title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Management of pediatric craniocervical arterial dissections. | Craniocervical arterial dissections (CCADs) represent a preventable cause of acute ischemic stroke (AIS). Our objective was to describe clinical presentation, imaging features, treatment strategies, and report clinical and imaging outcomes of CCADs at a large pediatric tertiary referral center. Electronic medical records were queried using variations of the word dissection for patients under 25 years of age with neuroimaging over a 13-year period. Medical and imaging records were reviewed to identify carotid, vertebral, or intracranial dissections. Demographics, presenting symptoms, presence of AIS, mechanism of injury, dissection location, dissection treatment, and complications stemming from treatment were collected. Clinical outcome was classified according to modified Rankin Scale (mRS) score. Imaging follow-up was obtained until the dissection healed or stabilized. A total 6,289 patients met initial search criteria. Of the 42 (0.7%) patients with CCADs, 23 (54.8%) had internal carotid artery (ICA) dissections, and 17 (40.5%) had vertebrobasilar (VB) dissections. More females had ICA dissections (p = 0.002), and more males had VB dissections (p = 0.01). CCADs associated with traumatic presentation occurred in 34 patients (81.0%), while 8 (19.0%) were spontaneous. Good outcomes (mRS 0-3) were noted for 36 patients, and 5 had poor outcomes (mRS 4-6). In the 17 patients with vessel occlusion, 50.0% had partial or complete recanalization at a mean follow-up of 23.9 months. CCAD is commonly related to trauma and presents with AIS. The majority of patients experience good clinical outcome. Recanalization of initial vessel occlusion occurs in half of cases at 2 years. | 25,227,167 | [
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A case report of a pediatric traumatic aneurysm with arteriovenous (A-V) fistula CASE-BASED UPDATE. | Traumatic intracranial aneurysms (TICAs) are rare, representing less than 5 % of all intracranial aneurysms. Most TICAs are located within the anterior circulation, and less than 10 % of TICAs occur in the posterior circulation. Histopathologically, most TICAs are false aneurysms and have a high risk of rupture or re-bleeding. When they are discovered, careful observation or treatment may be required. Once they are enlarged, they have a high risk of rupture, and immediate treatment is essential. For the first time in the literature, we report a rare case of an 8-year-old boy with a TICA in anterior inferior cerebellar artery (AICA) and arteriovenous (A-V) fistula after severe head trauma. Trapping of AICA and resection of the aneurysm was performed. Postoperatively, he has peripheral facial palsy but is otherwise neurologically normal. Surgical treatment for traumatic aneurysms is challenging because most of TICAs are histopathologically pseudoaneurysms. It may be technically difficult to perform direct surgery of aneurysms especially located in the posterior circulation, but when the treatment is successful, the outcome was favorable. | 25,227,169 | [
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Roles of glycosaminoglycans and glycanmimetics in tumor progression and metastasis. | Various tumor cells exhibit structural alterations in the sulfated modifications to glycosaminoglycans (GAGs). The altered expression of chondroitin sulfate (CS) and heparan sulfate (HS) on the surfaces of tumor cells is known to play a key role in malignant transformation and tumor metastasis. The receptor molecule for the CS chains containing E-disaccharide units (CS-E) expressed on Lewis lung carcinoma (LLC) cells was recently revealed to be Receptor for Advanced Glycation End-products (RAGE). RAGE is also involved in the development of various pathological conditions including aging, infection, pulmonary fibrosis, diabetes, and Alzheimer's disease, by binding to a wide range of ligands. RAGE binds strongly not only to CS-E, but also to HS-expressing LLC cells. Recombinant RAGE bound CS-E and HS with high affinity. Furthermore, in a mouse model, the colonization of the lungs by LLC cells was inhibited by intravenously injected CS-E, an anti-CS-E antibody, or an anti-RAGE antibody. These findings demonstrated that RAGE is at least one of the critical receptors for CS and HS chains expressed on the tumor cell surface and is involved in experimental lung metastasis, and also that CS/HS and RAGE are potential molecular targets for the treatment of pulmonary metastasis. We, hence, reviewed these findings and also several chemically synthesized small GAGmimetics that exhibit potent anti-metastatic and/or anti-tumor activities. | 25,227,175 | [
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Pressure monitoring during lipofilling procedures. | Grafting of autologous lipoaspirate for various clinical applications has become a common procedure in clinical practice. With an estimated mortality rate of 10-15 percent, fat embolism is among the most severe complications to be expected after lipofilling therapies. The aim of this study was to determine the level of interstitial pressure after the injection of defined volumes of lipoaspirate into the subcutaneous tissue of female breasts. It was hypothesized, that interstitial pressure levels exceed the physiologic capillary pressure during lipofilling procedures and hence increase the potential risk for fat embolism. Further it was investigated if external tissue expansion has the potential to significantly reduce interstitial tissue pressure. Interstitial pressure was monitored in 36 female patients, that underwent autologous fat injections into the breast. Measurements were conducted with a sensor needle connected to a pressure transducer (LogiCal Pressure Monitoring Kit, Smiths medical int. Ltd., UK). Patients were divided into 4 subcohorts differing in their pre-treatment regimen or local tissue conditions. Pre-treatment consisted of tissue expansion, achieved with the Brava™ (Brava LLC Miami, Fla., USA) vacuum-chamber. The increase in interstitial pressure after injection volumes of 100 ml (p = 0.006), 200 ml (p = 0.000) and between 100 ml and 200 ml (p = 0.004) respectively, were significant in non-mastectomized patients without pre-treatment. Patients pre-treated with Brava™ did not show such statistically significant differences in interstitial pressures before and after the injection of 100 ml and 200 ml of lipoaspirate (p = 0.178). The difference in interstitial pressure in mastectomized patients between 0 ml and 100 ml (p = 0.003), as well as 0 ml and 200 ml (p = 0.028) was significant. The difference in pressures between pre-treated patients and patients without pre-treatment did not differ significantly in the mastectomized patient cohort. During lipofilling procedures interstitial pressures are reached that exceed pressure limits defined as hazardous for fat embolism. To date it is unknown what pressure levels need to be considered critical for complications in soft tissue interventions. Further the results indicate higher interstitial pressures for patients that had undergone mastectomy, whereas pre-treatment with external tissue expansion seemed to diminish pressure values. | 25,227,189 | [
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Effect of radiographic contrast media (Iodixanol, Iopromide) on hemolysis. | Radiographic contrast media can lead to drastic changes of the morphology of erythrocytes. The change of the erythrocyte morphology is associated with a decreased deformability possibly resulting from distinctions in the loss of constituents of the membrane cytoskeleton. However, it is unclear whether there is an intravascular hemolysis as a consequence of the disintegration of the erythrocyte membrane. The results of this study showed, that free haemoglobin increased from 16.8 ± 10.0 mg/dl to 21.6 ± 12.6 mg/dl after Iopromide application (p = 0.240), while it slightly decreased from 20.5 ± 10.3 mg/dl to 19.5 ± 12.2 mg/dl after Iodixanol application (p = 0.547). The slight decrease of free haemoglobin after application of Iodixanol differed significantly compared to the increase of free haemoglobin after Iopromide application (p < 0.05). This different response is thought to give evidence to the assumption that the erythrocyte membrane integrity was compromised leading to the release of free haemoglobin as an indicator of hemolysis as well. | 25,227,190 | [
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Genetic engineering of mesenchymal stem cells by non-viral gene delivery. | Mesenchymal stem cells (MSCs) are an ideal cell source for tissue engineering and regenerative medicine as they possess self-renewal properties and multilineage differentiation potential. They can be isolated from various tissues and expanded easily through normal cell culture techniques. Genetic modifications of MSCs to further improve their therapeutic efficacy have been widely studied and extensively researched. Compared to viral gene delivery methods, non-viral methods generate less toxicity and immunogenicity and thus represent a promising and effective tool for the genetic engineering of MSCs. In the last decades, various non-viral gene delivery strategies have been developed and some of them have been applied for MSC transfection. This paper gives an overview of the techniques, influencing factors and potential applications of non-viral methods used for the genetic engineering of MSCs. | 25,227,201 | [
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Toward the harmonization of result presentation for the eosin-5'-maleimide binding test in the diagnosis of hereditary spherocytosis. | The eosin-5'-maleimide (EMA) Binding test measures reduced mean channel fluorescence (MCF) reading of EMA-labeled red cells (EMA-RBCs) from patients with hereditary spherocytosis (HS). Reporting test results can be either in the actual MCF reading or as a ratio by normalization of the test MCF result to the mean MCF value of six normal controls. The latter format has potential for universal reporting. We analyzed three years' archival MCF data from HS and non-HS patient groups for establishment of reference ranges of ratios for normal adults and HS. A prospective study used FC500 and FACS Canto II cytometers to analyze contemporaneously EMA-RBCs from several patient groups and normal donors. Statistical analyses of the prospective data determined the cut-off values, and the sensitivity and specificity for HS respectively for the MCF and the ratio result presentations. The effect of using fewer than six normal controls for the ratio denominator was explored. The FC500 gave a mean ratio of 0.782 (SD=0.086) in HS patients with an optimal cut-off ratio of 0.918 (98.7% specificity, 95.6% sensitivity), and gray area ratio of 0.868-0.918. The Canto II gave a mean ratio of 0.774 (SD=0.085) with an optimal cut-off ratio of 0.925 (97.1% specificity and 100% sensitivity), and gray area ratio of 0.859-0.925. Harmonization of result presentation is feasible with no apparent constraint by instrument design. Interpretation of gray-area data requires an assessment of patient's clinical presentation and family history or performing a family study. | 25,227,211 | [
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Treatment outcome of mineral trioxide aggregate or calcium hydroxide direct pulp capping: long-term results. | This controlled, historic cohort study project continues a previously reported trial aiming to assess treatment outcome of direct pulp capping with mineral trioxide aggregate (MTA) versus calcium hydroxide (CH). Potential prognostic factors were re-evaluated on the basis of a larger sample size and longer follow-up periods. Clinical and radiographic outcomes of 229 teeth treated with direct pulp capping between 2001 and 2011 were investigated 24 up to 123 months post-treatment (median = 42 months). Pre-, intra-, and postoperative information was evaluated and statistically analyzed using a logistic regression model as well as generalized estimating equation logit models. Two hundred five patients (229 teeth) were available for follow-up (74% recall rate). The overall success rates were 80.5% (95% confidence interval [CI], 74.5-86.5) of teeth in the MTA group (137/170) and 59% (95% CI, 46.5-71.5) of teeth in the CH group (35/59). Multivariate analyses (generalized estimating equation logit model) indicated a significantly increased risk of failure for teeth that were directly pulp capped with CH compared with MTA (odds ratio = 2.67; 95% CI, 1.36-5.25; P = .001). Teeth that were permanently restored ≥ 2 days after direct pulp capping had a significantly worse prognosis irrespective of the pulp capping material chosen (odds ratio = 3.18; 95% CI, 1.61-6.3; P = .004). The results of this study indicate that MTA provides better long-term results after direct pulp capping compared with CH. Placing a permanent restoration immediately after direct pulp capping is recommended. | 25,227,216 | [
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Serotonergic correlation with anger and aggressive behavior in acute stroke patients: an intensity dependence of auditory evoked potentials (IDAP) study. | Anger and aggressive behavior (AB) are two of the main post-stroke behavioral manifestations, which could imply both an anger trait (TA) or a state condition of anger (SA). Serotonergic system is thought to play an inhibitory control on aggressive impulse. Nevertheless, whether 5HT has the same role in TA and in SA, is still debated. Intensity dependence of auditory evoked potentials (IDAP) is thought to be inversely related to the central 5HT tone. The aim of this study was to evaluate, in acute stroke patients, the 5HT system involvement in AB by IDAP. Consecutive stroke patients were evaluated and compared with healthy controls. The Spielberger Trait Anger Scale (STAS) was used to assess AB, SA and TA. Patients with AB and TA showed a significantly increased IDAP value, whereas patients with SA had a significantly lower IDAP; this indicates an increased 5HT tone. In acute stroke patients with AB, there is a decreased central 5HT tone. Surprisingly, we found an opposite 5HT feature between patients with TA and those showing SA, suggesting that the hypothesis of aggression based on 5HT deficiency requires further investigations. This might open new strategies in the treatment of post-stroke AB. | 25,227,246 | [
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Impact of Percutaneous Interventions for Pulmonary Artery Stenosis in Alagille Syndrome. | The study aims to examine acute and midterm outcomes after percutaneous interventions for treatment of pulmonary artery stenosis (PAS) in patients with Alagille Syndrome (ALGS). PAS affects up to two thirds of ALGS patients. Responsiveness to transcatheter therapies may differ from other causes of PAS. To date, there has been no study to evaluate outcomes of transcatheter interventions on PAS exclusively in ALGS. In this single-center series, we reviewed procedural, hemodynamic, and angiographic data from patients with ALGS and PAS from 2007 to 2011 who underwent an interventional catheterization. Minimal luminal diameter (MLD) was assessed pre- and postintervention, and at follow-up catheterization(s) when available. Acute and midterm response to high-pressure balloon angioplasty (HBA), bare metal stent (BMS) placement, and cutting balloon angioplasty (CBA) were assessed. Nine patients (median age 9.1 years) underwent 16 cardiac catheterizations with 34 interventions performed (20 HBA, 11 BMS, 3 CBA). There was a significant acute increase in MLD for all three modalities (42% HBA, P < .01; 91% BMS, P < .01; 58% CBA, P = .04). Follow-up data were available for 19 treated lesions at a median of 11 months. There was no significant difference in the improvement of MLD from baseline between the HBA and BMS groups, although in contrast to the BMS group, the HBA group showed continued interval vessel growth. Transcatheter intervention for PAS in ALGS is generally safe and acutely effective. Although BMS implantation was associated with the greatest immediate improvement in MLD, HBA-treated vessels demonstrate interval growth, whereas BMS-treated lesions do not. | 25,227,273 | [
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In vivo assessment of arterial stiffness in the isoflurane anesthetized spontaneously hypertensive rat. | Rodent models are increasingly used to study the development and progression of arterial stiffness. Both the non-invasive Doppler derived Pulse Wave Velocity (PWV) and the invasively determined arterial elastance index (EaI) have been used to assess arterial stiffness in rats and mice, but the need for anesthetic agents to make these in vivo estimates may limit their utility. Thus, we sought to determine: 1) if known differences in arterial stiffness in spontaneously hypertensive rats (SHR) are detectable by PWV and EaI measurements when made under isoflurane anesthesia, and 2) if these two uniquely acquired assessments of arterial elasticity correlate. We obtained PWV and EaI measurements in isoflurane anesthetized young and old SHRs, which are known to have significant differences in arterial stiffness. Doppler pulse waves were recorded from carotid and iliac arteries and the distance (D) between probe applantation sites was recorded. Simultaneously, an EKG was obtained, and the time intervals between the R-wave of the EKG to the foot of the Doppler waveforms were measured and averaged over three cardiac cycles. Pulse-transit time (T) of the carotid to iliac artery was determined, and PWV was calculated as Distance (D)/Time (T), where D = the distance from the carotid to the iliac notch and T = (R to iliac foot) - (R to carotid foot). EaI was subsequently determined from pressure volumes loops obtained via left ventricle catheterization. PWV and EaI were found to be significantly faster in the older rats (13.2 ± 2.0 vs. 8.0 ± 0.8 m/sec, p < 0.001; 120 ± 20 vs. 97 ± 16 mmHg/μl/g, p <0.05). Bland-Altman analyses of intra- and inter-observer measures demonstrate a statistically significant relationship between readings (p < 0.0001). PWV and EaI measurements were found to be significantly and positively correlated with a correlation coefficient of 0.53 (p < 0.05). Our study suggests that isoflurane administration does not limit Doppler PWV or EaI measures in their ability to provide accurate, in vivo assessments of relative arterial stiffness in isoflurane anesthetised SHR rats. Furthermore, PWV data obtained in these rats correlate well with invasively determined EaI. | 25,227,282 | [
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A review of the epidemiology of inflammatory bowel disease with a focus on diet, infections and antibiotic exposure. | Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic debilitating diseases that occur in populations around the world. The underlying etiology is thought to be multifactorial. There is a well-defined genetic contribution to the diseases, but this does not fully explain the epidemiology. Environmental factors, including the composition of the gut microbiota, are also important. There is wide geographic variability in the incidence and prevalence of IBD. High incidence rates have been observed in the United Kingdom, Northern Europe, Canada, and the United States. Globally, there is evidence of increasing incidence of CD and UC over time. The rising incidence of IBD in Western countries has generally predated that in developing nations, supporting the hypothesis that 'Westernization' of our lifestyle has led to the increased incidence of IBD. Smoking, antibiotic use, and diet are potentially reversible risk factors for IBD. Recommendations to avoid smoking are appropriate for all people, for numerous reasons. Antibiotic use should be limited to appropriate indications, a recommendation that too is appropriate for all populations. Detangling the relationship between diet, the gut microbiome and IBD raises the potential to reduce the incidence of IBD through dietary modification, an approach that might be considered among those at the highest risk. | 25,227,291 | [
