Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- NADPH oxidase 2 mediates Angiotensin II-dependent cellular arrhythmias via PKA and CaMKII. [JOURNAL ARTICLE]
- J Mol Cell Cardiol 2014 Jul 26.
Angiotensin II (Ang II) signaling has been implicated in cardiac arrhythmogenesis, which involves induction of reactive oxygen species (ROS). It was shown that Ang II can activate Ca/Calmodulin kinase II (CaMKII) by oxidation via a NADPH oxidase 2 (NOX2)-dependent pathway leading to increased arrhythmic afterdepolarizations. Interestingly, cAMP-dependent protein kinase A (PKA) which regulates similar targets as CaMKII has recently been shown to be redox-sensitive as well.This study aims to investigate the distinct molecular mechanisms underlying Ang II-related cardiac arrhythmias with an emphasis on the individual contribution of PKA vs. CaMKII.Isolated ventricular cardiac myocytes from rats and mice were used. Ang II exposure resulted in increased NOX2-dependent ROS generation assessed by expression of redox-sensitive GFP and in myocytes loaded with ROS indicator MitoSOX. Whole cell patch clamp measurements showed that Ang II significantly increased peak Ca and Na current (ICa and INa) possibly by enhancing steady-state activation of ICa and INa. These effects were absent in myocytes lacking functional NOX2 (gp91phox(-/-)). In parallel experiments using PKA inhibitor H89, the Ang II effects on peak INa and ICa were also absent. In contrast, genetic knockout of CaMKIIδ (CaMKIIδ(-/-)) did not influence the Ang II-dependent increase in peak ICa and INa. On the other hand, Ang II enhanced INa inactivation, increased late INa and induced diastolic SR (sarcoplasmic reticulum) Ca leak (confocal Ca spark measurements) in a CaMKIIδ-, but not PKA-dependent manner. Surprisingly, only the increase in diastolic SR Ca leak was absent in gp91phox(-/-) myocytes suggesting that Ang II regulates INa inactivation in a manner dependent on CaMKII- but not on NOX2. Finally, we show that Ang II increased the propensity for cellular arrhythmias, for which PKA and CaMKII contribute, both dependent on NOX2.Ang II activates PKA and CaMKII via NOX2, which results in disturbed Na and Ca currents (via PKA) and enhanced diastolic SR Ca leakage (via CaMKII). Oxidative activation of PKA and CaMKII via NOX2 may represent important pro-arrhythmogenic pathways in the setting of increased Ang II stimulation, which may be relevant for the treatment of arrhythmias in cardiac disease.
- Lead in Shrimp Litopenaeus vannamei Boone in Sublethal Concentrations. [JOURNAL ARTICLE]
- J Toxicol Environ Health A 2014; 77(18):1084-1090.
Determination of the accumulation and elimination of sublethal lead (Pb) in different shrimp tissues may be useful as an indicator of uptake and elimination characteristics of this metal. Aquaculture ponds are particularly influenced by Pb contamination, where aquatic animals may acquire the metal through adsorption to exoskeletons or gills from the surrounding water. Cationic Pb is accumulated preferentially in the nonedible fraction of shrimp, followed by exoskeleton, and to a minor extent in muscle. Lead contents in different tissues were lower than metal levels in exoskeleton. However, the presence of Pb in sediment due to purging may exert adverse consequences on shrimp as bottom feeders.
- Assessment of Genotoxic Effects in Nurses Handling Cytostatic Drugs. [JOURNAL ARTICLE]
- J Toxicol Environ Health A 2014; 77(14-16):879-887.
Several antineoplastic drugs have been classified as carcinogens by the International Agency for Research on Cancer (IARC) on the basis of epidemiological findings, animal carcinogenicity data, and outcomes of in vitro genotoxicity studies. 5-Fluorouracil (5-FU), which is easily absorbed through the skin, is the most frequently used antineoplastic agent in Portuguese hospitals and therefore may be used as an indicator of surface contamination. The aims of the present investigation were to (1) examine surface contamination by 5-FU and (2) assess the genotoxic risk using cytokinesis-block micronucleus assay in nurses from two Portuguese hospitals. The study consisted of 2 groups: 27 nurses occupationally exposed to cytostatic agents (cases) and 111 unexposed individuals (controls). Peripheral blood lymphocytes (PBL) were collected in order to measure micronuclei (MN) in both groups. Hospital B showed a higher numerical level of contamination but not significantly different from Hospital A. However; Hospital A presented the highest value of contamination and also a higher proportion of contaminated samples. The mean frequency of MN was significantly higher in exposed workers compared with controls. No significant differences were found among MN levels between the two hospitals. The analysis of confounding factors showed that age is a significant variable in MN frequency occurrence. Data suggest that there is a potential genotoxic damage related to occupational exposure to cytostatic drugs in oncology nurses.
