title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Adaptive maternal immune deviations as a ground for autism spectrum disorders development in children. | Autism is a vexed problem today. Overall, there is a high frequency of birth children (1:80 - 1:150) with late diagnosed autism spectrum disorders (ASD) and this trend is getting progressively stronger. The causes for the currently increased frequency of ASD and the pathogenesis of ASD are not fully understood yet. One of the most likely mechanisms inducing ASD may be a maternal immune imprinting. This phenomenon is based on transplacental translocation of maternal antibodies of IgG class and, as a consequence, on the epigenetic "tuning" of immune system of the fetus and child. This mechanism provides development of child's anti-infection resistance before meeting with microorganisms, but it can be also a cause of inborn pathology including the ASD appearance. The quantitative changes in maternal blood serum autoantibodies depend on a specific microbial population, or are induced by environmental chemical pollutants in association with some individual features of the maternal metabolism. These immune changes are adaptive in most cases for the maternal organism, but can be pathogenic for the fetus in some cases. We discuss in the present paper the possibilities to predict the risk from abnormal development of nervous system in fetus and early diagnosis of ASD in high-risk group of children. | 25,181,843 | [
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Paroxysmal atrial fibrillation: dynamics of the main antioxidant enzymes--superoxide dismutase and catalase. | Researchers have a particularly strong interest in the mechanisms implicated in the clinical manifestation of atrial fibrillation. To examine dynamically the activity of the antioxidant enzymes, superoxide dismutase and catalase in patients with paroxysmal atrial fibrillation (duration < 48 hours). The studied parameters were examined in the erythrocytes of 51 patients (59.84 +/- 1.60, 26 men) immediately after their hospitalization, at 24 hours and 28 days after restoration of sinus rhythm. 52 controls (59.50 +/- 1.46, 26 men) were also included, none of which had a history of arrhythmia. Propafenone was used to manage the rhythm abnormality. The enzyme activity was determined by a spectrophotometric method. The average duration of atrial fibrillation episodes until the time of hospitalization was 8.14 hours (from 2 to 24 hours). During patient hospitalization the activity of superoxide dismutase and catalase was considerably higher compared to that of the controls (8.46 +/- 0.26 vs 5.81 +/- 0.14 U/mg Hb; 7.36 +/- 0.25 vs 4.76 +/- 0.12 E240/min/mg Hb; P < 0.001). This difference was maintained 24 hours after the rhythm regularization (7.19 +/- 0.25 vs 5.81 +/- 0.14 U/mg Hb, p < 0.001; 5.30 +/- 0.21 vs 4.76 +/- 0.12 E240/min/mg Hb, p < 0.05). Twenty-eight days after the restoration of sinus rhythm, the activity of catalase remained increased (5.11 +/- 0.08 vs 4.76 +/- 0.12 E240/min/mg Hb, p < 0.05). The paroxysmal atrial fibrillation in our study was characterized with significantly increased activity of superoxide dismutase and catalase even in the early hours of clinical manifestation of the disorder, which then slowly decreased with the restoration of sinus rhythm. Therefore, we can conclude that changes in oxidative status are closely related to the disease and are probably a part of the intimate mechanisms related to its initiation and clinical course. | 25,181,846 | [
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A case of TRAP sequence with immense acardiac twin. | Twin-reversed arterial perfusion sequence is a rare complication of monochorionic twin pregnancy in which an anomalous acardiac fetus is hemodynamically dependent on its structurally normal "pump" twin. Early diagnosis is essential for improving perinatal prognosis for the normal twin. In this case report we present a case of TRAP sequence with immense acardiac twin with favorable outcome, emphasizing the importance of ultrasound imaging, follow-up and timing of delivery in this complicated pregnancy. | 25,181,851 | [
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An old friend you've never met. | For 36 years, Simon Lillie has stood watch at Methodist Hospitals in Gary, Ind. The affable 64-year-old is never reluctant to extend a welcoming hand or lend an ear. | 25,181,908 | [
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Effects of supervised exercise on motivational outcomes in breast cancer survivors at 5-year follow-up. | Short-term physical activity (PA) has beneficial effects on symptom management and quality of life, however, longer-term adherence is likely needed for improved disease outcomes in breast cancer survivors (BCS). This study examined the effects of a supervised group exercise program on motivational outcomes and PA among BCS at 5-year follow-up. The original study was a two-armed, randomized controlled trial comparing a 12-week supervised group exercise program to usual care among 203 BCS. BCS for this follow-up study were contacted at 60 months postintervention and asked to complete assessments of motivational outcomes from the Theory of Planned Behavior and PA behavior using the Scottish Physical Activity Questionnaire. Overall, 87 participants provided 5-year follow-up data with no differences in participation by group. Analyses of covariance (ANCOVAs) revealed that supervised exercise had a significant positive effect on descriptive norm at 5-year follow-up (mean = +0.6; 95% CI = +0.1 to +1.1; d = +0.48; p = 0.021). Small positive effects were also noted for perceived behavioral control (d = +0.18), instrumental attitude (d = +0.26), and injunctive norm (d = +0.35), although they were not statistically significant. Moreover, BCS who were more active at 5-year follow-up also reported more favorable perceived behavioral control (d = +0.16), instrumental attitude (d = +0.28), injunctive norm (d = +0.24), and descriptive norm (d = +0.31), although these differences were not statistically significant. This trial provides suggestive evidence that a supervised exercise program has positive effects on motivational outcomes even after 5 years. Additional intervention strategies during follow-up may further improve long-term adherence and health outcomes in BCS. | 25,181,937 | [
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Flocking at a distance in active granular matter. | The self-organized motion of vast numbers of creatures in a single direction is a spectacular example of emergent order. Here, we recreate this phenomenon using actuated nonliving components. We report here that millimetre-sized tapered rods, rendered motile by contact with an underlying vibrated surface and interacting through a medium of spherical beads, undergo a phase transition to a state of spontaneous alignment of velocities and orientations above a threshold bead area fraction. Guided by a detailed simulation model, we construct an analytical theory of this flocking transition, with two ingredients: a moving rod drags beads; neighbouring rods reorient in the resulting flow like a weathercock in the wind. Theory and experiment agree on the structure of our phase diagram in the plane of rod and bead concentrations and power-law spatial correlations near the phase boundary. Our discovery suggests possible new mechanisms for the collective transport of particulate or cellular matter. | 25,181,961 | [
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Virtual screening for novel Staphylococcus Aureus NorA efflux pump inhibitors from natural products. | NorA is a member of the Major Facilitator Superfamily (MFS) drug efflux pumps that have been shown to mediate antibiotic resistance in Staphylococcus aureus (SA). In this study, QSAR analysis, virtual screening and molecular docking were implemented in an effort to discover novel SA NorA efflux pump inhibitors. Originally, a set of 47 structurally diverse compounds compiled from the literature was used to develop linear QSAR models and another set of 15 different compounds were chosen for extra validation. The final model which was estimated by statistical values for the full data set (n = 45, Q(2) = 0.80, RMSE = 0.20) and for the external test set (n = 15, R(2) = 0.60, |res|max = 0.75, |res|min = 0.02) was applied on the collection of 182 flavonoides and the traditional Chinese medicine (TCM) database to screen for novel NorA inhibitors. Finally, 33 lead compounds that met the Lipinski's rules of five/three and had good predicted pIC50 values from in silico screening process were employed to analyze the binding ability by docking studies on NorA homology model in place of its unavailable crystal structures at two active sites, the central channel and the Walker B. | 25,181,985 | [
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Professional care providers in dementia care in eight European countries; their training and involvement in early dementia stage and in home care. | Knowledge concerning professionals involved in dementia care throughout its trajectory is sparse; the focus has mainly been on nursing-home care and less on home care, diagnosis and treatment of the disease and its complications despite the fact that home care is the most prominent type of care. The aim of this study was to explore and describe professional care providers involved in dementia care and their educational level applying the International Standard Classification of Education (ISCED) and further to investigate practice in the RightTimePlaceCare-countries with regard to screening, diagnostic procedures and treatment of dementia and home care. The findings demonstrate more similarities than differences in terms of type of professionals involved among the countries although untrained staff were more common in some countries. Findings also show that many types of professionals are involved, who to turn to may not be clear, for instance in terms of medical specialities and it may be unclear who bears the ultimate responsibility. The professionals involved in diagnosis, treatment and care are educated to bachelor's level or above whilst everyday care is provided by people trained at a lower ISCED level or with no formal training. Registered nurses as well as occupational therapists have bachelor's degrees in most countries, but not in Germany or Estonia. Professionals specifically trained in dementia care are not so common. Further research is needed to reveal not only who provides the diagnostics and treatment, but also how home care is organised and quality assured. Many different types of professionals serve as providers along the trajectory of the disease which may be difficult for the patient and the informal caregiver to cope with. | 25,181,988 | [
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Experiential or behavioral processes: which one is prominent in physical activity? Examining the processes of change 1 year after an intervention of therapeutic education among adults with obesity. | Although physical activity (PA) is essential, most obese people will not engage in its practice. The transtheoretical model (TTM) and its processes of change (POC) contribute to the understanding of behavior change regarding PA. The present study aimed to test how POC are associated with a progression through the stages of change (SOC) and whether they predict BMI change. Interventional study. A total of 134 subjects participated in an education program, were called at 1 year and 62 of them provided follow-up data. Participants completed the SOC and POC questionnaires at baseline, at 1 year and were classified according to their SOC progression. Participants who progressed through SOC lost more weight (p<0.001). Significant interactions were found for three out of five POC (p<0.05). Progression through SOC was associated with an increased use of POC. Weight loss was predicted by two behavioral POC. Results support the previous cross-sectional studies showing that physically active people use more frequently POC. The present findings support the development of TTM-grounded behavioral interventions targeted to obese patients. Identifying methods to promote POC use to improve adherence to weight guidelines may lead to improved clinical outcomes and quality of life. | 25,181,999 | [
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Quantitative determination of cellular farnesyltransferase activity: towards defining the minimum substrate reactivity for biologically relevant protein farnesylation. | Prenylation is a post-translational modification wherein an isoprenoid group is attached to a protein substrate by a protein prenyltransferase. Hundreds of peptide sequences are in vitro substrates for protein farnesyltransferase (FTase), but it remains unknown which of these sequences can successfully compete for in vivo prenylation. Translating in vitro studies to predict in vivo protein farnesylation requires determining the minimum reactivity needed for modification by FTase within the cell. Towards this goal, we developed a reporter protein series spanning several orders of magnitude in FTase reactivity as a calibrated sensor for endogenous FTase activity. Our approach provides a minimally invasive method to monitor changes in cellular FTase activity in response to environmental or genetic factors. Determining the reactivity "threshold" for in vivo prenylation will help define the prenylated proteome and identify prenylation-dependent pathways for therapeutic targeting. | 25,182,009 | [
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Sevoflurane preconditioning-induced neuroprotection is associated with Akt activation via carboxy-terminal modulator protein inhibition. | Sevoflurane preconditioning has a neuroprotective effect, but the underlying mechanism is not fully understood. The aim of the present investigation was to evaluate whether sevoflurane-induced cerebral preconditioning involves inhibition of carboxy-terminal modulator protein (CTMP), an endogenous inhibitor of Akt, in a rat model of focal cerebral ischaemia. Male Sprague-Dawley rats were exposed to 2.7% sevoflurane for 45 min. One hour later, rats were subjected to 60 min of focal cerebral ischaemia. The phosphoinositide 3-kinase inhibitors wortmannin and LY294002 were administered 10 min before preconditioning. Rats in the lentiviral transduction group received an intracerebroventricular injection of lentiviral vector Ubi-MCS-CTMP 3 days before ischaemia. Neurological deficits and infarct volumes were evaluated 24 h and 7 days after reperfusion. Phosphorylation of Akt, glycogen synthase kinase-3β (GSK3β), and expression of CTMP were determined at 1, 3, 12, and 24 h after reperfusion. Akt activity was measured at 3 h after reperfusion. Sevoflurane preconditioning improved neurological score and reduced infarct size at 24 h of reperfusion. Pretreatment with wortmannin or LY294002 attenuated these neuroprotective effects. Expression of CTMP correlated with reduced Akt activity after ischaemia, while sevoflurane preconditioning preserved Akt activity and increased phosphorylation of GSK3β. CTMP over-expression diminished the beneficial effects of sevoflurane preconditioning. Activation of Akt signalling via inhibition of CTMP is involved in the mechanism of neuroprotection provided by sevoflurane preconditioning. | 25,182,017 | [
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Cow's milk allergy and neonatal short bowel syndrome: comorbidity or true association? | Neonatal short bowel syndrome (SBS) follows early intestinal resections that may expose the children to increased intestinal contact with undigested food proteins and to the risk of food allergy. We report three consecutive cases of cow's milk allergy (CMA) in SBS infants. We reviewed three cases of CMA developed in 37 children with neonatal SBS followed up in the last 10 years. The setting of the survey was the Gastroenterology-Hepatology and Nutrition Unit of the Pediatric Hospital 'Bambino Gesù' in Rome. The diagnosis of CMA was based on the oral food challenge and was supported by the results of the skin prick tests (SPT) and/or the specific immunoglobulin (Ig) E. Two patients had persistent liquid stools and periodic episodes of vomiting when they were fed with an intact milk protein-based formula, that disappeared with extensively hydrolyzed formula and amino-acid-based formulae, respectively. The third patient developed maculo-papular rash, flushing and angioedema, when he was introduced a regular formula. The challenge-confirmed CMA in all patients. Positive specific IgE for milk proteins was documented in all the three patients. Two out of the three patients had positive familial history for allergy and positive SPT. Our findings suggest that the SBS patients require a careful clinical monitoring of the tolerance for the cow's milk proteins, because CMA could be more frequent than expected. A prospective regular assessment for the potential cow milk sensitization by SPT and specific IgE may clarify the nature of the association and support the clinical surveillance. Multicenter studies are required to better evaluate this comorbidity. | 25,182,018 | [
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Role of the new rural cooperative medical system in alleviating catastrophic medical payments for hypertension, stroke and coronary heart disease in poor rural areas of China. | Hypertension, stroke and coronary heart disease (CHD) are common diseases that impose a heavy burden on patients and their families, particularly on those living in poor areas. This study examined catastrophic medical payments faced by patients with these diseases and the effectiveness of the new rural cooperative medical system (NRCMS) at alleviating the impact of the said diseases in fourth-class rural areas (i.e. those with annual income of less than RMB 1500/$240.2 per capita) of China. Data on medical payments, including out-of-pocket and NRCMS-reimbursed expenses were collected through self-administered questionnaires. The pre- and post-reimbursement (via the NRCMS) prevalence of household poverty, catastrophic medical payment (CMP) incidence (H cat), mean CMP gap (Gcat), mean positive CMP gap (MPG cat) and other determinants of CMP incidence were identified. Out-of-pocket payments for treatment of hypertension, stroke and CHD averaged RMB 580.1/$92.9, RMB 3028.4/$484.8 and RMB 1561.4/$250.0 per capita, respectively, in 2008. H cat, Gcat and MPG cat due to the three diseases were 17.0%, 16.6% and 97.6%, respectively, and reimbursement through the NRCMS reduced them to 13.5%, 11.8% and 87.4%, respectively. The difference between pre- and post-reimbursement H cat was not statistically significant. After adjusting the covariates for age [OR = 1.87, 95% confidence interval (CI) = 1.19-2.95], education (OR = 1.56, 95% CI = 1.07-2.27), marital status (OR = 1.67, 95% CI = 1.11-2.51), occupation (OR = 1.96, 95% CI = 1.34-2.85), annual income (OR = 4.95, 95% CI = 3.28-7.48), the multiple logistic regression analysis revealed that patients with stroke (OR = 3.94, 95% CI = 2.38-6.51) or CHD (OR = 2.25, 95% CI = 1.38-3.65) were more susceptible to CMP compared with patients with hypertension only. Out-of-pocket medical spending on hypertension, stroke and CHD imposes a heavy financial burden on the residents of fourth-class rural areas of China. The NRCMS has some impact on reducing catastrophic medical payments associated with these diseases, but improvement of the reimbursement rate is necessary to further improve its effectiveness. | 25,182,027 | [
