title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Tracking multiple particles in fluorescence time-lapse microscopy images via probabilistic data association. | Tracking subcellular structures as well as viral structures displayed as 'particles' in fluorescence microscopy images yields quantitative information on the underlying dynamical processes. We have developed an approach for tracking multiple fluorescent particles based on probabilistic data association. The approach combines a localization scheme that uses a bottom-up strategy based on the spot-enhancing filter as well as a top-down strategy based on an ellipsoidal sampling scheme that uses the Gaussian probability distributions computed by a Kalman filter. The localization scheme yields multiple measurements that are incorporated into the Kalman filter via a combined innovation, where the association probabilities are interpreted as weights calculated using an image likelihood. To track objects in close proximity, we compute the support of each image position relative to the neighboring objects of a tracked object and use this support to recalculate the weights. To cope with multiple motion models, we integrated the interacting multiple model algorithm. The approach has been successfully applied to synthetic 2-D and 3-D images as well as to real 2-D and 3-D microscopy images, and the performance has been quantified. In addition, the approach was successfully applied to the 2-D and 3-D image data of the recent Particle Tracking Challenge at the IEEE International Symposium on Biomedical Imaging (ISBI) 2012. | 25,252,280 | [
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[The evolution of human Y chromosome]. | The human Y chromosome is always intriguing for researchers, because of its role in gender determination and its unusual evolutionary history. The Y chromosome evolves from an autosome, and its evolution has been characterized by massive gene decay. The lack of recombination and protein-coding genes and high content of repetitive sequences have hindered the progress in our understanding of the Y chromosome biology. Recently, with the advances in comparative genomics and sequencing technology, the research on Y chromosome has become a hotspot, with an intensified debate about Y-chromosome final destination resulting from degeneration. This review focuses on the structure, inheritance characteristics, gene content, and the origin and evolution of Y chromosome. We also discuss the long-term destiny of Y chromosome. | 25,252,301 | [
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[Gene mining of sulfur-containing amino acid metabolic enzymes in soybean]. | The genes of sulfur-containing amino acid synthetases in soybean are essential for the synthesis of sulfur-containing amino acids. Gene mining of these enzymes is the basis for the molecular assistant breeding of high sulfur-containing amino acids in soybean. In this study, using software BioMercator2.1, 113 genes of sulfur-containing amino acid enzymes and 33 QTLs controlling the sulfur-containing amino acids content were mapped onto Consensus Map 4.0, which was integrated by genetic and physical maps of soybean. Sixteen candidate genes associated to the synthesis of sulfur-containing amino acids were screened based on the synteny between gene loci and QTLs, and the effect values of QTLs. Through a bioinformatic analysis of the copy number, SNP information, and expression profile of candidate genes, 12 related enzyme genes were identified and mapped on 8 linkage groups, such as D1a, M, A2, K, and G. The genes corresponding to QTL regions can explain 6%?38.5% genetic variation of sulfur-containing amino acids, and among them, the indirect effect values of 9 genes were more than 10%. These 12 genes were involved in sulfur-containing amino acid metabolism and were highly expressed in the cotyledons and flowers, showing an abundance of SNPs. These genes can be used as candidate genes for the development of functional markers, and it will lay a foundation for molecular design breeding in soybean. | 25,252,311 | [
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[The practice and discussion of the physical knowledge stepping into genetics teaching]. | Genetics, one of the core courses of biological field, play a key role in biology teaching and research. In fact, there exists high similarity between many genetic knowledge and physical knowledge. Due to strong abstract of genetic contents and the weak basis of genetics, some students lack of interests to study genetics. How to apply the strong physical knowledge which students had been learned in the middle school in genetics teaching is worthwhile for genetics teachers. In this paper, we would like to introduce an infiltrative teaching model on applying physical knowledge into genetic contents by establishing the intrinsic logistic relationship between physical knowledge and genetic knowledge. This teaching model could help students more deeply understand genetic knowledge and enhance students' self-studying ability as well as creating ability. | 25,252,313 | [
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Chlorine inactivation of hepatitis E virus and human adenovirus 2 in water. | Hepatitis E virus (HEV) is transmitted via the fecal-oral route and has been recognized as a common source of large waterborne outbreaks involving contaminated water in developing countries. Thus, there is the need to produce experimental data on the disinfection kinetics of HEV by chlorine in water samples with diverse levels of fecal contamination. Here, the inactivation of HEV and human adenovirus C serotype 2 (HAdV2), used as a reference virus, was monitored using immunofluorescence and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays. HEV has been shown to be susceptible to chlorine disinfection and presented equivalent kinetics to human adenoviruses. The C(t) values observed for a 2-log reduction of HEV were 0.41 in buffered demand-free water and 11.21 mg/L × min in the presence of 1% sewage. The results indicate that the inactivation kinetics of HEV and HAdV2 are equivalent and support the use of chlorine disinfection as an effective strategy to control HEV waterborne transmission. | 25,252,347 | [
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[Experience of application of nonsuture electrowelding technologies in thoracic surgery]. | Experience of application of nonsuture electrowelding technologies (NEWT) was analyzed while performing open and miniinvasive thoracoscopic operations in 116 patients. No essential differences were revealed while comparing domestic and foreign electrowelding surgical instruments. Possibility of wide application of NEWT in miniinvasive videothoracoscopic surgery was demonstrated. | 25,252,414 | [
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Avoiding narcotic analgesics in young children. | Recent warnings regarding the use of codeine in young children have triggered changes in postoperative pain management with a trend toward over the counter pain medicines. A summary of the recent FDA warnings and current pain protocols is contained within. | 25,252,426 | [
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Relationship between tooth dimensions and malocclusion. | To observe the difference in dimension of teeth among adult females with and without malocclusion. The cross-sectional study was conducted at Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, Dow University of Health Sciences, Karachi, from April 2011 to April 2013, and used non-probability consecutive sampling. Mesiodistal and buccolingual crown dimensions were measured on study casts by using digital sliding caliper in 2 groups of females. Group 1 had 150 subjects with normal occlusion, while Group 2 had 234 with malocclusion. Independent t test was conducted to evaluate the difference between the dimensions of teeth of the two groups. Statistical analysis was done on SPSS version 16, and p value was considered significant at 0.05. Overall, the difference between the groups showed a greater tooth dimension in the malocclusion group of population compared to the normal group, and the most significant difference was observed in the mesiodistal dimension of maxillary 2nd premolar, which was 0.9 +/- 0.6801mm greater in dimension in the malocclusion group compared to the normal group. The least difference was observed in the buccolingual dimension of the mandibular central incisor where the malocclusion group had only 0.08 +/- 0.5247mm larger mandibular central incisors in the buccolingual dimension compared to the normal group. Mesiodistal and buccolingual crown dimensions were characteristically larger in the malocclusion group. | 25,252,487 | [
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Pumpkin seed oil (prostafit) or prazosin? Which one is better in the treatment of symptomatic benign prostatic hyperplasia. | To assess the efficacy of drugs containing herbal extracts in the treatment of Benign Prostatic Hyperplasia. The clinical trial study was performed in 2011-2012 at Imam Reza Hospital, Mashhad, Iran. One hundred patients with Benign Prostatic Hyperplasia were randomly divided into 2 equal groups receiving prostafit and prazosin, respectively. Quality of life and International Prostatic Symptom Score questionnaire were filled and prostate specific antigen level, uroflowmetry and prostate volume were measured at baseline, 3 and 6 months after the medication. The data was analysed using SPSS 15 and repeated measure analysis of variance. No complications were observed during and after the treatment. International Prostatic Symptom Score had significant differences at baseline and 6 months after the treatment in both groups, specially in group 2 18 vs 22 (36% versus 44%). Quality of life was better in group 2, 25.5 vs 31.5 (51% versus 63%). prostate specific antigen level did not change after the treatment and there was no remarkable difference in either group. Prostafit is an effective and safe treatment in Benign Prostatic Hyperplasia but not as much as prozasin. | 25,252,490 | [
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Two cases of Creutzfeldt-Jakob disease from an ongoing dementia registry in Pakistan. | Creutzfeldt-Jakob disease (CJD) is a rare prion disease that leads to a rapidly progressive dementia (RPD) and associated neurological features. It is not well documented in our country; therefore its true prevalence in Pakistan is not known. Here we report two cases of sporadic probable CJD seen in our hospital. The first, a 62 years old female, presented with RPD and myoclonus. The second was a 72 years old female who presented with generalized axial and limb rigidity, mutisim, personality changes and hallucinations along with RPD. Both cases were diagnosed as CJD on the basis of clinical, MRI and EEG findings. | 25,252,497 | [
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Awareness among general population attending Civil Hospital Karachi about risk factors associated with infertility. | To evaluate awareness amongst general population attending Civil Hospital Karachi regarding risk factors associated with infertility. A descriptive study was conducted on subjects who were attendants to the patients admitted in Civil Hospital Karachi or had appointment in outpatient department. They were interviewed one-on-one after their verbal consent, through separate questionnaires for each gender, from September 2012 to January 2013. Minimal age of the respondents included was 18 years. Data was entered and analyzed in SPSS (version 20.0). A total of 289 attendants were interviewed, 150 were females, with mean age 38.1 +/- 11.3 years, remaining 139 were males having a mean age of 32.5 +/- 9.9 years. Correct knowledge about the risk factors causing infertility was found to be limited among people. Only 159 (66.9%) and 142 (49%) of the total respondents recognized obesity and diabetes as a threat. Just 54 (36%) and 72 (48%) of females were able to appreciate hirsutism and menorrhagia respectively as cause. Sixty (43%) and 67 (48%) of males considered mumps and smoking respectively as culprits. In contrast to previous researches, men received greater votes for being a probable victim of infertility (55%; 159 of the total respondents). Inadequacy of knowledge about infertility was clearly demonstrated through this study. This lack of knowledge explains why such a strong stigma is attached to infertility in the society. | 25,252,505 | [
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Effectiveness of behavioural management on migraine in adult patients visiting family practice clinics: a randomized controlled trial. | To assess the effectiveness of behavioural management in the treatment of migraine among adult patients. The randomised control trial was conducted from August 2011 to August 2012 at the Aga Khan University Hospital, Karachi, in which adult patients aged 18-65 years were recruited with diagnosis of migraine from five outpatient sites. The patients were randomised into 2 equal groups. The controls were given pharmacological treatment, while the cases were given a structured behavioural management and pharmacological treatment. Primary outcome was the change in frequency of migraine attacks. Secondary outcome included change in severity of migraine and effect on the quality of life. SPSS 19 was used for statistical analysis. Of the 90 subjects in the study, 72 (80%) were female. A significant reduction in the average frequency of migraine attacks was observed from baseline up to 4 weeks (p < 0.001) but no difference in the mean migraine attacks was observed in the two groups (p < 0.945). In the average score of severity of pain, significant reduction was observed for time (p < 0.001) as well as for the intervention status (p < 0.034). There was no significant difference (p < 0.450) between treatment type and duration of migraine, but a significantly better quality of life (p < 0.001) was observed in the trial group compared to the controls. There was significant decrease in frequency, severity and duration of migraine attacks in the trial group compared to the control group. The quality of life also showed improvement in the trial group. | 25,252,515 | [
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Recurrent meningitis in a child with IgG3 subclass deficiency. | Recurrent meningitis is an uncommon life-threatening condition. Here, the case of a 6-year-old boy is reported who had two episodes of meningitis with an IgG3 subclass deficiency. The boy had aseptic meningitis at the age of 3 years, followed by bacterial meningitis at the age of 4 years. Primary immunoglobulin deficiencies are a group of disorders associated with an increased incidence and/or severity of infection. Recurrent infections, sinusitis, bronchitis, and pneumonia are the most frequently observed illnesses in patients with IgG subclass deficiencies, of which an IgG3 subclass deficiency is the most common, especially in adults. Although cases of recurrent viral or bacterial meningitis have been reported, herein a patient is presented with recurrence of aseptic and bacterial meningitis 1 year after the initial episode. Some researchers recommend that all children with episodes of recurrent meningitis should be screened for primary immunoglobulin or complement deficiencies. | 25,252,530 | [
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Thyroid disorders and diabetes. | Thyroid disorders and diabetes mellitus are two of the most common endocrine conditions, which occur with greater frequency along with each other. This communication describes current knowledge about these twin diseases. Epidemiology, clinical features, laboratory abnormalities, screening and therapeutic implication of this relationship are discussed. The article underlines the clinical relevance of thyroid disorder in diabetes management. | 25,252,531 | [
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[The choice of pancreaticojejunal anastomosis based on the performance experience of 200 operations of pancreaticoduodenal resection]. | Analysis of the surgical treatment results in 200 patients, operated for obstructive diseases of the biliopancreatoduodenal zone, in whom pancreaticoduodenal resection (PDR) was performed in 1991 - 2013 yrs period, were presented. The choice of the pancreaticojejunoanastomosis (PJA) variant in PDR have depended on dimension of diameter of the pancreatic gland stump and the jejunum diameter, as well as from state of pancreatic parenchyma and duct. Application of differentiated approach to choice of the PJA variant have permitted to reduce the complications rate, including the sutures insufficiency. | 25,252,541 | [
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[Preoperative portal vein embolization: dynamics of portal pressure]. | The pressure dynamics was studied in a portal vein (PV) in patients, suffering focal hepatic pathology, to whom portal vein embolization (PVE) was performed as a stage of preparation to radical hepatic resection. In 236 patients the immediate measurement of pressure in a PV was performed intraoperatively before and after PVE, in 26 - catheter for control portography and monitoring of pressure in a PV was left in its trunk for 24 h postoperatively. There was noted a pressure rising in a PV immediately after its embolization by 86.7%, positive correlation was established between PVE volume and pressure gradient in a PV before and after it. While doing monitoring during 24 h there was observed the pressure rising in a PV during 3 h after its embolization with subsequent lowering down to initial. Application of PVE as a preparation procedure for performance of extended hepatic resection, together with enhancement of residual liver minimizes sharp postresectional pressure rising in PV, what constitutes essential factor of the hepatocytes damage of residual hepatic part in immediate postoperative period. | 25,252,551 | [
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[Improvement of approach to performance of lumbar sympathetic blockade in patients with tissue ischemia of the lower extremities]. | New access for performance of sympathic blockade in region of aortal bifurcation, was elaborated, basing on calculations, conducted on 30 spiral computeric tomograms of lumbar and sacral parts of vertebral column. Application of the method permits to escape such complications, as a renal and the main vessels damage, the sympathetic nerves blockade, do not demand roentgenological control. | 25,252,554 | [
