bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomodulatory role of chitosan‐based nanoparticles and oligosaccharides in cyclophosphamide‐treated mice
Authors: Mudgal Jayesh , Mudgal Piya Paul , Kinra Manas , Raval Ritu 
Published: January 2019

AbstractChitosan, the deacetylated form of chitin, a natural polysaccharide, is known for its various biomedical applications. The present study aimed at exploring the immunomodulatory properties of chitosan (CSNP) and gallic acid‐grafted chitosan (cGANP) nanoparticles in mice model of cyclophosphamide (CPA)‐induced immunosuppression. In addition, chitooligosaccharides, the hydrolysed form of chitin and chitosan, were also evaluated for its potential against immunosuppression in mice. CPA (80 mg/kg/ip) induced significant immunosuppression, which was reversed with cGANP treatment as indicated by a significant increase in the thymus and spleen indices compared to the CPA‐treated group. The CSNP and chitooligosaccharides (chitin and chitosan) failed to reverse CPA‐induced changes. ELISA revealed an elevation in the levels of IL‐6 and a reduction in IFN‐γ levels with CPA treatment. All the test compounds reduced the IL‐6 levels, whereas only the nanoparticle formulations (CSNP and cGANP) exhibited a significant augmentation in the IFN‐γ levels. Both the cytokines, IL‐6 and IFN‐γ, are secreted separately by two different types of T helper cells (Th cells), which mediate cellular and humoral immune responses in a coordinated manner. Th‐1 cells release IFN‐γ, facilitating cell‐mediated immunity, whereas IL‐6 is released by Th‐2 cells, expediting humoral immune response. The nanoparticles (CSNP and cGANP) seemed to be better immune enhancers than the chitooligosaccharides owing to their ability to reverse the cytokine changes induced by CPA. Overall, it was evident that the nanoparticles, most likely, boosted the cell‐mediated immunity through the induction of the Th‐1 branch of the immune response.
Effectiveness of a physical activity intervention in preschoolers: A cluster‐randomized controlled trial
Authors: Hacke Claudia , Ketelhut Sascha , Wendt Ulrike , Müller Götz , Schlesner Claudia , Ketelhut Kerstin 
Published: January 2019

Several activity interventions in preschool settings exist, but little attention has been paid to effects on hemodynamic factors. The study aimed to assess the effectiveness of an exercise program on health‐related outcomes including blood pressure (BP) and markers of vascular function in preschoolers, with focus on socioeconomic background. This study is a cluster‐randomized controlled trial, with preschool as unit of randomization and children as unit of analysis. Preschools with 3‐ to 6‐year‐old children, stratified by social area, were randomly allocated to: intervention (three clusters, n = 92) including 2 d·wk−1/45 min (6 months) exercise lessons or control (two clusters, n = 43). In total, 135 children (4.8 ± 0.8 y) had minimum one outcome measurement at baseline and follow‐up. Primary outcome: peripheral BP. Secondary outcomes: central BP, pulse wave velocity (PWV), BMI, waist circumference, physical activity measures, motor skills. Maternal education was used as an indicator of socioeconomic status. Mixed models were applied to evaluate differences in mean change. Group allocation had no effect on primary or secondary outcomes. However, the intervention was effective in reducing increases in peripheral systolic BP (−3.4 mm Hg; 95% CI: −6.6; −0.2; P = 0.037), central systolic BP (−3.8 mm Hg; −6.4; −1.1; P = 0.006), and PWV (−0.1 m/s; −0.2; −0.0; P = 0.045) among children whose mothers had the lowest educational level. We found no evidence for effectiveness of a 6‐months preschool‐based exercise program on hemodynamics, anthropometrics, activity, or motor skills, but lack of process evaluations and poor fidelity preclude interpretation of the causal relation. However, the results indicate that children from lower social backgrounds could benefit from early exercise‐promoting interventions.
High‐sensitivity troponin T in marathon runners, marathon runners with heart disease and collapsed marathon runners
Authors: Leckie Todd , Richardson Alan , Watkins Emily , Fitzpatrick Daniel , Galloway Rob , Grimaldi Rachael , Roberts Andrew , Baker Polly 
Published: January 2019