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Influence of real-world characteristics on outcomes for patients with methicillin-resistant Staphylococcal skin and soft tissue infections: a multi-country medical chart review in Europe. | Patient-related (demographic/disease) and treatment-related (drug/clinician/hospital) characteristics were evaluated as potential predictors of healthcare resource use and opportunities for early switch (ES) from intravenous (IV)-to-oral methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotic therapy and early hospital discharge (ED). This retrospective observational medical chart study analyzed patients (across 12 European countries) with microbiologically confirmed MRSA complicated skin and soft tissue infections (cSSTI), ≥3 days of IV anti-MRSA antibiotics during hospitalization (July 1, 2010-June 30, 2011), and discharged alive by July 31, 2011. Logistic/linear regression models evaluated characteristics potentially associated with actual resource use (length of IV therapy, length of hospital stay [LOS], IV-to-oral antibiotic switch), and ES and ED (using literature-based and expert-verified criteria) outcomes. 1542 patients (mean ± SD age 60.8 ± 16.5 years; 61.5% males) were assessed with 81.0% hospitalized for MRSA cSSTI as the primary reason. Several patient demographic, infection, complication, treatment, and hospital characteristics were predictive of length of IV therapy, LOS, IV-to-oral antibiotic switch, or ES and ED opportunities. Outcomes and ES and ED opportunities varied across countries. Length of IV therapy and LOS (r = 0.66, p < 0.0001) and eligibilities for ES and ED (r = 0.44, p < 0.0001) showed relatively strong correlations. IV-to-oral antibiotic switch patients had significantly shorter length of IV therapy (-5.19 days, p < 0.001) and non-significantly shorter LOS (-1.86 days, p > 0.05). Certain patient and treatment characteristics were associated with increased odds of ES (healthcare-associated/ hospital-acquired infection) and ED (patient living arrangements, healthcare-associated/ hospital-acquired infection, initiating MRSA-active treatment 1-2 days post cSSTI index date, existing ED protocol), while other factors decreased the odds of ES (no documented MRSA culture, ≥4 days from admission to cSSTI index date, IV-to-oral switch, IV line infection) and ED (dementia, no documented MRSA culture, initiating MRSA-active treatment ≥3 days post cSSTI index date, existing ES protocol). Practice patterns and opportunity for further ES and ED were affected by several infection, treatment, hospital, and geographical characteristics, which should be considered in identifying ES and ED opportunities and designing interventions for MRSA cSSTI to reduce IV days and LOS while maintaining the quality of care. | 25,182,029 | [
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Pharmacokinetic/pharmacodynamic evaluation of linezolid in hospitalized paediatric patients: a step toward dose optimization by means of therapeutic drug monitoring and Monte Carlo simulation. | To report on linezolid exposure in a paediatric population who routinely underwent therapeutic drug monitoring (TDM) for dosage optimization and to assess the factors affecting interpatient variability. We performed a retrospective study of patients whose plasma C(min) and Cmax levels were measured during linezolid treatment. Adequate exposure was defined as a C(min) of 2-7 mg/L and/or an estimated AUC24 of 160-300 mg · h/L. Patients were divided into two subgroups (Group 1, 2-11 years; Group 2, 12-18 years). Monte Carlo simulation was performed to investigate whether or not the currently recommended dosages might enable a high probability of target attainment (PTA) of two thresholds for linezolid efficacy (AUC24/MIC ≥ 80 or ≥ 100). Data on demographic characteristics, disease, microbiology and haematochemical parameters and outcomes were collected. A total of 23 patients were included. Standard dosages were suboptimal in 50.0% and 44.4% of patients in Group 1 and Group 2, respectively. Among those who underwent multiple instances of TDM, the dosages were increased in 33.3% of cases in both groups, and decreased in 6.6% and 9.5% of cases in Group 1 and Group 2, respectively. Co-treatment with phenobarbital, proton pump inhibitors and amiodarone accounted for most of the variability in C(min) (adjusted R(2) of 0.692). Simulations showed a PTA of ≥ 90% with the current dosing regimens in both groups only for pathogens with an MIC ≤ 1 mg/L. Higher dosages of linezolid may be needed, especially in Group 1 when in the presence of pathogens with an MIC >1 mg/L. The role of TDM should be encouraged for optimization of linezolid exposure in the paediatric setting in the presence of infections caused by pathogens with borderline susceptibility and/or for patients co-treated with drugs that may alter linezolid exposure. | 25,182,066 | [
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A smartphone controlled handheld microfluidic liquid handling system. | Microfluidics and lab-on-a-chip technologies have made it possible to manipulate small volume liquids with unprecedented resolution, automation and integration. However, most current microfluidic systems still rely on bulky off-chip infrastructures such as compressed pressure sources, syringe pumps and computers to achieve complex liquid manipulation functions. Here, we present a handheld automated microfluidic liquid handling system controlled by a smartphone, which is enabled by combining elastomeric on-chip valves and a compact pneumatic system. As a demonstration, we show that the system can automatically perform all the liquid handling steps of a bead-based HIV1 p24 sandwich immunoassay on a multi-layer PDMS chip without any human intervention. The footprint of the system is 6 × 10.5 × 16.5 cm, and the total weight is 829 g including battery. Powered by a 12.8 V 1500 mAh Li battery, the system consumed 2.2 W on average during the immunoassay and lasted for 8.7 h. This handheld microfluidic liquid handling platform is generally applicable to many biochemical and cell-based assays requiring complex liquid manipulation and sample preparation steps such as FISH, PCR, flow cytometry and nucleic acid sequencing. In particular, the integration of this technology with read-out biosensors may help enable the realization of the long-sought Tricorder-like handheld in vitro diagnostic (IVD) systems. | 25,182,078 | [
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The Inferior Alveolar Nerve of the Horse: Course and Anatomical Relationship with Mandibular Cheek Teeth. | The precise location of neurovascular structures within the relatively long mandibular canal of the horse is of paramount importance in surgical procedures of the area. The inferior alveolar nerve (IAN) enters the mandibular canal on the medial (lingual) surface of the mandible and innervates all the mandibular teeth. During its course, the nerve moves laterally, crossing the roots of the inferior cheek teeth. However, the exact anatomical relationships occurring between the IAN and the roots of the equine mandibular cheek teeth have not been described in detail. In this study, the mandibles of 40 horses were examined with CT scans and then used for bilateral detailed anatomical dissection, to assess the path of the IAN and its relationship to the roots of the lower cheek teeth. The data obtained show that the equine IAN is located ventral to the apices of the molar teeth (311/411, 310/410, 309/409 according to the Triadan numerical system). At the level of PM(4) (308/408), the IAN is located on the lingual side of the roots and coronally to its apices. At the level of PM(3) (307/407), the IAN is then found on the lingual side of the roots but in proximity to the apices. In 2 of 40 horses (=5%), the IAN moves towards the lingual side between the mesial and the distal root of PM(4). Our observations are valuable for planning a surgical approach to the ventral side of the mandible in the horse and to avoid potential post-operative complications. | 25,182,080 | [
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Long-term follow-up after bariatric surgery: a systematic review. | Bariatric surgery is an accepted treatment for obesity. Despite extensive literature, few studies report long-term follow-up in cohorts with adequate retention rates. To assess the quality of evidence and treatment effectiveness 2 years after bariatric procedures for weight loss, type 2 diabetes, hypertension, and hyperlipidemia in severely obese adults. MEDLINE and Cochrane databases were searched from 1946 through May 15, 2014. Search terms included bariatric surgery, individual bariatric procedures, and obesity. Studies were included if they described outcomes for gastric bypass, gastric band, or sleeve gastrectomy performed on patients with a body mass index of 35 or greater, had more than 2 years of outcome information, and had follow-up measures for at least 80% of the initial cohort. Two investigators reviewed each study and a third resolved study inclusion disagreements. Of 7371 clinical studies reviewed, 29 studies (0.4%, 7971 patients) met inclusion criteria. All gastric bypass studies (6 prospective cohorts, 5 retrospective cohorts) and sleeve gastrectomy studies (2 retrospective cohorts) had 95% confidence intervals for the reported mean, median, or both exceeding 50% excess weight loss. This amount of excess weight loss occurred in 31% of gastric band studies (9 prospective cohorts, 5 retrospective cohorts). The mean sample-size-weighted percentage of excess weight loss for gastric bypass was 65.7% (n = 3544) vs 45.0% (n = 4109) for gastric band. Nine studies measured comorbidity improvement. For type 2 diabetes (glycated hemoglobin <6.5% without medication), sample-size-weighted remission rates were 66.7% for gastric bypass (n = 428) and 28.6% for gastric band (n = 96). For hypertension (blood pressure <140/90 mm Hg without medication), remission rates were 38.2% for gastric bypass ( n = 808) and 17.4% for gastric band (n = 247). For hyperlipidemia (cholesterol <200 mg/dL, high-density lipoprotein >40 mg/dL, low-density lipoprotein <160 mg/dL, and triglycerides <200 mg/dL), remission rates were 60.4% for gastric bypass (n = 477) and 22.7% for gastric band (n = 97). Very few bariatric surgery studies report long-term results with sufficient patient follow-up to minimize biased results. Gastric bypass has better outcomes than gastric band procedures for long-term weight loss, type 2 diabetes control and remission, hypertension, and hyperlipidemia. Insufficient evidence exists regarding long-term outcomes for gastric sleeve resections. | 25,182,102 | [
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Thermal gelation of chitosan in an aqueous alkali-urea solution. | Chitosan can readily dissolve in a precooled aqueous alkali-urea solution, a solvent that has previously been developed to dissolve cellulose. Upon heating, the resulting solutions quickly become a gel. The thermal gelling of the chitosan solutions was studied by rheology. Initially, a temperature ramp test was used to determine the gelation temperatures (Tgel). It was found that Tgel does not significantly change with chitosan concentration. The in situ formed gels liquefy on cooling, but the liquefication temperature (Tliq) is considerably lower than Tgel, indicating a large hysteresis in the cooling process. In addition, Tliq decreases with increasing polymer concentration. The kinetics of thermal gelation was then studied by isothermal curing. The solution gels were cured not only at temperatures above the Tgel, which was determined in the temperature ramp test, but also at temperatures far below the Tgel, provided that the solution is cured at the temperature for a long enough time. The solutions become gel faster when cured at higher temperatures. When cured at the same temperature, higher concentration solutions become gel faster. The apparent activation energy for the thermal gelation of the chitosan solutions was determined to be ∼200 kJ mol(-1). Physical gels of pure chitosan were obtained by repeated soaking the in situ formed gels in water. Preliminary test shows that new gels are highly biocompatible. | 25,182,118 | [
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The expanding spectrum of PRPS1-associated phenotypes: three novel mutations segregating with X-linked hearing loss and mild peripheral neuropathy. | Next-generation sequencing is currently the technology of choice for gene/mutation discovery in genetically-heterogeneous disorders, such as inherited sensorineural hearing loss (HL). Whole-exome sequencing of a single Italian proband affected by non-syndromic HL identified a novel missense variant within the PRPS1 gene (NM_002764.3:c.337G>T (p.A113S)) segregating with post-lingual, bilateral, progressive deafness in the proband's family. Defects in this gene, encoding the phosphoribosyl pyrophosphate synthetase 1 (PRS-I) enzyme, determine either X-linked syndromic conditions associated with hearing impairment (eg, Arts syndrome and Charcot-Marie-Tooth neuropathy type X-5) or non-syndromic HL (DFNX1). A subsequent screening of the entire PRPS1 gene in 16 unrelated probands from X-linked deaf families led to the discovery of two additional missense variants (c.343A>G (p.M115V) and c.925G>T (p.V309F)) segregating with hearing impairment, and associated with mildly-symptomatic peripheral neuropathy. All three variants result in a marked reduction (>60%) of the PRS-I activity in the patients' erythrocytes, with c.343A>G (p.M115V) and c.925G>T (p.V309F) affecting more severely the enzyme function. Our data significantly expand the current spectrum of pathogenic variants in PRPS1, confirming that they are associated with a continuum disease spectrum, thus stressing the importance of functional studies and detailed clinical investigations for genotype-phenotype correlation. | 25,182,139 | [
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A mid-morning snack of almonds generates satiety and appropriate adjustment of subsequent food intake in healthy women. | To assess the effect of consuming a mid-morning almond snack (28 and 42 g) tested against a negative control of no almonds on acute satiety responses. On three test days, 32 healthy females consumed a standard breakfast followed by 0, 28 or 42 g of almonds as a mid-morning snack and then ad libitum meals at lunch and dinner. The effect of the almond snacks on satiety was assessed by measuring energy intake (kcal) at the two ad libitum meals and subjective appetite ratings (visual analogue scales) throughout the test days. Intake at lunch and dinner significantly decreased in a dose-dependent manner in response to the almond snacks. Overall, a similar amount of energy was consumed on all three test days indicating that participants compensated for the 173 and 259 kcals consumed as almonds on the 28 and 42 g test days, respectively. Subjective appetite ratings in the interval between the mid-morning snack and lunch were consistent with dose-dependent enhanced satiety following the almond snacks. However, in the interval between lunch and dinner, appetite ratings were not dependent on the mid-morning snack. Almonds might be a healthy snack option since their acute satiating effects are likely to result in no net increase in energy consumed over a day. | 25,182,142 | [
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Treating severe hypoglycemia: rapid mixing of lyophilized glucagon and diluent at point of care with the Enject GlucaPen. | Severe hypoglycemia (SH) is a common problem in type 1 diabetes (T1D). Annually, nearly 1 of 5 persons with long-standing T1D will have SH. Though injections of glucagon are effective in treating SH, liquid formulations of glucagon are biochemically very unstable. For this reason, available preparations of glucagon are lyophilized; the powder and the diluent must be mixed at the point of care prior to administration and any remaining drug must be discarded. The process of mixing and delivery is complex. Coupled with the emotional stress of the caregiver, errors in glucagon delivery are very common. For these reasons, workers at Enject, Inc are in the process of developing a device that addresses the shortcomings of this currently approved method of glucagon delivery. The Enject device will store the glucagon powder and the diluent in separate compartments and will rapidly mix and inject the components only upon activation of the pen at the point of care. | 25,182,147 | [
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Efficacy of β-sitosterol isolated from Evolvulus alsinoides L. as anti-hyperlipidemic and anti-tumor agent: Evidence from animal studies. | To explore the anti-hyperlipidemic and anti-tumor effect of ethanolic extract of Evolvulus alsinoides, its chloroform fraction and isolated components in Triton-induced hyperlipidemic rats. Animals were administered with intraperitoneal (i.p.) injection of Triton WR 1339 at a dose of 400 mg/kg body weight. After 24 h of Triton administration the test drugs were administered orally at a dose of 200 mg/kg body weight in rats. The ethanolic extract and stigmast-5-en-3β-ol from Evolvulus alsinoides were further investigated for the tumor take inhibitory activity in hybrid mice (of C57BL strain + Swiss albino strain). Preventive group animals were injected daily with the extract and stigmast-5-en-3β-ol at dose of 50 mg/kg body weight i.p. for 10 consecutive days. The animals were observed for the growth of tumor after injection of B16F10 melanoma cells into the dorsal skin of mice. Stigmast-5-en-3β-ol showed a marked antihyperlipidemic potential by reducing the total cholesterol, triglycerides, low density lipoproteins level, and significantly increased high density lipoprotein level compared with other isolated component. Pretreatment with the drug showed delay tumor growth by increasing the volume doubling time and growth delay. The stigmast-5-en-3β-ol showed better mean survival time. The supplementation of antioxidants and phytosterols rich food Evolvulus alsinoides has significant tumor take inhibitory activity. | 25,182,155 | [
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Prevalence of vascular disease in systemic lupus erythematosus compared with type-1 diabetes mellitus: a cross-sectional study of two cohorts. | Systemic lupus erythematosus (SLE) is associated with considerable cardiovascular morbidity that has not yet been directly compared with other diseases with known cardiovascular risk. Two hundred and forty-one patients of the multicentre Swiss SLE cohort study (SSCS) were cross-sectionally assessed for coronary heart disease (CHD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). SLE patients were compared with a cohort of 193 patients with type-1 diabetes mellitus being followed at the University Hospital Basel. A subgroup analysis of 50 age- and sex-matched patients from the University Hospital Basel was performed. Of patients within the SSCS 13.3% had one or more vascular events: 8.3% CHD, 5% CVD and 1.2% PAD. In type-1 diabetes mellitus patients, 15% had vascular events: 9.3% CHD, 3.1% CVD and 5.6% PAD. In the matched subgroup, 26% of SLE patients had vascular events (14% CHD) compared with 12% in type-1 DM patients (2% CHD). Cardiovascular risk factors were similar in both groups. Vascular events in SLE patients were associated with age, longer disease duration, dyslipidaemia, and hypertension. Cardiovascular morbidity in SLE is at least as frequent as in age- and sex-matched type-1 diabetes mellitus patients. Therefore, aggressive screening and management of cardiovascular risk factors should be performed. | 25,182,169 | [