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[Peculiarities of clinical course and factors impacting the results of surgical treatment of intracerebral hematoma in isolated cranio-cerebral trauma]. | Peculiarities of clinical course of intracerebral hematoma (ICH) in isolated cranio-cerebral trauma (CCT), and factors, influencing the surgical treatment results, were analyzed. Medical histories of 188 injured persons, suffering isolated CCT, were analyzed, in 14 of them ICH was revealed. In isolated CCT the brain contusion focus, revealed in first hours after trauma, in accordance to CT of the brain data, during 10 - 12 h may be transformed into ICH, with increase of the brain oedema severity, what constitutes bad prognostic sign. There are following unfavorable factors: severe state of the injured person while his admittance to hospital, decompensation of the CCT course, elderly age, absence of treatment on prehospital stage, the operation performance later than in 1 - 2 h after admittance to hospital, occurrence of cerebral and extracerebral complications postoperatively, including focus of encephalomalacia, meningoencephalitis, and pulmonary complications as well. | 25,252,556 | [
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[Feasibility study of septoplasties and septorhinoplasties in ambulatory surgery]. | Feasibility assessment of septoplasty and septorhinoplasty as ambulatory procedures, from analysis of the activity of a university ENT department. This is a retrospective analysis over 2 years. The demographic data, the distance between the patient's home and the ENT department, the cause of the septal deviation, the exact kind of surgery, the time of the beginning of the anaesthesia, the duration of the surgery, the postoperative data, the complications and the duration of hospitalization were collected. The operating durations were compared according to the sex, to the cause of the septal deviation, to previous surgery or not and to the kind of surgery performed, using Mann-Whitney's test. The correlations between the age, the operating duration and the time of the beginning of the anaesthesia were estimated using Spearman's test. Then, all the criteria of eligibility for an ambulatory surgical procedure were applied to this population, taking into account or not the distance between the patient's home and the ENT department. A financial analysis was realized on the eligible population, comparing the earnings for a traditional hospitalization with an ambulatory one. 424 patients were included, with an average age of 38 years old. 47 patients had an anaesthetic contraindication for the ambulatory surgery. 226 nasoseptal deviations were congenital (53.3%) and 198 post-traumatic (46.7%). 353 patients had never had a nasoseptal surgery (83.25%). The average time of the beginning of the anaesthesia was 10:55 am. The average durations were 75.8 +/- 32 min for septoplasty versus 127.5 +/- 44 min for the other acts (p < 10-5). There was a strong statistical difference of operating durations between a first surgery and a secondary surgical revision; as well as between a congenital cause and post-traumatic one (p < 10-5). There was an inverse correlation between the age and the operating duration (p < 10-4) and a correlation between the age and the time of the beginning of the anaesthesia (p < 10-5). 23 patients (5.42%) suffered from pains, nausea/vomitings and epistaxis within the 6 postoperative hours, that would have prevented them from going back home. 23 patients (5.42%) presented hematoma, infections, scar disunity, pains and faintness between day 4 and day 8 after surgery. In all, considering a distance shorter then an 1 hour drive from the ENT department, 69 patients (16.3%) were eligible retrospectively for an ambulatory surgery; they would have been 154 (40.8%) in the absence of this criteria. The medico-economic earnings would have been about 39,900 euros for 69 patients, for 2 years. 17 to 40% of the patients were potentially eligible for an ambulatory procedure, without endangering them. | 25,252,573 | [
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[Karapandzic flap for reconstruction of extensive defects of the lower lip]. | To discuss advantages and disadvantages of Karapandzic flap for reconstruction of extensive defects of the lower lip. Two clinical observations and a review of the literature are presented. The Karapandzic flap requires only one operating time. The tissue used to reconstruct the lower lip is very close to the resected lip. The functional result is satisfactory, the lips being continent, allowing speech and feeding. The main advantage of this technique is the preservation of the labial sphincter, which is vascularized, mobile and sensitive. The aesthetic result is acceptable. This flap keeps the vermilion, but with rounded commissures that corrects spontaneously. The main disadvantage of this flap is the microstomia, requiring only rarely further surgery. The Karapandzic flap is a good option for reconstruction of extensive defects of the lower lip. It recreates the labial sphincter, while maintaining its vascularization and innervation. Functionality is maintained, with an aesthetically acceptable result despite the presence of residual microstomia proportional to the defect. | 25,252,574 | [
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[Nasal tumours of the threshold and vestibule]. | The nasal vestibule tumors are not very frequent. The pronostic can be severe if the first treatment is not effective. The authors present a personnal nine pateints' serie. They point out the clinical aspect, the evolutivity of these tumors and more specially the local extension which can produce recurrencies. The differents aspects of the treatment are analysed and more specially the surgical reconstruction procedures. reconstruction. | 25,252,578 | [
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Comparing the risk of developing uveitis in patients initiating anti-tumor necrosis factor therapy for ankylosing spondylitis: an analysis of a large US claims database. | To compare the risk of developing uveitis in patients initiating anti-tumor necrosis factor (anti-TNF) agents (adalimumab, etanercept, and infliximab) for ankylosing spondylitis (AS). Anti-TNF-naive patients with a diagnosis of AS and without a history of uveitis (N = 2115) who subsequently initiated anti-TNF therapy for AS were identified in a large claims database (2005 to 2011). A multivariate Cox proportional-hazards model was used to compare the risk of uveitis in patients who received etanercept or infliximab vs adalimumab. The median number of days to the first occurrence of uveitis after initiation of anti-TNF was 191. Among the three anti-TNF groups, the median time to event of uveitis was longest in patients taking adalimumab (243 days), followed by etanercept (182 days) and infliximab (144 days). The incidence rate for uveitis over 1 year was lowest for patients who received adalimumab (2.4%, N = 717), highest for patients who received etanercept (4.5%, N = 1087), and intermediate for patients who received infliximab (3.2%, N = 311). The risk of uveitis was 1.9 times higher in patients receiving etanercept compared with those taking adalimumab (hazard ratio [HR]: 1.91, 95% confidence interval [CI]: 1.1 to 3.31). For patients taking infliximab, the risk of uveitis was not statistically significantly different (HR: 1.35, 95% CI: 0.62 to 2.95) compared to adalimumab. The results indicated that initial adalimumab therapy is associated with a significantly lower risk of developing uveitis compared to initial etanercept therapy in patients diagnosed with AS and no prior history of uveitis; however, the risk was not different between adalimumab and infliximab. Limitations to consider when interpreting this conclusion include that disease-level clinical data, such as disease duration, were not available for inclusion in the model and that risk of uveitis beyond 1 year was not evaluated. | 25,252,590 | [
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A thiazole coumarin (TC) turn-on fluorescence probe for AT-base pair detection and multipurpose applications in different biological systems. | Sequence-specific recognition of DNA by small turn-on fluorescence probes is a promising tool for bioimaging, bioanalytical and biomedical applications. Here, the authors report a novel cell-permeable and red fluorescent hemicyanine-based thiazole coumarin (TC) probe for DNA recognition, nuclear staining and cell cycle analysis. TC exhibited strong fluorescence enhancement in the presence of DNA containing AT-base pairs, but did not fluoresce with GC sequences, single-stranded DNA, RNA and proteins. The fluorescence staining of HeLa S3 and HEK 293 cells by TC followed by DNase and RNase digestion studies depicted the selective staining of DNA in the nucleus over the cytoplasmic region. Fluorescence-activated cell sorting (FACS) analysis by flow cytometry demonstrated the potential application of TC in cell cycle analysis in HEK 293 cells. Metaphase chromosome and malaria parasite DNA imaging studies further confirmed the in vivo diagnostic and therapeutic applications of probe TC. Probe TC may find multiple applications in fluorescence spectroscopy, diagnostics, bioimaging and molecular and cell biology. | 25,252,596 | [
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[Ultrasound diagnostics in ophthalmology (standardized echography): part 1: principles and diseases of the eyeball]. | Ultrasound diagnostics has been one of the most important additional diagnostic non-invasive techniques in ophthalmology for many decades and is essential for many intraocular and orbital diseases. When echographic investigations and analysis of the echograms obtained are correctly carried out, ultrasound diagnostics demonstrates a high degree of specificity and sensitivity. | 25,252,599 | [
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The REFLO-STEMI trial comparing intracoronary adenosine, sodium nitroprusside and standard therapy for the attenuation of infarct size and microvascular obstruction during primary percutaneous coronary intervention: study protocol for a randomised controlled trial. | Microvascular obstruction (MVO) secondary to ischaemic-reperfusion injury is an important but underappreciated determinant of short- and longer-term outcome following percutaneous coronary intervention (PCI) treatment of ST-elevation myocardial infarction (STEMI). Several small studies have demonstrated a reduction in the degree of MVO utilising a variety of vasoactive agents, with adenosine and sodium nitroprusside (SNP) being most evaluated. However, the evidence base remains weak as the trials have had variable endpoints, differing drug doses and delivery. As such, the results regarding benefit are conflicting. The REperfusion Facilitated by LOcal adjunctive therapy in STEMI (REFLO-STEMI) trial is a multicentre, prospective, randomised, controlled, open label, study with blinded endpoint analysis: Patients presenting within 6 h of onset of STEMI and undergoing planned primary PCI (P-PCI) with TIMI 0/1 flow in the infarct-related artery (IRA) and no significant bystander coronary artery disease on angiography, are randomised into one of three groups: PCI with adjunctive pharmacotherapy (intracoronary adenosine or SNP) or control (standard PCI). All receive Bivalirudin anticoagulation and thrombus aspiration. The primary outcome is infarct size (IS) (determined as a percentage of total left ventricular mass) measured by cardiac magnetic resonance imaging (CMRI) undertaken at 48 to 72 h post P-PCI. Secondary outcome measures include MVO (hypoenhancement within infarct core) on CMRI, angiographic markers of microvascular perfusion and MACE during 1-month follow-up. The study aims to recruit 240 patients (powered at 80% to detect a 5% absolute reduction in IS). The REFLO-STEMI study has been designed to address the weaknesses of previous trials, which have collectively failed to demonstrate whether adjunctive pharmacotherapy with adenosine and/or SNP can reduce measures of myocardial injury (infarct size and MVO) and improve clinical outcome, despite good basic evidence that they have the potential to attenuate this process. The REFLO-STEMI study will be the most scientifically robust trial to date evaluating whether adjunctive therapy (intracoronary adenosine or SNP following thrombus aspiration) reduces CMRI measured IS and MVO in patients undergoing P-PCI within 6 h of onset of STEMI. Trial registered 20th November 2012: ClinicalTrials.gov Identifier NCT01747174. | 25,252,600 | [
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Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy. | In the literature, HPV infection and/or p16 positivity have been consistently demonstrated to correlate with improved response rates in oropharyngeal squamous cell carcinoma (OPSCC) patients treated with primary radiotherapy (RT) alone and in combination with chemotherapy. However, the exact role of HPV/p16 positivity in patients treated with postoperative RT is still unclear. We analyzed tumor samples for HPV-DNA and p16 expression and correlated these variables with treatment outcome in a series of 63 consecutively treated oropharyngeal cancer patients (95% stage III/IV). HPV and p16 analysis were performed using validated test systems. Survival was estimated by the Kaplan-Meier method. Cox proportional hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. Expression of p16 or high-risk HPV-DNA was detected in 60.3% and 39.6% of the tumors, respectively. p16 expression [overall survival (OS) at 2 years: 91%] as well as HPV infection (OS at 2 years: 95%) was associated with improved OS. Mean survival in p16-positive patients was 112 months compared to 64.6 months in case of p16 negativity. All HPV-positive tumors stained positive for p16. In a multivariable analysis, p16 positivity was associated with improved OS and with disease-free survival. p16 expression and HPV infection are strongly associated with the outcome of postoperatively irradiated OPSCC patients. HPV and p16 double-negative OPSCC patients should be regarded as a distinct "very high-risk patient group" that may benefit from intensified or novel treatment combinations. | 25,252,603 | [
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Associations of macular thickness in spectral-domain OCT with ocular and systemic cardiovascular parameters - the MIPH Eye & Health Study. | Beyond in-vivo histological analysis of retinal tissue, optical coherence tomography (OCT) allows quantitative image analysis. This study evaluates associations of macular retinal thickness measured with spectral-domain OCT (SD-OCT) and ocular and systemic cardiovascular parameters in adult subjects. An epidemiological cross-sectional study was performed in the staff of a European high-tech company. Examination of known cardiovascular risk factors including biochemical blood analysis was performed, and ocular parameters such as refraction, tonometry, SD-OCT imaging of the macula and cornea, and fundus photography were evaluated. Retinal thickness measurements were evaluated according to the ETDRS grid. Associations of macular retinal thickness and systemic cardiovascular and ocular parameters were calculated by multivariate analysis using SPSS software. Four hundred and twenty-four probands were included. Macular thickness measurement were significantly associated with gender and refraction. Female persons had thinner retinal thickness in all zones. Macular thickness decreased with increasing myopia in all perifoveal measurements. Outer perifoveal measurements were associated with keratometry; a flatter corneal radius was linked to a thinner retina. Tonometry and systemic cardiovascular risk factors were not associated with macular retinal thickness in multivariate analysis (p > 0.05). Macular retinal thickness is associated with refraction and gender; cardiovascular risk factors or tonometry do not influence macular retinal thickness measurements. Keratometry might influence outer zone measurements. Our findings provide a dataset for quantitative evaluation of SD-OCT, and evaluate influencing factors. | 25,252,606 | [
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Crystal structure of class III chitinase from pomegranate provides the insight into its metal storage capacity. | Chitinase hydrolyzes the β-1,4-glycosidic bond in chitin. In higher plants, this enzyme has been regarded as a pathogenesis-related protein. Recently, we identified a class III chitinase, which functions as a calcium storage protein in pomegranate (Punica granatum) seed (PSC, pomegranate seed chitinase). Here, we solved a crystal structure of PSC at 1.6 Å resolution. Although its overall structure, including the structure of catalytic site and non-proline cis-peptides, was closely similar to those of other class III chitinases, PSC had some unique structural characteristics. First, there were some metal-binding sites with coordinated water molecules on the surface of PSC. Second, many unconserved aspartate residues were present in the PSC sequence which rendered the surface of PSC negatively charged. This acidic electrostatic property is in contrast to that of hevamine, well-characterized plant class III chitinase, which has rather a positively charged surface. Thus, the crystal structure provides a clue for metal association property of PSC. | 25,252,615 | [