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Antibiotics, probiotics and prebiotics in IBD. | The dysbiosis theory of inflammatory bowel disease (IBD) posits that there is an alteration in the gut microbiome as an important underpinning of disease etiology. It stands to reason then, that administering agents that could impact on the balance of microbes on the gut could be impactful on the course of IBD. Herein is a review of the controlled trials undertaken to assess the use of antibiotics that would kill or suppress potentially injurious microbes, probiotics that would overpopulate the gut with potentially beneficial microbes or prebiotics that provide a metabolic substrate that enhances the growth of potentially beneficial microbes. With regard to antibiotics, the best data are for the use of nitroimadoles postoperatively in Crohn's disease (CD) to prevent disease recurrence. Otherwise, the data are limited with the regard to any lasting benefit of antibiotics sustaining remission in either CD or ulcerative colitis (UC). A recent meta-analysis concluded that antibiotics are superior to placebo at inducing remission in CD or UC, although the meta-analysis grouped a variety of antibiotics with different spectra of activity. Despite the absence of robust clinical trial data, antibiotics are widely used to treat perineal fistulizing CD and acute and chronic pouchitis. Probiotics have not been shown to have a beneficial role in CD. However, Escherichia coli Nissle 1917 has comparable effects to low doses of mesalamine in maintaining remission in UC. VSL#3, a combination of 8 microbes, has been shown to have an effect in inducing remission in UC and preventing pouchitis. Prebiotics have yet to be shown to have an effect in any form of IBD, but to date controlled trials have been small. The use of antibiotics should be balanced against the risks they pose. Even probiotics may pose some risk and should not be assumed to be innocuous especially when ingested by persons with a compromised epithelial barrier. Prebiotics may not be harmful but may cause gastrointestinal side effects. Finally, the timing of ingestion of antibiotics and other dietary factors that may function as prebiotics, especially in early childhood, may be critical in shaping the gut microbiome and ultimately predisposing to or preventing IBD. Finding ways to impact on the gut microbiome to alter the course of IBD makes good sense, but should be undertaken in the setting of rigorously performed controlled trials to ensure that the interventions are truly effective and well tolerated. | 25,227,297 | [
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Subthalamic nucleus-deep brain stimulation for early motor complications in Parkinson's disease-the EARLYSTIM trial: early is not always better. | Subthalamic nucleus deep brain stimulation (STN-DBS) has revolutionized the management of disabling motor complications in Parkinson's disease. The EARLYSTIM trial applied this treatment to patients who had been experiencing motor complications for less than three years. STN-DBS significantly improved all primary and secondary outcome measures while best medical therapy failed to provide any improvement at the two-year follow-up time point. On face value these results strongly favor the application of STN-DBS far earlier than is currently applied, when patients are just beginning to experience problems with motor complications. Here we review the application of early DBS and the EARLYSTIM trial from the perspectives of clinical issues, health economics and study design and patient expectation of benefit. We conclude that the most relevant issue is not when to operate but on whom and that early is not always better. © 2014 International Parkinson and Movement Disorder Society. | 25,227,325 | [
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Government action could have prevented sepsis deaths. | MPs have criticised the government for a lack of urgency in preventing deaths from sepsis. | 25,227,345 | [
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Subcutaneous injection technique: an evidence-based approach. | Injections are routinely administered by nurses in acute care settings and in the community. Nurses require a thorough understanding of anatomy and physiology, pharmacological principles and equipment, and potential risks to the patient of injections. Nurses should also take an active approach to patient assessment before injecting medicines. This article, the first of two, provides an evidence-based review of injection administration, with particular reference to subcutaneous injections, and suggests a framework for best practice. | 25,227,387 | [
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Renal agenesis in Kallmann syndrome: a network approach. | Kallmann syndrome (KS) is defined by the combination of isolated hypogonadotrophic hypogonadism (IHH) and anosmia, with renal agenesis occurring in 30% of KS cases with KAL1 gene mutations. Unlike other KS-related disorders, renal agenesis cannot be directly associated with mutations in the KAL1 gene. We hypothesized that protein interaction networks may suggest a link between genes currently known to be associated with KS on the one hand and those associated with renal agenesis on the other hand. We created a STRING protein interaction network from KS-related genes and renal-agenesis-associated genes and analyzed it with Cytoscape 3.0.1 network software. The STRING protein interaction network provided a conceptual framework for current knowledge on the subject of renal morphogenesis in Kallmann syndrome. In addition, STRING and Cytoscape 3.0.1 software identified new potential KS renal-aplasia-associated genes (PAX2, BMP4, and SOX10). The use of protein-protein interaction networks and network analysis tools provided interesting insights and possible directions for future studies on the subject of renal aplasia in Kallmann syndrome. | 25,227,403 | [
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Oxidant-induced damage to equine erythrocytes from exposure to Pistacia atlantica, Pistacia terebinthus, and Pistacia chinensis. | Two horses were referred for methemoglobinemia and hemolytic anemia following 5 acute deaths in their herd from an unidentified toxin source. Horses have a greater risk than other mammalian species of developing methemoglobinemia and hemolytic anemia following ingestion of oxidizing toxins, due to deficiencies in the mechanisms that protect against oxidative damage in erythrocytes. Their susceptibility to oxidative erythrocyte damage is evident in the numerous cases of red maple (Acer rubrum) toxicosis. The suspected toxins causing A. rubrum toxicosis are tannic acid, gallic acid, and a metabolite of gallic acid, pyrogallol. These compounds can be found in a variety of plants, posing a risk to equine health. In order to quickly identify toxin sources, 2 rapid in vitro assays were developed to screen plant extracts for the ability to induce methemoglobin formation or cause hemolysis in healthy equine donor erythrocytes. The plant extract screening focused on 3 species of the genus Pistacia: P. atlantica, P. terebinthus, and P. chinensis, which were located in the horse pasture. Extracts of the seeds and leaves of each species induced methemoglobin formation and resulted in hemolysis, with seed extracts having greater potency. The in vitro assays used in the current study provide a useful diagnostic method for the rapid identification of oxidizing agents from unidentified sources. There is no effective treatment for oxidative erythrocyte damage in horses, making rapid identification and removal of the source essential for the prevention of poisoning. | 25,227,420 | [
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Virus-mediated compartmentalization of the host translational machinery. | Viruses require the host translational apparatus to synthesize viral proteins. Host stress response mechanisms that suppress translation, therefore, represent a significant obstacle that viruses must overcome. Here, we report a strategy whereby the mammalian orthoreoviruses compartmentalize the translational machinery within virus-induced inclusions known as viral factories (VF). VF are the sites of reovirus replication and assembly but were thought not to contain ribosomes. It was assumed viral mRNAs exited the VF to undergo translation by the cellular machinery, and proteins reentered the factory to participate in assembly. Here, we used ribopuromycylation to visualize active translation in infected cells. These studies revealed that active translation occurs within VF and that ribosomal subunits and proteins required for translation initiation, elongation, termination, and recycling localize to the factory. Interestingly, we observed components of the 43S preinitiation complex (PIC) concentrating primarily at factory margins, suggesting a spatial and/or dynamic organization of translation within the VF. Similarly, the viral single-stranded RNA binding protein σNS localized to the factory margins and had a tubulovesicular staining pattern that extended a short distance from the margins of the factories and colocalized with endoplasmic reticulum (ER) markers. Consistent with these colocalization studies, σNS was found to associate with both eukaryotic translation initiation factor 3 subunit A (eIF3A) and the ribosomal subunit pS6R. Together, these findings indicate that σNS functions to recruit 43S PIC machinery to the primary site of viral translation within the viral factory. Pathogen-mediated compartmentalization of the translational apparatus provides a novel mechanism by which viruses might avoid host translational suppression. Viruses lack biosynthetic capabilities and depend upon the host for protein synthesis. This dependence requires viruses to evolve mechanisms to coerce the host translational machinery into synthesizing viral proteins in the face of ongoing cellular stress responses that suppress global protein synthesis. Reoviruses replicate and assemble within cytoplasmic inclusions called viral factories. However, synthesis of viral proteins was thought to occur in the cytosol. To identify the site(s) of viral translation, we undertook a microscopy-based approach using ribopuromycylation to detect active translation. Here, we report that active translation occurs within viral factories and that translational factors are compartmentalized within factories. Furthermore, we find that the reovirus nonstructural protein σNS associates with 43S preinitiation complexes at the factory margins, suggesting a role for σNS in translation. Together, virus-induced compartmentalization of the host translational machinery represents a strategy for viruses to spatiotemporally couple viral protein synthesis with viral replication and assembly. | 25,227,463 | [
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The role of particle-to-cell interactions in dictating nanoparticle aided magnetophoretic separation of microalgal cells. | Successful application of a magnetophoretic separation technique for harvesting biological cells often relies on the need to tag the cells with magnetic nanoparticles. This study investigates the underlying principle behind the attachment of iron oxide nanoparticles (IONPs) onto microalgal cells, Chlorella sp. and Nannochloropsis sp., in both freshwater and seawater, by taking into account the contributions of various colloidal forces involved. The complex interplay between van der Waals (vdW), electrostatic (ES) and Lewis acid-base interactions (AB) in dictating IONP attachment was studied under the framework of extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) analysis. Our results showed that ES interaction plays an important role in determining the net interaction between the Chlorella sp. cells and IONPs in freshwater, while the AB and vdW interactions play a more dominant role in dictating the net particle-to-cell interaction in high ionic strength media (≥100 mM NaCl), such as seawater. XDLVO predicted effective attachment between cells and surface functionalized IONPs (SF-IONPs) with an estimated secondary minimum of -3.12 kT in freshwater. This prediction is in accordance with the experimental observation in which 98.89% of cells can be magnetophoretically separated from freshwater with SF-IONPs. We have observed successful magnetophoretic separation of microalgal cells from freshwater and/or seawater for all the cases as long as XDLVO analysis predicts particle attachment. For both the conditions, no pH adjustment is required for particle-to-cell attachment. | 25,227,473 | [
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The capacity of neural crest-derived stem cells for ocular repair. | Whether it is due to a particular epigenetic signature, or some other component of an embryonic differentiation program, accumulating evidence indicates that the origins of a stem cell has a profound impact on the potential of a tissue to regenerate and repair. Here, we focus on Müller glia, long considered the stem cells of the retina, and their surprising derivation from the neural crest. Whether the multipotent properties of a subset of Müller glia is associated with their neural crest origin remains a tantalizing possibility. | 25,227,475 | [
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Mutations in MFSD8, encoding a lysosomal membrane protein, are associated with nonsyndromic autosomal recessive macular dystrophy. | This study aimed to identify the genetic defects in 2 families with autosomal recessive macular dystrophy with central cone involvement. Case series. Two families and a cohort of 244 individuals with various inherited maculopathies and cone disorders. Genome-wide linkage analysis and exome sequencing were performed in 1 large family with 5 affected individuals. In addition, exome sequencing was performed in the proband of a second family. Subsequent analysis of the identified mutations in 244 patients was performed by Sanger sequencing or restriction enzyme digestion. The medical history of individuals carrying the MFSD8 variants was reviewed and additional ophthalmic examinations were performed, including electroretinography (ERG), multifocal ERG (mfERG), perimetry, optical coherence tomography (OCT), fundus autofluorescence, and fundus photography. MFSD8 variants, age at diagnosis, visual acuity, fundus appearance, color vision defects, visual field, ERG, mfERG, fundus autofluorescence, and OCT findings. Compound heterozygous variants in MFSD8, a gene encoding a lysosomal transmembrane protein, were identified in 2 families with macular dystrophy with a normal or subnormal ERG, but reduced mfERG. In both families, a heterozygous missense variant p.Glu336Gln was identified, which was predicted to have a mild effect on the protein. In the first family, a protein-truncating variant (p.Glu381*) was identified on the other allele, and in the second family, a variant (c.1102G>C) was identified that results in a splicing defect leading to skipping of exon 11 (p.Lys333Lysfs*3). The p.Glu336Gln allele was found to be significantly enriched in patients with maculopathies and cone disorders (6/488) compared with ethnically matched controls (35/18 682; P < 0.0001), suggesting that it may act as a genetic modifier. In this study, we identified variants in MFSD8 as a novel cause of nonsyndromic autosomal recessive macular dystrophy with central cone involvement. Affected individuals showed no neurologic features typical for variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), a severe and devastating multisystem lysosomal storage disease previously associated with mutations in MFSD8. We propose a genotype-phenotype model in which a combination of a severe and a mild variant cause nonsyndromic macular dystrophy with central cone involvement, and 2 severe mutations cause vLINCL. | 25,227,500 | [
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NMES with rTMS for moderate to severe dysfunction after stroke. | Motor dysfunction after stroke might be improved by neuromuscular electrical stimulation (NMES) combined with 1 Hz repetitive transcranial magnetic stimulation (rTMS) in patients with moderate and severe motor dysfunction. This preliminary study tested the effect of this treatment combination. Fifteen patients (60.5 ± 10.3 years old) participated in the study. All patients had been affected by cerebral artery infarction or hemorrhage and had moderate or severe motor dysfunction in their affected hand. The patients received NMES at paretic wrist extensor muscles combined with rTMS over the unaffected M1 hemisphere twice a day, six days/week over two weeks. All participants underwent the following battery of tests to evaluate the motor function of the affected hand: Upper limb Fugl-Meyer Assessment (UFMA), Wolf Motor Function Test (WMFT), and Box and Block Test (BBT). UFMA, WMFT, and BBT scores improved significantly after the study. These results suggest that NMES combined with rTMS could be useful for recovery of moderate and severe motor function after stroke. | 25,227,537 | [
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Immunocytochemical markers of neuronal maturation in human diagnostic neuropathology. | Histological descriptions of morphogenesis in human fetal brain and in malformations and tumours can now be supplemented by the timing and sequence of the maturation of individual neurons. In human neuropathology, this is principally achieved by immunocytochemical reactivities used as maturational markers of neuronal properties denoted by molecules and cell products. Cytological markers can appear early and then regress, often being replaced by more mature molecules, or might not exhibit the onset of immunoreactivity until a certain stage of neuronal differentiation is achieved, some early, others intermediate and some late during the maturational process. Inter-specific differences occur in some structures of the brain. The classification of markers of neuronal maturation can be based, in addition to those mentioned above, on several criteria: cytological localisation, water solubility, biochemical nature of the antigen, specificity and various technical factors. The most useful immunocytochemical markers of neuronal maturation in human neuropathology are NeuN, synaptophysin, calretinin and other calcium-binding molecules, various microtubule-associated proteins and chromogranins. Non-antibody histochemical stains that denote maturational processes include luxol fast blue for myelination, acridine orange fluorochrome for nucleic acids, mitochondrial respiratory chain enzymes and argentophilic impregnations. Neural crest derivatives of the peripheral nervous system, including chromaffin and neuroendocrine cells, have special features that are shared and others that differ greatly between lineages. Other techniques used in human diagnostic neuropathology, particularly as applied to tumours, include chromosomal and genetic analyses, the mTOR signalling pathway, BRAF V600E and other tumour-suppressor gene products, transcription products of developmental genes and the proliferation index of the tumour cells and of mitotic neuroepithelial cells. | 25,227,552 | [
