A light harvesting perylene derivative - zinc phthalocyanine complex in water: spectroscopic and thermodynamic studies.
A perylene derivative, namely N,N'-bis(2(trimethylammonium iodide)ethylene)perylene-3,4,9,10-tetracarboxyldiimide (TAIPDI) forms nanoscale columnar stacks in water that have been characterized by using optical absorption and emission measurements, dynamic light scattering (DLS), and transmission electron microscopy (TEM). This behaviour was compared with that of unstacked TAIPDI in methanol. Assembly formation between the one-dimensional TAIPDI stacks and zinc phthalocyanine tetrasulphonic groups (ZnPcS4) via strong π-π and ionic interactions has been described in an aqueous medium. The formation constant of the supramolecular dyad has been determined as 2.94 × 104 M-1 from both the absorption and fluorescence measurements. Upon addition of ZnPcS4, the fluorescence quenching of the singlet-excited state of TAIPDI was observed because of the electron transfer process from ZnPcS4 to TAIPDI via the singlet-excited states of ZnPcS4 and TAIPDI entities. The electrochemical studies supported the electron transfer pathways via the singlet states of ZnPcS4 and TAIPDI. The thermodynamic parameters of the supramolecular complex have been determined from stopped-flow measurements. The interaction between ZnPcS4 and TAIPDI occurs in two steps, where the rate constant of the second step with TAIPDI (207 ± 8 M-1 s-1) is much slower than the first one (3515 ± 101 M-1 s-1). Activation parameters for the complex formation (ΔH# = 76 ± 11 kJ mol-1 and ΔS# = 83 ± 37 J K-1 mol-1, and ΔH# = 221 ± 15 kJ mol-1 and ΔS# = 540 ± 50 J K-1 mol-1) were determined from variable temperature studies for the first and second steps, respectively. The significantly positive ΔS# values found for both steps of the interaction reactions are consistent with a dissociative mechanism.


Activating enhancer-binding protein-2β nucleolar localization predicts poor survival after stage I non-small cell lung cancer resection.
Activating enhancer-binding protein-2β (AP2β) is a transcription factor involved in apoptosis. The purpose of the current study was to assess the cellular location and level of AP2β in non-small cell lung cancer (NSCLC) and normal lung tissue and investigate whether the level and localization of AP2β expression is predictive of overall survival in patients with stage I NSCLC. We performed immunohistochemical analysis of tissue microarrays (TMAs) prepared from stage I NSCLC specimens with adjacent normal lung tissue from two independent sets of patients who underwent lung resection with curative intent at our institution. The AP2β intensity was assessed in TMAs, and AP2β staining patterns were classified as either diffuse or nucleolar in the TMAs. The AP2β intensity and localization were analyzed for correlation with patients' survival. Immunohistochemical analysis of TMAs showed that the intensity of AP2β immunohistochemical staining did not correlate with overall survival. When location of AP2β was analyzed in TMAs, all of the normal lung tissue had diffuse pattern of AP2β. In the first set of NSCLC, patients with nucleolar pattern had a significantly lower 5-year survival rate than patients with diffuse pattern (67% versus 100%; p=0.004); this finding was confirmed in the second set (64% versus 91%; p=0.02). Multivariate analysis revealed that nucleolar pattern was an independent predictor of poor overall survival in both sets. The AP2β, which is located in the nucleoplasm in normal lung tissue, is found in either nucleoplasm or nucleoli in NSCLC. The patients with AP2β in the nucleoli had poor survival compared with patients with AP2β in the cytoplasm.


Signaling mechanisms involved in the acute effects of estradiol on 5-HT clearance.
Estradiol was found previously to have an antidepressant-like effect and to block the ability of selective serotonin reuptake inhibitors (SSRIs) to have an antidepressant-like effect. The antidepressant-like effect of estradiol was due to estrogen receptor β (ERβ) and/or GPR30 activation, whereas estradiol's blockade of the effect of an SSRI was mediated by ERα. This study focuses on investigating signaling pathways as well as interacting receptors associated with these two effects of estradiol. In vivo chronoamperometry was used to measure serotonin transporter (SERT) function. The effect of local application of estradiol or selective agonists for ERα (PPT) or ERβ (DPN) into the CA3 region of the hippocampus of ovariectomized (OVX) rats on 5-hydroxytryptamine (5-HT) clearance as well as on the ability of fluvoxamine to slow 5-HT clearance was examined after selective blockade of signaling pathways or that of interacting receptors. Estradiol- or DPN-induced slowing of 5-HT clearance mediated by ERβ was blocked after inhibition of MAPK/ERK1/2 but not of PI3K/Akt signaling pathways. This effect also involved interactions with TrkB, and IGF-1 receptors. Estradiol's or PPT's inhibition of the fluvoxamine-induced slowing of 5-HT clearance mediated by ERα, was blocked after inhibition of either MAPK/ERK1/2 or PI3K/Akt signaling pathways. This effect involved interactions with the IGF-1 receptor and with the metabotropic glutamate receptor 1, but not with TrkB. This study illustrates some of the signaling pathways required for the effects of estradiol on SERT function, and particularly shows that ER subtypes elicit different as well as common signaling pathways for their actions.


Vardenafil improves erectile function in men with erectile dysfunction and associated underlying conditions, irrespective of the use of concomitant medications.
Men with erectile dysfunction (ED) are also likely to have associated underlying conditions. This retrospective analysis evaluated the efficacy and safety of vardenafil in men with ED and underlying conditions, including those taking concomitant medications. A total of 13 randomized, double-blind, placebo-controlled clinical studies were included. Vardenafil was administered at a starting dose of 10 mg, adjustable to 5 or 20 mg after 4 weeks. Efficacy analyses were performed on the intent-to-treat (ITT) population, using a last observation carried forward approach. Efficacy was assessed for subgroups of patients with diabetes, hypertension, dyslipidemia, or metabolic syndrome (as defined by International Diabetes Federation criteria). Incidence rates of treatment-emergent adverse events were analyzed overall and by subgroup for patients in the safety population. Primary efficacy measures were the erectile function domain of the International Index of Erectile Function (IIEF-EF), and Sexual Encounter Profile questions 2 and 3 (SEP2, SEP3). In total, 4,326 patients were randomized to treatment; the ITT population included 4,143 patients, with 4,266 patients valid for safety. At 12 weeks, vardenafil therapy was associated with statistically significant improvements from baseline in IIEF-EF scores, and SEP2 and SEP3 success rates, including patients with ED and diabetes, hypertension, dyslipidemia, or metabolic syndrome. These improvements were irrespective of level of glycemic control, or use of concomitant medications for the treatment of diabetes, hypertension, or dyslipidemia. Across all subgroups, the number and type of treatment-emergent adverse events were consistent with results from previous studies of phosphodiesterase type 5 inhibitors in men with ED and underlying conditions. Vardenafil demonstrated favorable efficacy and tolerability in this large pool of patients with ED and underlying conditions. Importantly, the use of concomitant medications was not associated with any noteworthy changes in the efficacy or safety profile of vardenafil.


Risk stratification for wilms tumor: current approach and future directions.
Wilms tumor, or nephroblastoma, has provided a paradigm for progressive improvement in clinical outcomes achieved through serial cooperative group studies. With modern surgery, chemotherapy, and radiation therapy approaches, the overall survival rate for patients with Wilms tumor has reached 90%. Remarkably, the increase in survival has been achieved with a reduction in therapy for most patient subgroups, leading not only to more survivors, but also to healthier survivors. A key contributor to improved outcomes has been the development of clinical and biologic prognostic markers that have enabled risk-directed therapy. Whereas the early cooperative group studies used only tumor stage for risk stratification, current Children's Oncology Group (COG) and International Society of Pediatric Oncology (SIOP) protocols employ a multitude of prognostic factors to guide therapy. Prognostic factors used in the current generation of COG studies include stage, histology, patient age, tumor weight, completeness of lung nodule response, and loss of heterozygosity at chromosomes 1p and 16q. Future COG studies seek to incorporate gain of chromosome 1q and methylation pattern of chromosome 11p15 into the risk classification schema. Prognostic factors used in the current SIOP studies include stage, histology, tumor volume, and responsiveness to therapy. Future SIOP studies seek to incorporate absolute blastemal volume and novel molecular markers for resistant blastema into the risk stratification approach.


Development and validation of triarchic psychopathy scales from the Multidimensional Personality Questionnaire.
Psychopathy is conceptualized by the triarchic model as encompassing 3 distinct phenotypic constructs: boldness, meanness, and disinhibition. In the current study, the Multidimensional Personality Questionnaire (MPQ), a normal-range personality measure, was evaluated for representation of these 3 constructs. Consensus ratings were used to identify MPQ items most related to each triarchic (Tri) construct. Scale measures were developed from items indicative of each construct, and scores for these scales were evaluated for convergent and discriminant validity in community (N = 176) and incarcerated samples (N = 240). Across the 2 samples, MPQ-Tri scale scores demonstrated good internal consistencies and relationships with criterion measures of various types consistent with predictions based on the triarchic model. Findings are discussed in terms of their implications for further investigation of the triarchic model constructs in preexisting datasets that include the MPQ, in particular longitudinal and genetically informative datasets.


The Healthy Baby Flipbook: piloting home-based counseling for refugee mothers to improve infant feeding and water, sanitation, and hygiene (WASH) practices.
Problems in growth and undernutrition manifest in early infancy, with suboptimal breastfeeding and inadequate complementary feeding remaining strong risk factors for chronic undernutrition in infants. No published studies exist on educational interventions to improve infant feeding practices among refugees or displaced persons in low and middle-income (LMIC) settings. The objective of this study was to create and pilot educational materials for home-based counseling of refugee mothers along the Thailand-Myanmar border to improve appropriate infant feeding and water, sanitation, and hygiene (WASH) behaviors. Mothers of infants received counseling on appropriate infant feeding and WASH practices on a monthly basis for a total of six months from infant age three months until nine months. Educational materials were designed to feature a basic script for health workers and photos of locally available, appropriate foods. Of the 20 mothers participating in this pilot, infant feeding and WASH behaviors improved within 1 to 2 months of the first visit, including exclusive breastfeeding, minimum acceptable diet, and safe disposal of infant stool. This pilot demonstrates improvement in maternal infant feeding and WASH practices in a small set of refugee mothers, providing evidence for counseling measures to improve infant health in vulnerable populations.