- Process Monitoring of an HIV Treatment as Prevention Program in British Columbia, Canada. [JOURNAL ARTICLE]
- J Acquir Immune Defic Syndr 2014 Jul 28.
In light of accumulated scientific evidence of the secondary preventive benefits of antiretroviral therapy, a growing number of jurisdictions worldwide have formally started to implement HIV Treatment as Prevention (TasP) programs. To date, no gold standard for TasP program monitoring has been described. Here, we describe the design and methods applied to TasP program process monitoring in British Columbia (BC), Canada.Monitoring indicators were selected through a collaborative and iterative process by an interdisciplinary team including representatives from all five regional health authorities, the BC Centre for Disease Control (BCCDC), and the BC Centre for Excellence in HIV/AIDS (BC-CfE). An initial set of 36 proposed indicators were considered for inclusion. These were ranked on the basis of eight criteria: data quality, validity, scientific evidence, informative power of the indicator, feasibility, confidentiality, accuracy, and administrative requirement. The consolidated list of indicators was included in the final monitoring report, which was executed using linked population-level data.A total of 13 monitoring indicators were included in the BC TasP Monitoring Report. Where appropriate, indicators were stratified by subgroups of interest, including HIV risk group and demographic characteristics. Six Monitoring Reports are generated quarterly: one for each of the regional health authorities and a consolidated provincial report.We have developed a comprehensive TasP process monitoring strategy using evidence-based HIV indicators derived from linked population-level data. Standardized longitudinal monitoring of TasP program initiatives is essential to optimize individual and public health outcomes and to enhance program efficiencies.
- Performance monitoring during associative learning and its relation to obsessive-compulsive characteristics. [JOURNAL ARTICLE]
- Biol Psychol 2014 Jul 26.
Neural responses to performance errors and external feedback have been suggested to be altered in obsessive-compulsive disorder. In the current study, an associative learning task was used in healthy participants assessed for obsessive-compulsive symptoms by the OCI-R questionnaire. The task included a condition with equivocal feedback that did not inform about the participants' performance. Following incorrect responses, an error-related negativity and an error positivity were observed. In the feedback phase, the largest feedback-related negativity was observed following equivocal feedback. Theta and beta oscillatory components were found following incorrect and correct responses, respectively, and an increase in theta power was associated with negative and equivocal feedback. Changes over time were also explored as an indicator for possible learning effects. Finally, event-related potentials and oscillatory components were found to be uncorrelated with OCI-R scores in the current non-clinical sample.
- ASA Score as a Predictor of 30-Day Perioperative Readmission in Patients with Orthopaedic Trauma Injuries: A NSQIP Analysis. [JOURNAL ARTICLE]
- J Orthop Trauma 2014 Jul 25.
Our purpose was to identify the impact of the American Society of Anesthesiologists (ASA) physical status on the 30-day readmission of patients receiving operative management of orthopaedic fractures using the NSQIP database.We analyzed all patients with orthopaedic trauma injuries in the ACS NSQIP database from 2005-2011. A total of 8,761 patients representing 91 orthopaedic trauma procedures were identified and included in analysis after selection. Logistic regressions were conducted to identify the predictive ability of ASA on the likelihood of readmission for patients in each anatomical category (upper extremity, pelvis/acetabulum, lower extremity) and the combined study population.The ASA physical status proved the strongest predictor of 30-day readmission for the selected orthopaedic trauma procedures. After controlling for age, gender, race, and medical comorbidities that were shown to be significant independent risk factors for readmission, ASA score continued to have a significant association on 30-day readmissions in the combined population (OR: 1.45 95% CI: 1.13-1.88, p = 0.001). For the combined analysis, compared to patients with an ASA score of 1, patients with an ASA score of 2 were 1.04 times as likely to have a readmission (p=0.001); patients with an ASA score of 3 were 3.77 times as likely to have a readmission (p=0.001); and patients with an ASA score of 4 were 13.7 times as likely to have a readmission (p=0.001).ASA classification is an indicator for variance in readmission for patients receiving operative treatment of orthopaedic fractures. Given that ASA classification is a universally collected data point, this method can be employed in almost any hospital system and for any operative service. This model may be used to more accurately predict a patient's post-operative course, and the expected risk for readmission, such that hospitals can target these "at risk" individuals and reduce 30-day readmissions.Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
- Is painting by elephants in zoos as enriching as we are led to believe? [Journal Article]
- PeerJ 2014.:e471.