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Performance of perfusion-weighted Fourier decomposition MRI for detection of chronic pulmonary emboli. | To evaluate the test performance of perfusion-weighted Fourier-decomposition (pw-FD) magnetic resonance imaging (MRI) in comparison to dynamic contrast-enhanced (DCE)-MRI as a reference standard in patients with known or suspected chronic pulmonary embolism (PE). In 64 patients, chronic PE was ruled out or confirmed by DCE-MRI using a time-resolved angiography with stochastic trajectories (TWIST) sequence in one breath-hold. Pw-FD-MRI was performed using a 2D fast low-angle shot (FLASH) sequence in free-breathing. After a nonrigid image registration, FD was applied to generate pw-images. Lungs were scored by two radiologists (2 and 12 years of lung MRI experience) visually for each lobe and segment for hypoperfused areas. For intra- and interobserver variability, the MR images were analyzed 2 months after the first analysis, blinded to the results of the first reader. PE was diagnosed by DCE-MRI in 39 patients. For the pw-FD MRI sensitivity, specificity, accuracy, and positive and negative predictive value for diagnosis of PE were 100%, 95%, 98%, 98%, and 100% on a per-patient basis, 94%, 94%, 94%, 95%, 94% on a per-lobe basis, and 82%, 92%, 88%, 88%, 88% on a segmental basis, respectively. Detection of subsegmental and segmental hypoperfusion using pw-FD MRI showed a moderate agreement with DCE-MRI (kappa of 0.68; 95% confidence interval: 0.64; 0.72). Pw-FD of the lung is a feasible test to diagnose chronic PE on a per-patient level during free-breathing without the use of ionizing radiation or contrast agents. | 25,227,559 | [
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Volatilize-controlled oriented growth of the single-crystal layer for organic field-effect transistors. | We demonstrate a solution method of volatilize-controlled oriented growth (VOG) to fabricate aligned single crystals of 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS pentacene) on a Si/SiO2 substrate. Through controlling the evaporation rate of the solvent, large-area-aligned single-crystal layers can be achieved on several substrates at the same time, covering over 90% on 2 × 1 cm substrates. The method provides a low-cost, maneuverable technology, which has potential to be used in batch production. We find that the atmosphere of the solvent with high dissolving capacity is in favor of aligned single-crystal growth. Besides, the growth mechanism of the VOG method is investigated in this paper. Top-contact organic field-effect transistors based on the single crystals of TIPS pentacene are achieved on a Si/SiO2 substrate. The optimal device exhibits a field-effect mobility of 0.42 cm(2) V(-1) s(-1) and an on/off current ratio of 10(5). Our research indicates that the VOG method is promising in single-crystal growth on a Si/SiO2 substrate for commercial production. | 25,227,560 | [
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The neural crest: a versatile organ system. | The neural crest is the name given to the strip of cells at the junction between neural and epidermal ectoderm in neurula-stage vertebrate embryos, which is later brought to the dorsal neural tube as the neural folds elevate. The neural crest is a heterogeneous and multipotent progenitor cell population whose cells undergo EMT then extensively and accurately migrate throughout the embryo. Neural crest cells contribute to nearly every organ system in the body, with derivatives of neuronal, glial, neuroendocrine, pigment, and also mesodermal lineages. This breadth of developmental capacity has led to the neural crest being termed the fourth germ layer. The neural crest has occupied a prominent place in developmental biology, due to its exaggerated migratory morphogenesis and its remarkably wide developmental potential. As such, neural crest cells have become an attractive model for developmental biologists for studying these processes. Problems in neural crest development cause a number of human syndromes and birth defects known collectively as neurocristopathies; these include Treacher Collins syndrome, Hirschsprung disease, and 22q11.2 deletion syndromes. Tumors in the neural crest lineage are also of clinical importance, including the aggressive melanoma and neuroblastoma types. These clinical aspects have drawn attention to the selection or creation of neural crest progenitor cells, particularly of human origin, for studying pathologies of the neural crest at the cellular level, and also for possible cell therapeutics. The versatility of the neural crest lends itself to interlinked research, spanning basic developmental biology, birth defect research, oncology, and stem/progenitor cell biology and therapy. | 25,227,568 | [
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The J-curve in arterial hypertension: fact or fallacy? | It is known that a large proportion of patients with arterial hypertension are undertreated. This may result in an increase of the incidence of cardiovascular events. On the other hand, aggressive reduction of blood pressure may increase cardiovascular events (J-curve phenomenon) in certain populations. This phenomenon may be seen in patients with coronary artery disease and left ventricular hypertrophy when the diastolic blood pressure decreases below 70-80 mm Hg, and the systolic blood pressure decreases below 130 mm Hg. This phenomenon is not seen in patients with stroke or renal disease. Thus, a safer and more conservative strategy should be applied in patients with coronary artery disease, left ventricular hypertrophy, elderly, and in patients with isolated systolic hypertension. This is depicted in the recently published European Society of Hypertension/European Society of Cardiology guidelines in which higher targets of blood pressure are suggested in certain cardiovascular diseases and in the elderly. | 25,227,573 | [
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Assessment of changing patterns of Le fort fracture lines using computed tomography scan: an observational study. | To assess the changing mid-face fracture patterns using a computed tomography scan. Fifty patients with mid-face trauma requiring open reduction and fixation were studied using 1.6 mm axial, sagittal, coronal and 3D images. Images were evaluated clinically, intra-operatively and finally were compared with standard Le Fort lines. Results. The male population dominated the female at a ratio of 11.5:1. The majority of the mid-face fractures were seen in the age group of 21-30 years. Road traffic accident (78%) was the major etiological factor followed by work-related accidents (12%) and assaults (10%). The CT scan analysis included categorizing the patients into three groups: (1) Fracture patterns resembling Le Fort lines (24%); (2) Fracture patterns partially resembling Le Fort lines (56%); and (3) Fracture patterns that do not resemble Le Fort lines (20%). With the change in the velocity of wounding object, there is a change in the mid-face fracture patterns. The majority of the cases present as a variant of classical Le Fort fractures. Computed tomography is a valuable diagnostic tool in assessing the fractures of the mid-face. 2D images are more sensitive than 3D images. However, both the images are required in delivery of an optimal treatment plan. | 25,227,590 | [
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Protective effect of the long pentraxin PTX3 against histone-mediated endothelial cell cytotoxicity in sepsis. | Pentraxin 3 (PTX3), a member of the long pentraxin subfamily within the family of pentraxins, is a soluble pattern recognition molecule that functions in the innate immune system. Innate immunity affords the infected host protection against sepsis, a potentially life-threatening inflammatory response to infection. Extracellular histones are considered to be the main cause of septic death because of their cytotoxic effect on endothelial cells, which makes them a potential therapeutic target. We found that PTX3 interacted with histones to form coaggregates, which depended on polyvalent interactions and disorder in the secondary structure of PTX3. PTX3 exerted a protective effect, both in vitro and in vivo, against histone-mediated cytotoxicity toward endothelial cells. Additionally, the intraperitoneal administration of PTX3 reduced mortality in mouse models of sepsis. The amino-terminal domain of PTX3, which was required for coaggregation with histones, was sufficient to protect against cytotoxicity. Our results suggest that the host-protective effects of PTX3 in sepsis are a result of its coaggregation with histones rather than its ability to mediate pattern recognition. This long pentraxin-specific effect provides a potential basis for the treatment of sepsis directed at protecting cells from the toxic effects of extracellular histones. | 25,227,610 | [
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Postresuscitation debriefing in the pediatric emergency department: a national needs assessment. | The objectives of this study were to assess current postresuscitation debriefing (PRD) practices in Canadian pediatric emergency departments (EDs) and identify areas for improvement. A national needs assessment survey was conducted to collect information on current PRD practices and perspectives on debriefing practice in pediatric EDs. A questionnaire was distributed to ED nurses, fellows, and attending physicians at 10 pediatric tertiary care hospitals across Canada. Summary statistics are reported. Data were analyzed from 183 participants (48.7% response rate). Although 88.8% of the participants believed that debriefing is an important process, 52.5% indicated that debriefing after real resuscitations occurs less than 25% of the time and 68.3% indicated that no expectation exists for PRD at their institution. Although 83.7% of participants believed that facilitators should have a specific skill set developed through formal training sessions, 63.4% had no previous training in debriefing. Seventy-two percent felt that medical and crisis resource management issues are dealt with adequately when PRD occurs, and 90.4% indicated that ED workload and time shortages are major barriers to effective debriefing. Most responded that a debriefing tool to guide facilitators might aid in multiple skills, such as creating realistic debriefing objectives and providing feedback with good judgment. PRD in Canadian pediatric EDs occurs infrequently, although most health care providers agreed on its importance and the need for skilled facilitators. | 25,227,647 | [
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0.08967825,
0.1008872... |
CLIC1 overexpression is associated with poor prognosis in gallbladder cancer. | The chloride intracellular channel 1 (CLIC1) gene family is a recently identified class of Cl channel proteins. Although CLIC1 involvement is well established in some cancers such as gastric cancer and colon cancer, its expression pattern in gallbladder cancer (GBC) remains unknown. The aim of our study was to investigate the expression of CLIC1 in relation to progression and prognosis of GBC. Eight fresh gallbladder cancers paired with adjacent non-tumour tissues were quantified using real-time PCR and Western blot. Tissue samples from resected gallbladder cancer (n = 75) and cholelithiasis (n = 75) were evaluated for CLIC1 expression by immunohistochemical staining. Their expression was correlated with different clinicopathological parameters. CLIC1 expression was significantly higher (62.7 %) in gallbladder cancer than in cholelithiasis (21.3 %, p < 0.001). CLIC1 levels were associated with the histological grade, TNM stage and perineural invasion (p < 0.05), but not with patient age, sex, lymph node metastasis or gallbladder stones (p > 0.05). Univariate Kaplan-Meier analysis showed that a positive CLIC1 expression was associated with a decreased overall survival (p < 0.001). Multivariate Cox regression analysis showed that CLIC1 expression and histological grade were independent risk factors for overall survival. Therefore, the expression of CLIC1 is closely related to the progression of GBC and may be used as an effective marker for predicting the prognosis of this disease. | 25,227,665 | [
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Pooling knowledge and improving safety for contracted works at a large industrial park. | At a large chemical park maintenance is contracted by the major companies operating the plants to many small firms. The cultural and psychological isolation of contractor workers was recognized a root cause of severe accidents in the recent years. That problem is common in chemical industry. The knowledge sharing has been assumed a good key to involve contractors and sub contractors in safety culture and contributing to injuries prevention. The selection of personal protective equipment PPE for the maintenance works has been taken as benchmark to demonstrate the adequateness of the proposed approach. To support plant operators, contractors and subcontractors in PPE discussion, a method has been developed. Its core is a knowledge-base, organized in an Ontology, as suitable for inferring decisions. By means of this tool all stakeholders have merged experience and information and find out the right PPE, to be provided, with adequate training and information package. PPE selection requires sound competencies about process and environmental hazards, including major accident, preventive and protective measures, maintenance activities. These pieces of knowledge previously fragmented among plant operators and contractors, have to be pooled, and used to find out the adequate PPE for a number of maintenance works. The PPE selection is per se important, but it is also a good chance to break the contractors' isolation and involve them in safety objectives. Thus by pooling experience and practical knowledge, the common understanding of safety issues has been strengthened. | 25,227,671 | [
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Targeting survival pathways to create infarct-spanning bridges of human embryonic stem cell-derived cardiomyocytes. | Generating myocyte grafts that bridge across infarcts could maximize their functional impact and best utilize small numbers of stem cells. To date, however, graft survival within acute infarcts has not been feasible. To enhance intrainfarct graft viability, human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were pretreated before implantation with cobalt protoporphyrin (CoPP), a pharmacologic inducer of cytoprotective heme oxygenase-1. After preculturing with CoPP (vs phosphate-buffered saline), hESC-CMs were injected intramyocardially into acutely infarcted rat hearts, using directed injections to span the infarct. A further group received CoPP-pretreated hESC-CMs plus 4 weekly doses of systemic CoPP to prolong exposure to cytoprotectants. Two control groups with infarcts received vehicle-only intramyocardial injections or weekly systemic CoPP without cell therapy. Postinfarct ventricular function was gauged by echocardiography and graft size quantified at 8 weeks by histomorphometry. CoPP-preconditioned hESC-CMs formed stable grafts deep within infarcted myocardium, while grafts without CoPP exposure survived mainly at the infarct periphery. Fractional shortening was improved at 4 and 8 weeks in all hearts receiving cell therapies (P < .01 vs vehicle-only injections). CoPP treatment of both graft hESC-CMs and recipient animals resulted in the largest grafts, highest fractional shortening, preserved wall thickness, and reduced infarct dimensions. Cellular therapy delivered acutely after infarction significantly improved postinfarct ventricular function at 1 and 2 months. CoPP pretreatment of cells resulted in stable hESC-CM grafts within infarcted myocardium. This design enables construction of directionally oriented, infarct-spanning bands of new cardiomyocytes that might further improve functional restoration as engrafted myocytes proliferate and mature. | 25,227,700 | [
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In situ single molecule imaging of cell membranes: linking basic nanotechniques to cell biology, immunology and medicine. | The cell membrane, which consists of a viscous phospholipid bilayer, different kinds of proteins and various nano/micrometer-sized domains, plays a very important role in ensuring the stability of the intracellular environment and the order of cellular signal transductions. Exploring the precise cell membrane structure and detailed functions of the biomolecules in a cell membrane would be helpful to understand the underlying mechanisms involved in cell membrane signal transductions, which could further benefit research into cell biology, immunology and medicine. The detection of membrane biomolecules at the single molecule level can provide some subtle information about the molecular structure and the functions of the cell membrane. In particular, information obtained about the molecular mechanisms and other information at the single molecule level are significantly different from that detected from a large amount of biomolecules at the large-scale through traditional techniques, and can thus provide a novel perspective for the study of cell membrane structures and functions. However, the precise investigations of membrane biomolecules prompts researchers to explore cell membranes at the single molecule level by the use of in situ imaging methods, as the exact conformation and functions of biomolecules are highly controlled by the native cellular environment. Recently, the in situ single molecule imaging of cell membranes has attracted increasing attention from cell biologists and immunologists. The size of biomolecules and their clusters on the cell surface are set at the nanoscale, which makes it mandatory to use high- and super-resolution imaging techniques to realize the in situ single molecule imaging of cell membranes. In the past few decades, some amazing imaging techniques and instruments with super resolution have been widely developed for molecule imaging, which can also be further employed for the in situ single molecule imaging of cell membranes. In this review, we attempt to summarize the characteristics of these advanced techniques for use in the in situ single molecule imaging of cell membranes. We believe that this work will help to promote the technological and methodological developments of super-resolution techniques for the single molecule imaging of cell membranes and help researchers better understand which technique is most suitable for their future exploring of membrane biomolecules; ultimately promoting further developments in cell biology, immunology and medicine. | 25,227,707 | [