Grey-scale inversion improves detection of lung nodules.
Objective The current study aims to establish whether detection of solitary pulmonary nodules can be improved by inverting the grey scale of posteroanterior (PA) chests. Methods 30 PA chest images were presented on 2 occasions to 16 senior radiologists on either primary or secondary class displays in the standard or inverted mode. 15 images within each group contained a single nodule positioned in a range of anatomical sites. A receiver operating characteristic (ROC) methodology was used to explore differences between the presentation modes. Results Improved ROC scores were evident with inverted (Az 0.77) compared with standard (Az 0.73) (p=0.02) images; however, this difference was seen only with the primary displays. The benefits seen are most likely owing to increased nodule luminance with the inverted images, particularly when using primary displays. Conclusion This study demonstrates that the inverted image can offer advantages in lung nodule detection over the standard presentation mode when images are viewed on high-specification viewing systems. The study has demonstrated that there is an improvement in the detectability of lung nodules on an inverted image with a primary display monitor that is not evident with secondary displays. This is likely to be the result of increased nodule luminance on primary displays when images are presented in the inverted mode.


Improving diagnosis and treatment of hypomagnesemia.
Magnesium is one of the most abundant cations in the body and acts as a cofactor in more than 600 biochemical reactions. Hypomagnesemia is a highly prevalent condition, especially in subjects with comorbid conditions, but has received less attention than other electrolyte disturbances. This review will discuss magnesium physiology, absorption, storage, distribution across the body, and kidney excretion. After reviewing the regulation of magnesium homeostasis, we will focus on the etiology and clinical presentation of hypomagnesemia. The role of laboratory medicine in hypomagnesemia will be the main purpose of this review, and we will discuss the laboratory tests and different samples and methods for its measurement. Although free magnesium is physiologically active, total serum magnesium is the most commonly used measurement in laboratory medicine and is apt for clinical purposes; however, it is not appropriately used, and many patients with hypomagnesemia remain undiagnosed and not treated. Using information technologies, laboratory medicine can largely improve the diagnosis and treatment of hypomagnesemia through the design and establishment of automatic demand management and result management interventions by acting in the first and last steps of the laboratory cycle, test requests, and actions taken after test results, to unmask patients with hypomagnesemia and improve the number of patients undergoing treatment.


Interactive effects of personality and perceptions of the work situation on workplace deviance.
Previous research on workplace deviance has examined the relationship of either personality or employees' situational perceptions with deviant behavior. In this study, the authors focused on the joint relationship of personality and perceptions of the work situation with deviant behavior. Using 4 samples of employees and multiple operationalizations of the core constructs, the authors found support for the hypothesis that positive perceptions of the work situation are negatively related to workplace deviance. In addition, consistent with hypotheses, the personality traits of conscientiousness, emotional stability, and agreeableness moderated this relationship. Specifically, the relationship between perceptions of the developmental environment and organizational deviance was stronger for employees low in conscientiousness or emotional stability, and the relationship between perceived organizational support and interpersonal deviance was stronger for employees low in agreeableness.


The relationship between parent-child conflict and adolescent antisocial behavior: confirming shared environmental mediation.
Prior studies have indicated that the relationship between parent-child conflict and adolescent antisocial behavior is at least partially shared environmental in origin. However, all available research on this topic (to our knowledge) relies exclusively on parent and/or adolescent informant-reports, both of which are subject to various forms of rater bias. As the presence of significant shared environmental effects has often been attributed to rater bias in the past (Baker et al. Journal of Abnormal Psychology 16:219-235, 2007; Bartels et al. Journal of the American Academy of Child and Adolescent Psychiatry 42:1351-1359, 2003, Twin Research 7:162-175, 2004; Hewitt et al. Behavior Genetics 22:293-317, 1992), it would be important to confirm that findings of shared environmental mediation persist when even examining (presumably more objective) observer-ratings of these constructs. The current study thus examined the origins of the relationship between parent-child conflict and adolescent acting-out behavior, as measured using both observer-ratings and various informant-reports. Participants included 1,199 adopted and non-adopted adolescents in 610 families from the Sibling Interaction and Behavior Study (SIBS). Results indicated that parent-child conflict consistently predicts acting-out behavior in adopted adolescents, and moreover, that this association is equivalent to that in biologically-related adolescents. Most importantly, these findings did not vary across parent- and adolescent-reported or observer-ratings of parent-child conflict and acting-out behavior. Such findings argue strongly against rater bias as a primary explanation of shared environmental mediation of the association between parent-child conflict and adolescent antisocial behavior.


The role of childhood adversity and prenatal mental health as psychosocial risk factors for adverse delivery and neonatal outcomes.
Exposure to adverse childhood experiences (ACEs) is a significant predictor for physical and mental health problems later in life, especially during the perinatal period. Prenatal common mental disorders (PCMDs) are well-established as a risk for obstetric interventions but knowledge on combined effects of multiple psychosocial risk factors is sparse. We aim to examine a comprehensive model of ACEs and PCMDs as risk factors for poor delivery and neonatal outcomes. With structural equation modeling, we examined direct and indirect pathways between psychosocial risk and delivery and neonatal outcomes in a prospective cohort from pregnancy to birth in Iceland. Exposure to ACEs increased risk of PCMDs [β = 0.538, p < .001, CI: 0.195-1.154] and preterm delivery [β = 0.768, p < .05, CI: 0.279-1.007)]. An indirect association was found between ACEs and increased risk of non-spontaneous delivery [β = 0.054, p < .05, CI: 0.004-0.152], mediated by PCMDs. Identical findings were observed for ACEs subcategories. ACEs are strong predictors for mental health problems during pregnancy. Both ACEs and PCMDs diagnosis are associated with operative delivery interventions and neonatal outcomes. Findings underscore the importance of identifying high-risk women and interventions aimed at decreasing psychosocial risk during the prenatal period.


[The judicialization of health in the Federal District of Brazil].
This paper seeks to analyze the Judiciary's approach with respect to demands for the judicialization of the right to health by means of a case study of civil lawsuits for access to health care in Brazil's Federal District. Judicialization of the right to health signifies the judicialization of various of the health services provided. This is a descriptive and exploratory case study that covers the Federal District and uses mixed techniques to gather and analyze data. This study analyzed 385 lawsuits (87% of the total number of cases of judicialization of health for the period from 2005 to 2010 that reached the Appellate court). The results indicate that the most judicialized service is access to intensive care unit, followed by drugs and health care. Almost all lawsuits are filed by public defenders, with medical prescriptions and recommendations from the public health service. The results of this study challenge some dominant themes in the national debate, particularly the claim that judicialization is a phenomenon of the elites and that the services judicialized are drugs. The study does not seek to make generalizations, but highlights the fact that the phenomenon of judicialization of health has different aspects encompassed under the same concept.


Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans.
Prospective studies in humans examining the effects of fructose consumption on biological markers associated with the development of metabolic syndrome are lacking. Therefore we investigated the relative effects of 10 wks of fructose or glucose consumption on plasma uric acid and RBP-4 concentrations, as well as liver enzyme (AST, ALT, and GGT) activities in men and women. As part of a parallel arm study, older (age 40-72), overweight and obese male and female subjects (BMI 25-35 kg/m2) consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 wks. Fasting and 24-h blood collections were performed at baseline and following 10 wks of intervention and plasma concentrations of uric acid, RBP-4 and liver enzyme activities were measured. Consumption of fructose, but not glucose, led to significant increases of 24-h uric acid profiles (P < 0.0001) and RBP-4 concentrations (P = 0.012), as well as plasma GGT activity (P = 0.04). Fasting plasma uric acid concentrations increased in both groups; however, the response was significantly greater in subjects consuming fructose (P = 0.002 for effect of sugar). Within the fructose group male subjects exhibited larger increases of RBP-4 levels than women (P = 0.024). These findings suggest that consumption of fructose at 25% of energy requirements for 10 wks, compared with isocaloric consumption of glucose, may contribute to the development of components of the metabolic syndrome by increasing circulating uric acid, GGT activity, suggesting alteration of hepatic function, and the production of RBP-4.


RV electrical activation in heart failure during right, left, and biventricular pacing.
To compare right ventricular (RV) activation during intrinsic conduction or pacing in heart failure (HF) patients. RV activation during intrinsic conduction or pacing in patients with left ventricular (LV) dysfunction is unclear but may affect the prognosis. In cardiac resynchronization therapy (CRT), timed LV pacing (CRT-LV) may be superior to biventricular pacing (CRT-BiV), and is hypothesized to be due to the merging of LV-paced and right bundle branch-mediated wavefronts, thus avoiding perturbation of RV electrical activation. Epicardial RV activation duration (RVAD) (onset to end of free wall activation) was evaluated noninvasively by electrocardiographic imaging in healthy control subjects (n = 7) and compared with that of HF patients (LV ejection fraction 23 +/- 10%, n = 14). RVAD in HF was contrasted during RV pacing, CRT-BiV, and CRT-LV at optimized AV intervals. During intrinsic conduction in HF (n = 12), the durations of QRS and precordial lead rS complexes were 158 +/- 24 and 77 +/- 17 ms, respectively, indicating delayed total ventricular depolarization but rapid initial myocardial activation. Echocardiography demonstrated no significant RV disease. RV epicardial voltage, activation patterns, and RVAD in HF did not differ from normal (RVAD 32 +/- 15 vs. 28 +/- 3 ms, respectively, p = 0.42). In HF, RV pacing generated variable areas of slow conduction and prolonged RVAD (78 +/- 33 ms, p < 0.001). RVAD remained delayed during CRT-BiV at optimized atrioventricular intervals (76 +/- 32 ms, p = 0.87). In contrast, CRT-LV reduced RVAD to 40 +/- 26 ms (p < 0.016), comparable to intrinsic conduction (p = 0.39) but not when atrioventricular conduction was poor or absent. In HF patients without RV dysfunction treated with CRT, normal RV free wall activation in intrinsic rhythm indicated normal right bundle branch-mediated depolarization. However, the RV was vulnerable to the development of activation delays during RV pacing, whether alone or with CRT-BiV. These were avoided by CRT-LV in patients with normal atrioventricular conduction.