Endurance exercise is an established cause of cardiac troponin (cTn) elevation, of further interest is whether this rise represents clinical significance. This study compared cTnT rise in three cohorts of marathon runners using a high‐sensitivity assay; control runners, those with known heart disease and runners who collapsed at the finish line. Control runners (n = 126) and runners with heart disease (n = 12) were prospectively recruited with cTnT levels measured pre‐race and at race completion. Collapsed runners (n = 15) were retrospectively recruited. A mixed model ANCOVA was used to compare the three groups. Pre‐race median cTnT for the control group and heart disease groups was 3.9 ng/L (IQR 3.1 ng/L) and 4.1 ng/L (IQR 3.4 ng/L). Post‐race values for the three groups were control 45.6 ng/L (IQR 42.5 ng/L), heart disease 41.2 ng/L (IQR 36.1 ng/L), and collapsed 41.9 ng/L (IQR 57.8 ng/L). Post‐race cTnT and cTnT change were significantly correlated with pre‐race cTnT within the control group (r = 0.38 and 0.30, P < 0.01). There was no difference in post‐race cTnT (adjusted for pre‐race cTnT) between the three groups. None of the runners reported symptoms suggestive of acute myocardial infarction on follow‐up. These results demonstrate that marathon running is associated with an asymptomatic cTnT rise for all runners, and this rise is significantly correlated to baseline cTnT levels, in addition, marathon runners with pre‐existing cardiac pathology or who collapse at the finish line do not exhibit an increased cTnT rise compared to healthy runners.
Low prevalence of MDR‐TB in Lao PDR: results from the first national anti‐tuberculosis drug resistance survey
Authors: Iem Vibol , Dean Anna , Zignol Matteo , Vongvichit Phouvang , Inthavong Donekham , Siphanthong Souvimone , Sorsavanh Theppouthone , Kim Sang Jae , Shin Soyoun , Sébert Jacques , Chittamany Phonenaly 
Published: January 2019

AbstractObjectiveTo present results of the first national anti‐tuberculosis (TB) drug resistance survey conducted in Lao PDR between May 2016 and August 2017 to determine the prevalence of resistance to first‐line anti‐TB drugs among new and previously treated pulmonary TB cases in the country.MethodsPatients with sputum smear‐positive pulmonary TB were enrolled from 42 TB laboratories distributed in 40 clusters throughout the country. Survey sites were selected using probability‐proportional‐to‐size sampling among all diagnostic centres in the country. In addition to smear microscopy, all patients underwent Xpert MTB/RIF testing and those found positive to Mycobacterium tuberculosis underwent sputum culture and drug susceptibility testing using the proportion method on solid Löwenstein–Jensen medium.ResultsAmong 1006 eligible patients, 946 sputum smear‐positive and Xpert MTB/RIF positive (Mycobacterium tuberculosis detected) patients were included in the survey, comprising 897 new and 49 previously treated TB cases. The prevalence of rifampicin‐resistant TB was 1.2% (95% CI: 0.5–2.0%, n = 11/897) among new cases and 4.1% (95% CI: 0–9.6%, n = 2/49) among previously treated cases. Among the 946 TB cases confirmed by Xpert MTB/RIF, phenotypic drug sensitivity testing was available for 820 (776 new and 44 previously treated). The prevalence of multidrug‐resistant TB (MDR‐TB) was 0.5% (95% CI: 0–1.0%, n = 4/776) among new cases and 2.3% (95% CI: 0–6.7%, n = 1/44) among previously treated cases. No resistance to second‐line injectable agents nor to fluoroquinolones was detected among MDR‐TB patients.ConclusionsThe first national anti‐TB drug resistance survey in Lao PDR demonstrated an encouragingly low prevalence of MDR‐TB. The results appear lower than previous WHO estimates, and in line with the routine surveillance based on Xpert MTB/RIF testing (conducted among 50% of presumptive TB patients in 2017). The country should continue to expand its Xpert MTB/RIF network and strive to achieve universal drug susceptibility testing.
Determination of minimum inhibitory concentrations for silver sulfadiazine and other topical antimicrobial agents against strains of Pseudomonas aeruginosa isolated from canine otitis externa
Authors: von Silva‐Tarouca Maritta S. E. , Wolf Georg , Mueller Ralf S. 
Published: January 2019