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Distant peer-tutoring of clinical skills, using tablets with instructional videos and Skype: A pilot study in the UK and Malaysia. | To assess the feasibility and impact of using low-cost Android tablets to deliver video tutorials and remote online peer-tutoring for clinical skills between two countries. Nine junior medical students from Malaysia were paired with five senior medical students from the UK, who played the role of peer-tutors. Students from Malaysia were given a low-cost Android tablet from which they could access instructional video tutorials. At the end of each week, the peer-tutors would observe their peer-learners as they performed a clinical examination. Tutors would then provide individual feedback using a videoconferencing tool. Outcomes were assessed using Observed Structured Clinical Examination (OSCE) scores, post-study questionnaires and semi-structured interviews with participants. Peer-learners reported an increased confidence in clinical examination of 8.4 (±1.0) on a 10-point scale and all nine said they would recommend the scheme to their peers. Both peer-tutors and peer-learners were able to establish a strong rapport over video, rating it as 8.4 (±0.6) and 8.4 (±0.9), respectively. Peer-learners' rated the sound and video quality of the tablet as 7.0 (±1.1) but were less satisfied with the screen resolution of the tablet, rating this as 4.0 (±1.5). This preliminary pilot study presents an innovative, low cost approach to international medical education with significant potential for future development. | 25,182,187 | [
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The overdue promise of short tandem repeat variation for heritability. | Short tandem repeat (STR) variation has been proposed as a major explanatory factor in the heritability of complex traits in humans and model organisms. However, we still struggle to incorporate STR variation into genotype-phenotype maps. We review here the promise of STRs in contributing to complex trait heritability and highlight the challenges that STRs pose due to their repetitive nature. We argue that STR variants are more likely than single-nucleotide variants to have epistatic interactions, reiterate the need for targeted assays to genotype STRs accurately, and call for more appropriate statistical methods in detecting STR-phenotype associations. Lastly, we suggest that somatic STR variation within individuals may serve as a read-out of disease susceptibility, and is thus potentially a valuable covariate for future association studies. | 25,182,195 | [
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Quantitative measurement of brain iron deposition in patients with haemodialysis using susceptibility mapping. | To compare the susceptibility of different brain structures in patients with haemodialysis with that in healthy controls using susceptibility mapping and explore the correlations with neuropsychiatric tests and clinical parameters. Fifty three patients with haemodialysis and forty-five age-and sex-matched healthy controls were recruited in this prospective study. Susceptibility maps (SM) were reconstructed from original phase data and used to compare the susceptibility of different brain structures between patients and healthy controls. The SM was compared with iron predictions from a classic cadaver brain study. Spearman's correlation and stepwise multiple regression analysis between susceptibility and neuropsychiatric tests and clinical parameters were calculated. In patients with haemodialysis, the susceptibility of the bilateral caudate head, putamen, substantia nigra, red nucleus and dentate nucleus were significantly higher than those in healthy controls (P < 0.01). There was positive correlation between susceptibility both from normal controls and patients and iron concentration from a classic post-mortem brain study (both r = 0.900, both P = 0.037). In patients with haemodialysis, the susceptibility of the left putamen (r = 0.944), right putamen (r = 0.882) and right thalamus (r = 0.852) were correlated to dialysis duration (all P < 0.05). The susceptibility of the left caudate head (r = -0.415) and right caudate head (r = -0.311) were mildly negatively correlated with neuropsychiatric test scores (all P < 0.05). In summary, our findings indicated that increased brain iron deposition does occur in patients with haemodialysis and correlated with duration of dialysis. | 25,182,196 | [
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Reviews and prospectives of signaling pathway analysis in idiopathic pulmonary fibrosis. | Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing disease with disappointing survival rate, and uneffective therapeutic progress has been made in the last few years, forcing the urgent need to improve research to this disease. The commonly accepted pathogenic hypothesis of IPF is the trigger from continuous alveolar epithelium microinjuries and in the following series events, many signaling pathways were reported to lead to abnormal tissue repair and lung structure derangement in IPF, such as TGF-β, wnt, VEGF and PI3K-Akt signaling pathways. Traditional research of IPF related signaling pathway always focus on the independent function of pathway and disease signals, but the crosstalks and interactions among them were rarely valued. In this review, we summarize the signaling pathways which were reported to play important roles in the pathologic changes of IPF and the synergistic effect among those pathways. Next we discuss the application of genomics research and bioinformatics tools on IPF related pathway analysis, and give a systems biology perspective by integrating multi-level disease related data. The novel prospective of pathway analysis could tease out the complex pathway interaction profiles of IPF, and is powerful to detect IPF related biomarkers for early diagnose and potential therapeutic targets. | 25,182,202 | [
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Four dermatomyositis-specific autoantibodies-anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5-in adult and juvenile patients with idiopathic inflammatory myopathies in a Hungarian cohort. | Idiopathic inflammatory myopathies (IIMs) are chronic systemic autoimmune diseases characterised by symmetrical, proximal muscle weakness. Dermatomyositis represents one subset of IIMs, in which skin rashes are present in addition to muscle weakness. Myositis-specific antibodies can only be detected in myositis, and they are directed against specific proteins found in the cytoplasm or in the nucleus of cells. With this case-based article, we introduce the recently detected anti-TIF1γ, anti-NXP2, anti-SAE and anti-MDA5 antibodies that form various clinical groups. These antibodies could be detected in patients with dermatomyositis. The myositis-specific autoantibodies of three hundred and thirty-seven Hungarian patients with IIM were detected. Retrospective analysis of the clinical findings has also been introduced by revision of the medical history. We had twelve patients with anti-TIF1γ positivity, four patients with anti-NXP2 positivity and four patients with anti-SAE positivity. We did not have any positive anti-MDA5 patients. The most relevant clinical findings were similar to those seen in previously published reports. Eleven of the twelve patients with anti-TIF1γ positivity had classical dermatomyositis. Three of the twelve anti-TIF1γ patients had cancer during the disease progression. This was two out of four for the anti-NXP2 subgroup and one in four for the anti-SAE subgroup. In two juvenile dermatomyositis cases, typical ulceration was seen in patients with anti-TIF1γ positivity. The frequency of pulmonary fibrosis during the disease progression was 2/12, 1/4 and 1/4 in anti-TIF1γ, anti-NXP2 and anti-SAE, respectively. Other extra-muscular manifestations, such as arthralgia, dysphagia, dysphonia and dyspnoea, were also detectable. The myositis subgroups determined by these myositis-specific autoantibodies differ from each other in their symptoms, prognosis and therapy responsiveness. Their detection is helpful for the preparation of an adequate treatment, but in daily diagnostic methods, these antibodies cannot be detected. By presenting our anti-TIF1γ, anti-NXP2 and anti-SAE cases, we would like to highlight the clinical role of these antibodies. | 25,182,203 | [
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Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients' population and review of the literature. | The clinical spectrum and prognosis of systemic sclerosis (SSc) seem to vary among patients' populations recruited during different time periods. In order to verify this possible evolution we investigated the clinico-serological and survival rate in a large Italian SSc series (821 patients; 746 females, 75 males; mean age 53.7±13.9SD years) recruited between 2000 and 2011. The observed findings were compared with previous studies of the world literature.Compared to older Italian SSc series, the present patients' population showed a significantly increased prevalence of limited cutaneous SSc (from 72 to 87.5%; p ≤.0001) and serum anti-centromere antibodies (from 39 to 47,4%; p ≤.001), with a significant reduction of lung (from 81 to 63.7%; p ≤.0001), heart (from 35 to 20.5%; p ≤.0001), and renal involvement (from 10 to 3.8%; p ≤.0001), and skin ulcers (from 54 to 16.5%; p ≤.0001). Cumulative 10th-year survival showed a clear-cut increase (80.7%) compared to our previous series (69.2%). These findings were mirrored by the results of survival studies published during the last five decades, grouped according to the time periods of patients'' recruitment at the referral centers. A clear progression of 10th-year survival rates was detectable, from the 54% median survival of the oldest studies (1935-1974) to 74% and 83.5% of the more recent SSc series, 1976-1999 and after 1999, respectively. In conclusion, the favorable evolution of SSc pathomorphosis and prognosis during the last decades might be related to more diffuse physician/patient awareness of this harmful disease and availability of diagnostic tools, the consequent wider recruitment of patients in the early stages of the disease, as well as to the improved therapeutic strategies. | 25,182,204 | [
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Identification of a novel myositis-associated antibody directed against cortactin. | The aim of this study is to describe a novel myositis-associated autoantibody (anti-cortactin antibody) and assess related clinical and immunological manifestations and its clinical significance. Adult patients with myositis (dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and inclusion body myositis), as well as patients with other autoimmune diseases and non-inflammatory myopathies were analyzed for the presence of anti-cortactin antibody using in-house developed ELISA and immunoblotting techniques with a commercial source of purified cortactin. The cut-off for positive status was determined in a group of healthy volunteers. Antibody against cortactin was positive in 7/34 (20%) polymyositis patients, 9/117 (7.6%) dermatomyositis, 2/7 (26%) immune-mediated necrotizing myopathy, and none of the 4 patients with inclusion body myositis. The antibody also tested positive in 3/101 patients with other autoimmune diseases (2 systemic sclerosis and 1 systemic lupus erythematosus), and in 1/29 patients with non-inflammatory myopathy. No relevant association with specific clinical features was found in patients with these antibodies. Anti-cortactin antibody was more frequently positive in patients with polymyositis and immune-mediated necrotizing myopathy than in the remaining myositis patients, and was the only myositis autoantibody found in sera of 3 patients from these groups. Our data indicate that cortactin is a novel target antigen in patients with autoimmune diseases, especially patients with polymyositis or immune-mediated necrotizing myopathy. Anti-cortactin can be considered a new myositis-associated antibody. | 25,182,205 | [
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Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. | X-VeRT is the first prospective randomized trial of a novel oral anticoagulant in patients with atrial fibrillation undergoing elective cardioversion. We assigned 1504 patients to rivaroxaban (20 mg once daily, 15 mg if creatinine clearance was between 30 and 49 mL/min) or dose-adjusted vitamin K antagonists (VKAs) in a 2:1 ratio. Investigators selected either an early (target period of 1-5 days after randomization) or delayed (3-8 weeks) cardioversion strategy. The primary efficacy outcome was the composite of stroke, transient ischaemic attack, peripheral embolism, myocardial infarction, and cardiovascular death. The primary safety outcome was major bleeding. The primary efficacy outcome occurred in 5 (two strokes) of 978 patients (0.51%) in the rivaroxaban group and in 5 (two strokes) of 492 patients (1.02%) in the VKA group [risk ratio 0.50; 95% confidence interval (CI) 0.15-1.73]. In the rivaroxaban group, four patients experienced primary efficacy events following early cardioversion (0.71%) and one following delayed cardioversion (0.24%). In the VKA group, three patients had primary efficacy events following early cardioversion (1.08%) and two following delayed cardioversion (0.93%). Rivaroxaban was associated with a significantly shorter time to cardioversion compared with VKAs (P < 0.001). Major bleeding occurred in six patients (0.6%) in the rivaroxaban group and four patients (0.8%) in the VKA group (risk ratio 0.76; 95% CI 0.21-2.67). Oral rivaroxaban appears to be an effective and safe alternative to VKAs and may allow prompt cardioversion. Clinicaltrials.gov; NCT01674647. | 25,182,247 | [
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MRI - what important findings can it show in children with back pain? | The percentage of school-age children who have already had an episode of back pain can be as high as 51%, and the incidence of the disease increases with age and physical activity. This paper summarizes the MR examinations of children with back pain carried out at the Institute of Mother and Child in Warsaw and highlights pathological findings, which have been shown in them. Analyses were done of 121 MR examinations carried out because of back pain in children. All of them were performed with a GE Signa HDxt 1.5 T scanner according to routine protocol: SE/T1-weighted images in sagittal and axial plane, FSE/T2-weighted images in sagittal and axial plane, STIR sequence in sagittal plane. If necessary, coronal plane was added and contrast agent was administered. Negative results - no changes - were obtained in 91 children (75.2%). Positive results were found in 30 children, which accounts for 24.8%. Among the lesions there were degenerative changes of intervertebral disks as an isolated finding in 9 children (7.4%), Scheuermann's disease in 2 (1.7%), intervertebral disks herniations in 13 (10.7%), spondylolisthesis in 2 (1.7%), sacroiliitis in 1 (0.8%), intervertebral facet joint arthritis in 1 (0.8%), tumors in 2 (1.7%). Back pain in children is a growing problem, and in ¼ of the cases is reflected by pathological changes visible on MRI, which is the best method of imaging the causes of back pain in children and adolescents. | 25,182,257 | [
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Pancreatic islet regeneration and some liver biochemical parameters of leaf extracts of Vitex doniana in normal and streptozotocin-induced diabetic albino rats. | To test two water soluble extracts (aqueous and ethanolic) obtained from the leaves of Vitex doniana in normal and streptozotocin-induced diabetic rats for their effects on pancreatic endocrine tissues and serum marker enzymes for a period of 21 d. A total of 55 rats divided into 11 groups of 5 rats each were assigned into diabetic and non-diabetic groups and followed by a daily administration of ethanolic and aqueous extracts for 21 d. Group 1 was the normal control while group 7 was treated with standard drug. The histopathological studies of the diabetic rats indicated increase in the volume density of islets, percent of β-cells and size of islet in the groups that received the plant extracts, which suggested regeneration of β-cells along with β-cells repairs, as compared with the non-treated diabetic control which showed complete degeneration of the islet cells. There was significant reduction (P<0.05) in the serum activities of marker enzymes, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in diabetes treated rats, whereas an insignificant increase (P>0.01) in the serum activities of marker enzymes was observed for non-diabetic treated rats. Results of total bilirubin, direct bilirubin and unconjugated bilirubin showed that diabetic control group was significantly higher (P<0.05) in total bilirubin and unconjugated bilirubin compared with treated groups while non-diabetic treated groups showed no significant increase (P>0.01) in total bilirubin and direct bilirubin compared with the normal control. This herbal therapy appears to bring about repair/regeneration of the endocrine pancreas and hepatic cells protection in the diabetic rat. | 25,182,283 | [
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Ameliorative effect of alkaloid extract of Cyclea peltata (Poir.) Hook. f. & Thoms. roots (ACP) on APAP/CCl4 induced liver toxicity in Wistar rats and in vitro free radical scavenging property. | To evaluate the hepatoprotective and antioxidant properties of alkaloid extract of Cyclea peltata (C. peltata) against paracetamol/carbon tetra chloride induced liver damage in Wistar rats. In vivo paracetamol/carbon tetrachloride induced liver damage in Wistar rats, in vitro free radical scavenging studies, HPTLC estimation of tetrandrine and direct analysis in real time- mass spectrometry of alkaloid extract of C. peltata were used for the validation. The results showed that pretreatment with alkaloid extract of C. peltata caused significant reduction of serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, serum alkaline phosphatase, serum cholesterol, liver malondialdehyde levels. The reduced glutathione, catalase, superoxide dismutase levels in liver were increased with alkaloid extract of C. peltata treatment. These results were almost comparable to silymarin and normal control. Histopathological studies also substantiated the biochemical findings. The in vitro hydroxyl, superoxide and DPPH scavenging study of alkaloid extract of C. peltata showed significant free radical scavenging property. The hepatoprotective property of alkaloid extract of C. peltata against paracetamol/carbon tetrachloride may be due the synergistic action of alkaloids especially tetrandrine, fangchinoline through free radical scavenging and thus preventing oxidative stress. | 25,182,286 | [