Electron correlation effects in the photoionization of CO and isoelectronic diatomic molecules.
This paper investigates the first sigma satellite band, which is by far the most prominent, in the valence photoelectron spectra for a set of isoelectronic diatomic molecules: carbon monoxide, carbon monosulfide, carbon monoselenide, silicon monoxide and boron monofluoride. In particular, we analyze the effect of the electronic structure, with the change of the atomic pair along the row and column of the periodic table on the position of the satellite peak as well as on the related dynamical observables profiles. For this investigation, highly correlated calculations have been performed on the primary ionic states and the satellite band for all the molecules considered. Cross sections for the primary ionic states, calculated using Dyson orbitals, have been compared with those obtained with Hartree-Fock and Density Functional Theory to probe the impact of the correlation in the bound states on the photoionization observables. Limitations of a simple intensity borrowing mechanism clearly result from the analysis of the satellite state, characterized by different features with respect to the relevant primary states.


Effects of spontaneous breathing during airway pressure release ventilation on intestinal blood flow in experimental lung injury.
In critical illness, the gut is susceptible to hypoperfusion and hypoxia. Positive-pressure ventilation can affect systemic hemodynamics and regional blood flow distribution, with potentially deleterious effects on the intestinal circulation. The authors hypothesized that spontaneous breathing (SB) with airway pressure release ventilation (APRV) provides better systemic and intestinal blood flow than APRV without SB. Twelve pigs with oleic acid-induced lung injury received APRV with and without SB. When SB was abolished, either the tidal volume or the ventilator rate was increased to maintain pH and arterial carbon dioxide tension constant as compared to APRV with SB. Systemic hemodynamics were determined by double indicator dilution. Blood flow to the intestinal mucosa-submucosa and muscularis-serosa was measured using colored microspheres. Systemic blood flow increased during APRV with SB. During APRV with SB, mucosal-submucosal blood flow (ml. g-1. min-1) was 0.39 +/- 0.21 in the stomach, 0.76 +/- 0.35 in the duodenum, 0.71 +/- 0.35 in the jejunum, 0.71 +/- 0.59 in the ileum, and 0.63 +/- 0.21 in the colon. During APRV without SB and high tidal volumes, it decreased to 0.19 +/- 0.03 in the stomach, 0.42 +/- 0.21 in the duodenum, 0.37 +/- 0.10 in the jejunum, 0.3 +/- 0.14 in the ileum, and 0.41 +/- 0.14 in the colon (P < 0.001, respectively). During APRV without SB and low tidal volumes, the respective mucosal-submucosal blood flows decreased to 0.24 +/- 0.10 (P < 0.01), 0.54 +/- 0.21 (P < 0.05), 0.48 +/- 0.17 (P < 0.01), 0.43 +/- 0.21 (P < 0.01), and 0.50 +/- 0.17 (P < 0.001) as compared to APRV with SB. Muscularis-serosal perfusion decreased during full ventilatory support with high tidal volumes in comparison with APRV with SB. Maintaining SB during APRV was associated with better systemic and intestinal blood flows. Improvements were more pronounced in the mucosal-submucosal layer.


Treatment of acute thoracic aortic syndromes using endovascular techniques.
Acute thoracic aortic syndrome (ATAS) is a novel term to define emergency aortic conditions with common clinical features and challenges. Traditional management of ATAS includes surgical replacement of the aorta and is correlated with high perioperative mortality and morbidity. We aimed to evaluate our experience and outcomes in patients presenting with ATAS, managed by endovascular techniques. This cohort consisted of 31 consecutive patients (24 males; mean age, 57.5±13.81 years; range, 19-84 years) with acute thoracic aortic pathologies who underwent endovascular repair between January 2011 and January 2015. The study was designed as a retrospective analysis of prospectively maintained data. Complicated acute type-B aortic dissection was the most common pathology (35.5%). All aortic stent-grafts (n=37) and dissection stents (n=9) were implanted with 100% procedural success. The overall in-hospital mortality was 9.7%. The mean follow-up duration of patients who were alive at 30 days was 25.9±11.49 months (3-53 months). So far, there have been no late deaths after 30 days. In the high-risk setting of ATAS, endovascular procedures come forward as novel therapeutic strategies with promising results. Endovascular repair of ATAS can be considered as a first-line treatment alternative under emergency conditions with encouraging results, particularly when conventional surgical repair cannot be implemented due to prohibitive comorbidities.


Influence of oversizing on outcome in thoracic endovascular aortic repair.
To investigate the influence of stent-graft oversizing on device-related complications after thoracic endovascular aortic repair (TEVAR) for thoracic aortic aneurysm (TAA). The study cohort was composed of patients enrolled in 4 clinical trials of the TAG thoracic stent-graft. A total of 337 TAA patients (222 men; mean age 72 years) treated in these trials had sufficient data for analysis of oversizing and post-procedure mortality and complications, such as endoleak, migration, rupture, and reinterventions. Mean oversizing at the proximal landing zone was 14.6% (range -3.4% to 39.7%). Patients were stratified based on the percentage of oversizing: <10% (n=85, group 1), 10%-20% (n=188, group 2), and >20% (n=64, group 3). Patients in group 1 had significantly larger preoperative proximal aortic diameters (32.6 vs. 31.3 vs. 28.2 mm, respectively; p<0.001) and neck lengths (6.9 vs. 5.8 vs. 5.2 cm (p=0.035). Overall, type I endoleak was the most frequent complication during the first 30 days of follow-up (35, 10.4%), but the incidences did not differ among the 3 groups (10.6% vs. 11.2% vs. 7.8%, respectively; p=0.809). Over a mean follow-up of 41.8±20.7 months, there were no significant differences in the occurrence of device-related complications among the groups, though the incidence of type I endoleaks was lower in group 2 (9.4% vs. 3.2% vs. 7.8%, respectively; p=0.073). Cox proportional hazards modeling showed no difference in the time to type I endoleak among oversizing groups [group 1 vs. 2: HR 1.24, 95% CI 0.65 to 2.36 (p=0.509) and group 3 vs. 2: HR 1.24, 95% CI 0.60 to 2.60 (p=0.562)]. The percentage of oversizing did not significantly affect the incidence of device-related complications after TEVAR for TAA. Although oversizing may enhance the radial force and help maintain a good proximal seal, additional oversizing seemed not to improve the overall outcome in this analysis. The current guidelines regarding stent-graft oversizing for TAA seem appropriate, though the correct percentage remains to be determined.


Non-symmetrical double-logistic analysis of 24-h blood pressure recordings in normotensive and hypertensive rats.
To determine the suitability of a new logistic curve fitting procedure to measure the diurnal rates of transition from the active to the asleep periods separately. We applied this method to 24-h telemetry recordings of systolic, mean, diastolic arterial pressure (SAP, MAP, DAP, respectively), heart rate (HR) and locomotor activity of normotensive Sprague-Dawley rats (SDR) and spontaneously hypertensive rats (SHR). There was a similar pattern of higher awake and lower sleep values (16 +/- 1 mmHg SAP, 77 +/- 2 bpm HR and 40 +/- 2 units activity) in SHR. In SDR, awake-asleep differences were less for SAP (9 +/- 1 mmHg) but similar for HR (83 +/- 2 bpm). In SHR, while the blood pressure patterns were symmetrical, the rate of rise in activity and HR during arousal was more rapid than the rate of decline during the dark to light transition. By contrast in SDR, the arousal rate of increase in blood pressure and HR was much less than the rate of decline. Thus SHR have an exaggerated arousal surge in DAP compared with SDR. Double logistic provides a better fit than Cosinor or square wave and better estimates of day-night differences than partial Fourier. Analysis of 24-h recordings by a new logistic curve method reveals distinct asymmetric circadian patterns of cardiovascular and activity changes in rats. The greater surge in arousal blood pressure in SHR is not associated with differences in HR or activity changes and may be inherent to the underlying mechanisms contributing to the hypertension in SHR.


Evolution of L-1, 2-propanediol catabolism in Escherichia coli by recruitment of enzymes for L-fucose and L-lactate metabolism.
A mutant strain of Escherichia coli capable of growth on l-1,2-propanediol was isolated previously. The mutant is characterized by constitutive production of a propanediol:nicotinamide adenenine dinucleotide (NAD) oxidoreductase which is essential for the new growth property. In the present study, it is shown that phage P1 cotransduces the genetic locus conferring this property and the genes for the utilization of l-fucose. A further indication of a relationship between these two growth properties is provided by the observation that wild-type E. coli excretes propanediol during fermentation of l-fucose. Under these conditions, a propanediol dehydrogenase (lactaldehyde reductase) is induced. This enzyme migrates on diethylaminoethyl-cellulose with the propanediol dehydrogenase produced constitutively by the mutant strain. A key event in the establishment of the ability to grow on propanediol is evidently a shift in the expression and function of propanediol dehydrogenase; an enzyme catalyzing formation of a reduced fermentation product anaerobically in wild-type cells functions aerobically to oxidize this same product in the mutant. l-Lactaldehyde, which is thus derived from propanediol, is converted to l-lactate by another dehydrogenase (l-lactaldehyde:NAD oxidoreductase) which is constitutively produced by both wild-type and mutant cells. The normal function of this enzyme is not yet established. l-Lactate is converted to pyruvate by an inducible NAD-independent l-lactate dehydrogenase. Thus, the carbons of propanediol are brought into the central metabolic network of the cell.