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Comorbidity between post-traumatic stress disorder and borderline personality disorder: a review. | Traditionally, the presence of post-traumatic stress disorder (PTSD) in subjects diagnosed with borderline personality disorder (BPD) has been the object of scant empirical research. The clarification of issues related to the different areas of study for this comorbidity is not only significant from a theoretical point of view but also relevant for clinical practice. The aim of this review is to describe the main theoretical findings and research conclusions about the comorbidity between PTSD and BPD. A literature review was carried out via PubMed and PsycINFO for the period between 1990 and September 2013. The descriptors used were 'post-traumatic stress disorder', 'borderline personality disorder', 'PTSD', 'complex PTSD' and 'BPD'. Epidemiological studies show that the risk of PTSD among BPD subjects is not regularly higher than in subjects with other personality disorders. Furthermore, there is no conclusive evidence about the main aetiopathogenic mechanism of this comorbidity, either of one disorder being a risk factor for the other one or of common underlying variables. Concerning comparative studies, several studies with PTSD-BPD subjects have found a higher severity of psychopathology and psychosocial impairment than in BPD subjects. With regard to nosological status, the main focus of controversy is the validation of 'complex PTSD', a clinical entity which may comprise a subgroup of PTSD-BPD subjects. With regard to treatment, there are preliminary evidences for the efficient treatment of psychopathology in both PTSD and BPD. These findings are remarkable for furthering the understanding of the link between PTSD and BPD and their implications for treatment. The results of this review are discussed, including methodological constraints that hinder external validity and consistency of referred findings. | 25,227,722 | [
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Autophagy-related gene Atg5 is essential for astrocyte differentiation in the developing mouse cortex. | Astrocyte differentiation is essential for late embryonic brain development, and autophagy is active during this process. However, it is unknown whether and how autophagy regulates astrocyte differentiation. Here, we show that Atg5, which is necessary for autophagosome formation, regulates astrocyte differentiation. Atg5 deficiency represses the generation of astrocytes in vitro and in vivo. Conversely, Atg5 overexpression increases the number of astrocytes substantially. We show that Atg5 activates the JAK2-STAT3 pathway by degrading the inhibitory protein SOCS2. The astrocyte differentiation defect caused by Atg5 loss can be rescued by human Atg5 overexpression, STAT3 overexpression, and SOCS2 knockdown. Together, these data demonstrate that Atg5 regulates astrocyte differentiation, with potential implications for brain disorders with autophagy deficiency. | 25,227,738 | [
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Effects of miglustat treatment in a patient affected by an atypical form of Tangier disease. | Tangier disease (TD) is a rare autosomal recessive disorder, resulting from mutations in the ATP binding cassette transporter (ABCA1) gene. The deficiency of ABCA1 protein impairs high density lipoprotein (HDL) synthesis and cholesterol esters trafficking. A 58 year-old female, presenting with complex clinical signs (splenomegaly, dysarthria, dysphagia, ataxia, tongue enlargement, prurigo nodularis, legs lymphedema, pancytopenia and bone marrow foam cells), was misdiagnosed as Niemann-Pick C (NPC) and treated with miglustat (300 mg/day), normalizing neurological symptoms and improving skin lesions and legs lymphedema. Subsequently filipin-staining and molecular analysis for NPC genes were negative. Lipid profiling showed severe deficiency of HDL, 2 mg/dl (n.v. 45-65) and apoAI, 5.19 mg/dl (n.v. 110-170), suggesting TD as a probable diagnosis. Molecular analysis of ABCA1 gene showed the presence of a novel homozygous deletion (c.4464-486_4698 + 382 Del). Miglustat treatment was then interrupted with worsening of some neurological signs (memory defects, slowing of thought processes) and skin lesions. Treatment was restarted after 7 months with neurological normalization and improvement of skin involvement. These results suggest miglustat as a possible therapeutic approach in this untreatable disease. The mechanisms by which miglustat ameliorates at least some clinical manifestations of TD needs to be further investigated. | 25,227,739 | [
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Targeting VEGF/VEGFR in the treatment of psoriasis. | Psoriasis is a common chronic skin disorder characterized by cutaneous inflammation and keratinocyte hyperproliferation. In the past decade, a number of novel effective biological agents have been developed to treat moderate-to-severe psoriasis. However, these drugs have potential serious side effects, particularly the development of infectious diseases. Therefore there is still a need for new therapies with better efficacy and less adverse effects. Angiogenesis is implicated in various pathological conditions including psoriasis. Direct targeting of angiogenesis becomes a new therapeutic strategy for the treatment of psoriasis. Vascular endothelial growth factor (VEGF), the most critical angiogenic factor, is thought to play important roles during the pathogenesis of psoriasis and may be a promising target for treating psoriasis. Therefore, we proposed that targeting VEGF/VEGFRs could lead to new treatments for psoriasis. | 25,227,750 | [
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Tubular reabsorption of high, middle and low molecular weight proteins according to the tubulo-interstitial damage marker N-acetyl-β-D-glucosaminidase in glomerulonephritis. | Proteinuria, the hallmark of glomerular diseases, is an independent predictor of end-stage renal disease (ESRD) progression. Proteinuria is a mixture of proteins of different molecular weight (MW) dependent on alterations of glomerular filtration barrier (GFB) and reabsorption impairment by proximal tubular epithelial cells (PTECs). We aimed to evaluate the excretion of different-MW proteins according to the tubulo-interstitial damage marker N-acetyl-β-D-glucosaminidase (NAG) in glomerulonephritides (GNs). In 189 patients [idiopathic membranous nephropathy (IMN) n = 84, primary focal segmental glomerulosclerosis (FSGS) n = 48, crescentic IgA nephropathy (CIgAN) n = 37, minimal change disease (MCD) n = 20] several urinary proteins were measured at biopsy: α2-macroglobulin/creatinine ratio; fractional excretion of IgG, transferrin, albumin and α1-microglobulin, and the NAG/creatinine ratio divided by estimated glomerular filtration rate (eGFR) (NAG/C/eGFR), as NAG excretion is dependent on functioning nephron mass. Protein excretion was compared between 4th vs. 1st quartile of NAG/C/eGFR. In IMN, FSGS and CIgAN high-MW proteins excretion (α2-macroglobulin, IgG) was greater than that of middle- (transferrin, albumin) and low-MW proteins (α1-microglobulin) in 4th vs. 1st quartile of NAG/C/eGFR; the mean fold excretion increase of high-MW proteins in 3 GNs was 74.9, higher than that of middle- (34.8) and low-MW proteins (12.0). Higher excretion of high-MW proteins may be dependent on lower reabsorption by PTECs. By contrast, in MCD the difference in excretion of different-MW proteins is probably due to high GFB selectivity. High-MW protein excretion is dependent on GFB alteration and reduced reabsorption; its prognostic significance is ominous because in several glomerular diseases progression is associated with high-MW protein excretion. | 25,227,764 | [
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Evaluating the social determinants of teenage pregnancy: a temporal analysis using a UK obstetric database from 1950 to 2010. | Teenage pregnancy is a known social problem which has been previously described using a number of deprivation measures. This study aimed to explore the temporal patterns of teenage pregnancy in Aberdeen, Scotland and to assess the discriminating ability of three measures of socioeconomic status. This was a population-based study from 1950 to 2010, using data from the Aberdeen Maternity Neonatal Databank (AMND). The main outcome variable was conceptions occurring in women aged less than 20 years. This study used two area-based measures, the Scottish Index of Multiple Deprivation (SIMD) and the Carstairs index, and one individual-based measure the Social Class based on Occupation (SCO). These measures were compared for their association with teenage conceptions using logistic regression models. The models were used to determine receiver operating characteristic (ROC) curves showing the discriminating ability of the measures. There was an overall decline in teenage conceptions over the 60-year period, but an increase in the rate ratio for deprived areas. All the measures of socioeconomic status were highly associated with teenage pregnancy. The adjusted OR of SIMD and teenage conception was 5.72 (95% CI 4.62 to 7.09), which compared the most deprived decile with the least deprived decile. The use of ROC curves showed that socioeconomic measures performed better than chance at determining teenage conceptions (χ(2)=21.67, p≤0.0001). They further showed that the SIMD had the largest area under the curve (AUC) with a value of 0.81 (95% CI 0.80 to 0.82), followed by the Carstairs index with an AUC of 0.80 (95% CI 0.78 to 0.80), then by SCO with an AUC of 0.79 (95% CI 0.78 to 0.80). Despite a slight decline in teenage pregnancies over the past decades, there is still an evident association between deprivation and teenage pregnancy. This study shows that all the measures of socioeconomic status were highly associated with teenage pregnancy, with the SIMD having the greatest discriminatory effect. | 25,227,769 | [
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The Social Gap Index and the prevalence of osteoarthritis in the community: a cross-sectional multilevel study in Mexico. | Multilevel studies have gained importance for highlighting social inequalities in health. These associations have been reported previously in diseases such as arthritis and chronic pain. We conducted a cross-sectional study using multilevel analysis to identify individual and contextual factors associated with the variation of prevalence of osteoarthritis (OA) in the Mexican population. The sample included 17,566 individuals of which 10,666 (60.7%) were women. The relationship between individual and contextual factors and OA were analyzed with a multilevel strategy. From the total population, 1,681 individuals had OA. Multilevel analysis showed that individual variables such as female gender (odds ratio (OR) = 1.3, 95% confidence interval (CI) 1.1, 1.4), age range 55-65 years (OR = 1.6, 95% CI 1.3, 2.0), musculoskeletal pain in the last 7 days (OR = 2.6, 95% CI 2.3, 3.0), and use of pain treatments (OR = 1.4, 95% CI 1.2, 1.7) were associated with OA. At the regional level, the Social Gap Index (SGIx) was associated with the diagnosis of OA (coefficient 0.5, 95% CI 0.2-1.1). The SGIx contextual variable was positively associated with the regional prevalence of OA and the variation in prevalence of OA in different regions. The larger the social gap, the greater the variation in OA prevalence. These factors were independently associated with the prevalence of OA: female gender, pain intensity, physical limitation, and the use of pain treatments were individual variables associated with OA. The association between OA prevalence and regional variations with SGIx reflects inequities in health provisions that should be considered in health programs. | 25,227,770 | [
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DNA fragmentation, caspase 3 and prostate-specific antigen genes expression induced by arsenic, cadmium, and chromium on nontumorigenic human prostate cells. | Prostate cancer is one of the most common cancers and the second cause of cancer-related deaths among men. Metals are recognized as chemical carcinogens where chronic exposures to such metals are implicated in the development of cancer, including prostate cancer. This in vitro study demonstrates the relative death sensitivity of prostatic (RWPE-1) cells to arsenic (As), cadmium (Cd), and chromium (Cr) as environmental pollutants through its apoptotic effects and the effect of these chemicals on prostate-specific antigen (PSA) gene expression as a marker for their carcinogecity. RWPE-1 cells were divided into three groups that were treated with As, Cd, and Cr in three replicates, at three different concentrations for each metal for 48 h. A control group consisted of untreated RWPE1 cells was used. Apoptosis was assessed using comet assay and caspase 3 gene expression; meanwhile, PSA gene expression was evaluated by semiqualitative real-time PCR (RT-PCR). One of the novel findings of this study is that arsenic and cadmium at low concentrations decreased apoptosis of RWPE-1 cells in a concentration-dependent manner while chromium induced significant concentration-dependent increase in apoptosis. Yet, at the highest concentrations, apoptosis was relatively more induced by all chemicals. Arsenic was the most chemical inhibiting apoptosis in RWPE-1 cells at low concentration. While at the moderate and highest concentrations, cadmium was the most inhibiting chemical of RWPE-1 cells' apoptosis. No distinct differences between treated and untreated cells for PSA gene expression were observed. It can be concluded that As and Cd, at low concentrations, can reduce apoptosis of prostatic cells in a concentration-dependent manner while chromium induced it; however, all metal salts used in this study did not induce PSA gene expression. | 25,227,780 | [
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Score based risk assessment of lung cancer and its evaluation for Bangladeshi people. | The problem of cancer, especially lung cancer, is very acute in Bangladesh. The present study was conducted to evaluate the risk of lung cancer among Bangladeshi people based on hereditary, socio-economic and demographic factors. This study was carried out in 208 people (patients-104, controls-104) from January 2012 to September 2013 using a structured questionnaire containing details of lung cancer risk factors including smoking, secondhand smoke, tobacco leaf intake, age, gender, family history, chronic lung diseases, radiotherapy in the chest area, diet, obesity, physical activity, alcohol consumption, occupation, education, and income. Descriptive statistics and testing of hypotheses were used for the analysis using SPSS software (version 20). According to this study, lung cancer was more prevalent in males than females. Smoking was the highest risk factor (OR=9.707; RR=3.924; sensitivity=0.8872 and P<0.0001) followed by previous lung disease (asthma, tuberculosis etc.) (OR=7.095; RR=1.508; sensitivity=0.316 and P<0.0001)) for male patients. Highly cooked food (OR=2.485; RR=1.126; sensitivity=0.418 and P=0.004)) and also genetic inheritance (OR=1.93; RR=1.335; sensitivity=0.163 and P=0.138) demonstrated significant correlation with lung cancer as risk factors after these two and alcohol consumption was not prevalent. On the other hand, for female patients, tobacco leaf intake represented the highest risk (OR=2.00; RR=1.429; sensitivity= 0.667 and P=0.5603) while genetic inheritance and highly cooked food also correlate with lung cancer but not so significantly. Socio- economic status and education level also play important roles in causing lung cancer. Some 78.5% male and 83.3% of female cancer patients were rural residents, while 58.2% lived at the margin or below the poverty line. Most male (39.8%) and female (50.0%) patients had completed only primary level education, and 27.6% male and 33.3% female patients were illiterate. Smoking was found to be more prevalent among the less educated persons. The results obtained in this study indicate the importance of creating awareness about lung cancer risk factors among Bangladeshi people and making appropriate access to health services for the illiterate, poor, rural people. | 25,227,785 | [
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Fatty acid synthesis pathway genetic variants and clinical outcome of non-small cell lung cancer patients after surgery. | Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Our data suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery. | 25,227,797 | [
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Second-line capecitabine and oxaliplatin combination for gemcitabine-resistant advanced pancreatic cancer. | The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin 130 mg/m2 and capecitabine 1000 mg/m2 twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95%CI: 16.6-29.5 weeks) and 12 weeks (95%CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2. | 25,227,800 | [
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Associations between the rs6010620 polymorphism in RTEL1 and risk of glioma: a meta-analysis of 20,711 participants. | Associations between the rs6010620 polymorphism in the regulator of telomere elongation helicase1 (RTEL1) gene and glioma have been widely reported but the results were not inconclusive. The aim of the current study was to investigate the association between the rs6010620 polymorphism in RTEL1 gene and risk of glioma by meta-analysis. We searched PubMed, Embase, Wanfang Weipu and CNKI (China National Knowledge Infrastructure) databases, which included all research published 05 May 2014. A total of 8,292 cases and 12,419 controls from 14 case-control studies involving the rs6010620 polymorphism in the RTEL1 gene were included. Statistical analysis was performed using STATA 12.0 software. The results indicated that the rs6010620 polymorphism in RTEL1 gene was indeed associated with risk of glioma (OR=1.474, 95%CI=1.282-1.694, p<0.001). On subgroup analysis by ethnicity, we found associations between the rs6010620 polymorphism in the RTEL1 gene and risk of glioma in both Caucasians and Asians. The current meta-analysis suggested that the rs6010620 polymorphism in the RTEL1 gene might increase risk of glioma. In future, larger case-control studies are needed to confirm our results. | 25,227,808 | [
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Clinical study on carboplatin for treating pediatric patients with Wilms tumors. | This analysis was conducted to evaluate the efficacy and safety of carboplatin based chemotherapy in treating pediatric patients with Wilms tumors. Clinical studies evaluating the efficacy and safety of carboplatin based regimens on response and safety for pediatric patients with Wilms tumors were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. In carboplatin based regimens, 4 clinical studies which including 127 patients with advanced Wilms tumors were considered eligible for inclusion. With this carboplatin based chemotherapy, 2 clinical studies included carboplatin, ifosfamide and etoposide. Systemic analysis suggested that, in all patients, the pooled PR was 64.5% (82/127) in carboplatin based regimens. Thrombocytopenia and leukocytopenia were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with carboplatin based treatment. This systemic analysis suggests that carboplatin based regimens are associated with a reasonable response rate and accepted toxicities for treating pediatric patients with Wilms tumors. | 25,227,828 | [