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Prevalence and antibiogram of bacterial isolates from urinary tract infections at Dessie Health Research Laboratory, Ethiopia. | To determine the prevalence and antimicrobial susceptibility of bacteria from suspected urinary tract infections. A retrospective analysis of bacterial pathogens and their antimicrobial susceptibility was done on urine samples at Dessie Regional Laboratory in the period 2003 to 2010. Antimicrobial susceptibility tests were done using disc diffusion technique as per the standard of Kirby-Bauer method. The male to female ratio of the patients was 1:1.96. Of the total 1 404 samples, 319 (22.7%) were culture positive. Escherichia coli was the dominant isolate (63.6%) followed by Klebsiella spp. (8.5%) and Proteus spp. (8.2%). The overall resistance rates to erythromycin, amoxycillin, and tetracycline were 85.6%, 88.9% and 76.7%, respectively. The three most frequently isolated bacteria had resistance rates of 80.1%-90.0% to, amoxycillin, and tetracycline and sensitivity rates of 0 to 25% to nitrofurantoin, ciprofloxacin and gentamicin. Antibiogram of isolates showed that 152 (47.85%) isolates were resistance to two and more antimicrobials. In the study area resistance rates to erythromycin, amoxycillin and tetracycline were high. Since most isolates were sensitive to nitrofurantoin and gentamicin, they are considered as appropriate antimicrobials for empirical treatment urinary tract infections. | 25,182,289 | [
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Peripheral blood mononuclear cell-based metabolomic profiling of a chronic unpredictable mild stress rat model of depression. | Major depressive disorder (MDD) is a debilitating mood disorder with various etiopathological hypotheses. However the pathogenesis and diagnosis are still unclear. Peripheral blood mononuclear cells (PBMCs) have been shown to be well-suited to biomarker investigation in major depressive disorder (MDD), as well as to unveil the underlying pathogenesis of MDD. In this study, PBMCs were obtained from a chronic unpredictable mild stress (CUMS) rodent model of depression. A gas chromatography-mass spectrometry (GC/MS) metabolomic approach coupled with principal component analysis (PCA) and open partial least-squares discriminant analysis (OPLS-DA) statistical analysis was used to detect differential metabolites in PBMCs of depressed rats. A total number of 18 differential metabolites were screened out. Seven metabolites showed lower levels in CUMS relative to healthy control rats, including aspartic acid, glutamic acid, dehydroascorbic acid, aminomalonic acid, glycine, β-alanine, and ethanolamine, while eleven metabolites showed an increase in CUMS relative to healthy control rats, namely erythronic acid, fructose, β-tocopherol, adenosine-5-monophosphate, 5-hydroxytryptamine, 5-hydroxytryptamine, glycolic acid, α-tocopherol, tetradecanoic acid, creatinine, 4,5-dimethyl-2,6-dihydroxypyrimidine, and myo-inositol. These molecular changes were closely related to perturbations in neurotransmitter metabolism, energy metabolism and oxidative stress metabolism. Biochemical function analysis of these differential metabolites suggested that altered neurotransmitter, energy and oxidative metabolism disorder might be evolved in the pathogenesis of MDD, which could be of valuable assistance in the clinical diagnosis of MDD. | 25,182,291 | [
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A composite cathode based on scandium doped titanate with enhanced electrocatalytic activity towards direct carbon dioxide electrolysis. | A composite cathode based on redox-stable La0.2Sr0.8TiO(3+δ) (LSTO) can perform direct carbon dioxide electrolysis; however, the insufficient electro-catalytic activity limits the electrode performances and current efficiencies. In this work, catalytically active scandium is doped into LSTO to enhance the electro-catalytic activity for CO2 electrolysis. The structures, electronic conductivities and ionic conductivities of La0.2Sr0.8Ti(1-x)Sc(x)O (LSTS(x)O) (x = 0, 0.05, 0.1, 0.15 and 0.2) are systematically studied and further correlated with electrode performances. The ionic conductivities of single-phase LSTS(x)O (x = 0, 0.05, 0.1 and 0.15) remarkably improve versus the scandium doping contents though the electrical conductivities gradually change in an adverse trend. Electrochemical measurements demonstrate promising electrode polarisation of LSTS(x)O electrodes and increasing scandium doping contents accordingly improve electrode performances. The Faradic efficiencies of carbon dioxide electrolysis are enhanced by 20% with LSTS0.15O in contrast to bare LSTO electrodes in a solid oxide electrolyser at 800 °C. | 25,182,301 | [
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Sublingual immunotherapy: current concepts for the U.S. practitioner. | Estimates of the prevalence of allergic rhinitis in the United States range from 20% to 40%. Allergen-specific immunotherapy (SIT) is typically recommended for patients with allergic rhinitis who fail medical treatment, desire an alternative to pharmacotherapy, or would like to pursue therapy that can potentially change the natural history of the disease. Sublingual immunotherapy (SLIT) involves dosing the allergen under the tongue of the sensitized individual in controlled amounts, frequently, over a period of several years, in order to increase immunologic tolerance and diminish symptoms to that allergen. The U.S. Food and Drug Administration (FDA) approved the use of SLIT tablets in 2014, whereas the use of aqueous SLIT by U.S. practitioners is considered an "off-label" use. This study is a review of published English language scientific literature, focusing on systematic reviews and randomized controlled trials of SLIT for inhalant allergic rhinitis. SLIT is a safe and effective immune modulating treatment that decreases symptoms and medication use for allergic rhinitis. Further study is needed to determine the relative effectiveness of SLIT compared to subcutaneous immunotherapy, the role of multiple-allergen vs single-allergen SLIT, the use of SLIT in special populations (pregnancy, patients taking beta-blockers), and optimal dosing of U.S. products. SLIT is safe and effective, and offers a convenient alternative to injection immunotherapy for appropriate patients with allergic rhinitis. | 25,182,357 | [
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Practical clinical approaches to the allergic rhinitis patient. | Numerous treatment strategies are available for the treatment of allergic rhinitis (AR), including environmental controls, pharmacotherapy, immunotherapy, and surgery in appropriately selected patients. A stepwise algorithmic approach based on disease severity and persistence of symptoms is often advocated to effectively manage patients with AR. A review is provided of current evidence and guidelines for the management of AR. Practical clinical strategies to improve patient adherence to therapy and outcome are described. Algorithms to manage AR are based on the severity and persistence of disease. A tailored strategy geared toward addressing symptoms that are most troublesome to the patient is beneficial, as is the assessment of comorbid conditions such as rhinosinusitis, asthma, and laryngopharyngeal reflux. Allergen-specific immunotherapy (AIT) is an underused treatment modality and patients with persistent AR should be considered candidates for desensitization, if appropriate. Assessment of patient outcome is important and the use of validated symptom surveys can provide an objective measure of quality of life. A large armamentarium of treatment options is available to the otolaryngologist treating the patient with AR. A step-wise and tailored approach with equal attention dedicated to patient education and assessment of patient outcome can be helpful to improve efficacy of treatment. | 25,182,359 | [
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Asthma and the otolaryngologist. | Asthma is a chronic inflammatory disease of the lower airway that is commonly encountered by the otolaryngologist. This article provides information on how to recognize patients with asthma and discuss issues related to diagnosis, treatment, and continued management within the context of current guidelines. A literature review was conducted and relevant sources are referenced concerning the epidemiology of asthma, the pathophysiology of asthma, diagnostic strategies, treatment options, and continued management. Asthma is a common condition worldwide and is often associated with other atopic diseases such as allergic rhinitis and eczema, though other genetic and environmental factors appear to be important as well. The lower airway and upper airways share similar histology, as well as patterns of inflammation in response to environmental triggers. The diagnosis of asthma involves a careful history and a complete physical exam, including auscultation of the lungs and pulmonary function testing. Pharmacotherapy represents the primary method of treating asthma, though current evidence supports a positive role for antigen-specific immunotherapy for both prevention and treatment. Guidelines are available that can assist the otolaryngologist in classifying the severity of asthma, determining the level of control and recommending modifications in the treatment plan. As airway specialists, otolaryngologists are in a unique position to recognize and manage asthma in their patients, particularly those with allergic disease. Maintaining a high index of suspicion and understanding the key elements of diagnosis and treatment are extremely important in order to achieve this goal. | 25,182,360 | [
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The feelings of adolescents connected with medical visits and their perception of the physicians' behaviour. | To analyze research results relating the feelings of adolescents connected with their medical visit and their perception of the physician's behaviour in treating them as patients during the visit. The research was conducted on a group of 14-15-year-olds (N=716), students of lower secondary schools located in 5 voivodeships. The research instrument was an anonymous authored questionnaire with questions concerning their last visit at the physician's: its time, purpose, and feelings connected with the visit, as well as reasons for these feelings and the variety of the physician's behaviours conducive to good communication with the adolescent patient. More than half (56%) of the respondents visited the physician within the previous 3 months, 64% because of illness, complaints or injury. The visit was accompanied by a range of different feelings, in most cases indifference (32%) and relief (21%). However, every seventh teenager showed anxiety and fear. The justification of these feelings varied and related to: the physician as a person, the physician's behaviour, the expectations and beliefs of the teenagers, the behaviour of other patients and the functioning of the healthcare system. Most of the teenagers (70-87%) decided that the physician undertook 8 out of the 11 ways of behaving named in the questionnaire as promoting good communication with the patient. Most physicians provided information about results of the study, used understandable words and actively listened to patients. The behaviours undertaken least often were asking encouraging questions and taking interest in the patient as an individual. Every fifth teenager was not examined in a way that showed respect to his/her privacy. Most young patients view the physician's behaviour towards them in a positive way. It should be pointed out to physicians how important it is to encourage adolescents to ask questions, treat them as individuals and respect their privacy. | 25,182,397 | [
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[Large dentigerous cyst caused by retained tooth 25]. | Follicular cysts are benign, non-inflammatory odontogenic cysts, usually painless and discovered during routine radiographic examination. The article describes a case of a large follicular cyst with retained tooth 25. Pantomographic x ray showed the presence of a large follicular cyst located on the side of the impacted 25 tooth. The cyst has been enucleated and the tooth extracted surgically with subsequent closure of oro-antral communication. After 3 months orthodontic treatment was initiated. | 25,182,400 | [
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[Multichannel electrogastrography in pediatrics - progress in standardisation and clinical application]. | Electrogastrography (EGG) is a non-invasive method to record gastric myoelectrical activity by means of electrodes placed on the abdominal surface. This technique allows to obtain information about gastric myoelectrical activity and indirectly about gastric motility, without affecting its physiological functions. Except traditional parameters of single channel EGG such as: dominant frequency and power, instability coefficient of dominant frequency and power, percentage of normo-, brady- and tachygastry, the multichannel electrogastrography allows for estimation and registration of the slow waves coupling and propagation as well as to improve detection of abnormalities in gastric myoelectrical activity. Many agents connected with signal detection and analysis, test meal and normative values affect the final result of EGG recording. The trials defining normative data for healthy children and optimal composition of the test meal are conducted. It seems that the establishment of standard protocol of EGG is essential. EGG in children is useful in variety of functional gastrointestinal disorders, as well as gastroesophageal reflux disease and some organic disorders e.g. diabetes mellitus. Some of these diseases are connected with gastric myoelectrical activity abnormalities but others are not easily associable with them and as such are in need of additional investigations. Despite of a rapid development of electrogastrography difficulties in finding correlations between disturbances in myoelectric stomach function and gastric motility, impaired gastric emptying and symptoms of particular disease still remain. On the other hand a normal EGG does not exclude the disease. | 25,182,402 | [
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Development of low postural tone compensatory patterns in children - theoretical basis. | Neurological literature indicates the existence of children with low postural tone without association with central nervous system damage. This fact induces to think about mechanisms, which allow these children to maintain upright posture. There is a suspicion that compensatory mechanism included in this process, enables to achieve upright posture, but at expense of body posture quality. Observations of children's developmental stages caused determination of some postural tone area, which comprise both children with normotonia and with low postural tone without characteristics of central nervous system (CNS) damage. Set of specific qualities allows determination of two types of low postural tone: spastoidal and atetoidal type. Spastoidal type is characterized by deep trunk muscles (local) low postural tone compensated by excessive tension of superficial muscles (global). Atetoidal type includes children with low postural tone in both deep and superficial muscles. At inefficient active subsystem, verticalization proceeds at excessive use of passive subsystem qualities, that is meniscus, ligament, bone shape, and muscles passive features. From neurodevelopmental point of view compensatory mechanisms can be used in children with low postural tone in order to achieve upright posture, but at expense of body posture quality. | 25,182,403 | [
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Active invasion of bacteria into living fungal cells. | The rice seedling blight fungus Rhizopus microsporus and its endosymbiont Burkholderia rhizoxinica form an unusual, highly specific alliance to produce the highly potent antimitotic phytotoxin rhizoxin. Yet, it has remained a riddle how bacteria invade the fungal cells. Genome mining for potential symbiosis factors and functional analyses revealed that a type 2 secretion system (T2SS) of the bacterial endosymbiont is required for the formation of the endosymbiosis. Comparative proteome analyses show that the T2SS releases chitinolytic enzymes (chitinase, chitosanase) and chitin-binding proteins. The genes responsible for chitinolytic proteins and T2SS components are highly expressed during infection. Through targeted gene knock-outs, sporulation assays and microscopic investigations we found that chitinase is essential for bacteria to enter hyphae. Unprecedented snapshots of the traceless bacterial intrusion were obtained using cryo-electron microscopy. Beyond unveiling the pivotal role of chitinolytic enzymes in the active invasion of a fungus by bacteria, these findings grant unprecedented insight into the fungal cell wall penetration and symbiosis formation. | 25,182,414 | [
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Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms. | In addition to its well-characterized role in the regulation of drug metabolism and transport by xenobiotics, pregnane X receptor (PXR) critically impacts on lipid homeostasis. In mice, both ligand-dependent activation and knockout of PXR were previously shown to promote hepatic steatosis. To elucidate the respective pathways in human liver, we generated clones of human hepatoma HepG2 cells exhibiting different PXR protein levels, and analyzed effects of PXR activation and knockdown on steatosis and expression of lipogenic genes. Ligand-dependent activation as well as knockdown of PXR resulted in increased steatosis in HepG2 cells. Activation of PXR induced the sterol regulatory element-binding protein (SREBP) 1-dependent lipogenic pathway via PXR-dependent induction of SREBP1a, which was confirmed in primary human hepatocytes. Inhibiting SREBP1 activity by blocking the cleavage-dependent maturation of SREBP1 protein impaired the induction of lipogenic SREBP1 target genes and triglyceride accumulation by PXR activation. On the other hand, PXR knockdown resulted in up-regulation of aldo-keto reductase (AKR) 1B10, which enhanced the acetyl-CoA carboxylase (ACC)-catalyzed reaction step of de novo lipogenesis. In a cohort of human liver samples histologically classified for non-alcoholic fatty liver disease, AKR1B10, SREBP1a and SREBP1 lipogenic target genes proved to be up-regulated in steatohepatitis, while PXR protein was reduced. In summary, our data suggest that activation and knockdown of PXR in human hepatic cells promote de novo lipogenesis and steatosis by induction of the SREBP1 pathway and AKR1B10-mediated increase of ACC activity, respectively, thus providing mechanistic explanations for a putative dual role of PXR in the pathogenesis of steatohepatitis. | 25,182,422 | [
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Surgical decision making in a teaching hospital: a linguistic analysis. | The aim of the study was to gain insight in the involvement of non-operating surgeons in intraoperative surgical decision making at a teaching hospital. The decision to proceed to clip and cut the cystic duct during laparoscopic cholecystectomy was investigated through direct observation of team work. Eleven laparoscopic cholecystectomies performed by consultant surgeons and specialty trainees at a London teaching hospital were audio and video recorded. Talk among the surgical team was transcribed and subjected to linguistic analysis, in conjunction with observational analysis of the video material, sequentially marking the unfolding operation. Two components of decision making were identified, participation and rationalization. Participation refers to the degree to which agreement was sought within the surgical team prior to clipping the cystic duct. Rationalization refers to the degree to which the evidential grounds for clipping and cutting were verbalized. The decision to clip and cut the cystic duct was jointly made by members of the surgical team, rather than a solitary surgeon in the majority of cases, involving verbal explication of clinical reasoning and verbal agreement. The extent of joint decision making appears to have been mitigated by two factors: trainee's level of training and duration of the case. | 25,182,451 | [