AICAR induces Nrf2 activation by an AMPK-independent mechanism in hepatocarcinoma cells.
Hepatocellular carcinoma is one of the most frequent tumor types worldwide and oxidative stress represents a major risk factor in pathogenesis of liver diseases leading to HCC. Nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor activated by oxidative stress that governs the expression of many genes which constitute the antioxidant defenses of the cell. In addition, oxidative stress activates AMP-activated protein kinase (AMPK), which has emerged in recent years as a kinase that controls the redox-state of the cell. Since both AMPK and Nrf2 are involved in redox homeostasis, we investigated whether there was a crosstalk between the both signaling systems in hepatocarcinoma cells. Here, we demonstrated that AMPK activator AICAR, in contrary to the A769662 allosteric activator, induces Nrf2 activation and concomitantly modulates the basal redox state of the hepatocarcinoma cells. When the expression of Nrf2 is knocked down, AICAR failed to induce its effect on redox state. These data highlight a major role of Nrf2 signaling pathway in mediating the AICAR effect on basal oxidative state. Furthermore, we demonstrated that AICAR metabolization by the cell is required to induce Nrf2 activation while, the silencing of AMPK does not have any effect on Nrf2 activation. This suggests that AICAR-induced Nrf2 activation is independent of AMPK activity. In conclusion, we identified AICAR as a potent modulator of the redox state of human hepatocarcinoma cells, via the Nrf2 signaling pathway and in an AMPK-independent mechanism.


Passive and active middle ear implants.
Besides eradication of chronic middle ear disease, the reconstruction of the sound conduction apparatus is a major goal of modern ear microsurgery. The material of choice in cases of partial ossicular replacement prosthesis is the autogenous ossicle. In the event of more extensive destruction of the ossicular chain diverse alloplastic materials, e.g. metals, ceramics, plastics or composits are used for total reconstruction. Their specialised role in conducting sound energy within a half-open implant bed sets high demands on the biocompatibility as well as the acoustic-mechanic properties of the prosthesis. Recently, sophisticated titanium middle ear implants allowing individual adaptation to anatomical variations are widely used for this procedure. However, despite modern developments, hearing restoration with passive implants often faces its limitations due to tubal-middle-ear dysfunction. Here, implantable hearing aids, successfully used in cases of sensorineural hearing loss, offer a promising alternative. This article reviews the actual state of affairs of passive and active middle ear implants.


Manipulative interventions for reducing pulled elbow in young children.
Pulled elbow (nursemaid's elbow) is a common injury in young children. It often results from a sudden pull on the arm, usually by an adult or taller person, which pulls the radius through the annular ligament, resulting in subluxation (partial dislocation) of the radial head. It can also be caused by a fall or twist. The child experiences sudden acute pain and loss of function in the affected arm. Pulled elbow is usually treated by manual reduction of the subluxed radial head. Various manoeuvres can be applied; most commonly, supination of the forearm, often combined with flexion, and (hyper-)pronation. It is unclear which is most successful. This is an update of a Cochrane review first published in 2009 and last updated in 2011. To compare the effects (benefits and harms) of the different methods used to manipulate pulled elbow in young children. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, LILACS, PEDro, clinical trial registers and reference lists of articles. Date of last search: September 2016. Randomised or quasi-randomised controlled clinical trials evaluating manipulative interventions for pulled elbow were included. Our primary outcome was failure at the first attempt, necessitating further treatment. Two review authors independently evaluated trials for inclusion, assessed risk of bias, and extracted data. We pooled data using a fixed-effect model. Overall, nine trials with 906 children (all younger than seven years old and 58% of whom were female) were included, of which five trials were newly identified in this update. Eight trials were performed in emergency departments or ambulatory care centres, and one was performed in a tertiary paediatric orthopaedic unit. Four trials were conducted in the USA, three in Turkey, one in Iran, and one in Spain. Five trials were at high risk of selection bias because allocation was not concealed and all trials were at high risk of detection bias due to the lack of assessor blinding. Eight trials compared hyperpronation with supination-flexion. We found low-quality evidence that hyperpronation resulted in less failure at first attempt than supination-flexion (9.2% versus 26.4%, risk ratio (RR) 0.35; 95% confidence interval (CI) 0.25 to 0.50; 811 participants, 8 studies). Based on an illustrative risk of 268 failures at first attempt per 1000 children treated using supination-flexion, this amounted to 174 fewer failures per 1000 children treated using hyperpronation (95% CI 134 to 201 fewer). Based on risk differences data, we also estimated a number needed to treat of 6 (95% CI 5 to 8); this means that six children would need to be treated with the hyperpronation method rather than the supination-flexion method to avoid one additional failure at the first attempt.The very low-quality evidence (from four studies) for pain during or after manipulation means that it is uncertain whether there is or is not a difference between pronation and supination-flexion. There was very low-quality evidence from six studies that repeat pronation may be more effective than repeat supination-flexion for the second attempt after initial failure. The remaining outcomes were either not reported (adverse effects, recurrence) or unsuitable for pooling (ultimate failure). Ultimate failure, reported for the overall population only because of the differences in the study protocols with respect to what to do after the first attempt failed, ranged from no ultimate failures in two studies to six failures (4.1% of 148 episodes) in one study.One trial compared supination-extension versus supination-flexion. It provided very low-quality evidence (downgraded three levels for very serious risk of bias and serious imprecision) of no clear difference in failure at first attempt between the two methods. There was low-quality evidence from eight small trials that the pronation method may be more effective at first attempt than the supination method for manipulating pulled elbow in young children. For other outcomes, no conclusions could be drawn either because of very low-quality evidence or the outcomes not being reported. We suggest that a high-quality randomised clinical trial comparing hyperpronation and supination-flexion is required to provide definitive evidence. We recommend that this is preceded by a survey among clinicians to establish the extent of clinical equipoise and to optimise the study design and recruitment.


Cranial ultrasonography and the prediction of cerebral palsy in infants weighing less than or equal to 1200 grams at birth.
The rôle of serial cranial ultrasonography in the prediction of cerebral palsy was examined in 116 surviving infants with birthweights less than or equal to 1200 g. All underwent serial real-time sonographic examinations of the brain on days one, five and 21, then monthly, until term corrected age. Intraventricular hemorrhage (IVH) was diagnosed in 48 infants, and three had periventricular leukomalacia. Of the 116 infants, 31 had ultrasound abnormalities at term. At 12 to 18 months corrected age 12 infants had cerebral palsy and 38 were classified as suspect; the other 66 were normal. There was a clear association between risk group, based on sonographic findings at term, and outcome. Infants with IVH whose cranial ultrasounds failed to become normal by term corrected age were at higher risk for cerebral palsy than those with normal examinations at term, regardless of the severity of IVH. Thus an abnormal ultrasound at term corrected age was highly predictive of cerebral palsy, especially among survivors of IVH. It remained the best predictor of cerebral palsy, even when other perinatal and neonatal variables were considered. In contrast, duration of mechanical ventilation, rather than sonographic findings, was the best predictor of suspect neuromotor status.


Association between emotional and behavioral problems and perceived parenting in attention deficit hyperactivity disorder: An exploratory study.
Parent-child relationship difficulties are seen in families of children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD), and they may contribute to long-term negative outcomes. Our aim was to examine perceived parenting and its correlation with emotional and behavioral problems in children and adolescents with a diagnosis of ADHD. This was a cross-sectional study involving 38 children and adolescents, between 8 and 16 years of age, diagnosed to have ADHD. Parents rated the children and adolescents on the Strengths and Difficulties Questionnaire (SDQ), whereas children/adolescents rated parents on the Alabama Parenting Questionnaire (APQ). The study population primarily consisted of males (86.8%), between 8 and 12 years (68%), and belonged to urban families (82%). Warm, attentive, and engaged parenting behaviors which were subsumed under the domain of parental involvement in the APQ were associated with fewer total problem behaviors as well as specifically lower conduct and peer problems on the SDQ. Similarly, parents who used positive disciplining strategies as per the APQ had fewer total behavioral problems as well as specifically lower emotional problems on the SDQ. Children with comorbid oppositional defiant disorder reported lesser mean scores in all domains of parenting and significantly in the domains of parental involvement and positive parenting as per the APQ. Parental involvement and positive parenting were significantly associated with fewer emotional and behavioral problems in children and adolescents diagnosed with ADHD. This has direct implications for clinical practice. Further studies are needed to adapt parenting strategies to the Indian context.


recA protein binding to the heteroduplex product of DNA strand exchange.
Following DNA strand exchange, recA protein remains associated with the heteroduplex DNA product of the reaction. This association exists without significant changes (as measured by nuclease protection, topological state of the heteroduplex DNA, and rates of ATP hydrolysis) for at least 30 min after strand exchange is complete. The heteroduplex DNA is unwound as a result of this association to an extent at least as great as the unwinding observed when recA protein is bound to duplex DNA at pH 6.35. The extensive unwinding, in combination with the rates of ATP hydrolysis reported elsewhere, provide evidence that recA protein binding is contiguous throughout the heteroduplex DNA. This binding is disrupted upon challenge with heterologous single-stranded DNA, with rapid migration of recA protein to the challenging DNA. These results are discussed in relation to the mechanism of recA protein-promoted branch migration.


Treatment of nonunion around the olecranon fossa of the humerus by intramedullary locked nailing.
Nonunion of fractures of the olecranon fossa of the humerus presents a difficult surgical problem. The distal fragment is usually small and osteoporotic and stable fixation is not easy to achieve. We describe a modification of the technique of locked nailing by which the distal aspect of the nail is placed in the subchondral region of the trochlea. Good results were obtained in seven out of eight patients with this technique.


Stop codon reassignments in the wild.
The canonical genetic code is assumed to be deeply conserved across all domains of life with very few exceptions. By scanning 5.6 trillion base pairs of metagenomic data for stop codon reassignment events, we detected recoding in a substantial fraction of the >1700 environmental samples examined. We observed extensive opal and amber stop codon reassignments in bacteriophages and of opal in bacteria. Our data indicate that bacteriophages can infect hosts with a different genetic code and demonstrate phage-host antagonism based on code differences. The abundance and diversity of genetic codes present in environmental organisms should be considered in the design of engineered organisms with altered genetic codes in order to preclude the exchange of genetic information with naturally occurring species.