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Evaluation of pre-induction temperature, cell growth at induction and IPTG concentration on the expression of a leptospiral protein in E. coli using shaking flasks and microbioreactor. | Leptospirosis is a zoonose that is increasingly endemic in built-up areas, especially where there are communities living in precarious housing with poor or non-existent sanitation infrastructure. Leptospirosis can kill, for its symptoms are easily confused with those of other diseases. As such, a rapid diagnosis is required so it can be treated effectively. A test for leptospirosis diagnosis using Leptospira Immunoglobulin-like (Lig) proteins is currently at final validation at Fiocruz. In this work, the process for expression of LigB (131-645aa) in E. coli BL21 (DE3)Star™/pAE was evaluated. No significant difference was found for the experiments at two different pre-induction temperatures (28 °C and 37 °C). Then, the strain was cultivated at 37 °C until IPTG addition, followed by induction at 28°C, thereby reducing the overall process time. Under this condition, expression was assessed using central composite design for two variables: cell growth at which LigB (131-645aa) was induced (absorbance at 600 nm between 0.75 and 2.0) and inducer concentration (0.1 mM to 1 mM IPTG). Both variables influenced cell growth and protein expression. Induction at the final exponential growth phase in shaking flasks with Abs(ind) = 2.0 yielded higher cell concentrations and LigB (131-645aa) productivities. IPTG concentration had a negative effect and could be ten-fold lower than the concentration commonly used in molecular biology (1 mM), while keeping expression at similar levels and inducing less damage to cell growth. The expression of LigB (131-645aa) was associated with cell growth. The induction at the end of the exponential phase using 0.1 mM IPTG at 28 °C for 4 h was also performed in microbioreactors, reaching higher cell densities and 970 mg/L protein. LigB (131-645aa) was purified by nickel affinity chromatography with 91% homogeneity. It was possible to assess the effects and interactions of the induction variables on the expression of soluble LigB (131-645aa) using experimental design, with a view to improving process productivity and reducing the production costs of a rapid test for leptospirosis diagnosis. | 25,252,618 | [
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Adrenal oncocytic phaeochromocytoma with putative adverse histologic features: a unique case report and review of the literature. | Oncocytic phaeochromocytomas are exceedingly rare tumours. To date, there are three reported cases in the literature. This report describes a case of adrenal oncocytic phaeochromocytoma with unique features and malignant potential in a 68-year-old man. The patient presented with an incidental non-functional mass discovered on routine radiological investigation, which was subsequently excised. Histologically, the tumour cells showed oncocytic features with high-grade nuclear abnormalities and foci of extension to the peri-adrenal fat. Immunohistochemistry performed was positive for chromogranin, CD56, S-100 and p53 and negative for inhibin, HMB-45, EMA, AE1/AE3, Cam 5.2 and calretinin. Electron microscopy showed electron dense granules of neurosecretory type, which confirmed the diagnosis. The malignant potential of the tumour was assessed on available histologic scoring systems, which demonstrated a high malignant potential. However, no recurrence was detected after 5 years of follow-up. Compared to all the previously reported cases of oncocytic phaeochromocytoma, this patient was the oldest on presentation, was the only case with identified high malignant potential and has the longest follow-up. A review of the literature showed that all the oncocytic phaeochromocytomas reported were non-functional, non-metastasizing and were described in women. To conclude, oncocytic phaeochromocytoma should be in the differential diagnoses of oncocytic tumours of the adrenal gland. Additional studies are needed to predict the behaviour of this entity. | 25,252,620 | [
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Therapeutic biomarkers in lung neuroendocrine neoplasia. | The well-known classification of neuroendocrine neoplasms of the lung into four major subtypes (including typical and atypical carcinoids and small- and large-cell neuroendocrine carcinomas) has a proven prognostic validity but only partially helps to predict the response to specific therapies. Therapeutic biomarkers are incompletely known and include morphological, immunophenotypic, and molecular markers. Morphology alone has no specific predictive role, nor has any immunophenotypic marker been proven to bear predictive implications. Ki67 is a relevant prognostic marker and can indirectly predict response to chemotherapy, when levels are extremely high in high-grade neuroendocrine (NE) carcinomas. The expression of somatostatin receptors, especially of the type 2A, has been shown to predict response to somatostatin analog treatments, paralleling the information derived from octreotide scintigraphy. mTOR pathway is targeted by specific inhibitors, but the exact cellular molecules predicting response are still to be defined. It seems that high levels of phosphorylated forms of mTOR and of its downstream factor S6K are associated to a better response to rapalogs in experimental models. Data from gene expression profiling and mutational analyses are currently emerging, providing a more detailed map of different molecular activation pathways, potentially leading to a more accurate molecular classification of lung NE tumors as well as to the discovery of new therapeutic targets. The combination of mutational profiles with those of upregulated or downregulated genes also by gene gains or losses may ultimately provide a better characterization of NE tumor histological types in terms of response to specific chemotherapy or biotherapy. | 25,252,622 | [
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Proteomic study reveals a functional network of cancer markers in the G1-Stage of the breast cancer cell cycle. | Cancer cells are characterized by a deregulated cell cycle that facilitates abnormal proliferation by allowing cells to by-pass tightly regulated molecular checkpoints such as the G1/S restriction point. To facilitate early diagnosis and the identification of new drug targets, current research efforts focus on studies that could lead to the development of protein panels that collectively can improve the effectiveness of our response to the detection of a life-threatening disease. Estrogen-responsive MCF-7 cells were cultured and arrested by serum deprivation in the G1-stage of the cell cycle, and fractionated into nuclear and cytoplasmic fractions. The protein extracts were trypsinized and analyzed by liquid chromatography--mass spectrometry (MS), and the data were interpreted with the Thermo Electron Bioworks software. Biological characterization of the data, selection of cancer markers, and identification of protein interaction networks was accomplished with a combination of bioinformatics tools provided by GoMiner, DAVID and STRING. The objective of this work was to explore via MS proteomic profiling technologies and bioinformatics data mining whether randomly identified cancer markers can be associated with the G1-stage of the cell cycle, i.e., the stage in which cancer cells differ most from normal cells, and whether any functional networks can be identified between these markers and placed in the broader context of cell regulatory pathways. The study enabled the identification of over 2000 proteins and 153 cancer markers, and revealed for the first time that the G1-stage of the cell cycle is not only a rich source of cancer markers, but also a host to an intricate network of functional relationships within the majority of these markers. Three major clusters of interacting proteins emerged: (a) signaling, (b) DNA repair, and (c) oxidative phosphorylation. The identification of cancer marker regulatory components that act not alone, but within networks, represents an invaluable resource for elucidating the moxlecular mechanisms that govern the uncontrolled proliferation of cancer cells, as well as for catalyzing the development of protein panels with biomarker and drug target potential, screening tests with improved sensitivity and specificity, and novel cancer therapies aimed at pursuing multiple drug targets. | 25,252,636 | [
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The effects of breast milk storage and freezing procedure on interleukine-10 levels and total antioxidant activity. | To compare interleukine-10 (IL-10) and total antioxidant capacity (TAC) levels after breast milk storage by studying premature and term mothers’ colostrum and mature milk and by analyzing those levels relative to gestational week. Fifty-four colostrum and mature breast milk samples were collected from both premature and term mothers. The samples were divided into three groups based on the time of analysis: fresh milk, at +4 °C for 72 h, and at -20 °C for 14 d. The IL-10 and TAC levels were measured quantitatively. Fresh colostrum and mature milk had similar IL-10 levels. Term mothers’ fresh-colostrum TAC levels were higher than their mature milk. The mature milk of the premature mothers’ had higher TAC levels than that of term mothers. Storage did not affect the IL-10 levels of breast milk, but fresh milk antioxidant capacity halved after 72 h and 14 d. Colostrum IL-10 and TAC levels did not correlate with gestational week. Mature milk IL-10 levels did not correlate with gestational week, but TAC levels negatively correlated with gestational week (r: -0.61: p < 0.01). The milk stored for 72 h at +4 °C and for 14 d at -20 °C did not maintain the same TAC levels as the fresh samples. This should be considered especially for sick infants who need more antioxidant capability in neonatal units. | 25,252,637 | [
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The immune response against Chlamydia suis genital tract infection partially protects against re-infection. | The aim of the present study was to reveal the characteristic features of genital Chlamydia suis infection and re-infection in female pigs by studying the immune response, pathological changes, replication of chlamydial bacteria in the genital tract and excretion of viable bacteria. Pigs were intravaginally infected and re-infected with C. suis strain S45, the type strain of this species. We demonstrated that S45 is pathogenic for the female urogenital tract. Chlamydia replication occurred throughout the urogenital tract, causing inflammation and pathology. Furthermore, genital infection elicited both cellular and humoral immune responses. Compared to the primo-infection of pigs with C. suis, re-infection was characterized by less severe macroscopic lesions and less chlamydial elementary bodies and inclusions in the urogenital tract. This indicates the development of a certain level of protection following the initial infection. Protective immunity against re-infection coincided with higher Chlamydia-specific IgG and IgA antibody titers in sera and vaginal secretions, higher proliferative responses of peripheral blood mononuclear cells (PBMC), higher percentages of blood B lymphocytes, monocytes and CD8⁺ T cells and upregulated production of IFN-γ and IL-10 by PBMC. | 25,252,649 | [
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[Autism in the first year]. | At present autism can be diagnosed with a high degree of reliability between the ages of 18 months and 2 years. Yet, the first symptoms are already present long before the diagnosis is made. This has led to a number of retrospective and prospective studies being conducted with the aim of detecting manifestations that allow a diagnosis to be reached as early as possible. The results of these studies have enabled researchers to detect symptoms that appear between the ages of 6 and 12 months. Although it has been observed that these symptoms are of limited diagnostic interest, they do provide invaluable information for the understanding of autism within the framework of neurodevelopmental disorders because they highlight a pattern of development that is initially common to several different disorders, but which progressively goes on to constitute a specific phenotype. | 25,252,657 | [
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[Epilepsy and cognition: the role of antiepileptic drugs]. | Multiple factors underlie the cognitive changes associated with epilepsy, including the effect of antiepileptic drug (AED) therapy itself. The use of AEDs in the management of epilepsy requires an ongoing risk-benefit analysis that attempts to maximize seizure control while minimizing adverse cognitive side-effects. This review focuses on the global and specific cognitive effects of the classic and the new AEDs. All of the established AEDs can produce cognitive side effects, which are increased with polypharmacy and with increasing dosage and anticonvulsant blood levels. The main disorders are a diminished reaction and information processing time with alterations affecting memory, attention and language. Further, there is much debate concerning the existence and clinical importance of differential AED cognitive side effects and a large portion of the literature examining the comparative cognitive effects of AEDs is limited by inadequate study designs. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. The role of cognitive side effects should be kept in proper perspective when choosing AED therapy. It is important to be able to recognize early these effects and to put them into perspective as to how they affect our patients. | 25,252,666 | [
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p53 as a retrovirus-induced oxidative stress modulator. | Infection of astrocytes by the neuropathogenic mutant of Moloney murine leukemia virus, ts1, exhibits increased levels of reactive oxygen species (ROS) and signs of oxidative stress compared with uninfected astrocytes. Previously, we have demonstrated that ts1 infection caused two separate events of ROS upregulation. The first upregulation occurs during early viral establishment in host cells and the second during the virus-mediated apoptotic process. In this study, we show that virus-mediated ROS upregulation activates the protein kinase, ataxia telangiectasia mutated, which in turn phosphorylates serine 15 on p53. This activation of p53 however, is unlikely associated with ts1-induced cell death. Rather p53 appears to be involved in suppressing intracellular ROS levels in astrocytes under oxidative stress. The activated p53 appears to delay retroviral gene expression by suppressing NADPH oxidase, a superoxide-producing enzyme. These results suggest that p53 plays a role as a retrovirus-mediated oxidative stress modulator. | 25,252,686 | [
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PARP1-driven poly-ADP-ribosylation regulates BRCA1 function in homologous recombination-mediated DNA repair. | BRCA1 promotes homologous recombination-mediated DNA repair (HRR). However, HRR must be tightly regulated to prevent illegitimate recombination. We previously found that BRCA1 HRR function is regulated by the RAP80 complex, but the mechanism was unclear. We have now observed that PARP1 interacts with and poly-ADP-ribosylates (aka PARsylates) BRCA1. PARsylation is directed at the BRCA1 DNA binding domain and downmodulates its function. Moreover, RAP80 contains a poly-ADP-ribose-interacting domain that binds PARsylated BRCA1 and helps to maintain the stability of PARP1-BRCA1-RAP80 complexes. BRCA1 PARsylation is a key step in BRCA1 HRR control. When BRCA1 PARsylation is defective, it gives rise to excessive HRR and manifestations of genome instability. BRCA1 PARsylation and/or RAP80 expression is defective in a subset of sporadic breast cancer cell lines and patient-derived tumor xenograft models. These observations are consistent with the possibility that such defects, when chronic, contribute to tumor development in BRCA1+/+ individuals. We propose a model that describes how BRCA1 functions to both support and restrict HRR. BRCA1 PARsylation is a key event in this process, failure of which triggers hyper-recombination and chromosome instability. Thus, hyperfunctioning BRCA1 can elicit genomic abnormalities similar to those observed in the absence of certain BRCA1 functions. | 25,252,691 | [
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Mutation-specific RAS oncogenicity explains NRAS codon 61 selection in melanoma. | NRAS mutation at codons 12, 13, or 61 is associated with transformation; yet, in melanoma, such alterations are nearly exclusive to codon 61. Here, we compared the melanoma susceptibility of an NrasQ61R knock-in allele to similarly designed KrasG12D and NrasG12D alleles. With concomitant p16INK4a inactivation, KrasG12D or NrasQ61R expression efficiently promoted melanoma in vivo, whereas NrasG12D did not. In addition, NrasQ61R mutation potently cooperated with Lkb1/Stk11 loss to induce highly metastatic disease. Functional comparisons of NrasQ61R and NrasG12D revealed little difference in the ability of these proteins to engage PI3K or RAF. Instead, NrasQ61R showed enhanced nucleotide binding, decreased intrinsic GTPase activity, and increased stability when compared with NrasG12D. This work identifies a faithful model of human NRAS-mutant melanoma, and suggests that the increased melanomagenecity of NrasQ61R over NrasG12D is due to heightened abundance of the active, GTP-bound form rather than differences in the engagement of downstream effector pathways. This work explains the curious predominance in human melanoma of mutations of codon 61 of NRAS over other oncogenic NRAS mutations. Using conditional "knock-in" mouse models, we show that physiologic expression of NRASQ61R, but not NRASG12D, drives melanoma formation. | 25,252,692 | [