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A novel mutant of human papillomavirus type 18 E6E7 fusion gene and its transforming activity. | Persistent human papillomavirus (HPV) infection, especially with high-risk types such as HPV16 and HPV18, has been identified as the primary cause of cervical cancer. E6 and E7 are the major onco-proteins of high-risk HPVs, which are consistently expressed in HPV infected tissues but absent in normal tissues and represent ideal therapeutic targets for immunotherapy of cervical cancer. In this study, the optimized fusion gene HPV18 E6E7 (HPV18 ofE6E7) was constructed according to genetic codon usage for human genes. At the same time, for safety future clinical application, a mutant of HPV18 ofE6E7 fusion gene was generated by site-directed mutagenesis at L52G for the E6 protein and C98G for the E7 protein. HPV18-E6E7 mutant (HPV18 ofmE6E7) constructed in this work not only lost the transformation capability for NIH 3T3 cells and tumorigenicity in BALB/c nude mice, but also maintained very good stability and antigenicity. These results suggest that the mutant should undergo further study for application as a safe antigen- specific therapeutic vaccine for HPV18-associated tumors. | 25,227,848 | [
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Comparison of 2-dimensional and 3-dimensional conformal treatment plans in gastric cancer radiotherapy. | Postoperative chemoradiotherapy is accepted as standard treatment for stage IB-IV, M0 gastric cancer. Radiotherapy (RT) planning of gastric cancer is important because of the low radiation tolerance of surrounding critical organs. The purpose of this study was to compare the dosimetric aspects of 2-dimensional (2D) and 3-dimensional (3D) treatment plans, with the twin aims of evaluating the adequacy of 2D planning fields on coverage of planning target volume (PTV) and 3D conformal plans for both covering PTV and reducing the normal tissue doses. Thirty-six patients with stage II-IV gastric adenocarcinoma were treated with adjuvant chemoradiotherapy using 3DRT. For each patient, a second 2D treatment plan was generated. The two techniques were compared for target volume coverage and dose to normal tissues using dose volume histogram (DVH) analysis. 3DRT provides more adequate coverage of the target volume. Comparative DVHs for the left kidney and spinal cord demonstrate lower radiation doses with the 3D technique. 3DRT produced better dose distributions and reduced radiation doses to left kidney and spinal cord compared to the 2D technique. For this reason it can be predicted that 3DRT will result in better tumor control and less normal tissue complications. | 25,227,849 | [
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Diagnostic values of serum levels of pepsinogens and gastrin-17 for screening gastritis and gastric cancer in a high risk area in northern Iran. | Gastric cancer (GC) is the second cause of cancer related death in the world. It may develop by progression from its precancerous condition, called gastric atrophy (GA) due to gastritis. The aim of this study was to evaluate the accuracy of serum levels of pepsinogens (Pg) and gastrin-17 (G17) as non-invasive methods to discriminate GA or GC (GA/GC) patients. Subjects referred to gastrointestinal clinics of Golestan province of Iran during 2010 and 2011 were invited to participate. Serum levels of PgI, PgII and G17 were measured using a GastroPanel kit. Based on the pathological examination of endoscopic biopsy samples, subjects were classified into four groups: normal, non-atrophic gastritis, GA, and GC. Receiver operating curve (ROC) analysis was used to determine cut-off values. Indices of validity were calculated for serum markers. Study groups were normal individuals (n=74), non-atrophic gastritis (n=90), GA (n=31) and GC patients (n=30). The best cut-off points for PgI, PgI/II ratio, G17 and HP were 80 μg/L, 10, 6 pmol/L, and 20 EIU, respectively. PgI could differentiate GA/GC with high accuracy (AUC=0.83; 95%CI: 0.76-0.89). The accuracy of a combination of PgI and PgI/II ratio for detecting GA/GC was also relatively high (AUC=0.78; 95%CI: 0.70-0.86). Our findings suggested PgI alone as well as a combination of PgI and PgI/II ratio are valid markers to differentiate GA/GC. Therefore, Pgs may be considered in conducting GC screening programs in high-risk areas. | 25,227,854 | [
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Performance of 3D, navigator echo-gated, contrast-enhanced, magnetic resonance coronary vein imaging in patients undergoing CRT. | The aims of this study were to evaluate the ability of contrast-enhanced MRI to visualize the coronary veins with validation by the gold standard, X-ray venography, and to determine whether MRI can visualize the coronary vein branch used for left ventricular (LV) lead implantation. Nineteen (19) patients undergoing cardiac resynchronization therapy (CRT) received a cardiac MRI at 1.5T 1 week before treatment. Coronary vein images were acquired using a 3D, navigator- and ECG-gated, contrast-enhanced, inversion-recovery, fast low-angle shot (FLASH) sequence. X-ray venography was performed during the CRT procedure to image the coronary venous anatomy and the LV lead location. MRI coronary vein images were graded on a 0-3 scale (0 = nonexistent, 1 = poor, 2 = good, 3 = excellent). MRI and X-ray venogram images were also graded using a binary visible/not visible scheme to compare the visibility of the coronary veins. The mean visibility scores for the coronary sinus, the posterior interventricular, the posterior vein of the left ventricle, the left marginal vein, and the anterior interventricular were 3.0 ± 0.2, 2.3 ± 0.7, 1.6 ± 1.1, 1.9 ± 0.8 and 2.4 ± 0.9, respectively. When compared to X-ray venography, MRI was capable of visualizing 90% of veins and all of the veins used for LV lead implantation. The vein used for LV lead implantation had an average vein image quality score of 1.9 on MRI images. Contrast-enhanced MRI was capable of visualizing 90% of the coronary venous anatomy and was able visualize the vein used for LV lead implantation in all patients. | 25,227,865 | [
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Catalytic imine-imine cross-coupling reactions. | We report here efficient catalytic imine-imine cross-coupling reactions based on an umpolung strategy; an imine bearing a 9-fluorenyl moiety on its nitrogen atom, which acted as a nucleophile, reacted with another imine to afford an imine-imine cross-coupling adduct in high yield. Furthermore, a chiral guanidine acted as a chiral catalyst for these coupling reactions, and optically active 1,2-diamines were obtained in high yields with high enantioselectivities. | 25,227,870 | [
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Experiences, utilisation and outcomes of maternity care in England among women from different socio-economic groups: findings from the 2010 National Maternity Survey. | The objective of this analysis was to explore the healthcare-seeking behaviours and experiences of maternity care among women from different socio-economic groups in order to improve understanding of why socially disadvantaged women have poorer maternal health outcomes in the UK. Secondary analysis of a national survey of women conducted 3 months after they had given birth. England. A total of 5332 women. Logistic regression analysis to investigate differences in outcomes among different socio-economic groups, classified by the Index of Multiple Deprivation (IMD). Healthcare-seeking behaviours, outcomes and experiences of maternity care. With each increase in IMD quintile (decrease in socio-economic position), women were shown to be 25% (adjusted odds ratio [aOR] 0.75; 95% confidence interval [95% CI] 0.63-0.90) less likely to have had any antenatal care and 15% (aOR 0.85; 95% CI 0.80-0.90) less likely to have had a routine postnatal check-up. They were 4% (aOR 1.04; 95% CI 0.99-1.10) more likely to have had an antenatal hospital admission, 7% (aOR 1.07; 95% CI 0.99-1.16) more likely to have been transferred during labour and 4% (aOR 1.04; 95% CI 0.99-1.09) more likely to have had a caesarean birth, although these results were not statistically significant. With decreasing socio-economic position women were more likely to report that they were not treated respectfully or spoken to in a way they could understand by doctors and midwives. This analysis suggests the need for a focusing of professionals and services towards pregnant women from lower socio-economic groups and more targeted maternal public health education towards socially disadvantaged women. | 25,227,878 | [
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[From fishing trip to the critical care unit : Successful resuscitation after a near drowning accident]. | In the context of the European Resuscitation Council (ERC) guidelines, modifications of the proposed treatment algorithm need to be performed in order to respond to different parameters. In this respect several factors interacting with cardiac arrest are essential and need to be included in the therapy. This case report demonstrates an example of resuscitation in the situation of hypothermia. After a near drowning accident and approximately 30 min underwater, a patient suffering from severe hypothermia initially required resuscitation after the rescue. A return of spontaneous circulation (ROSC) was successfully achieved within a short length of time and after 15 days on the intensive care unit the patient was discharged to a rehabilitation facility without any signs of focal neurological deficits. Section 8 of the ERC guidelines provides additional information for resuscitation under specific conditions. In this case report, hypothermia was one of the main criteria leading to an adjusted pharmacological therapy. Furthermore, selection of the appropriate hospital for an optimal advanced treatment including controlled warming of the patient and management of hypothermia-induced complications had to be evaluated. | 25,227,882 | [
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Impact of lauric arginate application form on its antimicrobial activity on the surface of a model meat product. | This study evaluated the antimicrobial effect of N(α)-Lauroyl-L-arginine ethyl estermonohydrochloride (lauric arginate), sodium lactate, and sodium diacetate at various concentrations against Listeria innocua, Escherichia coli C600, and Lactobacillus curvatus (10(2) CFU/g) on "Lyoner style" sausage slices as a function of application form. We want to investigate if the results of a surface application of lauric arginate in various applications forms may differ from that of an in-matrix application since different physicochemical processes occur at surfaces than in matrices. Lauric arginate was applied on the surface of meat emulsions as aqueous solution, as oil-in-water emulsion, and as solid lipid particles. The sausages slices were stored at 6 °C for 24 d and bacterial growth was assessed every 3rd day. The growth of L. curvatus was not impacted by lactate and diacetate at any tested concentration. In contrast, L. innocua and E. coli were inhibited over 24 d in the presence of ≥3.0 × 10(3) μg/g diacetate. Aqueous lauric arginate solutions of 2.0 and 2.5 × 10(3) μg/g were required for total inhibition of L. curvatus and L. innocua, respectively. The growth of E. coli was not affected by application of lauric arginate. The use of lauric arginate in an oil-in-water emulsion or solid lipid particles reduced antimicrobial effectiveness on the surface of Lyoner slices, which is in stark contrast to a previously conducted in-matrix application of the same systems. Results were attributed to molecular interactions and mass transport processes that rendered lauric arginate less active when applied as emulsions or solid lipid particles. Results highlight the importance of understanding physicochemical properties when using interfacially active antimicrobials. This study demonstrates that the antimicrobial efficacy of preservatives in a product depends on the type of preservative and the time of addition at which the preservative is introduced into the production process. Furthermore, application systems for preservatives can indeed prevent unwanted interaction with product ingredients and therefore a loss of antimicrobial activity but also in this case the time of addition is critical because the preservative must have the possibility to separate from the carrier system. | 25,227,890 | [
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Exome sequencing identifies a novel frameshift mutation of MYO6 as the cause of autosomal dominant nonsyndromic hearing loss in a Chinese family. | Autosomal dominant types of nonsyndromic hearing loss (ADNSHL) are typically postlingual in onset and progressive. High genetic heterogeneity, late onset age, and possible confounding due to nongenetic factors hinder the timely molecular diagnoses for most patients. In this study, exome sequencing was applied to investigate a large Chinese family segregating ADNSHL in which we initially failed to find strong evidence of linkage to any locus by whole-genome linkage analysis. Two affected family members were selected for sequencing. We identified two novel mutations disrupting known ADNSHL genes and shared by the sequenced samples: c.328C>A in COCH (DFNA9) resulting in a p.Q110K substitution and a deletion c. 2814_2815delAA in MYO6 (DFNA22) causing a frameshift alteration p.R939Tfs*2. The pathogenicity of novel coding variants in ADNSHL genes was carefully evaluated by analysis of co-segregation with phenotype in the pedigree and in light of established genotype-phenotype correlations. The frameshift deletion in MYO6 was confirmed as the causative variant for this pedigree, whereas the missense mutation in COCH had no clinical significance. The results allowed us to retrospectively identify the phenocopy in one patient that contributed to the negative finding in the linkage scan. Our clinical data also supported the emerging genotype-phenotype correlation for DFNA22. | 25,227,905 | [
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Treatment intensification with maraviroc (CCR5 antagonist) leads to declines in CD16-expressing monocytes in cART-suppressed chronic HIV-infected subjects and is associated with improvements in neurocognitive test performance: implications for HIV-associated neurocognitive disease (HAND). | HIV-associated neurocognitive disorders (HAND) continues to be prevalent (30-50%) despite plasma HIV-RNA suppression with combination antiretroviral therapy (cART). There is no proven therapy for individuals on suppressive cART with HAND. We have shown that the degree of HIV reservoir burden (HIV DNA) in monocytes appear to be linked to cognitive outcomes. HIV infection of monocytes may therefore be critical in the pathogenesis of HAND. A single arm, open-labeled trial was conducted to examine the effect of maraviroc (MVC) intensification on monocyte inflammation and neuropsychological (NP) performance in 15 HIV subjects on stable 6-month cART with undetectable plasma HIV RNA (<48 copies/ml) and detectable monocyte HIV DNA (>10 copies/10(6) cells). MVC was added to their existing cART regimen for 24 weeks. Post-intensification change in monocytes was assessed using multiparametric flow cytometry, monocyte HIV DNA content by PCR, soluble CD163 (sCD163) by an ELISA, and NP performance over 24 weeks. In 12 evaluable subjects, MVC intensification resulted in a decreased proportion of circulating intermediate (median; 3.06% (1.93, 6.45) to 1.05% (0.77, 2.26)) and nonclassical (5.2% (3.8, 7.9) to 3.2% (1.8, 4.8)) CD16-expressing monocytes, a reduction in monocyte HIV DNA content to zero log10 copies/10(6) cells and in levels of sCD163 of 43% by 24 weeks. This was associated with significant improvement in NP performance among six subjects who entered the study with evidence of mild to moderate cognitive impairment. The results of this study suggest that antiretroviral therapy with potency against monocytes may have efficacy against HAND. | 25,227,930 | [
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One- to four-year follow-up of endobronchial lung volume reduction in alpha-1-antitrypsin deficiency patients: a case series. | Lung volume reduction surgery can improve lung function and working capacity in severe heterogeneous emphysema. Endobronchial lung volume reduction (ELVR) performed by one-way valves inserted via a flexible bronchoscope can result in a moderate but significant improvement in lung function and exercise tolerance, eliminating the surgical risks. Most studies of this method have excluded patients with α1-antitrypsin (AAT) deficiency, but small series of cases with positive short-term outcome have been reported. The sustainability of results has been questioned and we here present our experience in AAT-deficient patients treated with ELVR followed up for up to 4 years. From August 2008 to January 2012, 15 patients were treated with ELVR. Inclusion criteria were homozygotic AAT deficiency, age <80 years, residual volume of 140% or more, forced expiratory volume in 1 s (FEV1) 15-45% of predicted, severe heterogeneous emphysema, symptoms severely restricting daily life, informed consent and absence of other serious diseases. One patient coughed up valves after 2 months, 1 developed pneumothorax and had valve displacement and subsequent removal, and 1 improved from an FEV1 of 0.62 to 0.84 liters, but after 4 months developed repeated and severe pneumonia and the valves had to be removed. Thus, 12 patients remained and were followed up for at least 1 year. In these patients, FEV1 increased (mean: 54%), the quality of life was much improved, and 2 patients could be taken off oxygen therapy. During the 4-year follow-up, patients demonstrated no significant deterioration in lung function. In carefully selected AAT deficiency patients with severe emphysema, ELVR can be safely performed with encouraging long-lasting results. | 25,227,936 | [
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Occurrence and fate of triclosan and triclocarban in a subtropical river and its estuary. | The occurrence of triclosan (TCS) and triclocarban (TCC) in a subtropical river (Jiulong River) and its estuary was investigated for two years. TCS and TCC were ubiquitously detected in the Jiulong River and its estuary. The levels of TCS and TCC ranged from less than the method detection limit to 64 ng/L and from 0.05 to 14.1 ng/L in the river, respectively. The levels of TCS and TCC in the estuary ranged from 2.56 to 27.25 ng/L and 0.38 to 5.76 ng/L, respectively. Temporal and spatial variations of TCS and TCC in the Jiulong River and its estuary were observed during the investigation. The weather conditions did not show significant correlations with TCS and TCC, whereas several water quality parameters showed high correlations with TCS and TCC. The microcosm studies showed that both direct photolysis and biodegradation contributed to TCS removal, whereas indirect photolysis was important for TCC removal in the surface water. | 25,227,953 | [
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Initial high-dose prednisolone combination therapy using COBRA and COBRA-light in early rheumatoid arthritis. | Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very effective in early rheumatoid arthritis (RA). COBRA combination therapy is superior to initial monotherapy of SSZ and MTX, is also associated with a good long-term outcome, is as safe as other treatment regimes, and performs as well as the combination of high-dose MTX and the tumor necrosis factor antagonist infliximab. A pilot study with an intensified version of the COBRA combination therapy showed that strict monitoring and aggressive treatment intensification based on the Disease Activity Score can result in a remission rate of 90% in patients with active early RA. Also, the first results indicate that an attenuated variation on COBRA combination therapy, called 'COBRA-light', is effective in decreasing disease activity and is generally well tolerated. Based on these results, we conclude that initial high-dose prednisolone in combination with MTX and SSZ could or should be the first choice in early active RA since it is effective and safe, and the cost price of the drugs is low. | 25,227,967 | [