Functional gold nanoparticles for the storage and controlled release of nitric oxide: applications in biofilm dispersal and intracellular delivery.
Gold nanoparticles (size 10 nm) were designed to store and release nitric oxide (NO), by functionalizing their surfaces with functional polymers modified with NO-donor molecules. Firstly, block copolymer chains consisting of poly(oligoethylene glycol methyl ether methacrylate)-b-poly(vinyl benzyl chloride) (P(OEGMA)-b-PVBC)) were prepared using RAFT polymerization. The chloro-functional groups were then reacted with hexylamine, to introduce secondary amine groups to the copolymer chains. The block copolymers were then grafted onto the surface of gold nanoparticles, exploiting the end-group affinity for gold - attaining grafting densities of 0.6 chain per nm2. The secondary amine functional groups were then converted to N-diazeniumdiolate NO donor molecules via exposure to NO gas at high pressure (5 atm). The NO-bearing, gold nanoparticles were characterized using a range of techniques, including transmission electron microscopy, dynamic light scattering (DLS), thermal gravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). The nanoparticles displayed slow release of the nitric oxide in biological media. Proof of potential utility was then demonstrated in two different application areas: Pseudomonas aeruginosa biofilm dispersal and cancer cell cytotoxicity.


Evaluating neuronal and glial growth on electrospun polarized matrices: bridging the gap in percussive spinal cord injuries.
One of the many obstacles to spinal cord repair following trauma is the formation of a cyst that impedes axonal regeneration. Accordingly, we examined the potential use of electrospinning to engineer an implantable polarized matrix for axonal guidance. Polydioxanone, a resorbable material, was electrospun to fabricate matrices possessing either aligned or randomly oriented fibers. To assess the extent to which fiber alignment influences directional neuritic outgrowth, rat dorsal root ganglia (DRGs) were cultured on these matrices for 10 days. Using confocal microscopy, neurites displayed a directional growth that mimicked the fiber alignment of the underlying matrix. Because these matrices are generated from a material that degrades with time, we next determined whether a glial substrate might provide a more stable interface between the resorbable matrix and the outgrowing axons. Astrocytes seeded onto either aligned or random matrices displayed a directional growth pattern similar to that of the underlying matrix. Moreover, these glia-seeded matrices, once co-cultured with DRGs, conferred the matrix alignment to and enhanced outgrowth exuberance of the extending neurites. These experiments demonstrate the potential for electrospinning to generate an aligned matrix that influences both the directionality and growth dynamics of DRG neurites.


Soybean (Glycine max) agglutinin binds to corneal endothelial cells during wound repair and alters their microfilament pattern.
In the present study we have examined soybean (Glycine max) agglutinin (SBA) binding to cells of the rat corneal endothelium during wound repair. Circular transcorneal freeze injuries were given to the endothelia and the tissues were organ cultured at 37 degrees C in basal media Eagle with 10% serum for up to 72 hrs. SBA failed to bind to the surface of non-injured corneal endothelium, but strongly bound to cells involved in the wound repair process. Punctate surface binding was detected 24 hrs. post-injury, but stronger binding was observed at 48 hrs. after wounding. In this case, binding appeared to be distinctly distributed around the cell periphery. To investigate SBA binding during wound repair, endothelia were cultured in the presence of SBA (100 and 200 micrograms/ml). Cell migration into the wound area, and hence subsequent wound repair, was not affected at these concentrations. However, both concentrations altered cell morphology and microfilament patterns. Phalloidin staining of cells 24 hrs. after injury revealed that microfilaments appeared thinner and less in number. In addition, distinct aggregations of actin-positive material were detected at cell-to-cell contacts. Cells around the tissue periphery do not partake in the repair process but displayed an SBA concentration dependent fragmentation of their circumferential microfilament bundles. At 48 hrs. post-injury, SBA-treated cells within the wound area, unlike their control counterparts, did not exhibit stress fibers. These results suggest that a SBA binding surface component is associated with the reorganization of actin during corneal endothelial wound repair, and that these cells can migrate across their natural basement membrane without the benefit of a highly organized microfilament cytoskeleton.


The importance of mode of birth after previous cesarean: success, satisfaction, and postnatal health.
The recent National Institutes of Health consensus conference on vaginal birth after cesarean (VBAC) recommended a focus on strategies that increase women's opportunities to make informed choices about VBAC. This study aimed to expand knowledge of women's experiences of planned VBAC by focusing on postnatal experiences of women who participated in an Australian birth-after-cesarean study. At 6 to 8 weeks after birth, 165 women who experienced childbirth after a previous cesarean rated satisfaction with their birth experiences using a 10-point visual analogue scale, reported on postnatal health problems, and indicated whether they would make the same birth choice again. Significant differences were found in satisfaction scores by mode of birth. Mean scores out of a possible score of 10 ranged from 8.86 for spontaneous vaginal birth, 7.86 for elective repeat cesarean delivery, 6.71 for emergency cesarean delivery, to 6.15 for instrumental vaginal birth (F = 5.33; P = .002). Mean satisfaction scores for spontaneous vaginal birth and elective repeat cesarean delivery were statistically higher than for instrumental vaginal birth and emergency cesarean birth. Women who experienced instrumental vaginal birth and emergency cesarean birth also reported a higher number of postnatal health-related problems and were least likely to agree that they would make the same birth choice again. Mode of birth was the most important determinant of postnatal satisfaction, postnatal health, and whether women felt they would make the same birth choice again. Clinicians, researchers, and policymakers should identify effective labor management practices that enhance women's opportunities to achieve spontaneous vaginal birth during planned VBAC.


A simplified and affordable approach to forest monitoring using single terrestrial laser scans and transect sampling.
Traditional forestry, ecology, and fuels monitoring methods can be costly and error-prone, and are often used beyond their original assumptions due to difficulty or unavailability of more appropriate methods. These traditional methods tend to be rigid and may not be useful for detecting new ecological changes or required data at modern levels of precision [1]. The integration of Terrestrial Laser Scanning (TLS) methods into forest monitoring strategies can cost effectively standardize data collection, improve efficiency, and reduce error, with datasets that can easily be analyzed to better inform management decisions. Affordable (sub-$20K) off-the-shelf TLS units-such as the Leica BLK360- have been used commercially in the built environment but have untapped potential in the natural world for monitoring. Here, we provide a methodology that successfully integrates LiDAR scanning with existing monitoring methods. This new method:•Allows for simplified and quick extraction of forestry, fuels and ecological vegetation variables from a single TLS point cloud and quick transect sampling.•Streamlines the data collection process, removes sampling bias, and produces data that can be easily processed to provide inputs for models and decision support frameworks.•Is adaptable to integrate additional or new environmental measurements.


Homologous recombination is stimulated by a decrease in dUTPase in Arabidopsis.
Deoxyuridine triphosphatase (dUTPase) enzyme is an essential enzyme that protects DNA against uracil incorporation. No organism can tolerate the absence of this activity. In this article, we show that dUTPase function is conserved between E. coli (Escherichia coli), yeast (Saccharomyces cerevisiae) and Arabidopsis (Arabidopsis thaliana) and that it is essential in Arabidopsis as in both micro-organisms. Using a RNA interference strategy, plant lines were generated with a diminished dUTPase activity as compared to the wild-type. These plants are sensitive to 5-fluoro-uracil. As an indication of DNA damage, inactivation of dUTPase results in the induction of AtRAD51 and AtPARP2, which are involved in DNA repair. Nevertheless, RNAi/DUT1 constructs are compatible with a rad51 mutation. Using a TUNEL assay, DNA damage was observed in the RNAi/DUT1 plants. Finally, plants carrying a homologous recombination (HR) exclusive substrate transformed with the RNAi/DUT1 construct exhibit a seven times increase in homologous recombination events. Increased HR was only detected in the plants that were the most sensitive to 5-fluoro-uracils, thus establishing a link between uracil incorporation in the genomic DNA and HR. Our results show for the first time that genetic instability provoked by the presence of uracils in the DNA is poorly tolerated and that this base misincorporation globally stimulates HR in plants.


The influence of tone inventory on ERP without focal attention: a cross-language study.
This study investigates the effect of tone inventories on brain activities underlying pitch without focal attention. We find that the electrophysiological responses to across-category stimuli are larger than those to within-category stimuli when the pitch contours are superimposed on nonspeech stimuli; however, there is no electrophysiological response difference associated with category status in speech stimuli. Moreover, this category effect in nonspeech stimuli is stronger for Cantonese speakers. Results of previous and present studies lead us to conclude that brain activities to the same native lexical tone contrasts are modulated by speakers' language experiences not only in active phonological processing but also in automatic feature detection without focal attention. In contrast to the condition with focal attention, where phonological processing is stronger for speech stimuli, the feature detection (pitch contours in this study) without focal attention as shaped by language background is superior in relatively regular stimuli, that is, the nonspeech stimuli. The results suggest that Cantonese listeners outperform Mandarin listeners in automatic detection of pitch features because of the denser Cantonese tone system.