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Bicarbonate increases binding affinity of Vibrio cholerae ToxT to virulence gene promoters. | The major Vibrio cholerae virulence gene transcription activator, ToxT, is responsible for the production of the diarrhea-inducing cholera toxin (CT) and the major colonization factor, toxin coregulated pilus (TCP). In addition to the two primary virulence factors mentioned, ToxT is responsible for the activation of accessory virulence genes, such as aldA, tagA, acfA, acfD, tcpI, and tarAB. ToxT activity is negatively modulated by bile and unsaturated fatty acids found in the upper small intestine. Conversely, previous work identified another intestinal signal, bicarbonate, which enhances the ability of ToxT to activate production of CT and TCP. The work presented here further elucidates the mechanism for the enhancement of ToxT activity by bicarbonate. Bicarbonate was found to increase the activation of ToxT-dependent accessory virulence promoters in addition to those that produce CT and TCP. Bicarbonate is taken up into the V. cholerae cell, where it positively affects ToxT activity by increasing DNA binding affinity for the virulence gene promoters that ToxT activates regardless of toxbox configuration. The increase in ToxT binding affinity in the presence of bicarbonate explains the elevated level of virulence gene transcription. | 25,182,489 | [
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Formation, structural characterization, and reactions of a unique cyclotrimeric vicinal Lewis pair containing (C6F5)2P-Lewis base and (C6F5)BH-Lewis acid components. | The synthesis of the new vicinal frustrated Lewis pair 5 containing (C6F5)2P-Lewis base and (C6F5)BH-Lewis acid functionality is described. It forms a unique cyclotrimer (5)3 which was structurally characterized by X-ray crystallography and high-resolution solid-state NMR spectroscopy. The relevant NMR Hamiltonian parameters ((11)B and (31)P chemical shielding tensors, (11)B quadrupolar coupling tensors, and (31)P-(11)B spin-spin coupling constants) indicate significant intramolecular covalent BP interactions, consistent with results from density functional theory (DFT) calculations. In addition, the (11)B/(31)P and (31)P/(31)P three-spin geometries are accurately reproduced by suitable high-resolution hetero- and homonuclear dipolar NMR experiments. As predicted from the bonding character portrayed by the solid-state NMR results, the cyclotrimer (5)3 possesses only moderate catalytic activity. However, it undergoes an addition reaction with pyridine and hydroboration reactions with benzaldehyde and tert-butylacetylene. The products of the hydroboration reactions form stable adducts with pyridine. | 25,182,524 | [
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Stroke prophylaxis in atrial fibrillation: searching for management improvement opportunities in the emergency department: the HERMES-AF study. | We determine the prevalence of stroke prophylaxis prescription in emergency department (ED) patients with atrial fibrillation and the factors associated with a lack of prescription of anticoagulation in high-risk patients without contraindications. This was a multicenter, observational, cross-sectional study with prospective standardized data collection carried out in 124 Spanish EDs. Clinical variables, risk factors for stroke, type of prophylaxis prescribed, and reasons for not prescribing anticoagulation in high-risk patients (congestive heart failure/left ventricular dysfunction, hypertension, age >75 years, diabetes and previous stroke/transient ischemic attack/systemic embolism [CHADS2] score ≥2 and the congestive heart failure/left ventricular dysfunction, hypertension, age >75 years, diabetes, previous stroke/transient ischemic attack/systemic embolism, vascular disease age 65 to 74 years and sex category [CHA2DS2-VASc] score ≥2) without contraindications were collected. Of 3,276 patients enrolled, 71.5% were at high risk according to CHADS2; 89.7% according to CHA2DS2-VASc. At discharge from the ED, 2,255 patients (68.8%) were receiving anticoagulants, 1,691 of whom (75%) were high-risk patients. Of the 1,931 patients discharged home, anticoagulation was prescribed for 384 patients (19.9%) de novo and for 932 patients (48.3%) previously receiving anticoagulation. The main reasons for not prescribing anticoagulation to eligible patients were considering antiplatelet therapy as adequate prophylaxis (33.1%), advanced age (15%), and considering stroke risk as low (8.3%). Advanced age (odds ratio 0.46; 95% confidence interval 0.30 to 0.69) and female sex (odds ratio 0.50; 95% confidence interval 0.36 to 0.71) were significantly associated with the lack of prescription of anticoagulation to eligible patients. In Spain, most patients with atrial fibrillation treated in EDs who do not receive anticoagulation are at high risk of stroke, with relevant differences with regard to the risk stratification scheme used. Anticoagulation is underused, mainly because the risk of stroke is underestimated by the treating physicians and the benefits of antiplatelets are overrated, principally in female patients and the elderly. Efforts to increase the prescription of anticoagulation in these patients appear warranted. | 25,182,543 | [
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Effects of melatonin on changes in cognitive performances and brain malondialdehyde concentration induced by sub-chronic co-administration of chlorpyrifos and cypermethrin in male Wister rats. | To evaluate the ameliorative effect of melatonin on sub-chronic chlorpyrifos (CPF) and cypermethrin (CYP)-evoked cognitive changes in male Wistar rats. Fifty adult male Wistar rats, divided into five groups of ten rats each, were used for the study. Groups 1 and II were given distilled water and soya oil (2 mL/kg) respectively. Group III was administered with melatonin at 0.5 mg/kg only. Group IV was administered with CPF [7.96 mg/kg (1/10th LD50)] and CYP [29.6 mg/kg (1/10th LD50)], and Group V was administered with CPF [7.96 mg/kg (1/10th LD50)] and CYP [29.6 mg/kg (1/10th LD50)] 30 min after melatonin (0.5 mg/kg). The regimens were administered by gavage once daily for 12 weeks. Thereafter, cognitive performances were determined and the brain was evaluated for malonaldehyde concentration. CPF and CYP induced cognitive deficits and increased brain malonaldehyde concentration, which were all ameliorated by melatonin. Cognitive deficits elicited by CPF and CYP was mitigated by melatonin due to its antioxidant property. | 25,182,558 | [
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Design, synthesis and evaluation of novel HDAC inhibitors as potential antitumor agents. | Phenyl imidazolidin-2-one was introduced as the linker for novel HDAC inhibitors. A focused library of 20 compounds was designed and synthesized, among which eight compounds showed equivalent or higher potencies against HDAC1 as compared to vorinostat. In vitro antitumor activity assays in HCT-116, PC-3 and HL-60 cancer cells revealed six compounds with potent antitumor activities, and compound 1o showed 6- to 9-fold higher potencies compared to vorinostat. In an HCT-116 nude mice xenograft model, compound 1o displayed significant antitumor activity in both continuous and intermittent dosing schedules. | 25,182,565 | [
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A likelihood-based biostatistical model for analyzing consumer movement in simultaneous choice experiments. | Consumer feeding preference among resource choices has critical implications for basic ecological and evolutionary processes, and can be highly relevant to applied problems such as ecological risk assessment and invasion biology. Within consumer choice experiments, also known as feeding preference or cafeteria experiments, measures of relative consumption and measures of consumer movement can provide distinct and complementary insights into the strength, causes, and consequences of preference. Despite the distinct value of inferring preference from measures of consumer movement, rigorous and biologically relevant analytical methods are lacking. We describe a simple, likelihood-based, biostatistical model for analyzing the transient dynamics of consumer movement in a paired-choice experiment. With experimental data consisting of repeated discrete measures of consumer location, the model can be used to estimate constant consumer attraction and leaving rates for two food choices, and differences in choice-specific attraction and leaving rates can be tested using model selection. The model enables calculation of transient and equilibrial probabilities of consumer-resource association, which could be incorporated into larger scale movement models. We explore the effect of experimental design on parameter estimation through stochastic simulation and describe methods to check that data meet model assumptions. Using a dataset of modest sample size, we illustrate the use of the model to draw inferences on consumer preference as well as underlying behavioral mechanisms. Finally, we include a user's guide and computer code scripts in R to facilitate use of the model by other researchers. | 25,182,616 | [
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Assessing probability of malignancy in solid solitary pulmonary nodules with a new Bayesian calculator: improving diagnostic accuracy by means of expanded and updated features. | A crucial point in the work-up of a solitary pulmonary nodule (SPN) is to accurately characterise the lesion on the basis of imaging and clinical data available. We introduce a new Bayesian calculator as a tool to assess and grade SPN risk of malignancy. A set of 343 consecutive biopsy or interval proven SPNs was used to develop a calculator to predict SPN probability of malignancy. The model was validated on the study population in a "round-robin" fashion and compared with results obtained from current models described in literature. In our case series, receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.893 for the proposed model and 0.795 for its best competitor, which was the Gurney calculator. Using observational thresholds of 5% and 10% our model returned fewer false-negative results, while showing constant superiority in avoiding false-positive results for each surgical threshold tested. The main downside of the proposed calculator was a slightly higher proportion of indeterminate SPNs. We believe the proposed model to be an important update of current Bayesian analysis of SPNs, and to allow for better discrimination between malignancies and benign entities on the basis of clinical and imaging data. • Bayesian analysis can help characterise solitary pulmonary nodules • Volume doubling time (VDT) is a good predictor of malignancy • A VDT of between 25 and 400 days is highly suggestive of malignancy • Nodule size, enhancement, morphology and VDT are the best predictors of malignancy. | 25,182,626 | [
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A population pharmacokinetic modeling approach shows that serum penicillin G concentrations are below inhibitory concentrations by two weeks after benzathine penicillin G injection in the majority of young adults. | Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of >0.02 mg/liter, a proposed protective threshold against group A Streptococcus pyogenes (GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of >0.02 mg/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of >0.02 mg/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks. | 25,182,635 | [
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Ramoplanin at bactericidal concentrations induces bacterial membrane depolarization in Staphylococcus aureus. | Ramoplanin is an actinomycetes-derived antibiotic with broad-spectrum activity against Gram-positive bacteria that has been evaluated in clinical trials for the treatment of gastrointestinal vancomycin-resistant enterococci (VRE) and Clostridium difficile infections. Recent studies have proposed that ramoplanin binds to bacterial membranes as a C2 symmetrical dimer that can sequester Lipid II, which causes inhibition of cell wall peptidoglycan biosynthesis and cell death. In this study, ramoplanin was shown to bind to anionic and zwitterionic membrane mimetics with a higher affinity for anionic membranes and to induce membrane depolarization of methicillin-susceptible Staphylococcus aureus (MSSA) ATCC 25923 at concentrations at or above the minimal bactericidal concentration (MBC). The ultrastructural effects of ramoplanin on S. aureus were also examined by transmission electron microscopy (TEM), and this showed dramatic changes to bacterial cell morphology. The correlation observed between membrane depolarization and bacterial cell viability suggests that this mechanism may contribute to the bactericidal activity of ramoplanin. | 25,182,650 | [
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Prognostic impact of splenomegaly on survival of Chinese with primary myelofibrosis. | Predicting survival in persons with primary myelofibrosis (PMF) is typically based on the International Prognostic Scoring System (IPSS), the Dynamic IPSS (DIPSS) or the DIPSS-Plus. These scoring systems use clinical and laboratory data developed predominately in persons of European descent. Splenomegaly is not a prognostic variable in any of these scoring systems. Recently, we reported differences in clinical and laboratory features between Chinese vs. persons of European descent with PMF. Based on this we developed a modified prognostic model to predict survival of Chinese subjects in which splenomegaly is an independent favorable prognostic factor. In the current study, we analyzed data from 874 Chinese with PMF including 495 with splenomegaly. Subjects with splenomegaly had significantly higher hemoglobin concentrations (P<0.001), higher levels of WBCs (P<0.001), platelets (P<0.001), excess blood blasts (≥ 1%; P=0.012), less RBC-transfusion-dependence (P<0.001) and lower DIPSS risk distribution (P=0.024). Frequency of JAK2(V617F) (62% vs. 50%; P=0.003) was also different. In univariate analyses subjects without splenomegaly had briefer survival (median, 64 mo [95% CI, 43-85] vs. 110 mo [95% CI, 67-153]; P<0.001). In multivariate analyses, splenomegaly was a favorable prognostic correlate of survival independent of DIPSS risk-cohort (hazard ratio [HR]=1.445; [95% CI, 1.101-1.895]; P=0.008). Our data suggest including splenomegaly improves the predictive accuracy of the prognostic model to estimate survival of Chinese with PMF. | 25,182,689 | [
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Antibacterial properties of lucifensin in Lucilia sericata maggots after septic injury. | To investigate the antibacterial properties of lucifensin in maggots of Lucilia sericata after septic injury. In our preliminary study we have shown that injuring the maggots with a needle soaked in lipopolysaccharide solution induced within 24 h lucifensin expression in the fat body and in the grease coupler of the salivary glands. It is assumed that lucifensin is secreted solely from this tissue into the haemolymph (similar to other insect defensins) and not into secreted/excreted products. We used high-performance liquid chromatography fractionation and radial diffusion assay to investigate the antibacterial properties of haemolymph extracted from larvae after septic injury. After septic injury, production of lucifensin in the haemolymph is increased. This led to higher antibacterial activity of such haemolymph in comparison to non-stimulated larvae. These results suggest that beside the previously demonstrated role of lucifensin in the debridement therapy, lucifensin is simultaneously important as a part of the systematic immune response. | 25,182,719 | [
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Tamarind seed coat extract restores reactive oxygen species through attenuation of glutathione level and antioxidant enzyme expression in human skin fibroblasts in response to oxidative stress. | To investigate the role and mechanism of tamarind seed coat extract (TSCE) on normal human skin fibroblast CCD-1064Sk cells under normal and oxidative stress conditions induced by hydrogen peroxide (H2O2). Tamarind seed coats were extracted with boiling water and then partitioned with ethyl acetate before the cell analysis. Effect of TSCE on intracellular reactive oxygen species (ROS), glutathione (GSH) level, antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activity including antioxidant protein expression was investigated. TSCE significantly attenuated intracellular ROS in the absence and presence of H2O2 by increasing GSH level. In the absence of H2O2, TSCE significantly enhanced SOD and catalase activity but did not affected on GPx. Meanwhile, TSCE significantly increased the protein expression of SOD and GPx in H2O2-treated cells. TSCE exhibited antioxidant activities by scavenging ROS, attenuating GSH level that could protect human skin fibroblast cells from oxidative stress. Our results highlight the antioxidant mechanism of tamarind seed coat through an antioxidant enzyme system, the extract potentially benefits for health food and cosmeceutical application of tamarind seed coat. | 25,182,723 | [
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Antisickling activity of butyl stearate isolated from Ocimum basilicum (Lamiaceae). | To perform phytochemical analyses on the leaves of Ocimum basilicum L. (O. basilicum), to elucidate the structure of isolate and then perform the antisickling activity on the crude extract and on the isolate. The Emmel test performed on the acidified methanolic extract of this plant was used to evaluate the antisickling activity. The structure characterization of the active compound was performed using chromatographic techniques for the separation and the spectroscopic ones for structure elucidation (1H-NMR, 13C-NMR, COSY, HMBC). The chemical screening on the crude extract revealed the presence of polyphenols (flavonoids, anthocyanins, leucoanthocyanins, tannins, quinones) alkaloids, saponins, triterpenoids and steroids. The obtained extract after evaporation yielded 34.50 g (11.5%) out of 300 g of powdered leaves of O. basilicum. The acidified methanolic extract and butyl stearate showed an interesting antisickling activity. The acidified methanolic extract and butyl stearate from O. basilicum displayed a good antisickling activity. To the best of our knowledge, this is the first time to report the antisickling activity of this compound in this plant. The synthesized compound presented the same spectroscopic characteristics than the natural one and the antisickling activities of its derivatives are understudying. | 25,182,725 | [