The relationship between the activity of painting and performance of stereotyped and other stress-related behaviour was investigated in four captive Asian elephants at Melbourne Zoo, Australia. The activity involved the elephant being instructed to paint on a canvas by its keeper in front of an audience. Painting by elephants in zoos is commonly believed to be a form of enrichment, but this assumption had not been based on any systematic research. If an activity is enriching we would expect stress-related behaviour to be reduced but we found no evidence of the elephants anticipating the painting activity and no effect on the performance of stereotyped or other stress-related behaviour either before or after the painting session. This indicates that the activity does not fulfil one of the main aims of enrichment. However, if an elephant was not selected to paint on a given day this was associated with higher levels of non-interactive behaviour, a possible indicator of stress. Behavioural observations associated with ear, eye and trunk positions during the painting session showed that the elephant's attentiveness to the painting activity or to the keeper giving instruction varied between individuals. Apart from positive reinforcement from the keeper, the results indicated that elephants gain little enrichment from the activity of painting. Hence, the benefits of this activity appear to be limited to the aesthetic appeal of these paintings to the people viewing them.
- Investigation of temporal vascular effects induced by focused ultrasound treatment with speckle-variance optical coherence tomography. [Journal Article]
- Biomed Opt Express 2014 Jul 1; 5(7):2009-22.
Focused ultrasound (FUS) can be used to locally and temporally enhance vascular permeability, improving the efficiency of drug delivery from the blood vessels into the surrounding tissue. However, it is difficult to evaluate in real time the effect induced by FUS and to noninvasively observe the permeability enhancement. In this study, speckle-variance optical coherence tomography (SVOCT) was implemented for the investigation of temporal effects on vessels induced by FUS treatment. With OCT scanning, the dynamic change in vessels during FUS exposure can be observed and studied. Moreover, the vascular effects induced by FUS treatment with and without the presence of microbubbles were investigated and quantitatively compared. Additionally, 2D and 3D speckle-variance images were used for quantitative observation of blood leakage from vessels due to the permeability enhancement caused by FUS, which could be an indicator that can be used to determine the influence of FUS power exposure. In conclusion, SVOCT can be a useful tool for monitoring FUS treatment in real time, facilitating the dynamic observation of temporal effects and helping to determine the optimal FUS power.
- Evaluation of coronal shift as an indicator of neuroaxial abnormalities in adolescent idiopathic scoliosis: a prospective study. [Journal Article]
- Scoliosis 2014.:9.
In previous studies, many indicator factors have been proposed to select patients who need an MRI screening of the spinal canal. In current study, the clinical and radiologic factors including coronal parameters of the curve were evaluated to find out which indicator is more important.A prospective study included 143 consecutive patients with the diagnosis of adolescent idiopathic scoliosis who were treated between 2010 and 2013 at our spinal clinics. Only patients with normal or subtle neurologic findings were included. All patients were evaluated by a total spine MRI protocol for examination of neuroaxial abnormalities. Known indicators and also coronal shift were analysed in all patients with or without abnormal MRI.The incidence of neuroaxial abnormalities was 11.9% (17 of 143); only 5 patients (3.5%) were operated to treat their neuroaxial problem. The significant indicators of the abnormalities in our patients were: younger age at onset, asymmetric superficial abdominal reflex and, coronal shift more than 15 mm (P = 0.03). Some previously known indicators like atypical curves, male gender, double curves and absence of thoracic lordosis were not different between two groups of the patients.A total spine MRI is recommended at presentation in patients with younger age, abnormal neurologic findings and severe coronal shift.
- Using a slit lamp-mounted digital high-speed camera for dynamic observation of phakic lenses during eye movements: a pilot study. [Journal Article]
- Clin Ophthalmol 2014.:1361-7.
To evaluate a digital high-speed camera combined with digital morphometry software for dynamic measurements of phakic intraocular lens movements to observe kinetic influences, particularly in fast direction changes and at lateral end points.A high-speed camera taking 300 frames per second observed movements of eight iris-claw intraocular lenses and two angle-supported intraocular lenses. Standardized saccades were performed by the patients to trigger mass inertia with lens position changes. Freeze images with maximum deviation were used for digital software-based morphometry analysis with ImageJ.Two eyes from each of five patients (median age 32 years, range 28-45 years) without findings other than refractive errors were included. The high-speed images showed sufficient usability for further morphometric processing. In the primary eye position, the median decentrations downward and in a lateral direction were -0.32 mm (range -0.69 to 0.024) and 0.175 mm (range -0.37 to 0.45), respectively. Despite the small sample size of asymptomatic patients, we found a considerable amount of lens dislocation. The median distance amplitude during eye movements was 0.158 mm (range 0.02-0.84). There was a slight positive correlation (r=0.39, P<0.001) between the grade of deviation in the primary position and the distance increase triggered by movements.With the use of a slit lamp-mounted high-speed camera system and morphometry software, observation and objective measurements of iris-claw intraocular lenses and angle-supported intraocular lenses movements seem to be possible. Slight decentration in the primary position might be an indicator of increased lens mobility during kinetic stress during eye movements. Long-term assessment by high-speed analysis with higher case numbers has to clarify the relationship between progressing motility and endothelial cell damage.