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Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial. | Remote ischaemic preconditioning (RIPC), using brief cycles of limb ischaemia/reperfusion, is a non-invasive, low-cost intervention that may reduce perioperative myocardial injury (PMI) in patients undergoing cardiac surgery. We investigated whether RIPC can also improve short-term clinical outcomes. One hundred and eighty patients undergoing elective coronary artery bypass graft (CABG) surgery and/or valve surgery were randomised to receive either RIPC (2-5 min cycles of simultaneous upper arm and thigh cuff inflation/deflation; N=90) or control (uninflated cuffs placed on the upper arm and thigh; N=90). The study primary end point was PMI, measured by 72 h area under the curve (AUC) serum high-sensitive troponin-T (hsTnT); secondary end point included short-term clinical outcomes. RIPC reduced PMI magnitude by 26% (-9.303 difference (CI -15.618 to -2.987) 72 h hsTnT-AUC; p=0.003) compared with control. There was also evidence that RIPC reduced the incidence of postoperative atrial fibrillation by 54% (11% RIPC vs 24% control; p=0.031) and decreased the incidence of acute kidney injury by 48% (10.0% RIPC vs 21.0% control; p=0.063), and intensive care unit stay by 1 day (2.0 days RIPC (CI 1.0 to 4.0) vs 3.0 days control (CI 2.0 to 4.5); p=0.043). In a post hoc analysis, we found that control patients administered intravenous glyceryl trinitrate (GTN) intraoperatively sustained 39% less PMI compared with those not receiving GTN, and RIPC did not appear to reduce PMI in patients given GTN. RIPC reduced the extent of PMI in patients undergoing CABG and/or valve surgery. RIPC may also have beneficial effects on short-term clinical outcomes, although this will need to be confirmed in future studies. ClinicalTrials.gov ID: NCT00397163. | 25,252,696 | [
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Disrupted reproduction, estrous cycle, and circadian rhythms in female mice deficient in vasoactive intestinal peptide. | The female reproductive cycle is gated by the circadian timing system and may be vulnerable to disruptions in the circadian system. Prior work suggests that vasoactive intestinal peptide (VIP)-expressing neurons in the suprachiasmatic nucleus (SCN) are one pathway by which the circadian clock can influence the estrous cycle, but the impact of the loss of this peptide on reproduction has not been assessed. In the present study, we first examine the impact of the genetic loss of the neuropeptide VIP on the reproductive success of female mice. Significantly, mutant females produce about half the offspring of their wild-type sisters even when mated to the same males. We also find that VIP-deficient females exhibit a disrupted estrous cycle; that is, ovulation occurs less frequently and results in the release of fewer oocytes compared with controls. Circadian rhythms of wheel-running activity are disrupted in the female mutant mice, as is the spontaneous electrical activity of dorsal SCN neurons. On a molecular level, the VIP-deficient SCN tissue exhibits lower amplitude oscillations with altered phase relationships between the SCN and peripheral oscillators as measured by PER2-driven bioluminescence. The simplest explanation of our data is that the loss of VIP results in a weakened SCN oscillator, which reduces the synchronization of the female circadian system. These results clarify one of the mechanisms by which disruption of the circadian system reduces female reproductive success. | 25,252,712 | [
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An ethnobotanical study of the less known wild edible figs (genus Ficus) native to Xishuangbanna, Southwest China. | The genus Ficus, collectively known as figs, is a key component of tropical forests and is well known for its ethnobotanical importance. In recent decades an increasing number of studies have shown the indigenous knowledge about wild edible Ficus species and their culinary or medicinal value. However, rather little is known about the role of these species in rural livelihoods, because of both species and cultural diversity. In this study we 1) collected the species and ethnic names of wild edible Ficus exploited by four cultural groups in Xishuangbanna, Southwest China, and 2) recorded the collection activities and modes of consumption through semi-structured interviews, 3) investigated the resource management by a statistical survey of their field distribution and cultivation, and 4) compared and estimated the usage intensities by the grading method. The young leaves, leaf buds and young or ripe syconia of 13 Ficus species or varieties are traditionally consumed. All the species had fixed and usually food-related ethnic names. All four cultural groups are experienced in the collection and use of edible Ficus species as vegetables, fruits or beverages, with the surplus sold for cash income. Different cultural groups use the Ficus species at different intensities because of differences in availability, forest dependency and cultural factors. Both the mountain and basin villagers make an effort to realize sustainable collection and meet their own and market needs by resource management in situ or cultivation. In comparison with reports from other parts of the world, ethnic groups in Xishuangbanna exploited more edible Ficus species for young leaves or leaf buds. Most of the edible species undergo a gradient of management intensities following a gradient of manipulation from simple field gathering to ex situ cultivation. This study contributes to our understanding of the origins and diffusion of the knowledge of perception, application and managing a group of particular plant species, and how the local culture, economic and geographical factors influence the process. | 25,252,723 | [
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Procedure-dependent construction of two isomers of trimeric self-assembled boronic esters. | A procedure-dependent selective construction of two isomers of trimeric boronic esters was realized. A capsule-like trimeric boronic ester was constructed by the direct connection of two kinds of self-assembled boronic esters via [3+2] cycloaddition, while the tricyclic trimeric boronic ester was obtained by the self-assembly of pre-connected components. | 25,252,724 | [
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[Predictive factors of anxiety disorders]. | Anxiety disorders are among the most frequent mental disorders in Europe (12-month prevalence 14%) and impose a high socioeconomic burden. The pathogenesis of anxiety disorders is complex with an interaction of biological, environmental and psychosocial factors contributing to the overall disease risk (diathesis-stress model). In this article, risk factors for anxiety disorders will be presented on several levels, e.g. genetic factors, environmental factors, gene-environment interactions, epigenetic mechanisms, neuronal networks ("brain fear circuit"), psychophysiological factors (e.g. startle response and CO2 sensitivity) and dimensional/subclinical phenotypes of anxiety (e.g. anxiety sensitivity and behavioral inhibition), and critically discussed regarding their potential predictive value. The identification of factors predictive of anxiety disorders will possibly allow for effective preventive measures or early treatment interventions, respectively, and reduce the individual patient's suffering as well as the overall socioeconomic burden of anxiety disorders. | 25,252,735 | [
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[Prognostic and predictively relevant factors for multiple sclerosis]. | The immunotherapy of multiple sclerosis (MS) is currently one of the most dynamic fields in clinical neurology. The comprehensive number of well-established and new innovative treatment options are a challenge for an intensive preoccupation with the differential indications and an activity-driven treatment control. In this context this review summarizes the known predictors of the natural course of MS and gives a review of challenges to be expected in association with predictors of treatment control. | 25,252,736 | [
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A systematic review of Hepatitis C virus treatment uptake among people who inject drugs in the European Region. | Fifteen million adults in the World Health Organization European Region are estimated to have active hepatitis C infection. Intravenous drug use is a major hepatitis C transmission route in this region, and people who inject drugs (PWID) constitute a high-risk and high-prevalence population. A systematic review was conducted to assess levels of hepatitis C treatment uptake among PWID in Europe. Searches in MEDLINE and EMBASE were carried out for articles in any language published between 1 January 2000 and 31 December 2012. Articles were included in the review if they presented original research findings about hepatitis C treatment uptake levels among people who reported injecting drugs currently or formerly, as well as those who reported using drugs currently or formerly (mode of consumption not specified). Treatment uptake data were extracted if uptake was measurable in relation to the number of patients who either: (a) tested HCV antibody-positive; (b) tested positive for HCV-RNA; or (c) tested positive for HCV-RNA and met additional treatment criteria. Twenty-five articles from 12 countries were included in the review. Among groups of drug-using study participants who were hepatitis C antibody-positive, the median treatment uptake level was 17%, and among those who were hepatitis C RNA-positive, the median was 30%. In the 11 studies reporting specifically on treatment uptake among current and former injecting drug users, hepatitis C RNA-positive study populations had a median treatment uptake level of 32%. Only one study reported on treatment uptake for current drug users. This systematic review indicates that hepatitis C treatment uptake is relatively low among drug users in several European countries, and also points to considerable knowledge gaps regarding treatment uptake levels in this population. There was large variability in treatment uptake levels, suggesting that there may be major differences between and within countries in relation to treatment availability, drug-using populations in need of treatment, and the existence of integrated health care services targeting drug users. Stronger national hepatitis C treatment policies are needed, along with efforts to increase knowledge and reduce misconceptions among physicians regarding the feasibility and importance of treating drug users who have hepatitis C. | 25,252,742 | [
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High sensitivity cardiac troponin assays in the clinical laboratories. | Immunoassays measuring cardiac troponins I or T have become firmly established as critical tools for diagnosing acute myocardial infarction. While most contemporary assays provide adequate diagnostic performance, the increased sensitivity and precision of the new, high sensitivity assays that have already been introduced into clinical practice, provide the potential to further shorten intervals between blood draws or the time needed to detect the first significant troponin elevation. In addition to the relatively modest benefits at the diagnostic end, the high sensitivity assays and the investigational ultrasensitive cardiac troponin assays offer improvements for predicting major adverse cardiovascular events, development of heart failure or transition to end-stage kidney disease. These novel high sensitivity assays can measure troponin concentrations in 50%-100% of healthy individuals and therefore allow for the distribution of troponin values within a healthy cohort to be measured, patient's baseline troponin levels to be monitored, and clinicians to be alerted of deteriorating cardiorenal conditions. We envisage that the high sensitivity assays will become important tools for predicting each patient's risk of future adverse events and for guiding and monitoring corresponding adjustments of preventative therapeutic interventions. | 25,252,753 | [
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The effect of a mandibular advancement appliance on cervical lordosis in patients with TMD and cervical pain. | A preliminary study to compare cervical lordosis by means of cervical cephalometric analysis, before and after six months of continuous mandibular advancement appliance (MAA) use, and to show how physical therapy posture re-education would improve the cervical lordosis angle. Twenty-two female patients with temporomandibular disorders (TMD) and cervical pain with lordosis <20° were included. Patients had to have a muscle pain history for at least six months, and with an intensity ⩾6, measured by means of a visual analog scale (a horizontal 0-10 numeric rating scale with 0 labeled as 'no pain' and 10 as 'worst imaginable pain'). Patients had to present the angle formed by the posterior tangents to C2 and C7 of equal or less than 20°. Cephalometric and clinical diagnostics were performed initially (baseline) and at the end of the study period (six months). During the third month with MAA treatment, a physical therapist evaluated the postural deficit and performed a program of postural re-education. Angular and linear dimension data presented a normal distribution (P>0·05; Shapiro Wilk Test), so the paired comparison of the cephalometric measurements was made by t-test for dependent samples. Angle 1 (OPT/7CVT); angle 3 (CVT/EVT) and angle 4 (2CL/7CL) showed a significant increase in the cervical lordosis. Angle 2 (MGP/OP), angle 5 (HOR/CVT) and the distances C0-C2 and Pt-VER, presented no significant changes. The increase in cervical lordosis implies that six months of continuous MAA use, together with a program of postural re-education, promotes the homeostasis of the craniocervical system. | 25,252,766 | [
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Factors associated with unhealthy behaviours and health outcomes: a cross-sectional study among Tuscan adolescents (Italy). | We aimed to determine the extent to which three core variables (school environment, peer group and family affluence) were associated with unhealthy behaviours and health outcomes among Tuscan adolescents. The unhealthy behaviours considered were smoking, alcohol consumption, sedentary lifestyle and irregular breakfast consumption; health outcomes were classified as self-reported health, multiple health complaints and life satisfaction. School environment was measured in terms of liking school, school pressure, academic achievement and classmate support; peer groups were evaluated in terms of the number of peers and frequency of peer contact. Family affluence was measured on a socioeconomic scale. Data were taken from the Tuscan 2009/10 survey of "Health Behaviour in School-aged Children", a WHO cross-national survey. A binary logistic multiple regression (95% confidence intervals) was implemented. The total sample comprised 3291 school students: 1135 11-year-olds, 1255 13-year-olds and 901 15-year-olds. Peer group and school environment were associated with unhealthy behaviours such as smoking, alcohol consumption and sedentary lifestyle. Family affluence proved to have less impact on unhealthy behaviours, except in the case of adolescents living in low-income families. Poor health outcomes were directly related to a negative school environment. Regarding the influence of family affluence, the results showed higher odds of life dissatisfaction and poor self-reported health status in medium-income families, while low-income families had higher odds only with regard to life dissatisfaction. A consistent pattern of gender differences was found in terms of both unhealthy behaviours and health outcomes. Unhealthy behaviours are strongly related to the school environment and peer group. A negative school environment proved to have the strongest relation with poor health outcomes. | 25,252,790 | [
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Pheromone receptor evolution in the cryptic leafroller species, Ctenopseustis obliquana and C. herana. | How new mate recognition systems evolve when changes are required in both the male and female components remains a conundrum. Here, we investigated the molecular basis of pheromone reception in two species of tortricid (leafroller) moth, Ctenopseustis obliquana and C. herana. Male C. obliquana are attracted to a 90:10 blend of (Z)-8-tetradecenyl acetate (Z8-14:OAc) and (Z)-5-tetradecenyl acetate (Z5-14:OAc), whereas C. herana males are attracted to Z5-14:OAc alone. We used a transcriptome sequencing approach from adult male and female antennae to identify 47 olfactory receptors (ORs) from each species and assessed their expression levels in male and female antennae using RNA-Seq counting and quantitative RT-PCR. Three male-biased and one female-biased OR were identified in C. obliquana by quantitative RT-PCR, and four male-biased and one female-biased receptor in C. herana. The male-biased receptors, CoblOR7, CoblOR30, CherOR7, CherOR30, CherOR1a and CherOR1b were tested for their ability to respond to sex pheromone components in a HEK293 cell calcium assay. CoblOR7 and CherOR7 responded to Z8-14:OAc, however, no receptor for Z5-14:OAc was identified. In addition to Z8-14:OAc, CherOR7 also responded to Z7-14:OAc, indicating that this receptor may be under relaxed constraint. Of the 29 amino acid differences between CoblOR7 and CherOR7, significantly more are located in the third and the sixth transmembrane domain regions. Overall, these findings are consistent with studies revealing the presence of neurons tuned to both Z8-14:OAc and Z5-14:OAc in both species, but that for C. herana males, the ability to detect Z8-14:OAc is currently not required. | 25,252,791 | [
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PuFFIN--a parameter-free method to build nucleosome maps from paired-end reads. | We introduce a novel method, called PuFFIN, that takes advantage of paired-end short reads to build genome-wide nucleosome maps with larger numbers of detected nucleosomes and higher accuracy than existing tools. In contrast to other approaches that require users to optimize several parameters according to their data (e.g., the maximum allowed nucleosome overlap or legal ranges for the fragment sizes) our algorithm can accurately determine a genome-wide set of non-overlapping nucleosomes without any user-defined parameter. This feature makes PuFFIN significantly easier to use and prevents users from choosing the "wrong" parameters and obtain sub-optimal nucleosome maps. PuFFIN builds genome-wide nucleosome maps using a multi-scale (or multi-resolution) approach. Our algorithm relies on a set of nucleosome "landscape" functions at different resolution levels: each function represents the likelihood of each genomic location to be occupied by a nucleosome for a particular value of the smoothing parameter. After a set of candidate nucleosomes is computed for each function, PuFFIN produces a consensus set that satisfies non-overlapping constraints and maximizes the number of nucleosomes. We report comprehensive experimental results that compares PuFFIN with recently published tools (NOrMAL, TEMPLATE FILTERING, and NucPosSimulator) on several synthetic datasets as well as real data for S. cerevisiae and P. falciparum. Experimental results show that our approach produces more accurate nucleosome maps with a higher number of non-overlapping nucleosomes than other tools. | 25,252,810 | [