BackgroundOtitis externa is a common presenting complaint in practice. Ear infections by Pseudomonas aeruginosa are particularly problematic due to the organism's high level of resistance and ability to damage the tympanum. Treatment should be based on susceptibility testing although minimum inhibitory concentrations (MICs) are not available for all treatment options. Silver sulfadiazine has been used in cases of recurrent P. aeruginosa otitis, although a MIC for silver sulfadiazine as a single agent has not been established.ObjectivesTo describe susceptibility patterns of P. aeruginosa isolated from canine otitis externa and determine the MIC for silver sulfadiazine and other topical antimicrobials.AnimalsThirty‐six P. aeruginosa isolates were collected from client‐owned dogs, suffering from otitis externa.Methods and materialsSusceptibility patterns were established using disc diffusion susceptibility testing against 17 antimicrobial agents. For determination of the MIC, selected strains were tested against increasing concentrations of marbofloxacin, enrofloxacin, gentamicin, polymyxin B and silver sulfadiazine using broth microdilution.ResultsFor nine of 17 antimicrobial agents, complete resistance was seen in all isolates tested via disk diffusion susceptibility testing. Approximately 94% and 96% of isolates were susceptible to gentamicin and imipenem, respectively. These findings were consistent with broth dilution, where all strains were susceptible to gentamicin. Resistance was higher against polymyxin B and the fluoroquinolones. Silver sulfadiazine was effective in vitro with a MIC ranging from 1 to 64 μg/mL.Conclusions and clinical significanceAs the MIC of silver sulfadiazine was lower than the concentration in a 1% preparation, such a product potentially represents a treatment option for dogs with P. aeruginosa otitis.
Associations between physical activity and asthma, eczema and obesity in children aged 12–16: an observational cohort study
Authors: Jago Russell , Salway Ruth E , Ness Andy R , Shield Julian P Hamilton , Ridd Matthew J , Henderson A John 
Published: January 2019

ObjectivesTo compare the physical activity of adolescents with three common long-term conditions (asthma, eczema and obesity) with adolescents without these conditions.DesignCross-sectional and longitudinal analyses of adolescents at ages 12, 14 and 16 in a large UK cohort study.SettingThe Avon Longitudinal Study of Parents and Children.Participants6473 adolescents with complete accelerometer data at at least one time point.MethodsMean minutes of moderate to vigorous intensity physical activity (MVPA) and sedentary time per day were derived from accelerometer-based measurements at ages 12, 14 and 16. Obesity was defined at each time point from height and weight measurements. Parents reported doctor-assessed asthma or eczema. Cross-sectional and longitudinal regression models examined any differences in MVPA or sedentary time for adolescents with asthma, eczema or obesity compared with those without.ResultsIn longitudinal models, boys engaged in an average of 69.7 (95% CI 67.6 to 71.7) min MVPA at age 12, declining by 3.1 (95% CI 2.6 to 3.6) min/year while girls’ average MVPA was 47.5 (95% CI 46.1 to 48.9) min at age 12, declining by 1.8 (95% CI 1.5 to 2.1) min/year. There was no strong evidence of differences in physical activity patterns of those with and without asthma or eczema. Obese boys engaged in 11.1 (95% CI 8.7 to 13.6) fewer minutes of MVPA, and obese girls in 5.0 (95% CI 3.3 to 6.8) fewer minutes than their non-obese counterparts. Cross-sectional models showed comparable findings.ConclusionsMean minutes of MVPA per day did not differ between adolescents with asthma or eczema and those without, but obese adolescents engaged in fewer minutes of MVPA. Findings reinforce the need for strategies to help obese adolescents be more active but suggest no need to develop bespoke physical activity strategies for adolescents with mild asthma or eczema.
Impact of automated OCT in a high-volume eye urgent care setting
Authors: Kaplan Richard I , Chen Masako , Gupta Meenakashi , Rosen Richard B 
Published: January 2019