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Soluble CD44 and CD44v6 and prognosis in children with B-cell acute lymphoblastic leukemia. | CD44v6 is an isoform of CD44 that can be present in soluble form (sCD44v6). The aim of this study is to evaluate the presence of soluble CD44 (sCD44) and sCD44v6 in serum of children with B-cell precursor acute lymphoblastic leukemia (B-ALL) and their relationship with prognosis. sCD44v6 and sCD44 levels were measured in the sera of patients and healthy children by enzyme-linked immunosorbent assay. The level of the molecules was analyzed in relation to laboratory and clinical characteristics of the patients at presentation and response to therapy. sCD44v6 was significantly lower in patients (103.4 ± 44 ng/mL) than in controls (173.5 ± 73.6 ng/mL) whereas the serum level of sCD44 showed no significant difference between the groups. In patients, sCD44v6 quantity was inversely correlated with sCD44 level (r = -0.57, P < 0.01). The mean serum level of sCD44 in patients with >20% positivity for CD44 surface expression was greater than that in patients with ≤20% positivity (1345 ± 409 ng/mL vs 1111 ± 390 ng/mL, P = 0.05). sCD44v6 showed no significant association with response to therapy and prognostic factors except the TEL/AML1 positivity, as it was higher in TEL/AML1 positive patients (157.3 ± 55.6 ng/mL) than negative ones (92 ± 43.6 ng/mL, P = 0.036). Conversely, sCD44 was lower in TEL/AML1 positive patients and showed a significant association with white blood cell number, blast percentage and extramedullary involvement. The lower level of sCD44v6 in patients than in controls suggests the possible diagnostic value of this molecule for B-ALL. The presence of an association with established prognostic factors despite of no relationship with disease outcome suggested these molecules for more studies in larger patient cohorts. | 25,227,983 | [
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Participants', caregivers', and professionals' experiences with a group-based rehabilitation program for Huntington's disease: a qualitative study. | Research suggests that rehabilitation is beneficial for persons with Huntington's disease (HD), but there is limited knowledge about participants' experiences with residential rehabilitation programs. We therefore did a study to explore patients', family caregivers', and health professionals' experiences with a group-based, residential rehabilitation program for individuals with early to mid-stage HD, focusing on three research questions: How did participants experience the structure and content of the program? What outcomes did patients experience? What challenges and success factors did health professionals report? Qualitative, explorative study, collecting data through in-depth interviews with nine family caregivers and 11 patients with early- and mid-stage HD, and focus group interviews with 15 health professionals. Data were analysed using systematic text condensation. Some participants reported difficulties with defining individual rehabilitation goals, but written individualised plans and schedules were appreciated by all participants. Participants highlighted being member of an "HD-group" as a valuable experience, though tensions and conflicts could occur in groups. Participants typically reported improved gait and balance, increased self-confidence, and social benefits as outcomes. The intensive schedule was acceptable for most participants, but adjustments had been made to allow participants more time to eat, shower and dress between sessions. Success factors reported by health professionals were assigning every patient with a contact person, using clinical tests results to motivate patients, and supervising health professionals in patients' local municipalities. Group-based residental rehabilitation was feasible for individuals with early- and mid-stage HD, and participants emphasised mental and social outcomes in addition to physical outcomes. The needs of persons with HD should be considerd when designing programs, to secure structure, continuity in personnel, and sufficient time between sessions. | 25,227,988 | [
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Prediction of positive resection margins in patients with non-palpable breast cancer. | In patients undergoing breast conserving surgery for non-palpable breast cancer, obtaining tumour free resection margins is important to prevent reexcision and local recurrence. We developed a model to predict positive resection margins in patients undergoing breast conserving surgery for non-palpable invasive breast cancer. A total of 576 patients with non-palpable invasive breast cancer underwent breast conserving surgery in five hospitals in the Netherlands. A prediction model for positive resection margins was developed using multivariate logistic regression. Calibration and discrimination of the model were assessed and the model was internally validated by bootstrapping. Positive resection margins were present in 69/576 (12%) patients. Factors independently associated with positive resection margins included mammographic microcalcifications (OR 2.14, 1.22-3.77), tumour size (OR 1.75, 1.20-2.56), presence of DCIS (OR 2.61, 1.41-4.82), Bloom and Richardson grade 2/3 (OR 1.82, 1.05-3.14), and caudal location of the lesion (OR 2.4, 1.35-4.27). The model was well calibrated and moderately able to discriminate between patients with positive versus negative resection margins (AUC 0.70, 95% CI, 0.63-0.77, and 0.69 after internal validation). The presented prediction model is moderately able to differentiate between women with high versus low risk of positive margins, and may be useful for surgical planning and preoperative patient counselling. | 25,228,054 | [
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Pulmonary tuberculosis in Asian elephants (Elephas maximus): histologic lesions with correlation to local immune responses. | Although Mycobacterium tuberculosis infection is an important health concern for Asian elephants (Elephas maximus), no studies have evaluated the associated local immune responses or histologic lesions. In primates including humans, latent tuberculosis is distinguished by well-organized granulomas with TH1 cytokine expression, whereas active disease is characterized by poorly organized inflammation and local imbalance in TH1/TH2 cytokines. This study examined archival, formalin-fixed, paraffin-embedded lung samples from 5 tuberculosis-negative and 9 tuberculosis-positive Asian elephants. Lesions were assessed by light microscopy, and lymphoid infiltrates were characterized by CD3 and CD20 immunolabeling. Expression of TH1 (interferon [IFN]-γ, tumor necrosis factor [TNF]-α) and TH2 (interleukin [IL]-4, IL-10, transforming growth factor [TGF]-β) cytokines was determined using in situ hybridization. In 6 of 9 samples, inflammation was similar to the pattern of primate active disease with low to moderate numbers of lymphocytes, most of which were CD20 positive. In 1 sample, inflammation was most similar to latent tuberculosis in primates with numerous CD3-positive lymphocytes. Expression of IFN-γ was detected in 3 of 8 tuberculosis-positive samples. Expression of TNF-α was detected in 3 of 8 positive samples, including the one with latent morphology. Low-level expression of IL-4 was present in 4 of 8 positive samples. Only single positive samples displayed expression of IL-10 and TGF-β. Tuberculosis-negative samples generally lacked cytokine expression. Results showed heterogeneity in lesions of elephant tuberculosis similar to those of latent and active disease in primates, with variable expression of both TH1 and TH2 cytokines. | 25,228,055 | [
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Life goal attainment in the adaptation process after acquired brain injury: the influence of self-efficacy and of flexibility and tenacity in goal pursuit. | To investigate attainment of important life goals and to examine whether self-efficacy, tenacity in goal pursuit and flexibility in goal adjustment contribute to adaptation by affecting levels of emotional distress and quality of life in patients with newly acquired brain injury. Data were collected from a prospective clinical cohort study of 148 patients assessed after discharge home (mean time since injury = 15 weeks) and one year later. At follow-up, attainment of life goals (set at baseline) and satisfaction with attainment was scored (10-point scale) and patients were asked how they adjusted unattained goals. Emotional distress was measured with the Hospital Anxiety and Depression Scale (HADS), quality of life with the Life Satisfaction Questionnaire (LiSat-9), self-efficacy with the TBI Self-efficacy Questionnaire (SEsx) and tenacity and flexibility with the Assimilative/Accommodative Coping Questionnaire (AACQ). Random effects regression analyses and structural equation modelling were used. In total, only 13 % of initial life goals were achieved in one year. Patients who maintained efforts to reach their original goals had higher average levels of tenacity, but did not differ in level of self-efficacy compared with patients that disengaged. Patients with higher self-efficacy were more successful in attaining important life goals, which correlated with higher quality of life. Patients with higher self-efficacy, higher tenacity in goal pursuit, and higher flexibility in goal adjustment were less emotionally distressed, again correlating with higher quality of life. To optimise adaptation it seems appropriate to promote self-efficacy and both tenacity and flexibility during rehabilitation treatment. | 25,228,056 | [
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An exploration of decision aid effectiveness: the impact of promoting affective vs. deliberative processing on a health-related decision. | Decision aids (DAs) are non-directive communication tools that help patients make value-consistent health-care decisions. However, most DAs have been developed without an explicit theoretical framework, resulting in a lack of understanding of how DAs achieve outcomes. To investigate the effect of promoting affective vs. deliberative processing on DA effectiveness based on dual-process theory. One hundred and forty-eight female university students participated in a randomized controlled experiment with three conditions: emotion-focused, information-focused and control. Preference-value consistency, knowledge, decisional conflict and satisfaction were compared across the conditions using planned contrast analyses. The intervention comprised two different DAs and instructional manipulations. The emotion-focused condition received a modified DA with affective content and instructions to induce an affective reaction. The information-focused and control conditions received the same DA without the affective content. The information-focused condition received additional instructions to induce deliberative processing. Controlling for the experiment-wise error rate at P < 0.017, the emotion-focused and information-focused conditions had significantly higher decisional satisfaction than the control condition (P < 0.001). The emotion-focused condition did not demonstrate preference-value consistency. There were no significant differences for decisional conflict and knowledge. Results suggest that the promotion of affective processing may hinder value-consistent decision making, while deliberative processing may enhance decisional satisfaction. This investigation of the effect of affective and deliberative processes in DA-supported decision making has implications for the design and use of DAs. DA effectiveness may be enhanced by incorporating a simple instruction to focus on the details of the information. | 25,228,065 | [
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Oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis. | Hyperactivity of the renin-angiotensin system (RAS) resulting in elevated Angiotensin II (Ang II) contributes to all stages of inflammatory responses including ocular inflammation. The discovery of angiotensin-converting enzyme 2 (ACE2) has established a protective axis of RAS involving ACE2/Ang-(1-7)/Mas that counteracts the proinflammatory and hypertrophic effects of the deleterious ACE/AngII/AT1R axis. Here we investigated the hypothesis that enhancing the systemic and local activity of the protective axis of the RAS by oral delivery of ACE2 and Ang-(1-7) bioencapsulated in plant cells would confer protection against ocular inflammation. Both ACE2 and Ang-(1-7), fused with the non-toxic cholera toxin subunit B (CTB) were expressed in plant chloroplasts. Increased levels of ACE2 and Ang-(1-7) were observed in circulation and retina after oral administration of CTB-ACE2 and Ang-(1-7) expressing plant cells. Oral feeding of mice with bioencapsulated ACE2/Ang-(1-7) significantly reduced endotoxin-induced uveitis (EIU) in mice. Treatment with bioencapsulated ACE2/Ang-(1-7) also dramatically decreased cellular infiltration, retinal vasculitis, damage and folding in experimental autoimmune uveoretinitis (EAU). Thus, enhancing the protective axis of RAS by oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells provide an innovative, highly efficient and cost-effective therapeutic strategy for ocular inflammatory diseases. | 25,228,068 | [
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Estimating overannotation across prokaryotic genomes using BLAST+, UBLAST, LAST and BLAT. | As the number of genomes in public databases increases, it becomes more important to be able to quickly choose the best annotated genomes for further analyses in comparative genomics and evolution. A proxy to annotation quality is the estimation of overannotation by comparing annotated coding genes against the SwissProt database. NCBI's BLAST (BLAST+) is the common software of choice to compare these sequences. Newer programs that run in a fraction of the time as BLAST+ might miss matches that BLAST+ would find. However, the results might still be useful to calculate overannotation. We thus decided to compare the overannotation estimates yielded using three such programs, UBLAST, LAST and the Blast-Like Alignment Tool (BLAT), and to test non-redundant versions of the SwissProt database to reduce the number of comparisons necessary. We found that all, UBLAST, LAST and BLAT, tend to produce similar overannotation estimates to those obtained with BLAST+. As would be expected, results varied the most from those obtained with BLAST+ in genomes with fewer proteins matching sequences in the SwissProt database. UBLAST was the fastest running algorithm, and showed the smallest variation from the results obtained using BLAST+. Reduced SwissProt databases did not seem to affect the results much, but the reduction in time was modest compared to that obtained from UBLAST, LAST, or BLAT. Despite faster programs miss sequence matches otherwise found by NCBI's BLAST, the overannotation estimates are very similar and thus these programs can be used with confidence for this task. | 25,228,073 | [
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Validation of the Endopep-MS method for qualitative detection of active botulinum neurotoxins in human and chicken serum. | Botulinum neurotoxins (BoNTs) are highly toxic proteases produced by anaerobic bacteria. Traditionally, a mouse bioassay (MBA) has been used for detection of BoNTs, but for a long time, laboratories have worked with alternative methods for their detection. One of the most promising in vitro methods is a combination of an enzymatic and mass spectrometric assay called Endopep-MS. However, no comprehensive validation of the method has been presented. The main purpose of this work was to perform a validation for the qualitative analysis of BoNT-A, B, C, C/D, D, D/C, and F in serum. The limit of detection (LOD), selectivity, precision, stability in matrix and solution, and correlation with the MBA were evaluated. The LOD was equal to or even better than that of the MBA for BoNT-A, B, D/C, E, and F. Furthermore, Endopep-MS was for the first time successfully used to differentiate between BoNT-C and D and their mosaics C/D and D/C by different combinations of antibodies and target peptides. In addition, sequential antibody capture was presented as a new way to multiplex the method when only a small sample volume is available. In the comparison with the MBA, all the samples analyzed were positive for BoNT-C/D with both methods. These results indicate that the Endopep-MS method is a valid alternative to the MBA as the gold standard for BoNT detection based on its sensitivity, selectivity, and speed and that it does not require experimental animals. | 25,228,079 | [
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Polymorphisms of progesterone receptor and ovarian cancer risk: a systemic review and meta-analysis. | Growing bodies of studies have investigated the associations between three progesterone receptor (PGR) polymorphisms, +331G/A, Alu insertion and Val660Leu, and susceptibility to ovarian cancer, but the results remain controversial and inconclusive. Thus, we conducted a meta-analysis to derive a more precise estimation of the associations. A total of 21 case-control studies from 16 publications that included analyses of Alu insertion (981 cases, 2136 controls), Val660Leu (2205 cases, 3222 controls) and +331G/A (2842 cases, 4305 controls) polymorphisms were identified. Significantly increased risks of ovarian cancer were found for Alu insertion (T2 T2 + T1 T2 vs T1 T1 ; odds ratio [OR], 1.504; 95% confidence interval [CI], 1.206-2.203) and Val660Leu (TT vs GT; OR, 1.524; 95% CI, 1.013-2.293). No significant association was found between +331G/A polymorphism and ovarian cancer. This meta-analysis suggests that the two polymorphisms of PGR, Alu insertion and Val660Leu, may contribute to ovarian cancer susceptibility as low-penetrance risk factors. | 25,228,088 | [
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Helical supramolecular aggregates of sugar-based perylene dyes: the effect of core-substituted groups. | Here we have shown that it is possible to modulate π-π stacking, hydrogen bonds and hydrophobic and hydrophilic interactions to further adjust the supramolecular helicity by simply changing the core-substituted group. These modulated supramolecular interactions provide a new pathway to the controlled production of helical superstructures. | 25,228,101 | [