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Global perspectives in hospitalized heart failure: regional and ethnic variation in patient characteristics, management, and outcomes. | Heart failure (HF) is a public health problem of global proportions afflicting more than 25 million patients worldwide. Despite stable or declining per capita hospitalization rates in the USA and several European countries, there are over one million hospitalizations for HF annually in the USA, with similar numbers in Europe, accounting for 6.5 million hospital days and the majority of the approximately $40 billion spent each year on HF-related care. Moreover, clinical trial data suggest that post-discharge survival and readmissions have largely remained unchanged. Thus, understanding geographic and ethnic variations in HF is essential to formulating public policy at the local, national, regional, and international levels and setting the agenda for basic, translational, and clinical research endeavors. This paper aims to describe regional and ethnic variations in patient characteristics, management, and outcomes in hospitalized HF. | 25,252,827 | [
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Identifying biochemical phenotypic differences between cryptic species. | Molecular genetic methods can distinguish divergent evolutionary lineages in what previously appeared to be single species, but it is not always clear what functional differences exist between such cryptic species. We used a metabolomic approach to profile biochemical phenotype (metabotype) differences between two putative cryptic species of the earthworm Lumbricus rubellus. There were no straightforward metabolite biomarkers of lineage, i.e. no metabolites that were always at higher concentration in one lineage. Multivariate methods, however, identified a small number of metabolites that together helped distinguish the lineages, including uncommon metabolites such as Nε-trimethyllysine, which is not usually found at high concentrations. This approach could be useful for characterizing functional trait differences, especially as it is applicable to essentially any species group, irrespective of its genome sequencing status. | 25,252,836 | [
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Experimental reduction in dietary omega-3 polyunsaturated fatty acids depresses sperm competitiveness. | The health benefits of diets containing rich sources of long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFA) are well documented and include reductions in the risk of several diseases typical of Western societies. The dietary intake of n-3 LC-PUFA has also been linked to fertility, and there is abundant evidence that a range of ejaculate traits linked to fertility in humans, livestock and other animals depend on an adequate intake of n-3 LC-PUFA from dietary sources. However, relatively few studies have explored how n-3 LC-PUFA influence reproductive fitness, particularly in the context of sexual selection. Here, we show that experimental reduction in the level of n-3 LC-PUFA in the diet of guppies (Poecilia reticulata) depresses a male's share of paternity when sperm compete for fertilization, confirming that the currently observed trend for reduced n-3 LC-PUFA in western diets has important implications for individual reproductive fitness. | 25,252,837 | [
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A knowledge translation tool improved osteoporosis disease management in primary care: an interrupted time series analysis. | Osteoporosis affects over 200 million people worldwide at a high cost to healthcare systems, yet gaps in management still exist. In response, we developed a multi-component osteoporosis knowledge translation (Op-KT) tool involving a patient-initiated risk assessment questionnaire (RAQ), which generates individualized best practice recommendations for physicians and customized education for patients at the point of care. The objective of this study was to evaluate the effectiveness of the Op-KT tool for appropriate disease management by physicians. The Op-KT tool was evaluated using an interrupted time series design. This involved multiple assessments of the outcomes 12 months before (baseline) and 12 months after tool implementation (52 data points in total). Inclusion criteria were family physicians and their patients at risk for osteoporosis (women aged ≥ 50 years, men aged ≥ 65 years). Primary outcomes were the initiation of appropriate osteoporosis screening and treatment. Analyses included segmented linear regression modeling and analysis of variance. The Op-KT tool was implemented in three family practices in Ontario, Canada representing 5 family physicians with 2840 age eligible patients (mean age 67 years; 76% women). Time series regression models showed an overall increase from baseline in the initiation of screening (3.4%; P < 0.001), any osteoporosis medications (0.5%; P = 0.006), and calcium or vitamin D (1.2%; P = 0.001). Improvements were also observed at site level for all the three sites considered, but these results varied across the sites. Of 351 patients who completed the RAQ unprompted (mean age 64 years, 77% women), the mean time for completing the RAQ was 3.43 minutes, and 56% had any disease management addressed by their physician. Study limitations included the inherent susceptibility of our design compared with a randomized trial. The multicomponent Op-KT tool significantly increased osteoporosis investigations in three family practices, and highlights its potential to facilitate patient self-management. Next steps include wider implementation and evaluation of the tool in primary care. | 25,252,858 | [
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ARYANA: Aligning Reads by Yet Another Approach. | Although there are many different algorithms and software tools for aligning sequencing reads, fast gapped sequence search is far from solved. Strong interest in fast alignment is best reflected in the $10(6) prize for the Innocentive competition on aligning a collection of reads to a given database of reference genomes. In addition, de novo assembly of next-generation sequencing long reads requires fast overlap-layout-concensus algorithms which depend on fast and accurate alignment. We introduce ARYANA, a fast gapped read aligner, developed on the base of BWA indexing infrastructure with a completely new alignment engine that makes it significantly faster than three other aligners: Bowtie2, BWA and SeqAlto, with comparable generality and accuracy. Instead of the time-consuming backtracking procedures for handling mismatches, ARYANA comes with the seed-and-extend algorithmic framework and a significantly improved efficiency by integrating novel algorithmic techniques including dynamic seed selection, bidirectional seed extension, reset-free hash tables, and gap-filling dynamic programming. As the read length increases ARYANA's superiority in terms of speed and alignment rate becomes more evident. This is in perfect harmony with the read length trend as the sequencing technologies evolve. The algorithmic platform of ARYANA makes it easy to develop mission-specific aligners for other applications using ARYANA engine. ARYANA with complete source code can be obtained from http://github.com/aryana-aligner. | 25,252,881 | [
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Stress induced acquisition of somatic embryogenesis in common bean Phaseolus vulgaris L. | Common bean Phaseolus vulgaris L. has been shown to be a recalcitrant plant to induce somatic embryogenesis (SE) under in vitro conditions. We used an alternative strategy to induce SE in common bean based upon the use of a cytokinin (BAP) coupled with osmotic stress adaptation instead of SE response that is induced by auxins. Explants derived from zygotic embryos of common bean were subjected to osmotic stress (sucrose 12 % w/v, 0.5 M) in the presence of BAP 10 mg/L and adenine free base 40 mg/L to induce somatic embryos from specific competent cells of the apical meristem and cotyledonary node. Somatic embryos were obtained from the competent cells in a direct response (direct SE). In a secondary response (secondary SE), those somatic embryos formed proembryogenic masses (PEM) that originated/developed into secondary somatic embryos and showed the SE ontogeny. Maturation of somatic embryos was achieved by using different osmolality media and converted to plants. Full-visible light spectrum was necessary to achieve efficient plant regeneration. Long-term recurrent SE was demonstrated by propagation of PEM at early stages of SE. This protocol is currently being applied for stable genetic transformation by means of Agrobacterium tumefaciens and bioballistics as well as for basic biochemical and molecular biology experiments. | 25,252,886 | [
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Characterization of the 'Xiangshui' lemon transcriptome by de novo assembly to discover genes associated with self-incompatibility. | Seedlessness is a desirable character in lemons and other citrus species. Seedless fruit can be induced in many ways, including through self-incompatibility (SI). SI is widely used as an intraspecific reproductive barrier that prevents self-fertilization in flowering plants. Although there have been many studies on SI, its mechanism remains unclear. The 'Xiangshui' lemon is an important seedless cultivar whose seedlessness has been caused by SI. It is essential to identify genes involved in SI in 'Xiangshui' lemon to clarify its molecular mechanism. In this study, candidate genes associated with SI were identified using high-throughput Illumina RNA sequencing (RNA-seq). A total of 61,224 unigenes were obtained (average, 948 bp; N50 of 1,457 bp), among which 47,260 unigenes were annotated by comparison to six public databases (Nr, Nt, Swiss-Prot, KEGG, COG, and GO). Differentially expressed genes were identified by comparing the transcriptomes of no-, self-, and cross-pollinated stigmas with styles of the 'Xiangshui' lemon. Several differentially expressed genes that might be associated with SI were identified, such as those involved in pollen tube growth, programmed cell death, signal transduction, and transcription. NADPH oxidase genes associated with apoptosis were highly upregulated in the self-pollinated transcriptome. The expression pattern of 12 genes was analyzed by quantitative real-time polymerase chain reaction. A putative S-RNase gene was identified that had not been previously associated with self-pollen rejection in lemon or citrus. This study provided a transcriptome dataset for further studies of SI and seedless lemon breeding. | 25,252,890 | [
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Classical against molecular-genetic methods for susceptibility testing of antituberculotics. | Tuberculosis currently belongs to rare respiratory diseases in Slovakia. However, the emergence and spread of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are major challenges for global tuberculosis control, since the treatment of resistant forms creates both medical and financial problems. Cultivation methods of diagnosis are time-consuming, many times exceeding the time of the initial phase of tuberculosis treatment. Therefore, in the presented study we compared the standard procedures, based on the cultivation of mycobacteria and subsequent drug susceptibility testing to antituberculotics, with molecular-genetic methods using PCR diagnostic kits. The molecular-genetic testing enables to obtain direct and fast evidence of Mycobacterium tuberculosis, with genomic verification of resistance to the most important anti-tuberculosis drugs - isoniazid and rifampicin in MDR-TB, and ethambutol, aminoglycosides, and fluoroquinolones in XDR-TB. In 2012-2013, we confirmed 19 cases of drug-resistant tuberculosis in Slovakia. The resistance to rifampicin was confirmed in all strains with both methods. In two cases, the molecular-genetic testing did not show resistance to isoniazid, as confirmed by conventional cultivation. Furthermore, two strains demonstrating susceptibility in conventional microbiological testing to ethambutol and five strains to fluoroquinolones were verified as actually being resistant using a PCR method. Rapid diagnosis and identification of MDR-TB or XDR-TB strains using molecular-genetic testing is an essential tool for the timely and appropriate drug treatment and prevention of spread of drug resistant strains. | 25,252,893 | [
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Antibiotic consumption pattern in the neonatal special care unit before and after implementation of the hospital's antibiotic policy. | Current and detailed knowledge of antibiotic use is essential in order to implement strategies for reducing the overuse of antibiotics. The objective of our study was to determine the effectiveness of the implementation of the hospital antibiotic policy (HAP) by assessing antibiotic consumption in the Special Neonatal Care Unit (SNCU) in Warsaw, Poland, before and after this intervention. Antibiotic use was calculated in daily defined doses (DDDs) per 100 patient-days and DDDs per 100 admissions. The antibiotics were ranked by volume of DDDs and the number of antibiotics, which accounted for 90 % and 100 % of the total volume, respectively: DU90% and DU100% (where DU stands for drug use). Total antibiotic consumption increased slightly after the introduction of the HAP: the total DDDS was 707.87 and 753.12 in 2011 and 2012, while the number of DDDs/100 admissions was 352.17 and 369.12 in 2011 and 2012, respectively. After the introduction of the HAP, an increase in ampicillin and aminoglycoside use was observed, along with a reduction in the DU100% and DU90% rates (15 vs. 9 and 4 vs. 3, respectively). The introduction of the HAP resulted in changes in antibiotic consumption patterns, but the general antibiotic consumption density remained the same. | 25,252,896 | [
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Quality of life and health care utilization in patients with chronic respiratory diseases. | High quality of life (QoL) may reduce the costs of medical care of chronically ill patients due to lower health care utilization. The purpose of this study was to establish the influence of the QoL of primary care patients with chronic respiratory diseases on the level of health care utilization and the predictors of hospitalization. The study group consisted of 594 adult patients with chronic respiratory diseases of the mean age 59.8±14.9 years. The highest QoL was observed in the social relationship domain and the lowest in the physical domain. Low QoL was associated with a low level of health care utilization among patients with chronic respiratory diseases. Most patients were hospitalized during the past 3 years. In a group of patients with chronic respiratory diseases, chances for hospitalization were: higher among patients with low QoL and health satisfaction, low QoL levels in the physical and social relationship domains, high QoL levels in the psychological domain, those with higher education, residents of rural areas, patients using frequent consultations over the phone, and those with at least an average index of services. | 25,252,901 | [
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Development of pod borer-resistant transgenic chickpea using a pod-specific and a constitutive promoter-driven fused cry1Ab/Ac gene. | We studied pod-specific msg promoter from soybean and developed different transgenic lines of chickpea expressing fused cry1Ab/Ac constitutively and pod specifically for resistance against the destructive pest Helicoverpa armigera. Crystal (Cry) proteins derived from the soil bacterium Bacillus thuringiensis (Bt) play an important role in controlling infestation of Helicoverpa armigera, which has been considered a serious problem in chickpea productivity. This study was undertaken to overcome the problem by introducing fused cry1Ab/Ac insecticidal gene under the control of pod-specific soybean msg promoter as well as rice actin1 promoter into chickpea var. DCP 92-3 by Agrobacterium-mediated transformation. Transgenic chickpea lines were characterized by real-time PCR, ELISA and insect bioassay. Expression of fused cry gene under constitutive and pod-specific promoter results in increase of 77- and 110-fold, respectively, compared to non-transgenic control plants. Levels of Cry toxins produced under the control of actin1 and soybean msg promoter were also estimated by ELISA in the leaves and pods, respectively. The higher expression of fused cry gene caused a lethal effect in larvae. The results of insect bioassay study revealed significant reduction in the survival rate of H. armigera reared on transgenic chickpea twigs as well as on pods. Pod-specific promoter-driven fused cry gene provides better and significant management strategy of pest control of chickpea without phenotypic cost. | 25,252,910 | [
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Ag-presenting CpG-activated pDCs prime Th17 cells that induce tumor regression. | Plasmacytoid dendritic cells (pDC) rapidly and massively produce type I IFN and other inflammatory cytokines in response to foreign nucleic acids, thereby indirectly influencing T-cell responses. Moreover, antigen (Ag)-presenting pDCs directly regulate T-cell differentiation. Depending on the immune environment, pDCs exhibit either tolerogenic or immunogenic properties. Here, we show that CpG-activated pDCs promote efficient Th17 differentiation. Indeed, Th17 responses are defective in mice selectively lacking MHCII on pDCs upon antigenic challenge. Importantly, in those mice, the frequency of Th17 cells infiltrating solid tumors is impaired. As a result, the recruitment of infiltrating leukocytes in tumors, including tumor-specific cytotoxic T lymphocytes (CTL), is altered and results in increased tumor growth. Importantly, following immunization with tumor Ag and CpG-B, MHCII-restricted Ag presentation by pDCs promotes the differentiation of antitumor Th17 cells that induce intratumor CTL recruitment and subsequent regression of established tumors. Our results highlight a new role for Ag presenting activated pDCs in promoting the development of Th17 cells and impacting on antitumor immunity. | 25,252,912 | [
