contrast, non-calibrated trend monitoring and esophageal doppler ultrasound devices were not commonly in use. Cerebral oximetry is increasingly emerging, but lacks clear indications. The majority of patients undergoing cardiac surgery, especially in university hospitals, required catecholamines during perioperative care, In case of low cardiac output syndrome, dobutamine (32%), epinephrine (30%) or phosphodiesterase inhibitors (8%) were first choice. In case of hypotension following vasoplegia, norepinephrine (96%) represented the most common catecholamine. 88% of the participating centers reported regular use of colloid fluids, with hydroxyethyl starches (HES) being first choice (64%). Choice of hemodynamic monitoring is homogenous throughout German centers treating cardiac surgery patients. Norepinephrine is the first line catecholamine in cases of decrease in peripheral vascular resistance. However, catecholamine choice for low cardiac output syndrome varies considerably. HES was the primary colloid used for fluid resuscitation. After conduct of this survey, HES use was restricted by European regulatory authorities in critically ill patients and should only be considered as second-line fluid in surgical patients without renal impairment or severe coagulopathy. Large clinical studies addressing catecholamine and fluid therapy in cardiac surgery patients are lacking. | 25,084,362 | [
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Unexpected σ bond rupture during the reaction of N-methyl-1,2,4-triazoline-3,5-dione with acenaphthylene and indene. | The reaction of N-methyl-1,2,4-triazoline-3,5-dione (MeTAD) with acenaphthylene and indene leads not only to the formation of the expected [2 + 2] diazetidine cycloadducts but also to unexpected 2:1 adducts of MeTAD with substrate. The structures of the products derived from acenaphthylene were confirmed by X-ray crystallography. A similar distribution of products was afforded from indene. The 2:1 adducts appear to derive from a diradical intermediate, the radical centers of which are strongly stabilized by the bridging urazoyl ring and benzylic delocalization. The triplet states of these diradical intermediates may be trapped via exposure to molecular oxygen to afford oxygen-containing adducts. Computational studies at the (U)B3LYP/6-31G* level provide additional support for the conclusions of our experimental work. | 25,084,364 | [
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Nonviral minicircle generation of induced pluripotent stem cells compatible with production of chimeric chickens. | Chickens are vitally important in numerous countries as a primary food source and a major component of economic development. Efforts have been made to produce transgenic birds through pluripotent stem cell [primordial germ cells and embryonic stem cells (ESCs)] approaches to create animals with improved traits, such as meat and egg production or even disease resistance. However, these cell types have significant limitations because they are hard to culture long term while maintaining developmental plasticity. Induced pluripotent stem cells (iPSCs) are a novel class of stem cells that have proven to be robust, leading to the successful development of transgenic mice, rats, quail, and pigs and may potentially overcome the limitations of previous pluripotent stem cell systems in chickens. In this study we generated chicken (c) iPSCs from fibroblast cells for the first time using a nonviral minicircle reprogramming approach. ciPSCs demonstrated stem cell morphology and expressed key stem cell markers, including alkaline phosphatase, POU5F1, SOX2, NANOG, and SSEA-1. These cells were capable of rapid growth and expressed high levels of telomerase. Late-passage ciPSCs transplanted into stage X embryos were successfully incorporated into tissues of all three germ layers, and the gonads demonstrated significant cellular plasticity. These cells provide an exciting new tool to create transgenic chickens with broad implications for agricultural and transgenic animal fields at large. | 25,084,370 | [
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Crystallographic characterization of the C-terminal coiled-coil region of mouse Bicaudal-D1 (BICD1). | Bicaudal-D1 (BICD1) is an α-helical coiled-coil protein which is evolutionarily conserved from Drosophila to mammals and facilitates the attachment of specific cargo factors to the dynein motor complex. The C-terminal coiled-coil region (CC3) of BICD1 plays an important role in sorting cargo, linking proteins such as the small GTPase Rab6 and the nuclear pore complex component Ran-binding protein 2 (RanBP2) to the dynein motor complex. This report describes the crystallization and X-ray data collection of the BICD1 CC3 region, as well as the preparation of the complex of BICD1 CC3 with a constitutively active mutant of Rab6. The crystals of the BICD1 CC3 region belonged to space group C2, with unit-cell parameters a = 59.0, b = 36.8, c = 104.3 Å, α = γ = 90, β = 99.8°. The X-ray diffraction data set was collected to 1.50 Å resolution. | 25,084,392 | [
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A new gasification and melting incineration process of MSW with co-current shaft furnace. | In all the municipal solid waste (MSW) disposal technology, incineration with gasification and melting has been taken as a environmentally sound and zero emission technology owing to avoiding second-pollution of heavy metals and dioxin. In this background, a new direct gasification and melting incineration process with co-current shaft furnace is put forward. In this process, MSW and combustion-supporting air are co-current from top to bottom in a shaft furnace. Fuel gas from pyrolysis and gasification burns completely in the bottom in order to offer energy for slag melting. The simulation experiment of the co-current shaft furnace has been done. The results of simulation experiment show that the temperature on the condition of co-current is much higher than on the condition of countercurrent at the bottom of reaction tube and so is the CO2 quantity discharged from reaction tube. It can be concluded that the co-current shaft furnace is more suitable for direct gasification and melting incineration process. | 25,084,404 | [
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0.324... |
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