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Non-invasive ménage à trois for the prediction of high-risk varices: stepwise algorithm using lok score, liver and spleen stiffness. | Liver stiffness (LS), spleen stiffness (SS) and serum markers have been proposed to non-invasively assess portal hypertension or oesophageal varices (EV) in cirrhotic patients. We aimed to evaluate the performance of a stepwise algorithm that combines Lok score with LS and SS for diagnosing high-risk EV (HREV) and to compare it with other already-validated non-invasive methods. We performed a cross-sectional study including 136 consecutive compensated cirrhotic patients with various aetiologies, divided into training (90) and validation (46) set. Endoscopy was performed within 6 months from inclusion for EV screening. Spleen diameter was assessed by ultrasonography. LS and SS were measured using Fibroscan. Lok score, platelet count/spleen diameter ratio, LSM-spleen diameter to platelet ratio score and oesophageal varices risk score (EVRS) were calculated and their diagnostic accuracy for HREV was assessed. The algorithm classified patients as having/not-having HREV. Its performance was tested and compared in both groups. In the training set, all variables could select patients with HREV with moderate accuracy, the best being LSPS (AUROC = 0.818; 0.93 sensitivity; 0.63 specificity). EVRS, however, was the only independent predictor of HREV (OR = 1.521; P = 0.032). The algorithm correctly classified 69 (76.66%) patients in the training set (P < 0.0001) and 36 (78.26%) in the validation one. In the validation group, the algorithm performed slightly better than LSPS and EVRS, showing 100% sensitivity and negative predicted value. The stepwise algorithm combining Lok score, LS and SS could be used to select patients at low risk of having HREV and who may benefit from more distanced endoscopic evaluation. | 25,228,102 | [
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Strategies for diagnosing leg oedema in primary care: a qualitative study of GPs' approaches. | The symptom leg oedema represents a broad range of possible underlying aetiologies. The background of leg oedema is multifactorial and usually the GP is the first contact point for patients presenting with this symptom. GPs rely on patient history and physical examination as their main diagnostic tools. To identify GPs' diagnostic approaches and heuristics in patients presenting with leg oedema. Interviews with 15 GPs (20-30 min) using a semi-structured interview-guideline were conducted. GPs described their individual diagnostic strategies concerning all patients presenting with leg oedema they had prospectively identified during the previous four weeks. Interviews were taped and transcribed verbatim. Qualitative analysis was conducted by two independent raters. GPs applied a variety of diagnostic approaches, which can be grouped in active and passive strategies. Active strategies comprised the use of decision rules and guidelines, Bayesian arguing, problem dichotomisation and discrepancy heuristics. Passive approaches included test of time, therapy as diagnosis, and taking patient assumptions into account. When dealing with leg oedema, GPs use prior information of individual patients in a specific way. There is a broad variety of diagnostic approaches that can be grouped in 'active' and 'passive' behaviour. Approaches mostly match with established diagnostic strategies in primary care. | 25,228,104 | [
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Transforaminal lumbar interbody debridement and fusion for the treatment of infective spondylodiscitis in the lumbar spine. | To determine the safety and efficacy of using a single posterior approach with transforaminal lumbar interbody debridement and fusion (TLIDF) plus pedicle screws fixation in treating infective spondylodiscitis in the lumbar spine. Between January 2009 and June 2011, 28 patients with infective spondylodiscitis who underwent TLIDF, using autogenous graft and posterior pedicle screws instrumentation, met the indications for surgery, and completed more than 18 months of follow-up, were included. Clinical outcomes were assessed using a visual analog scale (VAS), the Oswestry Disability Index (ODI), and Kirkaldy-Willis functional outcome criteria. Infection status was evaluated using C-reactive protein levels, erythrocyte sedimentation rate, and clinical symptoms. The interbody fusion status and sagittal alignment of the infected segments were assessed using radiographic studies. Intra-operative culture rate was 82.1 %. The most common pathogen was methicillin-resistant Staphylococcus aureus. One post-operative deep wound infection with septic implant loosening and one instance of early aseptic implant loosening were noted. Implants in both patients were subsequently removed. Two infections recurred within 3 months post-operatively, with both subsiding within 3 months after extended antibiotic treatment. VAS and ODI values were significantly improved. The interbody fusion rate was 82.1 % and the lordotic angle of the infected segments and the lumbar spine were corrected by 9.7° and 14.3°, respectively at the last follow-up. A single posterior approach with TLIDF and pedicle screws instrumentation for lumbar infective spondylodiscitis provided a satisfactory clinical outcome, adequate infection control and good fusion rate, and this strategy avoids the risks of anterior or staging surgeries. | 25,228,109 | [
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0.3196703,
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Characteristics of robotically harvested hair follicles in Koreans. | Recently, an automated robotic hair restoration device was developed and is increasingly being used for hair restoration. We sought to analyze the hair follicles of Korean patients that were harvested by a hair restoration robotic device. Data were reviewed from a total of 22 patients who underwent robotic follicular unit (FU) extraction hair restoration surgery at Seoul National University Bundang Hospital. Hair follicles collected from 3 grids in the central parts of the safe donor zone of each patient were analyzed. The total number of harvested FUs was 5213, and the total number of collected FUs was 4955. The average yield was 95.1% ± 3.5%. Among the 12,017 harvested hairs, 590 hairs were transected and the average transection rate was 4.91% ± 2.9%. FUs of double hairs made up the majority of harvested FUs (44.1%), followed by triple hairs (31.9%). The transection rate increases in FUs that contain multiple hairs. A relatively small sample size and lack of comparative study with conventional FU extraction modalities are limitations. The robotic system qualifies for use in hair restoration surgery. It efficiently harvests not only single hairs but multiple hairs as well. | 25,228,110 | [
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Brain targeted intranasal delivery of tramadol: comparative study of microemulsion and nanoemulsion. | The present investigation was aimed to develop and compare microemulsion and nanoemulsion for brain targeted intranasal delivery of tramadol to achieve maximum therapeutic efficacy in treatment of episodic and emergency pain. Tramadol microemulsion (TME) and tramadol nanoemulsion (TNE) were developed and evaluated for physical properties. Ex vivo diffusion and nasal toxicity of TME and TNE were assessed by using sheep nasal mucosa. Biodistribution, pharmacokinetic and pharmacodynamic studies in mice were also performed. Globule sizes of TME and TNE were 16.69 ± 3.21 and 136.3 ± 4.3 nm, respectively. TNE was found be safe with respect to multiple dosing via nasal route. Both TME and TNE were stable during accelerated stability studies. AUC<sub(0→24)</sub in mice brain for TME and TNE was significantly higher as compared with tramadol solution. TME and TNE displayed significantly higher antinociceptive effect for a period of 16 h as compared with tramadol solution. TME and TNE were delivered to brain, circumventing BBB in brisk manner, establishing immediately the minimum effective concentration required for therapeutic response. Significant enhancement in antinociceptive effect was observed after intranasal delivery of TME and TNE. Intranasal administration of TME and TNE would be effective in management of episodic and emergency pain treatment. | 25,228,122 | [
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What is single needle cannulation hemodialysis: is it adequate? | It is important to know the relative clearances obtained when using single-needle versus double-needle cannulation techniques. Twelve hemodialysis treatments were conducted using a machine that is capable of single-needle as well as double-needle cannulation. Single-needle and double-needle blood flow rates, as well as urea clearance, were compared. The measured blood flow rates were 368 ± 11 ml/min, 294 ± 4 ml/min, 200 ± 0 ml/min, and 100 ± 0 ml/min during double-needle hemodialysis and were 201 ± 10.9 ml/min, 173 ± 44.9 ml/min, 103 ± 4.1 ml/min, and 45 ± 4.9 ml/min during single-needle hemodialysis. The hemodialysis urea clearances at similar blood flow rate (approximately 200 ml/min) were 167 ± 4 ml/min and 161 ± 9 ml/min (paired t test; p > 0.05), respectively. The measured blood flow rates and urea clearances during single-needle hemodialysis were approximately half of the measured blood flow rate during double-needle hemodialysis, and should be used in selected settings. | 25,228,136 | [
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Construction of an immobilised acetylcholinesterase column and its application in screening insecticidal constituents from Magnolia officinalis. | Application of a matrix-immobilised target enzyme for screening inhibitors is widely used in drug development, but there are few studies in insecticide discovery. In this paper, an economical and effective immobilised acetylcholinesterase (AChE) column was prepared using the sol-gel embedment method, which was further combined with high-performance liquid chromatography for screening the AChE inhibitors and insecticidal compounds from complex natural products. AChE inhibitory constituents magnolol and honokiol were isolated from the ethanol extract of Magnolia officinalis, with IC50 values of 0.069 and 0.057 mM respectively. In an in vivo bioassay, magnolol and honokiol showed insecticidal activity against Nilaparvata lugens, with LC50 values of 0.324 and 0.137 mM, which are comparable with that of commonly used insecticide chlorpyrifos (0.233 mM). Moreover, molecular docking was carried out against a homology model of N. lugens AChE. The complexes showed that magnolol and honokiol placed themselves nicely into the active site of the enzyme and exhibited an interaction energy that was in accordance with our activity profile data. These results demonstrate that magnolol and honokiol have great applied potential to be developed as natural insecticides, and an immobilised AChE column is very useful as a rapid screening tool for target enzymes towards potent inhibitors. | 25,228,142 | [
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The role of neck dissection in squamous cell carcinoma of the head and neck. | Lymph node metastases in the neck are a major prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC). Assessment and treatment of lymph nodes in the neck are of utmost importance. Inappropriate management of lymph node metastases can result in regional failure. Radical neck dissection has been and is still considered the "gold standard" for the surgical management of lymph node metastases of HNSCC. However, the philosophy of treatment of the neck has evolved during the last decades. Surgeons progressively realized that extensive neck dissections were associated with a higher morbidity but not always with a better oncologic outcome than more limited procedures. Today, a comprehensive therapeutic approach of the neck is multidisciplinary, taking into account the patient's quality of life without jeopardizing cure and survival. A better understanding of the patterns of lymph node metastasis promoted the use of selective neck dissection in selected patients. Sentinel lymph node biopsy is a reliable diagnostic procedure for staging the neck in node-negative early oral cavity squamous cell carcinoma. With increasing use of chemoradiation in locally advanced HNSCC, paradigms are evolving. Currently, there are strong arguments supporting the position that neck dissection is no longer justified in patients without clinically residual disease in the neck. | 25,228,145 | [
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Dynamic nuclear polarization enhancement of protons and vanadium-51 in the presence of pH-dependent vanadyl radicals. | We report applications of dynamic nuclear polarization to enhance proton and vanadium-51 polarization of vanadyl sulfate samples doped with TOTAPOL under magic angle spinning conditions. The electron paramagnetic resonance response stemming from the paramagnetic (51)V species was monitored as a function of pH, which can be adjusted to improve the enhancement of the proton polarization. By means of cross-polarization from the proton bath, (51)V spins could be hyperpolarized. Enhancement factors, build-up times, and longitudinal relaxation times T1((1)H) and T1((51)V) were investigated as a function of pH. | 25,228,149 | [
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Salvage Pelvic Lymph Node Dissection after Radical Prostatectomy for Biochemical and Lymph Node Recurrence. | Prostate cancer is the most common male malignancy. Radiation therapy and radical prostatectomy are the main curative treatment options for organ confined disease. Despite the good long-term oncologic outcomes, roughly 40% of patients undergoing surgery develop biochemical recurrence, manifested as a rising prostate-specific antigen (PSA). Those patients are at higher risk of developing a local or distant recurrence. The diagnosis of a nodal recurrence is challenging. This report is about a 66-year-old male, who had a radical prostatectomy in 2006. Postoperatively, the PSA was never undetectable. Radiotherapy was delivered in 2007, but the PSA rose again. Anti-androgen therapy was started, but he developed painful mastodynia. A (11C) choline PET-CT showed an enlarged suspicious lymph node at the left common iliac and a salvage pelvic lymphadenectomy was performed. Postoperatively, the PSA remained undetectable for the last 5 years. The use of lesion - targeted therapy for oligometastatic disease is a new concept in urology, aiming at reducing the tumor burden. Therefore, even though this surgical approach might not be associated with a durable response over time, the tumor load is decreased and further cancer progression might be delayed, allowing to postpone the delivery of hormone therapy. | 25,228,162 | [
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Testicular resistive index determined by Doppler ultrasonography in men with spinal cord injury - a case series. | In this case series, the testicular resistive index was determined in men with spinal cord injury. In ten men participating in our fertility programme, the peak systolic and end-diastolic velocity of centripetal testicular arteries was measured in triplicates by Doppler ultrasonography to calculate the testicular resistive index. Furthermore, the right and left testicular volume was determined by ultrasonography, blood samples were obtained for hormonal evaluation, and sperm analysis was performed according to the WHO guidelines. The median testicular resistive index measured 0.69 and was significantly (P < 0.001) greater than the reported cut-off value of 0.6. The spermiograms were characterised by normal sperm count but decreased sperm motility and plasma membrane integrity. The median right and left testicular volume was significantly (P < 0.01) smaller compared to the volumes measured in able-bodied adult males without scrotal pathology and measured 8.4 ml and 7.2 ml respectively. There was a significant (P = 0.005) correlation (rs = 0.81) between testicular resistive index and sperm concentration. However, no correlations were observed between testicular resistive index and other variables. The testicular resistive index in men with spinal cord injury was significantly greater than 0.6. Measuring the testicular resistive index may represent a useful additional parameter in the assessment of infertility in spinal cord-injured men. | 25,228,165 | [
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Chronic expanding haematoma in a cat. | A 5-year-old cat developed a recurrent haematoma in the right hindlimb after receiving an intramuscular injection. Cold packs and a compressive bandage were applied without success. The haematoma resolved initially but recurred twice within a week after conservative treatment. Contrast computed tomography was performed after the second recurrence. A large cavernous lesion was found craniolateral to the right stifle. The lesion was removed surgically. No recurrence occurred during a 5 month follow-up. On histopathology the lesion was characterised as a chronic expansive haematoma. To our knowledge, this type of lesion has not previously been described in a small animal. | 25,228,168 | [
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The status of neuroendocrine tumor imaging: from darkness to light? | Diagnostic imaging plays a pivotal role in the diagnosis, staging, treatment selection and follow-up for neuroendocrine tumors. The available diagnostic strategies are morphologic imaging, including computed tomography, magnetic resonance imaging (MRI) and ultrasound techniques, and molecular imaging, including scintigraphy with (111)In-pentetreotide and positron emission tomography with (68)Ga-DOTA-peptides, (18)F-DOPA and (11)C-5-HTP. A combination of anatomic and functional techniques is routinely performed to optimize sensitivity and specificity. The introduction of diffusion-weighted MRI and dynamic contrast-enhanced techniques represents a promising advance in radiologic imaging, whereas new receptor-binding peptides, including somatostatin agonists and antagonists, represent the recent most favorable innovation in molecular imaging. Future development includes the short-term validation of these techniques, but in extension also a more comprehensive multilevel integration of biologic information pertaining to a specific tumor and patient, possibly encompassing genomic considerations, currently evolving as a new entity denoted 'precision medicine'. The ideal is a diagnostic sequence that captures the global status of an individual's tumor and encompasses a multidimensional characterization of tumor location, metabolic performance and target identification. To date, advances in imagery have focused on increasing resolution, discrimination and functional characterization. In the future, the fusion of imagery with the parallel analysis of biological and genomic information has the potential to considerably amplify diagnosis. | 25,228,173 | [
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Using the theory of planned behavior to predict infant restraint use in Saudi Arabia. | To determine whether the theory of planned behavior (TPB) predicted intent of child restraint system (CRS) use among pregnant women in the Kingdom of Saudi Arabia (KSA). In this cross-sectional study conducted in Dallah Hospital, Riyadh, KSA during June-July 2013, 196 pregnant women completed surveys assessing their beliefs regarding CRS. Simultaneous observations were conducted among a different sample of 150 women to determine CRS usage at hospital discharge following maternity stay. Logistic regression model with TPB constructs and covariates as predictors of CRS usage intent was significant (χ2=64.986, p<0.0001) and predicted 38% of intent. There was an increase in odds of intent for attitudes (31.5%, p<0.05), subjective norm (55.3%, p<0.001), and perceived behavioral control (76.9%, p<0.001). The 3 logistic regression models testing the association of the relevant set of composite belief scores were also significant for attitudes (χ2=16.803, p<0.05), subjective norm (χ2=29.681, p<0.0001), and perceived behavioral control (χ2=20.516, p<0.05). The behavioral observation showed that none of the 150 women observed used CRS for their newborn at discharge. The TPB constructs were significantly and independently associated with higher intent for CRS usage. While TPB appears to be a useful tool to identify beliefs related to CRS usage intentions in KSA, the results of the separate behavioral observation indicate that intentions may not be related to the actual usage of CRS in the Kingdom. Further studies are recommended to examine this association. | 25,228,177 | [