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A recurrent activating PLCG1 mutation in cardiac angiosarcomas increases apoptosis resistance and invasiveness of endothelial cells. | Primary cardiac angiosarcomas are rare tumors with unfavorable prognosis. Pathogenic driver mutations are largely unknown. We therefore analyzed a collection of cases for genomic aberrations using SNP arrays and targeted next-generation sequencing (tNGS) of oncogenes and tumor-suppressor genes. Recurrent gains of chromosome 1q and a small region of chromosome 4 encompassing KDR and KIT were identified by SNP array analysis. Repeatedly mutated genes identified by tNGS were KDR with different nonsynonymous mutations, MLL2 with different nonsense mutations, and PLCG1 with a recurrent nonsynonymous mutation (R707Q) in the highly conserved autoinhibitory SH2 domain in three of 10 cases. PLCγ1 is usually activated by Y783 phosphorylation and activates protein kinase C and Ca(2+)-dependent second messengers, with effects on cellular proliferation, migration, and invasiveness. Ectopic expression of the PLCγ1-R707Q mutant in endothelial cells revealed reduced PLCγ1-Y783 phosphorylation with concomitant increased c-RAF/MEK/ERK1/2 phosphorylation, increased IP3 amounts, and increased Ca(2+)-dependent calcineurin activation compared with ectopic expressed PLCγ1-wild-type. Furthermore, cofilin, whose activation is associated with actin skeleton reorganization, showed decreased phosphorylation, and thus activation after expression of PLCγ1-R707Q compared with PLCγ1-wild-type. At the cellular level, expression of PLCγ1-R707Q in endothelial cells had no influence on proliferation rate, but increased apoptosis resistance and migration and invasiveness in in vitro assays. Together, these findings indicate that the PLCγ1-R707Q mutation causes constitutive activation of PLCγ1 and may represent an alternative way of activation of KDR/PLCγ1 signaling besides KDR activation in angiosarcomas, with implications for VEGF/KDR targeted therapies. | 25,252,913 | [
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Cancer-associated adipose tissue promotes breast cancer progression by paracrine oncostatin M and Jak/STAT3 signaling. | Increasing evidence supports the critical roles played by adipose tissue in breast cancer progression. Yet, the mediators and mechanisms are poorly understood. Here, we show that breast cancer-associated adipose tissue from freshly isolated tumors promotes F-actin remodeling, cellular scattering, invasiveness, and spheroid reorganization of cultured breast cancer cells. A combination of techniques, including transcriptomics, proteomics, and kinomics enabled us to identify paracrine secretion of oncostatin M (OSM) by cancer-associated adipose tissue. Specifically, OSM, expressed by CD45(+) leucocytes in the stromal vascular fraction, induced phosphorylation of STAT3 (pSTAT3-) Y705 and S727 in breast cancer cells and transcription of several STAT3-dependent genes, including S100 family members S100A7, S100A8, and S100A9. Autocrine activation of STAT3 in MCF-7 cells ectopically expressing OSM-induced cellular scattering and peritumoral neovascularization of orthotopic xenografts. Conversely, selective inhibition of OSM by neutralizing antibody and Jak family kinases by tofacitinib inhibited STAT3 signaling, peritumoral angiogenesis, and cellular scattering. Importantly, nuclear staining of pSTAT3-Y705 identified at the tumor invasion front in ductal breast carcinomas correlates with increased lymphovascular invasion. Our work reveals the potential of novel therapeutic strategies targeting the OSM and STAT3 axis in patients with breast cancer harboring nuclear pSTAT3-Y705. | 25,252,914 | [
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Vitamin D suppresses leptin stimulation of cancer growth through microRNA. | Obesity is a pandemic and major risk factor for cancers. The reduction of obesity would have been an effective strategy for cancer prevention, but the reality is that worldwide obesity has kept increasing for decades, remaining a major avoidable cancer risk secondary only to smoke. The present studies suggest that vitamin D may be an effective agent to reduce obesity-associated cancer risks in women. Molecular analyses showed that leptin increased human telomerase reverse transcriptase (hTERT) mRNA expression and cell growth through estrogen receptor-α (ERα) activation in ovarian cancer cells, which was suppressed by 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The suppression was compromised when miR-498 induction by the hormone was depleted with microRNA (miRNA) sponges. In mice, high-fat diet (HFD) stimulation of ovarian tumor growth was remarkably suppressed by 1,25(OH)2D3 analogue EB1089, which was also compromised by miR-498 sponges. EB1089 did not alter HFD-induced increase in serum leptin levels but increased miR-498 and decreased the diet-induced hTERT expression in tumors. Quantitative RT-PCR analyses revealed an inverse correlation between hTERT mRNA and miR-498 in response to 1,25(OH)2D3 in estrogen-sensitive ovarian, endometrial, and breast cancers. The studies suggest that miR-498-mediated hTERT downregulation is a key event mediating the anti-leptin activity of 1,25(OH)2D3 in estrogen-sensitive tumors in women. | 25,252,917 | [
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High-risk anatomic variables and plaque characteristics in carotid artery stenting. | To determine anatomic and plaque-related risk factors for patients undergoing carotid artery stenting. A retrospective review of patients from a prospectively maintained database undergoing carotid artery stenting at our institution between 2001 and 2010 was performed. Preoperative imaging studies (ie, ultrasound, computed tomography angiography, magnetic resonance angiography, and angiograms) were reviewed for specific anatomic criteria and plaque characteristics. Primary outcomes included 30-day stroke or transient ischemic attack (TIA). Secondary outcomes included 30-day death and myocardial infarction (MI). Statistical significance was assumed for P = .05. Imaging was reviewed for 381 carotid arteries in 375 patients. There were 14 (3.7%) perioperative neurologic events, which included 8 TIA and 6 strokes. Thirty-day mortality and MI were 0.5% and 0.75%, respectively. Degree of internal carotid artery stenosis was associated with primary outcomes (P = .03), and the presence of arch calcification trended toward an increase in primary outcomes (P = .07). However, arch type, ostial involvement, tandem lesions, and plaque calcification did not correlate with primary outcomes. Differences were noted between the sexes, with females having more common carotid artery tortuosity than males (34% vs 27%, P = .04). Females also had a trend toward more plaque calcification and more severe arch calcification than males. These differences did not translate to differences in perioperative neurologic events. Our data suggest that degree of internal carotid artery stenosis and aortic arch calcification may be associated with increased perioperative neurologic risk during carotid stenting, but arch type is not. | 25,252,921 | [
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Mapping the Shh long-range regulatory domain. | Coordinated gene expression controlled by long-distance enhancers is orchestrated by DNA regulatory sequences involving transcription factors and layers of control mechanisms. The Shh gene and well-established regulators are an example of genomic composition in which enhancers reside in a large desert extending into neighbouring genes to control the spatiotemporal pattern of expression. Exploiting the local hopping activity of the Sleeping Beauty transposon, the lacZ reporter gene was dispersed throughout the Shh region to systematically map the genomic features responsible for expression activity. We found that enhancer activities are retained inside a genomic region that corresponds to the topological associated domain (TAD) defined by Hi-C. This domain of approximately 900 kb is in an open conformation over its length and is generally susceptible to all Shh enhancers. Similar to the distal enhancers, an enhancer residing within the Shh second intron activates the reporter gene located at distances of hundreds of kilobases away, suggesting that both proximal and distal enhancers have the capacity to survey the Shh topological domain to recognise potential promoters. The widely expressed Rnf32 gene lying within the Shh domain evades enhancer activities by a process that may be common among other housekeeping genes that reside in large regulatory domains. Finally, the boundaries of the Shh TAD do not represent the absolute expression limits of enhancer activity, as expression activity is lost stepwise at a number of genomic positions at the verges of these domains. | 25,252,942 | [
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Effective innate and adaptive antimelanoma immunity through localized TLR7/8 activation. | Intratumoral immune activation can induce local and systemic antitumor immunity. Imiquimod is a cream-formulated, TLR7 agonist that is Food and Drug Administration approved for the treatment of nonmelanoma skin cancers, but it has limited activity against melanoma. We studied the antitumor activity and mechanism of action of a novel, injectable, tissue-retained TLR7/8 agonist, 3M-052, which avoids systemic distribution. Intratumoral administration of 3M-052 generated systemic antitumor immunity and suppressed both injected and distant, uninjected wild-type B16.F10 melanomas. Treated tumors showed that an increased level of CCL2 chemokines and infiltration of M1 phenotype-shifted macrophages, which could kill tumor cells directly through production of NO and CCL2, were essential for the antitumor activity of 3M-052. CD8(+) T cells, B cells, type I IFN, IFN-γ, and plasmacytoid dendritic cells were contributed to efficient tumor suppression, whereas perforin, NK cells, and CD4 T cells were not required. Finally, 3M-052 therapy potentiated checkpoint blockade therapy with anti-CTLA-4 and anti-programmed death ligand 1 Abs, even when checkpoint blockade alone was ineffective. Our findings suggest that intratumoral treatment with 3M-052 is a promising approach for the treatment of cancer and establish a rational strategy and mechanistic understanding for combination therapy with intratumoral, tissue-retained TLR7/8 agonist and checkpoint blockade in metastatic cancer. | 25,252,955 | [
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Anterior and posterior corneal curvature: normal values in healthy Iranian population obtained with the Orbscan II. | The objective of study was to determine the normative values of anterior and posterior best fit sphere (A-BFS and P-BFS) measured with Orbscan II Topography System. In this cross-sectional study, patients (age range: 18-40 years) referred to the Khatam Eye Hospital (Mashhad, Iran) were put in an observational cross-sectional study. The A-BFS and P-BFS were measured with the Orbscan II. The differences between genders, between right and left eyes, and age-related changes were evaluated. A total of 977 healthy participants consisted of 614 female and 363 male subjects aged 18-35 years participated. The average A-BFS in our study population was recorded as 43.060 ± 1.541 D (median: 43.00 D, mode: 43.10 D, range: 38.80-55.80 D). The average P-BFS in our study population was recorded as 52.702 ± 2.190 D (median: 52.60 D, mode: 53.10 D range: 46.9-62.20 D). The A-BFS and P-BFS were respectively 42.753 ± 1.629 and 52.327 ± 2.376 D in males and 43.242 ± 1.457 and 52.924 ± 2.041 D in females, which were statistically different between the genders (P < 0.001). However, A-BFS and P-BFS were not statistically different between right and left eyes (P = 0.649 and P = 0.688 respectively). In addition, A-BFS and P-BFS were not correlated with the age (r = 0.038, P = 0.096 and r = -0.142, P = 0.178 respectively). Considering 95 % confidence interval, A-BFS less than 43.13 D and greater than 42.99 D and P-BFS less than 52.80 D and greater than 52.60 D would be considered abnormal. Detailed description and analysis of A-BFS and P-BFS with Orbscan demonstrated that the obtained average value of BFS were higher in male than female and did not change with increasing age. | 25,252,965 | [
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Utility of the N-back task in survivors of childhood acute lymphoblastic leukemia. | The N-back task is often used in functional brain imaging studies to activate working memory networks; however, limited information is available on its association to clinical outcomes in children or cancer survivors. A total of 137 survivors of acute lymphoblastic leukemia (ALL; mean current age = 14.3 years, SD = 4.8; time since diagnosis = 7.6 years, SD = 1.6) completed the N-back task and comprehensive neurocognitive testing, including standardized measures of attention, processing speed, and working memory. Results indicated that females demonstrated significantly slower reaction times (0-back p = .02; 1-back p = .03) than males. Survivors <15 years old at the time of testing demonstrated a significant decrease in accuracy as working memory load increased compared to survivors ≥15 years old (p < .001). Performance on the N-back task was associated with nonverbal working memory (rs = .56, p < .001) in survivors ≥15 years of age. For younger survivors, N-back performance was more strongly associated with attention skills. Results suggest the N-back assesses different cognitive constructs at younger compared to older childhood ages. These age differences should be considered in interpreting functional brain imaging results. | 25,252,969 | [
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Rb suppresses human cone-precursor-derived retinoblastoma tumours. | Retinoblastoma is a childhood retinal tumour that initiates in response to biallelic RB1 inactivation and loss of functional retinoblastoma (Rb) protein. Although Rb has diverse tumour-suppressor functions and is inactivated in many cancers, germline RB1 mutations predispose to retinoblastoma far more strongly than to other malignancies. This tropism suggests that retinal cell-type-specific circuitry sensitizes to Rb loss, yet the nature of the circuitry and the cell type in which it operates have been unclear. Here we show that post-mitotic human cone precursors are uniquely sensitive to Rb depletion. Rb knockdown induced cone precursor proliferation in prospectively isolated populations and in intact retina. Proliferation followed the induction of E2F-regulated genes, and depended on factors having strong expression in maturing cone precursors and crucial roles in retinoblastoma cell proliferation, including MYCN and MDM2. Proliferation of Rb-depleted cones and retinoblastoma cells also depended on the Rb-related protein p107, SKP2, and a p27 downregulation associated with cone precursor maturation. Moreover, Rb-depleted cone precursors formed tumours in orthotopic xenografts with histological features and protein expression typical of human retinoblastoma. These findings provide a compelling molecular rationale for a cone precursor origin of retinoblastoma. More generally, they demonstrate that cell-type-specific circuitry can collaborate with an initiating oncogenic mutation to enable tumorigenesis. | 25,252,974 | [
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Regulation of RNA polymerase II activation by histone acetylation in single living cells. | In eukaryotic cells, post-translational histone modifications have an important role in gene regulation. Starting with early work on histone acetylation, a variety of residue-specific modifications have now been linked to RNA polymerase II (RNAP2) activity, but it remains unclear if these markers are active regulators of transcription or just passive byproducts. This is because studies have traditionally relied on fixed cell populations, meaning temporal resolution is limited to minutes at best, and correlated factors may not actually be present in the same cell at the same time. Complementary approaches are therefore needed to probe the dynamic interplay of histone modifications and RNAP2 with higher temporal resolution in single living cells. Here we address this problem by developing a system to track residue-specific histone modifications and RNAP2 phosphorylation in living cells by fluorescence microscopy. This increases temporal resolution to the tens-of-seconds range. Our single-cell analysis reveals histone H3 lysine-27 acetylation at a gene locus can alter downstream transcription kinetics by as much as 50%, affecting two temporally separate events. First acetylation enhances the search kinetics of transcriptional activators, and later the acetylation accelerates the transition of RNAP2 from initiation to elongation. Signatures of the latter can be found genome-wide using chromatin immunoprecipitation followed by sequencing. We argue that this regulation leads to a robust and potentially tunable transcriptional response. | 25,252,976 | [
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Incorporating breast cancer care data into clinical assessment. | Participation in the ONS Foundation-supported Breast Cancer Care Quality Measures Set pilot study was an opportunity for staff at a National Cancer Institute-designated comprehensive cancer center to improve their process for introducing a change in practice. The institution's treatment area revised a documentation tool, and the medical practice area embarked on an education project based on evidence-based practice from the Oncology Nursing Society's Putting Evidence Into Practice initiative. After implementation, an increase in the number of patients being assessed for the quality measures of fatigue and sleep-wake disturbances was noted. In addition, the number of patients being educated on neutropenia using evidence-based information increased. | 25,252,988 | [