Background/AimsOptical coherence tomography (OCT) has become standard of care in the diagnosis and management of a myriad of retinal and optic nerve pathology. Access to diagnostic equipment and skilled imaging personnel in the after-hours setting is often limited. We examined the utility and diagnostic indications for automated OCT in a high-volume after-hours clinic within an eye institute.MethodsOCT images obtained over a period of 15 months were reviewed in the context of electronic patient records. Residents and fellows were surveyed regarding their experience with the OCT and its value in emergency patient management.Results202 patients and 359 eyes were examined. Complaints prompting imaging included flashes/floaters, metamorphopsia, decreased vision and scotomas. Diagnoses included vascular occlusion, retinal detachment, macular hole, cystoid macular oedema and central serous retinopathy. Of the 25 residents and fellows surveyed, most agreed that the OCT that facilitated delivery of optimal urgent management. OCT also aided in the triage of patients to specialty clinics.ConclusionExpanded access to automated OCT in the urgent care setting shows promise for improving the accuracy and timeliness of diagnosis, which can be critical for optimising patient outcomes. OCT also provides clear, immediate documentation of pathology for substantiating medical decision-making.
OPEN INNOVATION GROUNDWORK
Authors: WIKHAMN BJORN REMNELAND , STYHRE ALEXANDER 
Published: January 2019

Although the concept of open innovation has gained much attention in the field of innovation management, few studies have so far theorized how such initiatives are being enacted in practice. This study is based on an inductive empirical analysis of how AstraZeneca, a large biopharmaceutical corporation, implemented an open innovation initiative called BioVentureHub. In the paper we introduce a theoretical model of open innovation enactment based on four interrelated processes. Three of these processes — conceptualization, mobilization, and operationalization — include activities related to preparing for open innovation, what we call open innovation groundwork. The fourth process — facilitation — involves translating the groundwork into actual open innovation. The study contributes to the broader open innovation domain by its detailed account and theorizing of how open innovation is established in practice. Our methodological approach complements the previous research on open innovation that mostly are based on retrospective accounts or are conceptual in nature. Moreover, the study contributes by illustrating a novel initiative from the life science industry, where open innovation is frequently discussed but where still only a few empirical examples are found in academic literature
Duration of Electrocardiographic Monitoring of Emergency Department Patients With Syncope
Authors: Thiruganasambandamoorthy Venkatesh , Rowe Brian H. , Sivilotti Marco L.A. , McRae Andrew D. , Arcot Kirtana , Nemnom Marie-Joe , Huang Longlong , Mukarram Muhammad , Krahn Andrew D. , Wells George A. , Taljaard Monica 
Published: January 2019

Background:
The optimal duration of cardiac rhythm monitoring after emergency department (ED) presentation for syncope is poorly described. We sought to describe the incidence and time to arrhythmia occurrence to inform decisions regarding duration of monitoring based on ED risk stratification.

Methods:
We conducted a prospective cohort study with enrolled adult patients (≥16 years old) presenting within 24 hours of syncope at 6 EDs. We collected baseline characteristics, time of syncope and ED arrival, and the Canadian Syncope Risk Score (CSRS) risk category. We followed subjects for 30 days, and our adjudicated primary outcome was serious arrhythmic conditions (arrhythmias, interventions for arrhythmias, and unexplained death). After excluding patients with an obvious serious condition on ED presentation and those with missing CSRS predictors, we used Kaplan-Meier analysis to describe the time to serious arrhythmic outcomes.

Results:

A total of 5581 patients (mean age, 53.4 years; 54.5% females; 11.6% hospitalized) were available for analysis, including 346 (6.2%) for whom the 30-day follow-up was incomplete and who were censored at the last follow-up time. A total of 417 patients (7.5%) experienced serious outcomes, 207 of which (3.7%; 95% CI, 3.3%–4.2%) were arrhythmic (161 arrhythmias, 30 cardiac device implantations, 16 unexplained deaths). Overall, 4123 (73.9%) were classified as CSRS low risk, 1062 (19.0%) medium risk, and 396 (7.1%) high risk. The CSRS accurately stratified subjects as low risk (0.4% risk for 30-day arrhythmic outcome), medium risk (8.7% risk), and high risk (25.3% risk). One-half of arrhythmic outcomes were identified within 2 hours of ED arrival in low-risk patients and within 6 hours in medium- and high-risk patients, and the residual risk after these cut points were 0.2% for low-risk, 5.0% for medium-risk, and 18.1% for high-risk patients. Overall, 91.7% of arrhythmic outcomes among medium- and high-risk patients, including all ventricular arrhythmias, were identified within 15 days. None of the low-risk patients experienced ventricular arrhythmia or unexplained death, whereas 0.9% of medium-risk patients and 6.3% of high-risk patients experienced them (
P
<0.0001).