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In vivo NIRF imaging-guided delivery of a novel NGR-VEGI fusion protein for targeting tumor vasculature. | Pathological angiogenesis is crucial in tumor growth, invasion and metastasis. Previous studies demonstrated that the vascular endothelial growth inhibitor (VEGI), a member of the tumor necrosis factor superfamily, can be used as a potent endogenous inhibitor of tumor angiogenesis. Molecular probes containing the asparagine-glycine-arginine (NGR) sequence can specifically bind to CD13 receptor which is overexpressed on neovasculature and several tumor cells. Near-infrared fluorescence (NIRF) optical imaging for targeting tumor vasculature offers a noninvasive method for early detection of tumor angiogenesis and efficient monitoring of response to anti-tumor vasculature therapy. The aim of this study was to develop a new NIRF imaging probe on the basis of an NGR-VEGI protein for the visualization of tumor vasculature. The NGR-VEGI fusion protein was prepared from prokaryotic expression, and its function was characterized in vitro. The NGR-VEGI protein was then labeled with a Cy5.5 fluorophore to afford Cy5.5-NGR-VEGI probe. Using the NIRF imaging technique, we visualized and quantified the specific delivery of Cy5.5-NGR-VEGI protein to subcutaneous HT-1080 fibrosarcoma tumors in mouse xenografts. The Cy5.5-NGR-VEGI probe exhibited rapid HT-1080 tumor targeting, and highest tumor-to-background contrast at 8 h post-injection (pi). Tumor specificity of Cy5.5-NGR-VEGI was confirmed by effective blocking of tumor uptake in the presence of unlabeled NGR-VEGI (20 mg/kg). Ex vivo NIRF imaging further confirmed in vivo imaging findings, demonstrating that Cy5.5-NGR-VEGI displayed an excellent tumor-to-muscle ratio (18.93 ± 2.88) at 8 h pi for the non-blocking group and significantly reduced ratio (4.92 ± 0.75) for the blocking group. In conclusion, Cy5.5-NGR-VEGI provided highly sensitive, target-specific, and longitudinal imaging of HT-1080 tumors. As a novel theranostic protein, Cy5.5-NGR-VEGI has the potential to improve cancer treatment by targeting tumor vasculature. | 25,182,731 | [
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Pulse wave velocity as a marker of cognitive impairment in the elderly. | Carotid-femoral pulse wave velocity (PWV), an index of large artery stiffness, is a good proxy of arterial aging and also an independent marker of cardiovascular disease. A consistently growing number of studies has shown a significant inverse association of arterial aging and cognitive function: the greater the PWV, the lower the cognitive performance (and the greater its decline over time)-regardless of heterogeneity in study populations, sample size, and measure of cognitive functions adopted in each study. Therefore the epidemiological evidence and the biological plausibility require adoption of strategies to foster the routine measurement of PWV and cognitive function measurements in each and every older subject, particularly those at higher cardiovascular risk. Consistently, limited available healthcare resources should be progressively shifted from a sterile differential diagnosis between Alzheimer-type and vascular dementia to interventions aimed to reduce PWV and, thus, to prevent dementia before its onset or to decrease its rate of progression. | 25,182,740 | [
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I716F AβPP mutation associates with the deposition of oligomeric pyroglutamate amyloid-β and α-synucleinopathy with Lewy bodies. | Autosomal dominant familial Alzheimer's disease (AD) is associated with mutations in the AβPP, PSEN1, and PSEN2 genes. The clinical phenotype associated with AβPP mutations is mainly characterized by dementia or by strokes related to cerebral amyloid angiopathy (CAA). We present a comprehensive clinical, neuropathological, genetic, and biochemical study on a patient affected by familial AD associated with the I716F mutation in the AβPP gene. The clinical phenotype was characterized by early age of onset of 47 years, and rapidly progressive cerebellar ataxia, myoclonic jerks, rigidity, and dementia reminiscent of Creutzfeldt-Jakob disease (CJD), followed by a prolonged persistent vegetative state. Neuropathological evaluation of the proband revealed AD-related pathology but also α-synucleinopathy compatible with dementia with Lewy bodies neocortical stage or Parkinson's disease corresponding to Braak stage 6. Tau-pathology in the form of neurofibrillary degeneration corresponded to stage VI according to the Braak classification. The severe Aβ pathology included CAA, numerous plaques, and deposition of N-truncated pyroglutamate-modified Aβ peptides. Remarkably, pyroglutamate Aβ oligomers were also present intracellularly in Purkinje cells corresponding to the ataxic phenotype. The detection of a CJD-like phenotype expands the spectrum of clinical presentations associated with familial AD. Our study supports the concept that the neuropathology of familial AD expands beyond the classical AD-related pathology as defined by plaques and tangles. Finally, we provide evidence for the first time that oligomeric pyroglutamate Aβ is present in a specific pattern correlating with the clinical symptoms of a patient with AβPP I716F mutation. | 25,182,745 | [
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Mouse monoclonal antibodies against estrogen receptor. | The production of monoclonal antibodies, by cloning hybridoma derived from the fusion of myeloma cells and spleen lymphocytes, has allowed to obtain great advances in many fields of biological knowledge. The use of specific antibodies to the estrogen receptor, in fact, has been an invaluable method to bring out its mechanisms of action and its effects, both genomic and extra-genomic. Here we describe, step by step, the production of monoclonal antibodies, starting from protocol for antigen preparation to the selection of antibody-secreting hybridoma. | 25,182,770 | [
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[Serum levels and clinical significance of high mobility group protein B1 in patients with delayed encephalopathy after acute carbon monoxide poisoning]. | To investigate the changes in serum level of high mobility group protein B1 (HMGB1) in patients with delayed encephalopathy after acute carbon monoxide poisoning and the clinical significance of these changes. Thirty-four patients with delayed encephalopathy after acute carbon monoxide poisoning (delayed encephalopathy group), 30 normal controls (control group), and 32 cases of acute carbon monoxide poisoning without delayed encephalopathy (carbon monoxide poisoning group) were recruited in this study. The serum HMGB1 level was determined by enzyme-linked immunosorbent assay. The correlation between serum HMGB1 level and scores of the activity of daily living scale (ADL), Information-Memory-Concentration Test (IMCT), and Hasegawa dementia scale (HDS) was determined. In the acute stage of carbon monoxide poisoning, the serum HMGB1 level of delayed encephalopathy group was significantly higher than those of the carbon monoxide poisoning group and the control group (P < 0.01). In the delayed encephalopathy group, serum HMGB1 level in the convalescent stage was significantly lower than that in the acute stage (P < 0.05); ADL score was higher and HDS and IMCT scores were lower in the acute stage than in the convalescent stage (P < 0.01). In the delayed encephalopathy group, serum HMGB1 level was positively correlated with HDS and ADL scores in both acute stage and convalescent stage (correlation coefficients: 0.612, 0.607, 0.609, and 0.612, P < 0.01). HMGB1, as an important late mediator of inflammation, is involved in the inflammatory reaction in delayed encephalopathy, and is positively correlated with HDS and ADL scores, indicating that it can be used as one of the major indicators in monitoring carbon monoxide poisoning. | 25,182,828 | [
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Fibrinogen and factor XIII at the intersection of coagulation, fibrinolysis and inflammation. | Fibrinogen and factor XIII are two essential proteins that are involved directly in fibrin gel formation as the final step of a sequence of reactions triggered by a procoagulant stimulus. Haemostasis is the most obvious function of the resulting fibrin clot. Different variables affect the conversion of fibrinogen to fibrin as well as the mode of fibrin polymerisation and fibrin crosslinking, hereby, critically influencing the architecture of the resulting fibrin network and consequently determining its mechanical strength and resistance against fibrinolysis. Due to fibrinogen's structure with a multitude of domains and binding motifs the fibrin gel allows for complex interactions with other coagulation factors, with profibrinolytic as well as antifibrinolyic proteins, with complement factors and with various cellular receptors. These interactions enable the fibrin network to control its own further state (i. e. expansion or degradation), to influence innate immunity, and to function as a scaffold for cell migration processes. During the whole process of fibrin gel formation biologically active peptides and protein fragments are released that additionally influence cellular processes via chemotaxis or by modulating cell-cell interactions. Thus, it is not surprising that fibrinogen and factor XIII in addition to their haemostatic function influence innate immunity as well as cell-mediated reactions like wound healing, response to tissue injury or inflammatory processes. The present review summarises current knowledge of fibrinogen's and factor XIII's function in coagulation and fibrinolysis giving special emphasis on their relation to inflammation control. | 25,182,841 | [
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Pericentral retinopathy and racial differences in hydroxychloroquine toxicity. | To describe patterns of hydroxychloroquine retinopathy distinct from the classic parafoveal (bull's eye) maculopathy. Retrospective case series. Patients from a large multi-provider group practice and a smaller university referral practice diagnosed with hydroxychloroquine retinopathy. Patients with widespread or "end-stage" retinopathy were excluded. Review of ophthalmic studies (fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, multifocal electroretinography, visual fields) and classification of retinopathy into 1 of 3 patterns: parafoveal (retinal changes 2°-6° from the fovea), pericentral (retinal changes ≥ 8° from the fovea), or mixed (retinal changes in both parafoveal and pericentral areas). Relative frequency of different patterns of hydroxychloroquine retinopathy and comparison of risk factors. Of 201 total patients (18% Asian) with hydroxychloroquine retinopathy, 153 (76%) had typical parafoveal changes, 24 (12%) also had a zone of pericentral damage, and 24 (12%) had pericentral retinopathy without any parafoveal damage. Pericentral retinopathy alone was seen in 50% of Asian patients but only in 2% of white patients. Patients with the pericentral pattern were taking hydroxychloroquine for a somewhat longer duration (19.5 vs. 15.0 years, P < 0.01) and took a larger cumulative dose (2186 vs. 1813 g, P = 0.02) than patients with the parafoveal pattern, but they were diagnosed at a more severe stage of toxicity. Hydroxychloroquine retinopathy does not always develop in a parafoveal (bull's eye) pattern, and a pericentral pattern of damage is especially prevalent among Asian patients. Screening practices may need to be adjusted to recognize pericentral and parafoveal hydroxychloroquine retinopathy. | 25,182,842 | [
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A point of care test for the determination of amniotic fluid interleukin-6 and the chemokine CXCL-10/IP-10. | Intra-amniotic inflammation is a mechanism of disease implicated in preterm labor, preterm prelabor rupture of membrane, cervical insufficiency, a short cervix, and idiopathic vaginal bleeding. Determination of interleukin (IL)-6 with immunoassays has been proven for more than two decades to be an excellent method for the detection of intra-amniotic inflammation. However, assessment of IL-6 for this indication has been based on immunoassays which are not clinically available, and this has been an obstacle for the implementation of this test in clinical practice. It is now possible to obtain results within 20 min with a point of care (POC) test which requires minimal laboratory support. This test is based on lateral flow-based immunoassay. The objective of this study was to compare amniotic fluid (AF) IL-6 and interferon-γ - inducible protein 10 (IP-10 or CXCL-10) concentrations determined using lateral flow-based immunoassay or POC test and standard enzyme-linked immunosorbent assay (ELISA) techniques. AF samples were collected from patients with singleton gestations and symptoms of preterm labor (n = 20). AF IL-6 and IP-10 concentrations were determined by lateral flow-based immunoassay and ELISA. Intra-amniotic inflammation was defined as AF IL-6 ≥ 2.6 ng/ml. AF IL-6 and IP-10 concentrations between two assays were compared. (1) Lateral flow-based immunoassay POC AF IL-6 and IP-10 test results were strongly correlated with concentrations of this cytokine/chemokine determined by ELISA (Spearman's ρ = 0.92 and 0.83, respectively, both p < 0.0001); (2) AF IL-6 concentrations determined by the lateral flow-based immunoassay test were, on average, 30% lower than those determined by ELISA, and the median difference was statistically significant (p < 0.0001); and (3) in contrast, AF IP-10 concentrations determined by the lateral flow-based immunoassay test were, on average, only 7% lower than those determined by ELISA, and the median difference was not statistically significant (p = 0.81). AF IL-6 and IP-10 concentrations determined using a lateral flow-based immunoassay POC are strongly correlated with concentrations determined by conventional ELISA. This justifies further studies about the diagnostic indices and predictive values of this POC test. | 25,182,862 | [
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The efficacy of risk scores for predicting abdominal wound dehiscence: a case-controlled validation study. | The medical literature includes two risk scores predicting the occurrence of abdominal wound dehiscence. These risk indices were validated by the authors on the populations studied. However, whether these scoring systems can accurately predict, abdominal wound dehiscence in other populations remains unclear. A retrospective analysis was performed using the medical records of patients treated at a tertiary-care teaching hospital between 2008 and 2011. Patients that underwent laparotomy procedures complicated by the development of postoperative abdominal wound dehiscence were included into the study. For each of the cases, three controls were selected. Among the 1,879 patients undergoing intra-abdominal, 56 patients developed wound dehiscence and 168 patients included in the control group. Calculation of risk scores for all patients, revealed significantly higher scores in the abdominal wound dehiscence group (p < 0.001). The median score was 24 (range: 3-46) and 4.95 (range: 2.2-7.8) vs.10 (range:-3-45) and 3.1 (range:0.4-6.9), for the Veterans Affairs Medical Center (VAMC) and Rotterdam abdominal wound dehiscence risk score in the dehiscence and control groups, respectively. The area under the curve, on the ROC plot, was 0.84 and 0.76; this confirmed a good and moderate predictive value for the risk scores. The fit of the model was good in both cases, as shown by the Hosmer and Lemeshow test. Both the VAMC and Rotterdam scores can be used for the prediction of abdominal wound dehiscence. However, the VAMC prognostic score had better calibration and discriminative power when applied to the population in this study and taking into consideration our method of control selection. | 25,182,865 | [
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Mobile van drives up to screen TB. | Specialist tuberculosis (TB) nurses have been providing chest X-rays, blood testing and education for homeless people from a mobile van. | 25,182,884 | [
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Waterlogged app. | Set up a daily goal of how much water you would like to drink to stay hydrated and this excellent app will keep track of your intake and do all the arithmetic for you. | 25,182,911 | [
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The problem of obesity in the NHS all comes down to cost. | Well done to NHS England chief executive Simon Stevens for speaking up about the sensitive issue of obese nurses and the need for NHS staff to be healthy advocates (Analysis August 13, Editorial and Letters August 20 and Wright Angle August 27). | 25,182,916 | [
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Rugged and breathable forms of stretchable electronics with adherent composite substrates for transcutaneous monitoring. | Research in stretchable electronics involves fundamental scientific topics relevant to applications with importance in human healthcare. Despite significant progress in active components, routes to mechanically robust construction are lacking. Here, we introduce materials and composite designs for thin, breathable, soft electronics that can adhere strongly to the skin, with the ability to be applied and removed hundreds of times without damaging the devices or the skin, even in regions with substantial topography and coverage of hair. The approach combines thin, ultralow modulus, cellular silicone materials with elastic, strain-limiting fabrics, to yield a compliant but rugged platform for stretchable electronics. Theoretical and experimental studies highlight the mechanics of adhesion and elastic deformation. Demonstrations include cutaneous optical, electrical and radio frequency sensors for measuring hydration state, electrophysiological activity, pulse and cerebral oximetry. Multipoint monitoring of a subject in an advanced driving simulator provides a practical example. | 25,182,939 | [
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Target contact and exploration strategies in haptic search. | In a haptic search task, one has to detect the presence of a target among distractors using the sense of touch. A salient target can be detected faster than a non-salient target. However, little is known about the exploration strategies that are used, especially in 3D search tasks where items are held in the hand. In this study, we investigated which parts of the hand were used to contact the target and which strategies were performed. Blindfolded participants performed search tasks in four conditions, where the targets differed in relevant property and saliency. The positions of the target and the hand were tracked during exploration. It was found that target saliency had a large effect on the use of the hand parts and the strategies. In the non-salient target conditions, the fingers, especially the thumb, contacted the target more often than in the salient target conditions. This could also be seen in the strategies, where the thumb was used to explore the items in a serial way by moving them in the hand or touching them individually. In the salient target conditions, more parallel strategies like grasping or shuffling of the items in the hand were used. | 25,182,940 | [