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[Elution properties of linezolid bone cement]. | To explore the elution properties of linezolid bone cement so as to guide the clinical application of linezolid bone cement in the treatment of infection after total joint arthroplasty. The specimens of bone cement (40 g each) were divided into 6 groups depending on mixed different contents with linezolid (5 specimens in each group), group I (1.2 g), group II (2.4 g), group III (3.6 g), group IV (4.8 g), group V (6.0 g) and group VI (7.2 g). The time-dependent elution of linezolid from bone cement was measured by high performance liquid chromatography (HPLC). The release rate of linezolid bone cement samples was positively correlated with the concentration of antibiotics. And he release rate increased with the rising concentrations. The release of all groups dropped dramatically at Day 1. And as of Day 2 there was a slow release at a very low level. The elution of all groups persisted through 7 weeks. The analysis of variance between groups showed significant differences in release rates. And further examination by q test revealed that the release of group of 3.6-7.2 g was significantly higher than other groups. The drainage tube should be clamped at Day 1 post-operation so that there is a full release of high concentration of linezolid. Adding 3.6 g linezolid to 40 g cement may provide better cost-effective outcomes. | 25,253,015 | [
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β-amyloid induces a dying-back process and remote trans-synaptic alterations in a microfluidic-based reconstructed neuronal network. | Recent histopathological studies have shown that neurodegenerative processes in Alzheimer's and Parkinson's Disease develop along neuronal networks and that hallmarks could propagate trans-synaptically through neuronal pathways. The underlying molecular mechanisms are still unknown, and investigations have been impeded by the complexity of brain connectivity and the need for experimental models allowing a fine manipulation of the local microenvironment at the subcellular level. In this study, we have grown primary cortical mouse neurons in microfluidic (μFD) devices to separate soma from axonal projections in fluidically isolated microenvironments, and applied β-amyloid (Aβ) peptides locally to the different cellular compartments. We observed that Aβ application to the somato-dendritic compartment triggers a "dying-back" process, involving caspase and NAD(+) signalling pathways, whereas exposure of the axonal/distal compartment to Aβ deposits did not induce axonal degeneration. In contrast, co-treatment with somatic sub-toxic glutamate and axonal Aβ peptide triggered axonal degeneration. To study the consequences of such subcellular/local Aβ stress at the network level we developed new μFD multi-chamber devices containing funnel-shaped micro-channels which force unidirectional axon growth and used them to recreate in vitro an oriented cortico-hippocampal pathway. Aβ application to the cortical somato-dendritic chamber leads to a rapid cortical pre-synaptic loss. This happens concomitantly with a post-synaptic hippocampal tau-phosphorylation which could be prevented by the NMDA-receptor antagonist, MK-801, before any sign of axonal and somato-dendritic cortical alteration. Thanks to μFD-based reconstructed neuronal networks we evaluated the distant effects of local Aβ stress on neuronal subcompartments and networks. Our data indicates that distant neurotransmission modifications actively take part in the early steps of the abnormal mechanisms leading to pathology progression independently of local Aβ production. This offers new tools to decipher mechanisms underlying Braak's staging. Our data suggests that local Aβ can play a role in remote tauopathy by distant disturbance of neurotransmission, providing a putative mechanism underlying the spatiotemporal appearance of pretangles. | 25,253,021 | [
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Receiving Instrumental Support in Late Parent-Child Relationships and Parental Depression. | This study investigates the role of gender, functional limitations, and social interaction in the association between instrumental support from adult children and parental depression. We apply self-determination theory to hypothesize about the role of physical needs and social resources on parental depression in a European context. A sample of 6,268 parents older than 65 who have nonresident children from the first wave of Survey of Health, Ageing and Retirement in Europe (2004) is analyzed. We estimate logistic regression models to test for the association between instrumental support and depression. Physical needs, gender, and social interaction are used as moderators. Net of core factors that contribute to depression, including previous history of depression, there is a U-shaped pattern between receiving instrumental support and depression that persists across country regimes. For respondents with medium physical limitations, too little or too frequent support from children is associated with higher depression. For respondents with severe limitations, receiving at least some support is better than receiving none at all. The receipt of too frequent support from children increases the level of depression more for women than men. All interaction effects are comparable across country regimes. Heterogeneity in physical needs and resources of older individuals must be taken into account when assessing the effects of instrumental support on mental health. | 25,253,024 | [
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The Healthy Lifestyle and Personal Control Questionnaire (HLPCQ): a novel tool for assessing self-empowerment through a constellation of daily activities. | The main goal of stress management and health promotion programs is to improve health by empowering people to take control over their lives. Daily health-related lifestyle choices are integral targets of these interventions and critical to evaluating their efficacy. To date, concepts such as self-efficacy, self-control and empowerment are assessed by tools that only partially address daily lifestyle choices. The aim of this study is to validate a novel measurement tool, the Healthy Lifestyle and Personal Control Questionnaire (HLPCQ), which aims to assess the concept of empowerment through a constellation of daily activities. Therefore, we performed principal component analysis (PCA) of 26 items that were derived from the qualitative data of several stress management programs conducted by our research team. The PCA resulted in the following five-factor solution: 1) Dietary Healthy Choices, 2) Dietary Harm Avoidance, 3) Daily Routine, 4) Organized Physical Exercise and 5) Social and Mental Balance. All subscales showed satisfactory internal consistency and variance, relative to theoretical score ranges. Subscale scores and the total score were significantly correlated with perceived stress and health locus of control, implying good criterion validity. Associations with sociodemographic data and other variables, such as sleep quality and health assessments, were also found. The HLPCQ is a good tool for assessing the efficacy of future health-promoting interventions to improve individuals' lifestyle and wellbeing. | 25,253,039 | [
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Biofilm bacterial communities in urban drinking water distribution systems transporting waters with different purification strategies. | Biofilm formation in drinking water distribution systems (DWDS) has many adverse consequences. Knowledge of microbial community structure of DWDS biofilm can aid in the design of an effective control strategy. However, biofilm bacterial community in real DWDS and the impact of drinking water purification strategy remain unclear. The present study investigated the composition and diversity of biofilm bacterial community in real DWDSs transporting waters with different purification strategies (conventional treatment and integrated treatment). High-throughput Illumina MiSeq sequencing analysis illustrated a large shift in the diversity and structure of biofilm bacterial community in real DWDS. Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Nitrospirae, and Cyanobacteria were the major components of biofilm bacterial community. Proteobacteria (mainly Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria) predominated in each DWDS biofilm, but the compositions of the dominant proteobacterial classes and genera and their proportions varied among biofilm samples. Drinking water purification strategy could shape DWDS biofilm bacterial community. Moreover, Pearson's correlation analysis indicated that Actinobacteria was positively correlated with the levels of total alkalinity and dissolved organic carbon in tap water, while Firmicutes had a significant positive correlation with nitrite nitrogen. | 25,253,043 | [
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Diffusive and non-diffusive photo-induced proton coupled electron transfer from hydrogen bonded phenols to meso-tetrakis-5,10,15,20-pentafluorophenyl porphyrin. | Enhanced reductive fluorescence quenching of meso-tetrakis-5,10,15,20-pentafluorophenyl porphyrin (H2F20TPP) by two different phenols, 4-methoxy phenol (4-MeOPhOH) and 2,6-dimethoxy phenol (2,6-DiMeOPhOH) in the presence of various pyridine bases in dichloromethane solution is studied using steady state and time resolved fluorescence spectroscopic methods by employing time correlated single photon counting (TCSPC) and fluorescence up-conversion techniques. An enhanced quenching behaviour of H2F20TPP is observed when phenols are hydrogen bonded to various pyridine bases. Quenching observed in the steady state and time resolved studies in the nanosecond time domain follows second order kinetics and generates quenching rate constants and hydrogen bond equilibrium constants, the latter of which agree quite closely with those obtained from independent spectroscopic measurements. A significant kinetic deuterium isotope effect is observed, indicating the importance of proton movement in the quenching processes. This quenching effect is attributed to be due to a tri-molecular transition state involving H2F20TPP and a hydrogen bonded phenol complex, in which electron transfer from phenol to excited H2F20TPP is concerted with proton movement from the phenol to hydrogen bonded base. Observed quenching behaviours are rationalized by invoking diffusion controlled proton coupled electron transfer. Fluorescence up-conversion studies in the 100 ps time domain confirm ultrafast PCET for 4-MeOPhOH and base pairs which fall in a non-diffusive regime. | 25,253,044 | [
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Immobilization of phosphorus from water and sediment using zirconium-modified zeolites. | Adding sorbents to sediments has been suggested as an effective technology for contaminated sediment remediation. In this study, a zirconium-modified zeolite (ZrMZ) was prepared, characterized, and used as a sediment amendment to control phosphorus (P) release from eutrophic lake sediments. The efficiency of ZrMZ in immobilizing P from water and sediments was investigated through a series of experiments. The phosphate adsorption capacity for ZrMZ decreased with increasing water pH. The adsorption of phosphate on ZrMZ followed a pseudo-second-order kinetic model. The equilibrium adsorption data of phosphate on ZrMZ could be well described by the Langmuir isotherm model with a maximum monolayer adsorption capacity of 10.2 mg P/g at pH 7 and 25 °C. Sequential extraction of P from the phosphate-adsorbed ZrMZ suggested that most of P bound by ZrMZ existed as the NaOH extractable P (NaOH-P) and residual P (Res-P) and was unlikely to be released under natural pH and reducing conditions. The addition of ZrMZ into sediments reduced the inorganic P activity in the sediments by transforming bicarbonate-dithionite extractable P (BD-P) to NaOH-P and Res-P. The contents of bioavailable P such as water-soluble P (WS-P), NaHCO3 extractable P (Olsen-P), and algal available P (AAP) in sediments reduced after the sediments were mixed with ZrMZ, making P in the sediments more stable. The addition of ZrMZ into sediments significantly reduced the releasing flux of P from the sediments to the water column under different conditions. Results of this study indicate that the ZrMZ is a promising sediment amendment for controlling the internal P loading of lake sediments. | 25,253,056 | [
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Therapeutic effects of tibial support braces on posterior stability after posterior cruciate ligament reconstruction with autogenous hamstring tendon graft. | In the patients who have to be in supine position for most of the time after posterior cruciate ligament (PCL) reconstruction, the tibia tends to shift backwards due to the gravity of the lower leg and the tensed hamstring muscle. To observe the effects of tibial support braces on rehabilitation after PCL reconstruction. Retrospective study. Inpatients. Thirty-nine patients were divided into regular brace (N.=18) and tibial support brace (N.=21) groups according to using different types of braces after PCL reconstruction. The follow-up time was more than 2 years in all patients. The function of the affected knee joint was evaluated with International Knee Documentation Committee (IKDC) score, Lysholm knee score, Tegner activity rating, range of motion (ROM) and kneelax arthrometer before and after PCL reconstruction, respectively. The function of the affected knee joint was significantly improved in both groups after PCL reconstruction. Compared with regular brace group, postoperative Lysholm and IKDC scores were significantly increased in tibial support brace group (P<0.05). However, there were no statistical differences in Tegner activity rating and ROM between regular brace group and tibial support brace group (P<0.05). Tibial support brace can obtain better therapeutic effects for PCL reconstruction. This study suggests that compared with regular brace, tibial support brace can significantly improve the mechanical stability and functional outcomes of the affected knee after PCL reconstruction. | 25,253,078 | [
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Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology. | The mechanism through which the protein kinase Akt (also called PKB), protects the heart against acute ischaemia-reperfusion injury (IRI) is not clear. Here, we investigate whether Akt mediates its cardioprotective effect by modulating mitochondrial morphology. Transfection of HL-1 cardiac cells with constitutively active Akt (caAkt) changed mitochondrial morphology as evidenced by an increase in the proportion of cells displaying predominantly elongated mitochondria (73 ± 5.0 % caAkt vs 49 ± 5.8 % control: N=80 cells/group; p< 0.05). This effect was associated with delayed time taken to induce mitochondrial permeability transition pore (MPTP) opening (by 2.4 ± 0.5 fold; N=80 cells/group: p< 0.05); and reduced cell death following simulated IRI (32.8 ± 1.2 % caAkt vs 63.8 ± 5.6 % control: N=320 cells/group: p< 0.05). Similar effects on mitochondrial morphology, MPTP opening, and cell survival post-IRI, were demonstrated with pharmacological activation of Akt using the known cardioprotective cytokine, erythropoietin (EPO). The effect of Akt on inducing mitochondrial elongation was found to be dependent on the mitochondrial fusion protein, Mitofusin-1 (Mfn1), as ablation of Mfn1 in mouse embryonic fibroblasts (MEFs) abrogated Akt-mediated mitochondrial elongation. Finally, in vivo pre-treatment with EPO reduced myocardial infarct size (as a % of the area at risk) in adult mice subjected to IRI (26.2 ± 2.6 % with EPO vs 46.1 ± 6.5 % in control; N=7/group: p< 0.05), and reduced the proportion of cells displaying myofibrillar disarray and mitochondrial fragmentation observed by electron microscopy in adult murine hearts subjected to ischaemia from 5.8 ± 1.0 % to 2.2 ± 1.0 % (N=5 hearts/group; p< 0.05). In conclusion, we found that either genetic or pharmacological activation of Akt protected the heart against acute ischaemia-reperfusion injury by modulating mitochondrial morphology. | 25,253,080 | [
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A general framework for analyzing tumor subclonality using SNP array and DNA sequencing data. | Intra-tumor heterogeneity reflects cancer genome evolution and provides key information for diagnosis and treatment. When bulk tumor tissues are profiled for somatic copy number alterations (sCNA) and point mutations, it may be difficult to estimate their cellular fractions when a mutation falls within a sCNA. We present the Clonal Heterogeneity Analysis Tool, which estimates cellular fractions for both sCNAs and mutations, and uses their distributions to inform macroscopic clonal architecture. In a set of approximately 700 breast tumors, more than half appear to contain multiple recognizable aneuploid tumor clones, and many show subtype-specific differences in clonality for known cancer genes. | 25,253,082 | [
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Exploring different types of Hatha yoga for patients with cancer. | Yoga has been practiced for more than 5,000 years and is based on the collective experiences of yoga practitioners over time. Western countries and sophisticated medical facilities use this practice as a complementary therapy with standard medical treatments. Yoga has been shown to improve quality of life. Several types of yoga potentially can benefit people with cancer, including Hatha yoga. The type of recommended Hatha yoga is dependent on the physical conditions and fitness level of patients. This article explores the impact of different types of Hatha yoga on various cancer-related symptoms in patients with cancer. The article also provides guidelines for healthcare personnel-particularly nurses-to help choose the right kind of Hatha yoga that suits their patients' needs and interests. Additional information is provided on measures and instructions that are essential for healthcare providers to know before recommending any yoga type to their patients. Evidence of the feasibility and potential efficacy of yoga for patients with cancer is provided. | 25,253,113 | [