Conclusions:
Serious underlying arrhythmia was often identified within the first 2 hours of ED arrival for CSRS low-risk patients and within 6 hours for CSRS medium- and high-risk patients. Outpatient cardiac rhythm monitoring for 15 days for selected medium-risk patients and all high-risk patients discharged from the hospital should also be considered.
Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke
Authors: Pfeiffer Dorothea , Chen Bowang , Schlicht Kristina , Ginsbach Philip , Abboud Sherine , Bersano Anna , Bevan Steve , Brandt Tobias , Caso Valeria , Debette Stéphanie , Erhart Philipp , Freitag-Wolf Sandra , Giacalone Giacomo , Grau Armin J. , Hayani Eyad , Jern Christina , Jiménez-Conde Jordi , Kloss Manja , Krawczak Michael , Lee Jin-Moo , Lemmens Robin , Leys Didier , Lichy Christoph , Maguire Jane M. , Martin Juan J. , Metso Antti J. , Metso Tiina M. , Mitchell Braxton D. , Pezzini Alessandro , Rosand Jonathan , Rost Natalia S. , Stenman Martin , Tatlisumak Turgut , Thijs Vincent , Touzé Emmanuel , Traenka Christopher , Werner Inge , Woo Daniel , Del Zotto Elisabetta , Engelter Stefan T. , Kittner Steven J. , Cole John W. , Grond-Ginsbach Caspar , Lyrer Philippe A. , Lindgren Arne ,   on behalf of CADISP; GISCOME; SiGN studies; and ISGC
Published: January 2019

Background and Purpose—
We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS).

Methods—
Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0–2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs—a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry.

Results—

The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP:
P
=0.0007; odds ratio=0.89; 95% CI, 0.82–0.95 and SiGN/GISCOME:
P
=0.0036; odds ratio=0.94; 95% CI, 0.91–0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80–0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89–0.98) whereas imbalance without ohnologs lacked such an association.

Conclusions—
Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
Spot Urine Sodium-to-Potassium Ratio Is a Predictor of Stroke
Authors: Averill Michelle M. , Young Rebekah L. , Wood Alexis C. , Kurlak Emily O. , Kramer Holly , Steffen Lyn , McClelland Robyn L. , Delaney Joseph A. , Drewnowski Adam 
Published: January 2019

Background and Purpose—
Dietary sodium reduction with concurrent increase in potassium intake is a current public health priority to reduce risk of cardiovascular events. This study explored associations between the spot urine sodium-to-potassium ratio and cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) longitudinal cohort.

Methods—
The MESA is a prospective cohort study of 6814 adults from 4 ethnic groups (European-, Asian-, African- and Hispanic-American) with a mean age of 62 (±10.2) years and an average of 11.7 (±2.2) years of follow-up. Participants were free of clinical cardiovascular disease at baseline. Spot urine sodium and potassium excretion, as a marker of dietary intake, was collected at baseline. The impact of urinary sodium-to-potassium ratio on adjudicated cardiovascular events was assessed using Cox proportional hazards models.

Results—
Only 39% of MESA participants had a urinary sodium-to-potassium ratio ≤1, and these participants experienced only 74 of the 236 strokes. A sodium-to-potassium ratio >1 was associated with a hazard ratio of 1.47 (95% CI,1.07–2.00) for risk of stroke, adjusting for age, sex, race, cardiovascular risk factors, socio-demographic characteristics, body size, and kidney function.

Conclusions—
The spot urine sodium-to-potassium ratio (measurable in routine care) is associated with stroke. A urine sodium-to-potassium ratio of ≤1, may be related to a clinically relevant reduction in stroke risk and is a feasible target for health interventions.