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A retrospective evaluation of the quality of malaria case management at twelve health facilities in four districts in Zambia. | To establish the appropriateness of malaria case management at health facility level in four districts in Zambia. This study was a retrospective evaluation of the quality of malaria case management at health facilities in four districts conveniently sampled to represent both urban and rural settings in different epidemiological zones and health facility coverage. The review period was from January to December 2008. The sample included twelve lower level health facilities from four districts. The Pearson Chi-square test was used to identify characteristics which affected the quality of case management. Out of 4 891 suspected malaria cases recorded at the 12 health facilities, more than 80% of the patients had a temperature taken to establish their fever status. About 67% (CI 95 66.1-68.7) were tested for parasitemia by either rapid diagnostic test or microscopy, whereas the remaining 22.5% (CI 95 21.3.1-23.7) were not subjected to any malaria test. Of the 2 247 malaria cases reported (complicated and uncomplicated), 71% were parasitologically confirmed while 29% were clinically diagnosed (unconfirmed). About 56% (CI 95 53.9-58.1) of the malaria cases reported were treated with artemether-lumefantrine (AL), 35% (CI 95 33.1-37.0) with sulphadoxine-pyrimethamine, 8% (CI 95 6.9-9.2) with quinine and 1% did not receive any anti-malarial. Approximately 30% of patients WHO were found negative for malaria parasites were still prescribed an anti-malarial, contrary to the guidelines. There were marked inter-district variations in the proportion of patients in WHOm a diagnostic tool was used, and in the choice of anti-malarials for the treatment of malaria confirmed cases. Association between health worker characteristics and quality of case malaria management showed that nurses performed better than environmental health technicians and clinical officers on the decision whether to use the rapid diagnostic test or not. Gender, in service training on malaria, years of residence in the district and length of service of the health worker at the facility were not associated with diagnostic and treatment choices. Malaria case management was characterised by poor adherence to treatment guidelines. The non-adherence was mainly in terms of: inconsistent use of confirmatory tests (rapid diagnostic test or microscopy) for malaria; prescribing anti-malarials which are not recommended (e.g. sulphadoxine-pyrimethamine) and prescribing anti-malarials to cases testing negative. Innovative approaches are required to improve health worker adherence to diagnosis and treatment guidelines. | 25,182,953 | [
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KIT and BRAF heterogeneous mutations in gastrointestinal stromal tumors after secondary imatinib resistance. | Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the digestive tract and characterized by expression of KIT protein. Imatinib is the frontline therapy for metastatic and unresectable GIST patients showing clinical responses in 80 % of cases. Despite the often long-lasting clinical benefit seen in most patients treated with imatinib, many will eventually suffer disease progression. The most frequent mechanism of imatinib resistance in GIST is the acquisition of secondary mutations in either KIT or PDGFRA. There are also some imatinib-resistant GIST patients lacking an identifiable mechanism of treatment failure. Recently, activating BRAF mutation was detected in a small percentage of GISTs. In this study, we report a case of GIST with acquired resistance to imatinib during therapy. Histological, immunohistochemical, Western blot and mutational analyses were performed on GIST tissues before and after imatinib resistance. The imatinib-resistant tumor showed not only heterogeneous mutations of KIT and BRAF besides the primary mutation, but also transdifferentiation into a rhabdomyosarcoma phenotype. According to Western blot analysis, in imatinib-resistant GIST with both KIT V559D and BRAF V600E mutations, the inhibition of KIT V559D by imatinib caused a strong decrease of AKT phosphorylation, while ERK1/2 phosphorylation was not affected. This finding, in combination with the loss of KIT expression, suggests the possibility of activation of RAS-RAF-MEK-ERK pathways driven by a KIT-independent oncogenic mechanism. Understanding the genetic aberrations beyond KIT and PDGFRA may lead to the identification of additional therapeutic targets for GISTs. | 25,182,956 | [
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Prevalence of the BLM nonsense mutation, p.Q548X, in ovarian cancer patients from Central and Eastern Europe. | A nonsense mutation, p.Q548X, in the BLM gene has recently been associated with an increased risk for breast cancer. In the present work, we investigated the prevalence of this Slavic founder mutation in 2,561 ovarian cancer cases from Russia, Belarus, Poland, Lithuania or Germany and compared its frequency with 6,205 ethnically matched healthy female controls. The p.Q548X allele was present in nine ovarian cancer patients of Slavic ancestry (0.5 %; including one case with concurrent BRCA1 mutation). The mutation was not significantly more frequent in cases than in controls (Mantel-Haenszel OR 1.14, 95 % CI 0.49; 2.67). Ovarian tumours in p.Q548X carriers were mainly of the serous subtype, and there was little evidence for an early age at diagnosis or pronounced family history of cancer. These findings indicate that the BLM p.Q548X mutation is not a strong risk factor for ovarian cancer. | 25,182,961 | [
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GMO quantification: valuable experience and insights for the future. | Cultivation and marketing of genetically modified organisms (GMOs) have been unevenly adopted worldwide. To facilitate international trade and to provide information to consumers, labelling requirements have been set up in many countries. Quantitative real-time polymerase chain reaction (qPCR) is currently the method of choice for detection, identification and quantification of GMOs. This has been critically assessed and the requirements for the method performance have been set. Nevertheless, there are challenges that should still be highlighted, such as measuring the quantity and quality of DNA, and determining the qPCR efficiency, possible sequence mismatches, characteristics of taxon-specific genes and appropriate units of measurement, as these remain potential sources of measurement uncertainty. To overcome these problems and to cope with the continuous increase in the number and variety of GMOs, new approaches are needed. Statistical strategies of quantification have already been proposed and expanded with the development of digital PCR. The first attempts have been made to use new generation sequencing also for quantitative purposes, although accurate quantification of the contents of GMOs using this technology is still a challenge for the future, and especially for mixed samples. New approaches are needed also for the quantification of stacks, and for potential quantification of organisms produced by new plant breeding techniques. | 25,182,968 | [
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Biogenesis of lysosome-related organelles complex-1 subunit 1 (BLOS1) interacts with sorting nexin 2 and the endosomal sorting complex required for transport-I (ESCRT-I) component TSG101 to mediate the sorting of epidermal growth factor receptor into endosomal compartments. | Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a component of the molecular machinery required for the biogenesis of specialized organelles and lysosomal targeting of cargoes via the endosomal to lysosomal trafficking pathway. BLOS1, one subunit of BLOC-1, is implicated in lysosomal trafficking of membrane proteins. We found that the degradation and trafficking of epidermal growth factor receptor (EGFR) were delayed in BLOS1 knockdown cells, which were rescued through BLOS1 overexpression. A key feature to the delayed EGFR degradation is the accumulation of endolysosomes in BLOS1 knockdown cells or BLOS1 knock-out mouse embryonic fibroblasts. BLOS1 interacted with SNX2 (a retromer subunit) and TSG101 (an endosomal sorting complex required for transport subunit-I) to mediate EGFR lysosomal trafficking. These results suggest that coordination of the endolysosomal trafficking proteins is important for proper targeting of EGFR to lysosomes. | 25,183,008 | [
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MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression. | Derangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. | 25,183,011 | [
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Complications from catheter ablation of atrial fibrillation: impact of current and emerging ablation technologies. | Catheter ablation has emerged as an important therapy for atrial fibrillation. The past decade has seen tremendous growth in the use of this technology, as well as the use of novel sources and methods of energy delivery. As the volume and complexity of catheter ablation procedures for atrial fibrillation have increased, our understanding of the range of procedural complications has also grown. Thromboembolic events, esophageal injury, and phrenic nerve palsy represent some of the potential complications of atrial fibrillation ablation that remain challenging to prevent and manage. In this review, we discuss the strategies for the diagnosis, prevention, and treatment of complications from catheter ablation of atrial fibrillation. Rapid recognition and treatment of these complications are critical for the improvement of patient outcomes. | 25,183,020 | [
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Individual and joint toxic effects of cadmium sulfate and α-naphthoflavone on the development of zebrafish embryo. | This paper aims to evaluate the individual and joint toxicities of cadmium sulfate (CdSO4) and α-naphthoflavone (ANF) in zebrafish embryos. As a result, CdSO4 caused both lethal and sub-lethal effects, such as 24 h post-fertilization (hpf) death and 72 hpf delayed hatching. However, ANF only caused sub-lethal effects, including 48 hpf cardiac edema and 72 hpf delayed hatching. Taking 24 hpf death and 48 hpf cardiac edema as endpoints, the toxicities of CdSO4 and ANF were significantly enhanced by each other. Consistently, both CdSO4 and ANF caused significant oxidative stress, including decreases in the reduced glutathione (GSH) level, inhibition of superoxide dismutase (SOD) activity, as well as increases in malondialdehyde (MDA) content in zebrafish embryos, but these mixtures produced much more significant alterations on the biomarkers. Co-treatment of CdSO4 and ANF significantly down-regulated the mRNA level of multidrug resistance-associated protein (mrp) 1 and cytochrome P450 (cyp) 1a, which constituted the protective mechanisms for zebrafish embryos to chemical toxins. In conclusion, co-treatment of CdSO4 and ANF exhibited a much more severe damage in zebrafish embryos than individual treatment. Meanwhile, production of oxidative stress and altered expression of mrp1 and cyp1a could be important components of such joint toxicity. | 25,183,031 | [
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A novel variant in TBX20 (p.D176N) identified by whole-exome sequencing in combination with a congenital heart disease related gene filter is associated with familial atrial septal defect. | Congenital heart disease (CHD) is the leading cause of birth defects, and its etiology is not completely understood. Atrial septal defect (ASD) is one of the most common defects of CHD. Previous studies have demonstrated that mutations in the transcription factor T-box 20 (TBX20) contribute to congenital ASD. Whole-exome sequencing in combination with a CHD-related gene filter was used to detect a family of three generations with ASD. A novel TBX20 mutation, c.526G>A (p.D176N), was identified and co-segregated in all affected members in this family. This mutation was predicted to be deleterious by bioinformatics programs (SIFT, Polyphen2, and MutationTaster). This mutation was also not presented in the current Single Nucleotide Polymorphism Database (dbSNP) or National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP). In conclusion, our finding expands the spectrum of TBX20 mutations and provides additional support that TBX20 plays important roles in cardiac development. Our study also provided a new and cost-effective analysis strategy for the genetic study in small CHD pedigree. | 25,183,037 | [
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TGF-beta induced RBL2 expression in renal cancer cells by down-regulating miR-93. | TGF-beta can induce G1 arrest via many mechanisms including up-regulating p21, p27, and Rb. However, as the member of Rb family, whether RBL2 is induced by TGF-beta treatment remains exclusive. The expression of RBL2 and miR-93 after TGF-beta treatment was determined by quantitative real-time PCR and western blot. The growth of renal cancer cells was determined by CCK-8 assays and cell cycle was determined by PI staining. The binding of miR-93 on RBL2 3'-UTR was determined by double luciferase system. In renal cancer cells, TGF-beta treatment induced expression of RBL2 in a time- and concentration-dependent manner, and RBL2 mediated TGF-beta induced growth inhibition and cell cycle arrest in renal cancer cells. Furthermore, we found that miR-93 directly targeted RBL2 by binding to its 3'-UTR in renal cancer cells. Over-expression of miR-93 significantly reduced the expression of RBL2, whereas knock down of miR-93 up-regulated the expression of RBL2. More importantly, TGF-beta treatment inhibited miR-93 expression, which resulted in up-regulation of RBL2 after TGF-beta treatment. TGF-beta induced RBL2 expression through down-regulating miR-93 in renal cancer cells. The newly identified TGF-beta/miR-93/RBL2 signal pathway reveals a new mechanism of TGF-beta induced growth arrest in renal cancer. | 25,183,046 | [
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Pattern, challenges and correlates of condom use among Nigerians living with HIV infection. | To determine the pattern, challenges and correlates of condom use among Nigerians living with HIV Infection. A cross sectional questionnaire study among HIV positive adults attending an HIV treatment centre in Lagos, Nigeria. Data entry and analysis were done with Epi-info version 3.5.1. The mean age of respondents was 35 (SD=7.7; range: 17-58 years) and mean age at sexual debut was 20 years old (range: 7-37 years). Majority were women (66.6%), had at least secondary school education(91.1%), married (68.2%)), on ART (50.7%) and knew their partners HIV status(60.9%). The rate of condom use at last sex act was 65.9%, but only 48.8% used condom consistently. Factors associated with condom use were male gender (OR=2.43, CI=1.35-4.33, P=0.002), less than secondary school education (OR=3.12, CI=1.04-9.28, P=0.05) and Not knowing partner's HIV status (OR=1.90, CI=1.04-3.80, P=0.04). Refusal to use condom (28.4%) were as a result of pregnancy intention, undesirability of condom in marriage and decreased sexual pleasure. There is low consistent condom use rate of 48.8% among this cohort despite their exposure to behavioural change messages. A review of the present counselling strategy and combination prevention is therefore advocated. | 25,183,080 | [
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Ethno botanical and Phytophrmacological potential of Abrus precatorius L.: A review. | Medicinal plants are being widely used, either as a single drug or in combination in health care delivery system. Medicinal plants can be important source of previously unknown chemical substances with potential therapeutic effects. Abrus precatorius L. is commonly known as Gunja or Jequirity and abundantly found all throughout the plains of India, from Himalaya down to Southern India and Ceylon. This plant is having medicinal potential to cure various diseases. The roots, leaves and seeds of this plant are used for different medicinal purpose. It principally contains flavonoids, triterpene glycosides, abrin and alkaloids. The plant have been reported for neuromuscular effects, neuro-protective, abortifacient, antiepileptic, anti-viral, anti-malarial, antifertility, nephroprotective, immunomodulator, immunostimulatory properties, anti-inflammatory activity, antidiabetic effect, etc. As this is a potential medicinal plant, present review reveals chemical constituents of leaf, root and seeds of Abrus precatorius. The plant is considered as a valuable source of unique natural products for development of medicines against various diseases and also for the development of industrial products. | 25,183,095 | [
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Studies on the antibacterial activity of Khaya senegalensis [(Desr.) A. Juss)] stem bark extract on Salmonella enterica subsp. enterica serovar Typhi [(ex Kauffmann and Edwards) Le Minor and Popoff]. | To study the phytochemical screening and antibacterial activity of the stem bark extracts of Khaya senegalensis (K. senegalensis) against Salmonella enterica subsp. enterica serovar Typhi. The plant components were extracted using methanol, ethanol and water. The phytochemical screening of the stem bark extracts were carried out using a standard method. The antibacterial assay of the stem bark extracts against Salmonella Typhi (S. Typhi) using the agar well diffusion method with different concentrations of 50, 100, 200, 400 and 500 mg/mL and the corresponding concentrations of the control was carried out and the result compared with a standard antibiotic, amoxicillin as the control. The results obtained from the phytochemical screening of the three plant bark extracts of K. senegalensis showed 10 plant secondary metabolites including saponins, tannins, reducing sugars, aldehyde, phlobatannins, flavonoids, terpenoids, alkaloids, cardiac glycoside and anthroquinones. The ethanol and aqueous extracts showed antibacterial activities against S. Typhi at concentration of 50 mg/mL with the zone diameter of inhibition (ZDI) of 14 mm and 15 mm respectively. The ethanol and aqueous extracts also showed zone diameter of inhibition of 23 mm and 25 mm respectively at 250 mg/mL and 27 mm each at 500 mg/mL. The ethanol and aqueous stem bark extracts gave the highest ZDI at 500 mg/mL while 100 mg/mL gave the least ZDI for ethanol extract and 50 mg/mL for the aqueous extract. This was followed by 400 mg/mL that gave 24 mm ZDI of the aqueous extract and 27 mm of the ethanol extract. The methanol extract showed intermediate susceptibility evidenced by ZDI of 10 mm at 100 mg/mL concentration. The methanol extract also showed antibacterial activity of 24 mm ZDI against the test organism at a higher concentration of 250 mg/mL and 26 mm at 500 mg/mL concentration. The methanol, ethanol and aqueous extracts displayed antibacterial activities against S. Typhi with a statistical significant difference at (P≤0.05). The extracts compared favourably with the standard antibiotic, the control. The minimum inhibitory concentration of the extracts was 250, 200, 200 and 100 mg/mL for methanol, ethanol, aqueous extracts and amoxicillin (control) respectively. The minimum lethal concentration of the extracts was 250, 250, 400 and 200 mg/mL for methanol, ethanol, aqueous extracts and control respectively. The antibacterial properties of K. senegalensis stem bark extract can be harnessed for the production of new antibiotics or the enhancement of already existing antibiotics. | 25,183,098 | [