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Nursing expertise and the evaluation of psychosocial distress in patients with cancer and survivors. | The number of cancer survivors in the United States will continue to grow because of improved screening, early detection practices, and advances in treatment. The cancer experience has a significant impact on the patient and his or her family, which increases the risk for psychosocial distress. Untreated distress experienced by a patient with cancer contributes to poorer treatment adherence, medical outcomes, and quality of life. To provide high-quality, safe patient care, oncology nurses must increase clinical expertise and knowledge. The current article provides an overview of clinical tools available for nurses to use when screening for distress in patients throughout the cancer care continuum. | 25,253,116 | [
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Influence of lung function on course of disease and response to antibiotic therapy in adult primary care patients with acute cough: a post hoc analysis of patients enrolled in a prospective multicentre study. | In acute cough patients, impaired lung function as present in chronic lung conditions like asthma and chronic obstructive pulmonary disease (COPD) are often thought to negatively influence course of disease, but clear evidence is lacking. To investigate the influence of lung function abnormalities on course of disease and response to antibiotic therapy in primary care patients with acute cough. A total of 3,104 patients with acute cough (⩽28 days) were included in a prospective observational study with a within-nested trial, of which 2,427 underwent spirometry 28-35 days after inclusion. Influence of the lung function abnormalities fixed obstruction (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7) and bronchodilator responsiveness (FEV1 increase of ⩾12% or 200 ml after 400 μg salbutamol) on symptom severity, duration and worsening were evaluated using uni- and multivariable regression models. Antibiotic use was defined as the reported use of antibiotics ⩾5 days in the first week. Interaction terms were calculated to investigate modifying effects of lung function on antibiotic effect. The only significant association was the effect of severe airway obstruction on symptom severity on days 2-4 (difference=0.31, 95% confidence interval (CI)=0.03-0.60, P=0.03). No evidence of a differential effect of lung function on the effect of antibiotics was found. Prior use of inhaled steroids was associated with a 30% slower resolution of symptoms rated 'moderately bad' or worse (hazard ratio=0.75, 95% CI=0.63-0.90, P=0.00). In adult patients with acute cough, lung function abnormalities were neither significantly associated with course of disease nor did they modify the effect of antibiotics. | 25,253,123 | [
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Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study. | Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort. We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype-phenotype relationships. Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). Similar results were obtained when German patients with ACP were compared with those with alcohol-associated cirrhosis or alcohol dependence. In the overall population of patients with NACP, association with rs10273639 was absent (OR, 0.93; 95% CI 0.79 to 1.01), whereas rs7057398 of the X chromosomal single nucleotide polymorphisms was associated with NACP in women only (OR, 1.32; 95% CI 1.15 to 1.51). The single-nucleotide polymorphisms rs10273639 at the PRSS1-PRSS2 locus and rs7057398 and rs12688220 at the CLDN2-MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients. | 25,253,127 | [
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Examination of whole cell galectin binding by solid phase and flow cytometric analysis. | We have utilized simple flow cytometric and fluorescence-based solid phase assays to study the interaction of glycan-binding proteins (GBP) to cell surface glycoconjugates. These methods utilize commonly employed flow cytometry techniques and commercially available streptavidin-coated microplates to immobilize various biotinylated ligands, such as glycopeptides, oligosaccharides, and whole cells. Using this approach, fluorescently labeled GBPs, in particular, members of the galectin family, can be interrogated for potential interactions with cell surface carbohydrates, including elucidation of the potential impact of alterations in glycosylation on carbohydrate recognition. Using these approaches, we present examples of flow cytometric and fluorescence-based solid phase assays to study galectin-carbohydrate interactions. | 25,253,135 | [
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Methods for assessing the effects of galectins on leukocyte trafficking. | Numerous protocols exist for investigating leukocyte recruitment both in vitro and in vivo. Here we describe three of these methods; an in vitro flow chamber assay, intravital microscopy, and zymosan-induced peritonitis, and give details as to how they can be used to study the actions of galectins on this crucial process. | 25,253,138 | [
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Examination of the role of galectins in plasma cell differentiation. | Plasma cells are terminally differentiated B cells that develop via the stimulation of mature B cells with various agents such as antigens and mitogens. Recently, we found that plasma cell differentiation can be modulated by galectin-1 and galectin-8; these galectins appear to play additive and redundant roles in promoting the production of antibody. Here, we describe the protocols for how to investigate the roles of galectins in plasma cell differentiation. These methods include the preparation of recombinant galectins from Escherichia coli for exogenously treating primary B cells, generation of galectin_Fc(m) fusion proteins for determining their binding to B cells, introduction of ectopic galectins in primary B cells using retroviral vectors, and inhibition of the binding of galectins to B cells by synthetic disaccharides. | 25,253,139 | [
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A novel, stable, aqueous glucagon formulation using ferulic acid as an excipient. | Commercial glucagon is unstable due to aggregation and degradation. In closed-loop studies, it must be reconstituted frequently. For use in a portable pump for 3 days, a more stable preparation is required. At alkaline pH, curcumin inhibited glucagon aggregation. However, curcumin is not sufficiently stable for long-term use. Here, we evaluated ferulic acid, a stable breakdown product of curcumin, for its ability to stabilize glucagon. Ferulic acid-formulated glucagon (FAFG), composed of ferulic acid, glucagon, L-methionine, polysorbate-80, and human serum albumin in glycine buffer at pH 9, was aged for 7 days at 37°C. Glucagon aggregation was assessed by transmission electron microscopy (TEM) and degradation by high-performance liquid chromatography (HPLC). A cell-based protein kinase A (PKA) assay was used to assess in vitro bioactivity. Pharmacodynamics (PD) of unaged FAFG, 7-day aged FAFG, and unaged synthetic glucagon was determined in octreotide-treated swine. No fibrils were observed in TEM images of fresh or aged FAFG. Aged FAFG was 94% intact based on HPLC analysis and there was no loss of bioactivity. In the PD swine analysis, the rise over baseline of glucose with unaged FAFG, aged FAFG, and synthetic native glucagon (unmodified human sequence) was similar. After 7 days of aging at 37°C, an alkaline ferulic acid formulation of glucagon exhibited significantly less aggregation and degradation than that seen with native glucagon and was bioactive in vitro and in vivo. Thus, this formulation may be stable for 3-7 days in a portable pump for bihormonal closed-loop treatment of T1D. | 25,253,164 | [
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Informant agreement for youth with autism spectrum disorder or intellectual disability: a meta-analysis. | This study investigated informant agreement on emotional and behavior problems and social skills in youth with autism spectrum disorder or intellectual disability using meta-analytic methods. Forty-nine studies were included, consisting of 107 effect sizes. The mean weighted effect size across all raters and all behaviors was .36, reflecting moderate agreement. Consistent with meta-analyses in typically developing youth, pairs of similar informants (e.g., parent-parent) demonstrated higher agreement compared to pairs of different raters (e.g., parent-teacher). With all rater pairs combined, agreement was significantly higher for externalizing problems (r = .42) than either internalizing problems (r = .35) or social skills (r = .30). Several factors appear to moderate the level of agreement among informants, including the youth's diagnosis, age, and IQ. | 25,253,177 | [
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ILP-based maximum likelihood genome scaffolding. | Interest in de novo genome assembly has been renewed in the past decade due to rapid advances in high-throughput sequencing (HTS) technologies which generate relatively short reads resulting in highly fragmented assemblies consisting of contigs. Additional long-range linkage information is typically used to orient, order, and link contigs into larger structures referred to as scaffolds. Due to library preparation artifacts and erroneous mapping of reads originating from repeats, scaffolding remains a challenging problem. In this paper, we provide a scalable scaffolding algorithm (SILP2) employing a maximum likelihood model capturing read mapping uncertainty and/or non-uniformity of contig coverage which is solved using integer linear programming. A Non-Serial Dynamic Programming (NSDP) paradigm is applied to render our algorithm useful in the processing of larger mammalian genomes. To compare scaffolding tools, we employ novel quantitative metrics in addition to the extant metrics in the field. We have also expanded the set of experiments to include scaffolding of low-complexity metagenomic samples. SILP2 achieves better scalability throughg a more efficient NSDP algorithm than previous release of SILP. The results show that SILP2 compares favorably to previous methods OPERA and MIP in both scalability and accuracy for scaffolding single genomes of up to human size, and significantly outperforms them on scaffolding low-complexity metagenomic samples. Equipped with NSDP, SILP2 is able to scaffold large mammalian genomes, resulting in the longest and most accurate scaffolds. The ILP formulation for the maximum likelihood model is shown to be flexible enough to handle metagenomic samples. | 25,253,180 | [
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Building capacity to improve respiratory care: the education strategy of the International Primary Care Respiratory Group 2014-2020. | Significant attention has been given to the global burden of noncommunicable diseases including respiratory diseases and the potential of primary care to address this challenge. The International Primary Care Respiratory Group (IPCRG) has a potentially significant role to build capacity through research and education in a complex global network with varying degrees of capability. In this paper we outline a comprehensive strategy, which revisits the IPCRG's educational role, our aims, audiences and approach in this context. The paper was developed through a collaborative process involving experts in global health, primary care and respiratory education, leading to a consensus educational strategy statement. This is further informed by a review of recent trends in continuing medical education. Professional education and training of health-care workers is a core component of the global response to the challenge of managing respiratory conditions in primary care. This paper offers a revised strategy for building capacity and improving clinical practice in IPCRG member countries by revisiting and broadening our aims, exploring the key audiences, focus and approaches. | 25,253,230 | [
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Akt recruits Dab2 to albumin endocytosis in the proximal tubule. | Proximal tubule epithelial cells have a highly sophisticated endocytic machinery to retrieve the albumin in the glomerular filtrate. The megalin-cubilin complex and the endocytic adaptor disabled-2 (Dab2) play a pivotal role in albumin endocytosis. We previously demonstrated that protein kinase B (Akt) regulates albumin endocytosis in the proximal tubule through an interaction with Dab2. Here, we examined the nature of Akt-Dab2 interaction. The pleckstrin homology (PH) and catalytic domains (CD) of Akt interacted with the proline-rich domain (PRD) of Dab2 based on yeast-two hybrid (Y2H) experiments. Pull-down experiments utilizing the truncated constructs of Dab2 demonstrated that the initial 11 amino acids of Dab2-PRD were sufficient to mediate the interaction between Akt and Dab2. Endocytosis experiments utilizing Akt1- and Akt2-silencing RNA revealed that both Akt1 and Akt2 mediate albumin endocytosis in proximal tubule epithelial cells; therefore, Akt1 and Akt2 may play a compensatory role in albumin endocytosis. Furthermore, both Akt isoforms phosphorylated Dab2 at Ser residues 448 and 449. Ser-to-Ala mutations of these Dab2 residues inhibited albumin endocytosis and resulted in a shift in location of Dab2 from the peripheral to the perinuclear area, suggesting the physiological relevance of these phosphorylation sites in albumin endocytosis. We conclude that both Akt1 and Akt2 are involved in albumin endocytosis, and phosphorylation of Dab2 by Akt induces albumin endocytosis in proximal tubule epithelial cells. Further delineation of how Akt affects expression/phosphorylation of endocytic adaptors and receptors will enhance our understanding of the molecular network triggered by albumin overload in the proximal tubule. | 25,253,241 | [
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Luminex(®) multiplex bead suspension arrays for the detection and serotyping of Salmonella spp. | In this chapter we describe two commercially available bead-based molecular assays for detection, identification and serotyping of Salmonella. The xTAG(®) Gastrointestinal Pathogen Panel (GPP) is a qualitative multiplex test for the simultaneous detection of nucleic acids from Salmonella plus 14 other gastroenteritis-causing bacteria, viruses, and parasites from stool specimens. xTAG GPP uses the Luminex(®) xTAG universal array technology for the identification of specific target sequences combined with the xMAP(®) bead multiplexing platform for detection of the targets that were present in the starting sample. The xMAP Salmonella Serotyping Assay (SSA) is a multiplex nucleic acid-based direct hybridization assay for molecular identification of the serotype of Salmonella isolates. In xMAP SSA, target sequences amplified from cultured Salmonella isolates are captured by hybridization to sequence-specific capture probes which have been coupled to the multiplexed bead sets. Herein we provide detailed protocols for each of these assays and present data which describe their performance characteristics for detection and serotyping Salmonella. | 25,253,245 | [
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Study of the Stn protein in Salmonella; a regulator of membrane composition and integrity. | Our studies were undertaken to develop new insights into the function of the Salmonella Stn protein. An analysis of total cell membrane protein fraction suggested the possibility that Stn associates with OmpA. This possibility was confirmed by immunogold labeling using anti-OmpA antibody and far-western blotting. From these results, we conclude that Stn regulates membrane composition and integrity in Salmonella. | 25,253,253 | [
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Live cell imaging of intracellular Salmonella enterica. | During the intracellular phase of the pathogenic lifestyle, Salmonella enterica massively alters the endosomal system of its host cells. Two hallmarks are the remodeling of phagosomes into the Salmonella-containing vacuole (SCV) as a replicative niche, and the formation of tubular structures, such as Salmonella-induced filaments (SIFs). To study the dynamics and the fate of these Salmonella-specific compartments, live cell imaging (LCI) is a method of choice. In this chapter, we compare currently used microscopy techniques and focus on considerations and requirements specific for LCI. Detailed protocols for LCI of Salmonella infection with either confocal laser scanning microscopy (CLSM) or spinning disk confocal microscopy (SDCM) are provided. | 25,253,257 | [
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In vitro modeling of gallbladder-associated Salmonella spp. colonization. | The host-pathogen interactions occurring in the gallbladder during Salmonella Typhi colonization contribute to typhoid fever pathogenesis during the acute and chronic stages of disease. The gallbladder is the primary reservoir during chronic typhoid carriage. In this organ, Salmonella encounters host-barriers including bile, immunoglobulins, and mucus. However, the bacterium possesses mechanisms to resist and persist in this environment, in part by its ability to attach to and invade into the gallbladder epithelium. Such persistence in the gallbladder epithelium contributes to chronic carriage. In addition, patients harboring gallstones in their gallbladders have increased risk of becoming carriers because these abnormalities serve as a substrate for Salmonella biofilm formation. Our laboratory has studied the Salmonella interactions in this specific environment by developing in vitro methods that closely mimic the gallbladder and gallstones niches. These methods are reproducible and provide a platform for future studies of acute and chronic bacterial infections in the gallbladder. | 25,253,258 | [
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