A prospective 2-site parallel intervention trial of a research-based film to increase exercise amongst older hemodialysis patients.
Evidence suggests that exercise training for hemodialysis patients positively improves morbidity and mortality outcomes, yet exercise programs remain rare and are not systematically incorporated into care. We developed a research-based film, Fit for Dialysis, designed to introduce, motivate, and sustain exercise for wellness amongst older hemodialysis patients, and exercise counseling and support by nephrologists, nurses, and family caregivers. The objective of this clinical trial is to determine whether and in what ways Fit for Dialysis improves outcomes and influences knowledge/attitudes regarding the importance of exercise for wellness in the context of end-stage renal disease. This 2-site parallel intervention trial will recruit 60 older hemodialysis patients from two urban hospitals. The trial will compare the film + a 16-week exercise program in one hospital, with a 16-week exercise-only program in another hospital. Physical fitness and activity measures will be performed at baseline, 8 and 16 weeks, and 12 weeks after the end of the program. These include the 2-min Walk Test, Grip Strength, Duke Activity Status Index, and the Timed Up-and-Go Test, as well as wearing a pedometer for one week. Throughout the 16-week exercise program, and at 12 weeks after, we will record patients' exercise using the Godin Leisure-time Exercise Questionnaire. Patients will also keep a diary of the exercise that they do at home on non-dialysis days. Qualitative interviews, conducted at baseline, 8, and 16 weeks, will explore the impact of Fit for Dialysis on the knowledge/attitudes of patients, family caregivers, and nephrology staff regarding exercise for wellness, and in what ways the film is effective in educating, motivating, or sustaining patient exercise during dialysis, at home, and in the community. This research will determine for whom Fit for Dialysis is effective, why, and under what conditions. If Fit for Dialysis is proven beneficial to patients, nephrology staff and family caregivers, research-based film as a model to support exercise promotion and adherence could be used to support the National Kidney Foundation's guideline recommendation (NKF-KDOQI) that exercise be incorporated into the care and treatment of dialysis patients. NCT02754271 (ClinicalTrials.gov), retroactively registered on April 21, 2016.


Combined Glia Inhibition and Opioid Receptor Agonism Afford Highly Potent Analgesics without Tolerance.
Commonly prescribed opioid analgesics produce tolerance upon chronic use due in part to induction of hyperalgesia. Given that two reported bivalent ligands (MMG22 and MCC22) produce potent antinociception without tolerance only in inflamed mice, we have investigated the possible cellular and receptor targets of these ligands. The selective microglia inhibitors, minocycline and SB290157, antagonized intrathecal (i.t.) MCC22 antinociception orders of magnitude more potently than MMG22, suggesting that MCC22 selectively targets activated microglia. The astrocyte toxin, l-α-aminoadipic acid antagonized MMG22 antinociception 126-fold without reducing the potency of MCC22, indicating that activated astrocytes are targets of MMG22. MK-801 and Ro25-6981 antagonism of MMG22 antinociception, but not MCC22, is consistent with selective inhibition of activated NMDAR in astrocytes. The antinociception produced by i.t. MMG22 or MCC22 were both antagonized by the selective mu opioid receptor antagonist, β-FNA, implicating interaction of these ligands with MOR in spinal afferent neurons. MCC22 antinociception was potently blocked by kainate or AMPA ion channel antagonists (LY382884; NBQX), in contrast to MMG22. It is concluded that i.t. MMG22 and MCC22 produce exceptional antinociception via potent inhibition of activated spinal glia, thereby leading to desensitization of spinal neurons and enhanced activation of neuronal MOR. Thus, the present study suggests a new approach to treatment of chronic inflammatory pain without tolerance through a single molecular entity that simultaneously inhibits activated glia and stimulates MOR in spinal neurons.


Activating transcription factor 6 is necessary and sufficient for alcoholic fatty liver disease in zebrafish.
Fatty liver disease (FLD) is characterized by lipid accumulation in hepatocytes and is accompanied by secretory pathway dysfunction, resulting in induction of the unfolded protein response (UPR). Activating transcription factor 6 (ATF6), one of three main UPR sensors, functions to both promote FLD during acute stress and reduce FLD during chronic stress. There is little mechanistic understanding of how ATF6, or any other UPR factor, regulates hepatic lipid metabolism to cause disease. We addressed this using zebrafish genetics and biochemical analyses and demonstrate that Atf6 is necessary and sufficient for FLD. atf6 transcription is significantly upregulated in the liver of zebrafish with alcoholic FLD and morpholino-mediated atf6 depletion significantly reduced steatosis incidence caused by alcohol. Moreover, overexpression of active, nuclear Atf6 (nAtf6) in hepatocytes caused FLD in the absence of stress. mRNA-Seq and qPCR analyses of livers from five day old nAtf6 transgenic larvae revealed upregulation of genes promoting glyceroneogenesis and fatty acid elongation, including fatty acid synthase (fasn), and nAtf6 overexpression in both zebrafish larvae and human hepatoma cells increased the incorporation of 14C-acetate into lipids. Srebp transcription factors are key regulators of lipogenic enzymes, but reducing Srebp activation by scap morpholino injection neither prevented FLD in nAtf6 transgenics nor synergized with atf6 knockdown to reduce alcohol-induced FLD. In contrast, fasn morpholino injection reduced FLD in nAtf6 transgenic larvae and synergistically interacted with atf6 to reduce alcoholic FLD. Thus, our data demonstrate that Atf6 is required for alcoholic FLD and epistatically interacts with fasn to cause this disease, suggesting triglyceride biogenesis as the mechanism of UPR induced FLD.


The moderating effects of aging and cognitive abilities on the association between work stress and negative affect.
Given that the association between work stress and negative affect can exacerbate negative health and workplace outcomes, it is important to identify the protective and risk factors that moderate this association. Socioemotional aging and cognitive abilities might influence how people utilize emotion regulation skills and engage in practical problem solving to manage their work stress. The aim of this study is to examine whether age and cognitive abilities independently and interactively moderate the association between work-related stress and negative affect. A diverse working adult sample (N = 139, age 25-65, 69% of females) completed a cross-sectional survey that assessed chronic work stress, negative affect, and fluid and crystallized cognitive abilities. Results from regression analyses suggested that both fluid and crystallized cognitive abilities, but not age, moderated the association between work stress and negative affect. Further, we found that crystallized cognition had a stronger attenuating effect on the work stress-negative affect association for older compared to younger workers. The moderating effect of fluid cognition was invariant across age. Our findings demonstrate that cognitive abilities are an important personal resource that might protect individuals against the negative impacts of work stress and negative affect. Although the role that fluid cognition plays in work stress-negative affect association is comparably important for both younger and older workers, crystallized cognition might play a more valuable role for older than younger workers.


Phosphoinositides: tiny lipids with giant impact on cell regulation.
Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.


Differential localization of brain-type and epidermal-type fatty acid binding proteins in the adrenal gland of mice.
In immuno-light and -electron microscopy, brain-type fatty acid binding protein (B-FABP) is localized in the sustentacular cells enclosing the chromaffin cells in the adrenal medulla. This represents another new feature commonly shared by the sustentacular cells and ganglionic satellite cells, the latter of which has already been reported to localize this molecule, and suggests a common feature in lipid metabolism shared by the two cells enclosing peripheral neurons and paraneurons. On the other hand, epidermal-type fatty acid binding protein (E-FABP) is localized in two discrete cells in the adrenal gland: the one is a subpopulation of intra-adrenal macrophages which are intensely immunoreactive for F4/80, a marker of macrophages, and are rich in pleomorphic lysosomes. Because of their direct apposition to adjacent cortical endocrine cells and medullary chromaffin cells, the macrophages may be involved not only in phagocytosis of degenerating adrenal cells but also in exertion of some yet unknown effects on the endocrine function of the cortical and medullary cells via humoral factors such as cytokines which have recently been known to be secreted by macrophages. The other is a population of cells having scanty perikaryal cytoplasm poor in organneles and several thinny extended processes in the cortex and exhibiting weak immunoreactivity for E-FABP. The possible natures of these cells immunoreactive for E-FABP are discussed in view of a subpopulation of endothelial cells or the dendritic cells of antigen-presenting property.


Awareness and use of cervical cancer tests in a southern Appalachian community.
The knowledge and use of cervical cancer screening (Papanicolaou smear test) by female members of a prepaid health plan (Health Maintenance Organization--foundation-type) based in souther Appalachia were surveyed. Of the 105 members of the plan interviewed, 81 indicated that they had experienced one or more Papanicolaou tests. This percentage (77.1%) was greater than might have been expected on the basis of a review of previous research. Factors contributing to this higher percentage were the subjects' membership in the prepaid health care plan and the increasing tendency of physicians to perform cervical cancer screening tests on patients who visit them for reasons unrelated to cancer detection. The latter phenomenon, coupled with inadequate patient education at the time of the service, is viewed as a major cause of the discrepancy found between the women's Papanicolaou test experience and their Papanicolaou test awareness. Of the 81 women in the study reporting one or more previous cervical cancer screening tests, only 49 were able to identify a specific test for detecting cervical cancer. Most of the results of previous research concerning the relationship of Papanicolaou test experience to age, to education, to economic, employment, and marital status, or to number of children were supported by the current study. The results of this study, conducted in a relatively isolated American community, suggest that the nationwide cervical cancer educational efforts of a multitude of agencies and individuals have met with considerable success.


Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2- Breast Cancer.
neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting. Postmenopausal women with stage I-IIIB HR+/HER2- breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response. Abemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell-cycle arrest after 2 weeks of treatment compared with anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell-cycle arrest (58%/68% vs. 14%, P < 0.001). At the end of treatment, following 2 weeks lead-in and 14 weeks of combination therapy, 46% of intent-to-treat patients achieved a radiologic response, with pathologic complete response observed in 4%. The most common all-grade adverse events were diarrhea (62%), constipation (44%), and nausea (42%). Abemaciclib, anastrozole, and the combination inhibited cell-cycle processes and estrogen signaling; however, combination therapy resulted in increased cytokine signaling and adaptive immune response indicative of enhanced antigen presentation and activated T-cell phenotypes. Abemaciclib plus anastrozole demonstrated biological and clinical activity with generally manageable toxicities in patients with HR+/HER2- early breast cancer. Abemaciclib led to potent cell-cycle arrest, and in combination with anastrozole, enhanced immune activation.