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Microbiological quality of indoor air in university libraries. | To evaluate the concentration of bacteria and fungi in the indoor environment of Jimma University libraries, so as to estimate the health hazard and to create standards for indoor air quality control. The microbial quality of indoor air of eight libraries of Jimma University was determined. The settle plate method using open Petri-dishes containing different culture media was employed to collect sample twice daily. Isolates were identified according to standard methods. The concentrations of bacteria and fungi aerosols in the indoor environment of the university libraries ranged between 367-2595 CFU/m(3). According to the sanitary standards classification of European Commission, almost all the libraries indoor air of Jimma University was heavily contaminated with bacteria and fungi. In spite of their major source difference, the average fungi density found in the indoor air of libraries did appear to follow the same trend with bacterial density (P=0.001). The bacteria isolates included Micrococcus sp., Staphylococcus aureus, Streptococcus pyogenes, Bacillus sp. and Neisseria sp. while Cladosporium sp., Alternaria sp., Penicillium sp. and Aspergillus sp. were the most isolated fungi. The indoor air of all libraries were in the range above highly contaminated according to European Commission classification and the most isolates are considered as potential candidates involved in the establishment of sick building syndromes and often associated with clinical manifestations like allergy, rhinitis, asthma and conjunctivitis. Thus, attention must be given to control those environmental factors which favor the growth and multiplication of microbes in indoor environment of libraries to safeguard the health of users and workers. | 25,183,103 | [
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Production, purification and characterization of bacteriocin from Lactobacillus murinus AU06 and its broad antibacterial spectrum. | To study the production, purification and characterization of bacteriocin from Lactobacillus murinus AU06 isolated from marine sediments and its broad spectrum of inhibition against fish pathogens. The selected strain was used in production, purification and characterized of bacteriocin. In addition, purified bacteriocin was tested for its antimicrobial activity against fish pathogens. In the present study, the bacteriocin production was found to be higher at 35 °C, pH 6.0 and was purified to 4.74 fold with 55. 38 U/mg of specific activity with the yield of 28.92%. The molecular weight of the purified bacteriocin was estimated as 21 kDa. The purified bacteriocin exhibited complete inactivation of antimicrobial activity when treated with proteinase K, pronase, chymotrypsin, trypsin, pepsin and papain. The purified bacteriocin exhibited broad inhibitory spectrum against both Gram positive and negative bacteria. It is concluded that the ability of bacteriocin in inhibiting a wide-range of pathogenic bacteria is of potential interest for food safety and may have future applications in food preservative. | 25,183,102 | [
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Antioxidant and anti-acetylcholinesterase activities of extracts and secondary metabolites from Acacia cyanophylla. | To investigate the antioxidant potential and anti-acetycholinesterase activity of compounds and extracts from Acacia cyanophylla (A. cyanophylla). Three polyphenolic compounds were isolated from ethyl acetate extract of A. cyanophylla flowers. They have been identified as isosalipurposide 1, quercetin 2 and naringenin 3. Their structures were elucidated by extensive spectroscopic methods including 1D and 2D NMR experiments as well as ES-MS. The prepared extracts and the isolated compounds 1-3 were tested for their antioxidant activity using 1'-1'-diphenylpicrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays and reducing power. They have been also investigated for inhibitory effect against acetylcholinesterase using the microplate assay. In the DPPH test, the EtOAc extract of flowers exhibited the highest antioxidant effect (67.26 µg/mL). Isosalipurposide 1 showed a significant antiradical power against DPPH (81.9 µg/mL). All extracts showed a dose-dependent acetylcholinesterase inhibition. In terms of the IC50 value, the butanolic extract (16.03 µg/mL) was the most potent sample. Isosalipurposide 1 was found to be active against AChE with an IC50 value of 52.04 µg/mL. The results demonstrated the important antioxidant and anti-acetylcholinesterase activity of pure compounds and extracts from A. cyanophylla. | 25,183,120 | [
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Evaluation of plasma H2S levels and H2S synthesis in streptozotocin induced Type-2 diabetes-an experimental study based on Swietenia macrophylla seeds. | To evaluate the plasma H2S levels and H2S synthesis activity in streptozotocin induced type 2 diabetes rats compared to the healthy controls and also to observe the effect of the aqueous extract of Swietenia macrophylla (S. macrophylla) seeds on the experimental groups. Seeds of S. macrophylla were separated, washed, shed-dried and finally extract was prepared. Thirty two wistar rats were selected for the experimental study. Streptozotocin was used for the induction of diabetes. H2S concentration in plasma was measured. H2S synthesizing activity in plasma was measured. Statistical analysis have done using Microsoft excel, Office 2003. Values were expressed by mean±SD. P<0.05 were considered statistically significant. Fasting blood glucose level (7.74±0.02) mmol/L was significantly increased in diabetic rats. The glucose levels are significantly lowered in the rats treated with metformin (5.48±0.03) mmol/L as well as with aqueous extract of S. macrophylla seeds (3.72±0.04) mmol/L. The HbA1c percentages in different groups of study subjects also indicate similar trends. Our study shows both the plasma H2S levels (22.07±0.73) mmol/L and plasma H2S synthesis activity (0.411±0.005 mmol/100 g) are significantly reduced in the streptozotocin induced diabetic rats. Although considering a small sample size, it can conclude that the fasting blood glucose levels are inversely related to plasma H2S levels as well as H2S synthesis activity in plasma and the extract of S. macrophylla is associated with increased plasma H2S levels with effective lowering of blood glucose in streptozotocin induced diabetic rats. | 25,183,134 | [
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Antibacterial activity of the essential oils of myrtle leaves against Erysipelothrix rhusiopathiae. | To evaluate the antibacterial activity of the essential oil of Myrtus communis (M. communis) L. against Erysipelothrix rhusiopathiae (E. rhusiopathiae) in vitro. Wild populations of M. communis collected from Khuzestan and Lorestan provinces, Southwest Iran, were examined for antibacterial activity and chemical variability in leaves. The in vitro antibacterial activity against E. rhusiopathiae was performed by agar disc diffusion and micro-dilution assays. The essential oils of M. communis have strong antibacterial against E. rhusiopathiae in both assays. The results showed that the major components of the oil were α-pinene (22.3%-55.2%), 1,8-cineole (8.7%-43.8%) and linalool (6.4%-14.5%). The inhibition zones and MIC values for bacteria which were sensitive to the essential oils of M. communis were in the range of 14.7-27.0 mm and 0.031-0.25 mg/mL, respectively. This study demonstrates that products with valuable antibacterial activity can be produced from leaves of M. communis against E. rhusiopathiae. | 25,183,140 | [
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-... |
Urinary excretion of N-nitroso compounds in rats fed sodium nitrite and/or hot dogs. | Nitrite-treated meat is a reported risk factor for colon cancer. Mice that ingested sodium nitrite (NaNO2) or hot dogs (a nitrite-treated product) showed increased fecal excretion of apparent N-nitroso compounds (ANC). Here, we investigated for the first time whether rats excrete increased amounts of ANC in their urine after they are fed NaNO2 and/or hot dogs. Rats were treated for 7 days with NaNO2 in drinking water or were fed hot dogs. Their 24 h urine samples were analyzed for ANC by thermal energy analysis on days 1-4 after nitrite or hot dog treatment was stopped. For two rats fed 480 mg NaNO2/L drinking water, mean urinary ANC excretion on days 1-4 was 30, 5.2, 2.5, and 0.8 nmol/day, respectively. For two to eight rats/dose given varied NaNO2 doses, mean urinary ANC output on day 1 increased from 0.9 (for no nitrite) to 37 (for 1000 mg NaNO2/L drinking water) nmol ANC/day. Urine samples of four rats fed 40-60% hot dogs contained 12-13 nmol ANC on day 1. Linear regression analysis showed highly significant correlations between urinary ANC excretion on day 1 after stopping treatment and varied (a) NaNO2 level in drinking water for rats fed semipurified or commercials diet and (b) hot dog levels in the diet. Some correlations remained significant up to 4 days after nitrite treatment was stopped. Urinary output of ANC precursors (compounds that yield ANC after mild nitrosation) for rats fed semipurified or commercial diet was 11-17 or 23-48 μmol/day, respectively. Nitrosothiols and iron nitrosyls were not detected in urinary ANC and ANCP. Excretion of urinary ANC was about 60% of fecal ANC excretion for 1 to 2 days after NaNO2 was fed. Administered NaNO2 was not excreted unchanged in rat urine. We conclude that urinary ANC excretion in humans could usefully be surveyed to indicate exposure to N-nitroso compounds. | 25,183,213 | [
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0.2748005,
-0.1209647... |
Cosmetic lower limb lengthening by Ilizarov apparatus: what are the risks? | Compelled by the psychosocial implications of short stature, patients with short stature are increasingly undergoing distraction osteogenesis for cosmetic limb lengthening. To the degree that this is true, evaluation of the risks and benefits of this treatment are very important, but to date, there are few studies reporting on using distraction osteogenesis for this indication. We reviewed a group of patients undergoing cosmetic lower-extremity lengthening in terms of (1) soft tissue challenges, (2) bone-related complications, and (3) functional and subjective clinical outcomes. The study was retrospective by reviewing data from medical records and radiographs. Between 1983 and 2006, we treated 138 somatically normal patients with bilateral lower-limb distraction osteogenesis for cosmetic purposes at our center using an Ilizarov external fixator, of whom 131 (95%; 65 males, 66 females) had complete clinical and radiographic data a minimum of 1 year after treatment (mean, 6 years; range, 1-14 years) and were reviewed for this report. The mean age of these patients was 25 years (range, 14-68 years) and their mean preoperative height was 159 cm (range, 130-174 cm). One hundred twenty-four (95%) patients had lengthening of the tibia alone, of which 66 (53%) were monofocal and 58 (47%) were bifocal. Six patients (4.58%) had crossed contralateral lengthening of the femur and tibia and one patient (0.76%) had bilateral lengthening of the femur. The mean height gained was 6.9 cm (range, 2-13 cm), 7.3 cm (range, 3.5-13 cm) in males and 6.5 cm (range, 2-13 cm) in females. The mean lengthening, maturation, and external fixator indexes were 12 days/cm (range, 4.3-24 days/cm), 19 days/cm (range, 5.2-63 days/cm), and 31 days/cm (range, 12-78 days/cm), respectively. Forty-eight patients (37%) had 59 complications related to treatment. Thirty-seven were soft tissue related (28%), of which 17 (46%) needed reinterventions, and 22 were bone related (17%), of which 16 (73%) needed reinterventions. At final followup, the outcome was excellent for 72 patients (55%), good for 52 (40%), satisfactory for six (4.58%), and poor for one (0.77%). One hundred thirty of 131 patients subjectively felt satisfied and had improved self-esteem. Distraction osteogenesis using the Ilizarov external fixator is an option for carefully selected motivated patients with awareness of this technique. Soft tissue and bone-related complications including those that necessitate reinterventions should be expected during the course of treatment, although most can be managed without permanent sequelae or disability. Future studies with more robust methods will need to determine whether the risks and benefits of this procedure are well balanced. Preoperative counseling, considering the ethical questions this procedure can raise, is of paramount importance for the patient to weigh the risk versus anticipated benefits. Studies from other centers will be important as we move forward. Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence. | 25,183,215 | [
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Impact of treatment on survival in polymyositis and dermatomyositis. A single-centre long-term follow-up study. | To assess the long-term outcome in polymyositis (PM) and dermatomyositis (DM), with a particular emphasis on mortality and influence of treatment. Diagnosis was based according to the Bohan and Peter's criteria. Patients have been followed up by a standardised protocol. Deaths were registered and causes of death were ascertained. Survival probability at 5 and 10years was estimated according to the Kaplan-Meier method, in the overall series and by a diagnostic group and an initial treatment. Mortality hazard ratios (95% CI) for major clinical and demographic features were estimated through univariate and multivariate Cox proportional hazard models. 91 patients (43 PM and 48 DM) were available for the study. Baseline characteristics were not different from those previously reported. Twenty-two patients (24%) died after a median follow-up of 8.7years. As for idiopathic myositis, the survival probabilities at 5 and 10years from the diagnosis were 96.2% and 88.8% for PM respectively; and 93.9% for DM, whereas a higher mortality was documented for cancer-associated myositis and overlap myositis. Male sex [HR=2.4, 95% CI 1.0 to 5.6], heart involvement (HR=1.8), interstitial lung disease (HR=2.3) and arthritis (HR=1.8) increased the risk of mortality, these risk excesses were confirmed in the multivariate analysis. Independent of these features, a higher mortality was documented for patients treated with glucocorticoids (HR=2.3) or immunosuppressants (HR=2.1) when compared to patients treated with immunoglobulins. Our study, with longitudinal and statistical analyses, suggests that survival has considerably increased in patients with PM/DM. Prognostic factors for mortality are male sex, and heart and lung involvement. Immunoglobulin treatment, intravenously or subcutaneously, is associated with a better survival. | 25,183,232 | [
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0.2840082,
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... |
Adaptable synthesis of C-lactosyl glycoclusters and their binding properties with galectin-3. | We report here the syntheses of mono- to tetravalent glycoclusters containing 1-methylene-C-β-lactose. The 1-methylene-C-β-lactose moiety has been synthesized from octa-acetyl-β-lactose using the key carbonyl insertion reaction and linked to a series of alkynlated scaffolds via CuAAC reaction to afford mono- to tetravalent glycoclusters. The binding affinities of the final products to galectin-3 were found in the range of 10-100 μM. | 25,183,239 | [
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0.04155244,
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0.3637308,
0.1060772,
-0.259253,
0.02646... |
Microfluidic platform for the quantitative analysis of leukocyte migration signatures. | Leukocyte migration into tissues is characteristic of inflammation. It is usually measured in vitro as the average displacement of populations of cells towards a chemokine gradient, not acknowledging other patterns of cell migration. Here, we designed and validated a microfluidic migration platform to simultaneously analyse four qualitative migration patterns: chemoattraction, -repulsion, -kinesis and -inhibition, using single-cell quantitative metrics of direction, speed, persistence and fraction of cells responding. We find that established chemokines, complement component 5a and IL-8 induce chemoattraction and repulsion in equal proportions, resulting in the dispersal of cells. These migration signatures are characterized by high persistence and speed and are independent of the chemokine dose or receptor expression. Furthermore, we find that twice as many T lymphocytes migrate away than towards stromal cell-derived factor 1 and their directional migration patterns are not persistent. Overall, our platform helps discover migratory signature responses and uncovers an avenue for precise characterization of leukocyte migration and therapeutic modulators. | 25,183,261 | [
0.1164782,
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0.03668202,
0.2167626,
0.08256111,
... |
Cytotoxicity screening of Melastoma malabathricum extracts on human breast cancer cell lines in vitro. | To screen the cytotoxic activity of Melastoma malabathricum (M. malabathricum) against human breast cancer cell line (MCF-7) in vitro. A three steps extraction protocol using n-hexane, chloroform and methanol as the solvents systems was carried out on leaves, stems and flowers of M. malabathricum. Dimethyl sulfoxide was used in extracts dilution and serial dilutions were conducted to obtain five different extract concentrations (100 µg/mL, 50 µg/mL, 25 µg/mL, 12.5 µg/mL and 6.25 µg/mL). The evaluation of cell growth was determined using methylene blue assay. Methanol extract from the leaves showed significant anticancer activity against MCF-7 cell lines with the IC50 value of 7.14 µg/ml while methanol and chloroform extract from the flowers exhibited a moderate activity towards MCF-7 cell line with the IC50 value of 33.63 µg/mL and 45.76 µg/mL respectively after 72 h of treatment. The extracts from leaves and flowers of M. malabathricum showed promising anticancer activity toward human breast cancer cell lines with the lowest IC50 at 7.14 µg/mL while the extracts from stems showed less growth inhibition activity. | 25,183,274 | [
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Modified technique of Wolbachia removal from Malaysian Aedes albopictus. | To develop an artificial and modified Wolbachia removal technique using tetracycline from naturally Wolbachia infected Aedes albopictus (Ae. albopictus) so as to be able to produce generations of Wolbachia free offsprings. In this study, seven different tetracycline treatment methods were conducted to obtain the best removal method. Four methods focused on larvae tetracycline treatment, one method on both larvae and adult tetracycline treatment and the last two methods on adult mosquito sucrose treatment. All larval tetracycline treatments resulted in either high larvae mortality, sterile F0 adult mosquitoes or unsuccessful Wolbachia removal. Treatment of both larvae and adults resulted in reduced larvae mortality, successful Wolbachia removal but slow mosquito fecundity. As for the adult treatment, 1.0 mg/mL as previously published was not able to completely remove Wolbachia in F1 generation whereas 1.25 mg/mL successfully removed Wolbachia from F1 and F2 mosquitoes in 2 weeks. This method is different from the previously published methods as it provides an improved Wolbachia removal technique from Ae. albopictus with high egg hatchability, low larvae mortality, increased fecundity and better Wolbachia removal rate. | 25,183,276 | [
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-0.01339387,
-0.2691853,
... |
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