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Measuring adherence rate to quality indicators for diabetes care identified by primary health care in Bahrain. | To measure the quality of care for patients with diabetes mellitus at the outpatient clinics from 12 general practitioners clinics (GPC) and one diabetes care clinic (DCC). A cross-sectional study was conducted at the Al-Razi Health Center, Manama, Bahrain, and health records from January to December 2012 were reviewed. The study consisted of 120 patients from GPC, and 80 patients from DCC. Information regarding quality indicators on the management of diabetic care was gathered, which consisted of data on the adherence rate for each of the 8 processes and 4 intermediate outcomes indicators, and was then compared to the standard target. The average rate for the examination of measurement in GPC for diabetic retina was 0%, diabetic foot was 2%, second microalbuminuria retesting was 13%, and glycosylated hemoglobin test order (HbA1c) was 18%, and in the DCC, 87% (diabetic retina), 97% (diabetic foot), 58% (second microalbuminuria retesting), and 79% (HbA1c). The differences were statistically significant between DCC and GPC. This study has found significant differences in the adherence rate of process and clinical outcome indicators across the GPC, an area that requires further improvements. The DCC, however, highly exceeded the target in 7 indicators, while it was relatively far from the target in the other 3 indicators. The study revealed that adherence to process indicators was not associated with good intermediate outcomes. | 25,228,179 | [
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Descending necrotizing mediastinitis. | Descending necrotizing mediastinitis (DNM) is a rare but severe life threatening complication of oropharyngeal infections. We report a young lady who had severe pharyngitis complicated by anterior neck infection that descended to the mediastinum causing necrotizing mediastinitis. The course of her illness was complicated with septic shock, acute kidney injury, tracheo-esophageal fistula, and critical illness polyneuropathy. There was considerable delay in her diagnosis; however, she survived after aggressive surgical intervention, wide spectrum antibiotics, and appropriate intensive care management. Early and repeated chest imaging using computed tomography was vital for the detection and follow up of this case. There is a need to increase physicians' awareness of this condition that can complicate odontogentic or pharyngeal infection, procedures, or trauma. | 25,228,187 | [
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Extreme oral myiasis. | Extreme oral myiasis is a rare condition, mostly affecting bedridden patients whose oral health care measures are neglected. Single stage manual removal of the maggots along with the necrotic tissue, debridement, and suturing under general anesthesia is the most effective way to treat the condition. Preventive measures are also equally important to eliminate the cause and recurrence. | 25,228,190 | [
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Retrospective analysis of fetal anterior abdominal wall defects. | To analyze fetal abdominal defects diagnosed during the prenatal period in the perinatology department in a tertiary center in Turkey. This retrospective study consisted of 27 cases diagnosed with fetal abdominal wall defects between January 2011 and February 2014 in the perinatology outpatient clinic of Celal Bayar University, Manisa, Turkey. Eighteen (66.7%) cases were diagnosed with omphalocele, 6 (22.2%) had gastroschisis, and 3 (11.1%) had limb body wall defects. Twenty-one (77.7%) patients diagnosed either as omphalocele or limb body wall defect were offered karyotype analysis; 11 (52.4%) of them accepted the intervention, and 2 of the 11 patients (18.2%) had abnormal karyotype. Regarding the omphalocele cases; 12 (66.6%) cases had isolated omphalocele, whereas 6 of the 18 cases (33.3%) had associated anomalies. Expectant management was performed in 8 (66.7%) of 12 isolated omphalocele cases. Two of the isolated omphalocele group (16.7%) had missed abortion, the other 2 (16.7%) had termination of the pregnancy because of the associated chromosomal anomaly (47,XXY and 45,X0). Three of the gastroschisis group (50%) had missed abortion, and the other 3 (50%) had expectant management with cesarean delivery between 38-39 gestational weeks. Cases with limb body wall defect were terminated due to the lethal condition. The prenatal diagnosis of fetal abdominal wall defects is important, because they differ greatly in terms of perinatal and neonatal morbidity and mortality due to underlying chromosomal abnormalities and associated structural anomalies. | 25,228,194 | [
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Origin of cold bias over the Arabian Sea in Climate Models. | Almost all climate models in Coupled Model Inter-comparison Project phase five (CMIP5) were found to have a cold bias in Sea Surface Temperature (SST) over the northern Arabian Sea, which is linked to the biases in the Indian Summer Monsoon (ISM). This cold SST bias was attributed to the anomalous cold winds from the north-western part of south Asian landmass during boreal winter. However, the origin of the anomalously strong cold winds over the Arabian Sea and its association with the large-scale circulation is obscure. Here we show that an equatorward bias in subtropical Jetstream during boreal spring season anomalously cools down the northern Arabian Sea and adjoining land regions in CMIP5 models. The models with stronger equatorward bias in subtropical jet are also the ones with stronger cold SST bias over the Arabian Sea. The equatorward shift coupled with enhanced strength of the subtropical jet produce a stronger upper tropospheric convergence, leading to a subsidence and divergence at lower levels over the Arabian deserts. The low entropy air flowing from the Arabian land mass cools the northern Arabian Sea. The weaker meridional temperature gradients in the colder models substantially weaken ISM precipitation. | 25,228,235 | [
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Over 1200-day support with dual Jarvik 2000 biventricular assist device. | We report the successful longest biventricular support using dual Jarvik 2000 biventricular assist device (BVAD; Jarvik Heart, Inc., New York, NY, USA) as a bridge to transplant. A 27-year old woman with arrhythmogenic right ventricular cardiomyopathy underwent implantation of two Jarvik 2000s as a left ventricular assist device and right ventricular assist device. Although several BVAD-related complications including haemolysis, hepatic dysfunction, heart failure and pulmonary valve insufficiency developed at a very late stage, she was successfully bridged to heart transplantation after 1245 days of biventricular support, which is the longest in the literature. Despite advances in continuous-flow ventricular assist devices, their long-term use for biventricular support remains limited. We report a successful case of 1245 days of biventricular support with dual Jarvik 2000 axial flow pumps in a patient with a small body surface area. | 25,228,243 | [
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Inappropriate prescription of allopurinol and febuxostat and risk of adverse events in the elderly: results from the REPOSI registry. | To investigate the prevalence of xanthine oxidase (XO) inhibitors prescription at admission and discharge in elderly hospital in-patients, to analyze the appropriateness of their use in relation to evidence-based indications, to evaluate the predictors of inappropriate prescription at discharge and the association with adverse events 3 months after hospital discharge. This cross-sectional study, based upon a prospective registry, was held in 95 Italian internal medicine and geriatric hospital wards. The sample included 4035 patients aged 65 years or older at admission and 3502 at discharge. The prescription of XO inhibitors was considered appropriate in patients with diagnosis of gout, gout nephropathy, uric acid nephrolithiasis, tophi, and chemotherapy-induced hyperuricemia. In order to evaluate the predictors of inappropriate prescription of XO inhibitors, we compared the characteristics of patients considered inappropriately treated with those appropriately not treated. Among the 4035 patients eligible for the analysis, 467 (11.6 %) were treated with allopurinol or febuxostat at hospital admission and 461 (13.2 %) among 3502 patients discharged. At admission, 39 (8.6 %) of patients receiving XO inhibitors and 43 (9.4 %) at discharge were appropriately treated. Among those inappropriately treated, hyperuricemia, polytherapy, chronic renal failure, diabetes, obesity, ischemic cardiomyopathy, heart failure, and cardiac dysrhythmias were associated with greater prescription of XO inhibitors. Prescription of XO inhibitors was associated with a higher risk of adverse clinical events in univariate and multivariate analysis. Prevalence of inappropriate prescription of XO inhibitors remained almost the same at admission and discharge. Inappropriate use of these drugs is principally related to treatment of asymptomatic hyperuricemia and various cardiovascular diseases. | 25,228,251 | [
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... |
Mechanical stresses, arterial stiffness, and brain small vessel diseases: Shimanami Health Promoting Program Study. | Arterial stiffness, a risk factor of brain small vessel diseases (SVD), causes hemodynamic changes. Mechanical stresses, circumferential wall tension (WT), and shear stress (SS) may change with arterial stiffness and be related to SVD. We investigated the associations between mechanical stresses and arterial stiffness and SVD. A total of 1296 subjects without apparent cardiovascular diseases were recruited. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an arterial stiffness index. Silent lacunar infarction and deep subcortical white matter hyperintensity were evaluated as SVD indices. Circumferential WT and SS at peak systole and end diastole were measured at the common carotid artery. Second peak of systolic blood pressure was obtained from the radial waveform and used as a central systolic blood pressure substitute. baPWV was associated positively with WT (P<0.0001) and negatively with SS (P=0.0007) even after correction for confounding parameters including baPWV. SVD was associated with significantly higher WT (P<0.0001) and lower SS (P<0.0001). After adjustment for confounding parameters (including baPWV), second peak of systolic blood pressure WT (odds ratio, 1.30; P=0.0017) and end diastolic WT (odds ratio, 1.60; P=0.0038) were related to presence of silent lacunar infarction, whereas peak systolic (odds ratio, 0.95; P=0.014) and end diastolic SS (odds ratio, 0.94; P=0.014) were associated with presence of deep subcortical white matter hyperintensity grade >3. Regression lines between blood pressure and WT were significantly steeper in subjects with SVD than without SVD (β=0.02; P<0.0001). These findings indicate that SVD is phenotype-specifically associated with alterations in WT and SS independently of arterial stiffness. | 25,228,261 | [
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RNA sequencing: current and prospective uses in metabolic research. | Previous global RNA analysis was restricted to known transcripts in species with a defined transcriptome. Next generation sequencing has transformed transcriptomics by making it possible to analyse expressed genes with an exon level resolution from any tissue in any species without any a priori knowledge of which genes that are being expressed, splice patterns or their nucleotide sequence. In addition, RNA sequencing is a more sensitive technique compared with microarrays with a larger dynamic range, and it also allows for investigation of imprinting and allele-specific expression. This can be done for a cost that is able to compete with that of a microarray, making RNA sequencing a technique available to most researchers. Therefore RNA sequencing has recently become the state of the art with regards to large-scale RNA investigations and has to a large extent replaced microarrays. The only drawback is the large data amounts produced, which together with the complexity of the data can make a researcher spend far more time on analysis than performing the actual experiment. | 25,228,274 | [
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Nutritional interventions for the adjunctive treatment of schizophrenia: a brief review. | Schizophrenia is a chronic condition that impacts significantly not only on the individual and family, but the disorder also has wider consequences for society in terms of significant costs to the economy. This highly prevalent condition affects approximately 1% of the worldwide population, yet there are few therapeutic options. The predominant treatment strategy for schizophrenia is anti-psychotic medication (with or without additional talking therapy) even though this approach lacks efficacy in managing the negative symptoms of the condition, is not effective in one-third of the patient group and the side effects of the medication can be severe and debilitating. In recent years, a number of pathophysiological processes have been identified in groups of people with schizophrenia including oxidative stress, one-carbon metabolism and immune-mediated responses. A number of studies have shown that these altered physiological mechanisms can be ameliorated by nutritional interventions in some individuals with schizophrenia. This review briefly describes the aforementioned processes and outlines research that has investigated the utility of nutritional approaches as an adjunct to anti-psychotic medication including antioxidant and vitamin B supplementation, neuroprotective and anti-inflammatory nutrients and exclusion diets. Whilst none of these interventions provides a 'one-size-fits-all' therapeutic solution, we suggest that a personalised approach warrants research attention as there is growing agreement that schizophrenia is a spectrum disorder that develops from the interplay between environmental and genetic factors. | 25,228,271 | [
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Tamoxifen induces apoptosis through cancerous inhibitor of protein phosphatase 2A-dependent phospho-Akt inactivation in estrogen receptor-negative human breast cancer cells. | Tamoxifen, a selective estrogen receptor (ER) modulator, may affect cancer cell survival through mechanisms other than ER antagonism. In the present study, we tested the efficacy of tamoxifen in a panel of ER-negative breast cancer cell lines and examined the drug mechanism. In total, five ER-negative breast cancer cell lines (HCC-1937, MDA-MB-231, MDA-MB-468, MDA-MB-453 and SK-BR-3) were used for in vitro studies. Cellular apoptosis was examined by flow cytometry and Western blot analysis. Signal transduction pathways in cells were assessed by Western blot analysis. The in vivo efficacy of tamoxifen was tested in xenograft nude mice. Tamoxifen induced significant apoptosis in MDA-MB-231, MDA-MB-468, MDA-MB-453 and SK-BR-3 cells, but not in HCC-1937 cells. Tamoxifen-induced apoptosis was associated with inhibition of cancerous inhibitor of protein phosphatase 2A (CIP2A) and phospho-Akt (p-Akt) in a dose-dependent manner. Ectopic expression of either CIP2A or Akt protected MDA-MB-231 cells from tamoxifen-induced apoptosis. In addition, tamoxifen increased protein phosphatase 2A (PP2A) activity, and tamoxifen-induced apoptosis was attenuated by the PP2A antagonist okadaic acid in the sensitive cell lines, but not in resistant HCC-1937 cells. Moreover, silencing CIP2A by small interfering RNA sensitized HCC-1937 cells to tamoxifen-induced apoptosis. Furthermore, tamoxifen regulated CIP2A protein expression by downregulating CIP2A mRNA. Importantly, tamoxifen inhibited the in vivo growth of MDA-MB-468 xenograft tumors in association with CIP2A downregulation, whereas tamoxifen had no significant effect on CIP2A expression and anti-tumor growth in HCC-1937 tumors. Inhibition of CIP2A determines the effects of tamoxifen-induced apoptosis in ER-negative breast cancer cells. Our data suggest a novel "off-target" mechanism of tamoxifen and suggest that CIP2A/PP2A/p-Akt signaling may be a feasible anti-cancer pathway. | 25,228,280 | [
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Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 1: does restrictive fluid resuscitation in penetrating chest injury affect outcome? | A short cut review was carried out to establish whether restrictive fluid administration in penetrating thoracic trauma impacted on patients' mortality. 143 papers were found using the reported searches, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these are tabulated. It is concluded that there is paucity of relevant research and there is limited scientific evidence to inform fluid administration in these patients. | 25,228,286 | [
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Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: D-dimer levels during normal menstrual cycle. | A short cut review was carried out to establish whether d-dimer concentrations are increased during normal menstruation-. - studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that there is little evidence on the question, but what there is suggests that d-dimer concentrations are not raised during normal menstruation. | 25,228,288 | [
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Influence of lowland forests on subsurface salt accumulation in shallow groundwater areas. | In flat sedimentary plains in areas with a sub-humid climate, tree planting on grasslands and arable lands creates strong hydrological shifts. As a result of deep rooting and high water uptake of trees, groundwater levels drop and subsurface salt accumulation increases. Tree planting has expanded globally and in Hungary it reached rates of 15 000 ha year(-1), being focused mainly in the Great Hungarian Plain where forests replace grasslands and crops in a region with widespread shallow groundwater. We performed soil and groundwater observations in 31 pairs of forest and control plots in the region, including gradients of initial water table depth and salinity, soil layering, and tree species and age. Accumulated tree biomass was positively correlated with soil salinization rates following tree planting, being also affected by species (poplar > common oak > black locust) and stand age. Differences among tree species effects appeared to be related to their growth rates. Due to downward deep percolation and salt leaching episodes during the Hungarian winters, the observed salt accumulation rates were lower than those described under similar settings in the warmer Argentine Pampas. | 25,228,311 | [
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