Effect of surgical clipping versus endovascular coiling on recovery from oculomotor nerve palsy in patients with posterior communicating artery aneurysms: A retrospective comparative study and meta-analysis.
Oculomotor nerve palsy (OMNP) is a well-recognized complication of posterior communicating artery (PCOM) aneurysms. Only a few comparative studies have assessed the effect of clipping versus coiling on recovery from OMNP in PCOM aneurysms. A retrospective review and meta-analysis was conducted to assess the relationship between PCOM aneurysm treatment and OMNP. Medical records of all patients presenting between January 2000 and February 2013 with intracranial aneurysm were searched. All patients with OMNP secondary to PCOM aneurysm were included for analysis. Patients undergoing surgical clipping or endovascular coiling were compared with respect to complete resolution of OMNP after aneurysm surgery (i.e., primary outcome). A meta-analysis of published studies of OMNP associated with PCOM aneurysm was performed after a MEDLINE search. Seventeen patients with OMNP secondary to PCOM aneurysms met the inclusion criteria. Surgical clipping (seven of eight patients, or 87.5%) resulted in greater complete resolution of OMNP compared with endovascular coiling (four of nine patients, or 44.4%), P = 0.13. A meta-analysis of similar studies revealed that complete resolution of OMNP was more commonly associated with surgical clipping (36 of 43 patients, or 83.7%) than with endovascular coiling (29 of 55 patients, or 52.7%), yielding an adjusted odds ratio (OR) of 6.04 [confidence interval (CI) =1.88-19.45, P = 0.003]. Multivariate analysis found that the degree of pre-operative OMNP (OR = 0.07, CI = 0.02-0.28, P = 0.001) and surgical clipping (OR = 6.37, CI = 1.73-23.42, P = 0.005) were significant factors that affected the complete recovery of OMNP. Complete recovery of OMNP with PCOM aneurysms is more commonly associated with surgical clipping than with endovascular coiling. Also, the degree of pre-operative OMNP and the treatment modality are significant factors that affect the complete recovery of OMNP.


Mass-energy absorption coefficient and backscatter factor ratios for kilovoltage x-ray beams.
For low-energy (up to 150 kV) x-rays, the ratio of mass-energy absorption coefficients for water to air, (mu(en)/rho)w.air, and the backscatter factor B are used in the conversion of air kerma, measured free-in-air, to water kerma on the surface of a water phantom. For clinical radiotherapy, similar conversion factors are needed for the determination of the absorbed dose to biological tissues on (or near) the surface of a human body. We have computed the mu(en)/rho ratios and B factor ratios for different biological tissues including muscle, soft tissue, lung, skin and bone relative to water. The mu(en)/rho ratios were obtained by integrating the respective mass-energy absorption coefficients over the in-air primary photon spectra. We have also calculated the mu(en)/rho ratios at different depths in a water phantom in order to convert the measured in-phantom water kerma to the absorbed dose to various biological tissues. The EGS4/DOSIMETER Monte Carlo code system has been used for the simulation of the energy fluence at different depths in a water phantom irradiated by a kilovoltage x-ray beam of variable beam quality (HVL: 0.1 mm Al-5 mm Cu), field size and source-surface distance (SSD). The same code was also used in the calculation of the B factor ratios, soft tissue to water and bone to water. The results show that the B factor for bone differs from the B factor for water by up to 20% for a 100 kV beam (HVL: 2.65 mm Al) with a 100 cm2 field. On the other hand, the difference in the B factor between water and soft tissue is insignificant (well within 1% generally). This means that the B factors for water may be directly used to convert the 'in-air' water kerma to surface kerma for human soft tissues.


Anisotropic polyvinyl alcohol-Bacterial cellulose nanocomposite for biomedical applications.
Compliance mismatch between the synthetic graft and the surrounding native tissue has been reported as a major factor in ultimate failure of the currently used cardiovascular graft replacements. Thus, developing biomaterials that display close mechanical properties as the tissue it is replacing is an important objective in biomedical devices design. Polyvinyl alcohol (PVA) is a biocompatible hydrogel with characteristics desired for biomedical applications. It can be crosslinked by a low temperature thermal cycling process. By using a novel thermal processing method under an applied strain and with the addition of a small amount of bacterial cellulose (BC) nanofibers, an anisotropic PVA-BC nanocomposite was created. The stress-strain tensile properties of porcine aorta were closely matched in both the circumferential and the axial directions by one type of anisotropic PVA-BC nanocomposite (10% PVA with 0.3% BC at 75% initial strain and cycle 2) within physiological range, with improved resistance to further stretch beyond physiological strains. The PVA-BC nanocomposite gives a broad range of mechanical properties, including anisotropy, by controlling material and processing parameters. PVA-BC nanocomposites with controlled degree of anisotropy that closely match the mechanical properties of the soft tissue it might replace, ranging from cardiovascular to other connective tissues, can be created.


Association between perceived coercion and perceived level of information in involuntarily admitted patients: Results from a multicenter observational study in Switzerland.
Involuntary admissions (IA) to psychiatric hospitals are controversial because they interfere with people's autonomy. In some situations, however, they appear to be unavoidable. Interestingly, not all patients perceive the same degree of coercion during IA. The aim of this study was to assess whether the level of knowledge about one's own IA is associated with perceived coercion. This multicenter observational study was conducted on n = 224 involuntarily admitted patients. Interviews were conducted at five study centers from April 2021 to November 2021. The Macarthur Admission Experience Survey was administered to assess perceived coercion. Knowledge of involuntary admission, perceptions of information received, and attitudes towards legal aspects of involuntary admission were also assessed. We found that higher levels of knowledge about IA were negatively associated with perceived coercion at admission. Perceived coercion did not differ between study sites. Only half of the patients felt well informed about their IA, and about a quarter found the information they received difficult to understand. Legislation in Switzerland requires that patients with IA be informed about the procedure. Strategies to improve patients' understanding of the information given to them about IA might be helpful to reduce perceived coercion, which is known to be associated with negative attitudes towards psychiatry, a disturbed therapeutic relationship, avoidance of psychiatry, and the risk of further coercion.


Prevalence of ESβL, AmpC and Colistin-Resistant E. coli in Meat: A Comparison between Pork and Wild Boar.
A global increase in Escherichia coli (E. coli) resistant to cephalosporins (extended-spectrum β-lactamases (ESβLs) and AmpC β-lactamases) has been recorded in the last 20 years. Similarly, several studies have reported the spread of colistin resistance in Enterobacteriaceae isolated from food and the environment. The aim of the present study was to evaluate the prevalence of ESβL, AmpC and colistin-resistant E. coli isolated from pork and wild boar meat products in the Emilia Romagna region (North Italy). The isolates were analysed phenotypically (considering both resistant and intermediate profiles) and genotypically. The prevalence of genotypically confirmed ESβL and AmpC E. coli was higher in pork meat products (ESβL = 11.1% vs. AmpC = 0.3%) compared to wild boar meat (ESβL = 6.5% vs. AmpC = 0%). Intermediate profiles for cefotaxime (CTX) and ceftazidime (CAZ) were genotypically confirmed as ESβL in pork meat isolates but not for wild boar. Four E. coli from wild boar meat were resistant to colistin but did not harbour the mcr-1 gene. E. coli isolated from wild boar meat seem to show aspecific antimicrobial resistance mechanisms for cephalosporins and colistin. The prevalence of resistant isolates found in wild boar is less alarming than in pork from farmed domestic pigs. However, the potential risk to consumers of these meat products will require further investigations.


The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study.
The durability of isoniazid preventive therapy (IPT) in preventing tuberculosis (TB) is limited in high-prevalence settings. The underlying mechanism (reactivation of persistent latent TB or reinfection) is not known. We aimed to investigate the timing of TB incidence during and after IPT and associated risk factors in a very high TB and HIV-prevalence setting, and to compare the observed rate with a modelled estimate of TB incidence rate after IPT due to reinfection. In a post-hoc analysis of a cluster-randomized trial of community-wide IPT among South African gold miners, all intervention arm participants that were dispensed IPT for at least one of the intended 9 months were included. An incident TB case was defined as any participant with a positive sputum smear or culture, or with a clinical TB diagnosis assigned by a senior study clinician. Crude TB incidence rates were calculated during and after IPT, overall and by follow-up time. HIV status was not available. Multivariable Cox regression was used to analyse risk factors by follow-up time after IPT. Estimates from a published mathematical model of trial data were used to calculate the average reinfection TB incidence in the first year after IPT. Among 18,520 participants (96% male, mean age 41 years, median follow-up 2.1 years), 708 developed TB. The TB incidence rate during the intended IPT period was 1.3/100 person-years (pyrs; 95% confidence interval (CI), 1.0-1.6) and afterwards 2.3/100 pyrs (95% CI, 1.9-2.7). TB incidence increased within 6 months followed by a stable rate over time. There was no evidence for changing risk factors for TB disease over time after miners stopped IPT. The average TB incidence rate attributable to reinfection in the first year was estimated at 1.3/100 pyrs, compared to an observed rate of 2.2/100 pyrs (95% CI, 1.8-2.7). The durability of protection by IPT was lost within 6-12 months in this setting with a high HIV prevalence and a high annual risk of M. tuberculosis infection. The observed rate was higher than the modelled rate, suggesting that reactivation of persistent latent infection played a role in the rapid return to baseline TB incidence.


Quality Improvement in Clinical Nutrition: Screening and Mealtime Protection for the Hospitalized Patient.
The purpose of the quality improvement project was to (1) enhance awareness, accuracy, and use of the validated nutrition screening tool by the nurse and (2) improve compliance to the nutrition care plan that included increasing patient meal intake percentage. Nurses were provided with an in-depth educational program focused on the implementation of the nutrition screening tool on patient admission to the clinical site. Second, a unit-level patient protected mealtime program was implemented in an effort to decrease unnecessary mealtime interruptions and promote nurses and nursing assistants to assist with meals during mealtime to improve patient meal intake percentage and, finally, to encourage collaboration between the clinical nurse specialist, unit level nurses, and registered dietitians to improve patient nutritional care. The results indicate that the quality improvement strategies were successful in promoting the patient protected mealtime program and use of the nutrition screening tool. The clinical nurse specialist plays a valuable role in program development, implementation, and evaluation to achieve quality healthcare through interdisciplinary collaboration. Adhering to nutrition guidelines for the hospitalized adult patient improves nutrition care plan guidance and meal intake.


Principles of gene therapy: potential applications in the treatment of cerebral ischaemia.
In this review we explore gene therapy as a possible treatment for conditions causing cerebral ischaemia and briefly consider other neurological pathologies such as brain tumours. DNA transfer may be achieved using retrovirus, herpes simplex virus, adenovirus, and adeno-associated virus vectors or liposomes. After cerebral ischaemia, these vectors are used to upregulate genes that increase survival and inhibit those that promote death in the injured cells. In contrast, in brain tumours gene therapy aims to kill the target cells. Examples from studies using cell culture, animal models and patients are presented. We conclude that manipulation of gene expression has potential for the treatment of cerebral ischaemia and brain tumours, although, at present, there are formidable technical obstacles to be overcome before clinical applications become a reality.


Level of behavior and knowledge concerning human papillomavirus among university students of a nursing college.
Human pappilomavirus is one of the most common sexually transmitted diseases, and persistent HPV infection is considered the most important cause of cervical cancer. It is detected in more than 98% of this type of cancer. This study aimed to determine the level of knowledge concerning human papillomavirus among nursing college students of a private educational institution located in the City of Bauru, SP, and correlate their knowledge according to the course year. A descriptive study with a quantitative approach, performed with a questionnaire that permitted the quantification of data and opinions, thus guaranteeing the precision of the results without distortions in analysis or interpretation. The survey was applied to randomly selected 1st, 2nd, 3rd, and 4th-year nursing college students. Twenty students from each level were selected during August 2009, totaling 80 students of both genders. Observation revealed that 4th-year students had greater knowledge than 1st-year students, reflecting the greater period of study, the lack of knowledge of 1st-year students was due to the low level of information acquired before entering college. The need for complementary studies which determine the profile and knowledge of a larger number of teenagers in relation to HPV was established. The need for educational programs that can overcome this lack of information is undeniable, especially those aimed at making adolescents less susceptible to HPV and other STDs.


Mental health service use by adolescents of Indian and White origin.
Despite the available epidemiological evidence on the prevalence of mental health problems in childhood and adolescence, there is limited knowledge on whether there are differences in the level of need and service utilisation by young ethnic minority groups. Adolescents of 13-15 years from nine schools in two English cities in which children of Indian ethnicity were over-represented (n=2900), completed rating scales on different types of mental health problems, contacts with services and informal supports. Indian adolescents scored significantly lower on general mental health and depression symptoms. They were also less likely than White adolescents to self-report having mental health problems, even for a similar level of need. Among those with mental health scores within the clinical range, Indian adolescents were less likely to have visited specialist services. Instead, they were more likely to first approach family members, teachers or general practitioners. Rather than a blanket approach being applied to policy and service planning to meet the needs of diverse communities of young people, more specific evidence needs to be gained about patterns of referrals of minority groups and their strategy of accessing supportive adults.


Evolution of virulence in fungal plant pathogens: exploiting fungal genomics to control plant disease.
The propensity of a fungal pathogen to evolve virulence depends on features of its biology (e.g. mode of reproduction) and of its genome (e.g. amount of repetitive DNA). Populations of Leptosphaeria maculans, a pathogen of Brassica napus (canola), can evolve and overcome disease resistance bred into canola within three years of commercial release of a cultivar. Avirulence effector genes are key fungal genes that are complementary to resistance genes. In L. maculans these genes are embedded within inactivated transposable elements in genomic regions where they are readily mutated or deleted. The risk of resistance breakdown in the field can be minimised by monitoring disease severity of canola cultivars and virulence of fungal populations using high throughput molecular assays and by sowing canola cultivars with different resistance genes in subsequent years. This strategy has been exploited to avert yield losses due to blackleg disease in Australia.


Neurons derived from radial glial cells establish radial units in neocortex.
The neocortex of the adult brain consists of neurons and glia that are generated by precursor cells of the embryonic ventricular zone. In general, glia are generated after neurons during development, but radial glia are an exception to this rule. Radial glia are generated before neurogenesis and guide neuronal migration. Radial glia are mitotically active throughout neurogenesis, and disappear or become astrocytes when neuronal migration is complete. Although the lineage relationships of cortical neurons and glia have been explored, the clonal relationship of radial glia to other cortical cells remains unknown. It has been suggested that radial glia may be neuronal precursors, but this has not been demonstrated in vivo. We have used a retroviral vector encoding enhanced green fluorescent protein to label precursor cells in vivo and have examined clones 1-3 days later using morphological, immunohistochemical and electrophysiological techniques. Here we show that clones consist of mitotic radial glia and postmitotic neurons, and that neurons migrate along clonally related radial glia. Time-lapse images show that proliferative radial glia generate neurons. Our results support the concept that a lineage relationship between neurons and proliferative radial glia may underlie the radial organization of neocortex.


Aerococcus viridans and Public Health: Oral Carriage and Antimicrobial Resistance in Stray Dogs and Cats in Algeria.
The current study aimed to determine the occurrence and antimicrobial resistance of oral Aerococcus viridans in stray dogs and cats in Algeria. Oral swabs from 200 stray animals (100 dogs and 100 cats) were collected and cultured on Columbia agar medium supplemented with 5% defibrinated sheep blood. Isolates were identified using analytical profile index Rapid 20 Strep commercial kits, and antibiotic susceptibility was determined using the disk diffusion method. Of the 200 animals sampled, 34 carried A. viridans in their oral cavities, with 26 isolates (76.47%) resistant to at least 2 drugs. Multidrug resistance profiles (to more than three different antimicrobials) were observed only in cats (26.08% of isolates). More isolates were resistant to erythromycin and tetracycline (71% and 65%, respectively) than to other antimicrobials. This is the first research study in Algeria detecting antimicrobial resistance in oral A. viridans isolated from dogs and cats and highlights potential public health concerns. Clinical trials registration number: 01/2018.


Variations in gamma-glutamyl transpeptidase glycosylation and kinetic parameters in cultured liver cells.
In rat hepatocytes; the tumorigenic rat liver cell line ARL-16; and the human hepatoma line, Hep G2, 50% of the total gamma-glutamyl transpeptidase (GGT) activity was bound by a Concanavalin-A Sepharose 4B column, calling for alpha-methylmannoside elution (Peak I). Non-binding GGT was distributed between a rapidly eluting Peak II and a slightly retained Peak III. The Km for gamma-glutamyl-p-nitroanalide for either hydrolysis or transpeptidation, or glutathione (GSH) transpeptidation did not vary with peak number or cell type. The GSH hydrolysis Km was essentially constant in Peak I and II GGT. Peak III GGT exhibited a lower Km for GSH hydrolysis with Hep G2 Peak III GGT being the lowest. Peak III GGT increased to 50% of the GGT activity in Hep G2 cells cultured with GSH as the sole cysteine source.


Major therapeutic developments and current challenges in advanced melanoma.
Malignant melanoma is rising in incidence. The treatment options have been very limited but advances in molecular biology and immunology have led to a greater understanding of the pathogenesis of the disease. Four drugs have been approved for the treatment of advanced melanoma in the past 2 years and two new classes of agents have recently been shown to lead to durable responses in a substantial minority of patients. The identification of biomarkers has helped clinicians and researchers segregate patients into molecular subgroups, which facilitates the selection of therapy. Preliminary work has begun on determining the ideal sequences of the various therapies. Investigations have been carried out on why these treatments work and what the mechanisms of resistance are to these therapies. It is hoped that combinations of therapies will emerge that lead to a high percentage of durable responses.


Expression of herpes simplex virus type 1 DNA polymerase in Saccharomyces cerevisiae and detection of virus-specific enzyme activity in cell-free lysates.
The herpes simplex virus type 1 (HSV-1) (strain 17) DNA polymerase gene has been cloned into an Escherichia coli-yeast shuttle vector fused to the galactokinase gene (GAL-1) promoter. Genes controlled by the GAL-1 promoter are induced by galactose, uninduced by raffinose, and repressed by glucose. Cell extracts from a strain of Saccharomyces cerevisiae harboring this vector (Y-MH202, expresser cells) grown in the presence of galactose and assayed in high salt (100 mM ammonium sulfate) contained a novel DNA polymerase activity. No significant high-salt DNA polymerase activity was detected in extracts from expresser cells grown in the presence of raffinose or in extracts from control cells containing the E. coli-yeast shuttle vector without the HSV-1 DNA polymerase gene grown in the presence of raffinose of galactose. Immunoblot analysis of the cell extracts by using a polyclonal rabbit antiserum prepared against a highly purified HSV-1 DNA polymerase preparation revealed the specific induction of the HSV-1 approximately 140-kilodalton DNA polymerase polypeptide in expresser cells grown in galactose. Extracts from the same cells grown in raffinose or control cells grown in either raffinose or galactose did not contain this immunoreactive polypeptide. The high-salt DNA polymerase activity in the extracts from expresser cells grown in galactose was inhibited greater than 90% by either acyclovir triphosphate or aphidicolin, as expected for HSV-1 DNA polymerase. In addition, the high-salt polymerase enzyme activity could be depleted from extracts by immunoprecipitation by using purified immunoglobulin G from this same polyclonal rabbit antiserum. These results demonstrate the successful expression of functional HSV-1 DNA polymerase enzyme in S. cerevisiae.


Human reliability analysis (HRA) techniques and observational clinical HRA.
This review explains the nature of human reliability analysis (HRA) methods developed and used for predicting safety in high-risk human activities. HRA techniques have evolved over the years and have become less subjective as a result of inclusion of (i) cognitive factors in the man-machine interface and (ii) high and low dependency levels between human failure events (HFEs). All however remain probabilistic in the assessment of safety. In the translation of these techniques, developed for assessment of safety of high-risk industries (nuclear, aerospace etc.) where catastrophic failures from the man-machine complex interface are fortunately rare, to the clinical operative surgery (with its high incidence of human errors), the system loses subjectivity since the documentation of HFEs can be assessed and studied prospectively on the basis of an objective data capture of errors enacted during a defined clinical activity. The observational clinical-HRA (OC-HRA) was developed specifically for this purpose, initially for laparoscopic general surgery. It has however been used by other surgical specialties. OC-HRA has the additional merit of objective determination of the proficiency of a surgeon in executing specific interventions and is adaptable to the evaluation of safety and proficiency in clinical activities within the preoperative and postoperative periods.