A scoping review of asthma and machine learning.

OBJECTIVE: The objective of this study was to determine the extent of machine learning (ML) application in asthma research and to identify research gaps while mapping the existing literature. DATA SOURCES: We conducted a scoping review. PubMed, ProQuest, and Embase Scopus databases were searched with an end date of September 18, 2020. STUDY SELECTION: DistillerSR was used for data management. Inclusion criteria were an asthma focus, human participants, ML techniques, and written in English. Exclusion criteria were abstract only, simulation-based, not human based, or were reviews or commentaries. Descriptive statistics were presented. RESULTS: A total of 6,317 potential articles were found. After removing duplicates, and reviewing the titles and abstracts, 102 articles were included for the full text analysis. Asthma episode prediction (24.5%), asthma phenotype classification (16.7%), and genetic profiling of asthma (12.7%) were the top three study topics. Cohort (52.9%), cross-sectional (20.6%), and case-control studies (11.8%) were the study designs most frequently used. Regarding the ML techniques, 34.3% of the studies used more than one technique. Neural networks, clustering, and random forests were the most common ML techniques used where they were used in 20.6%, 18.6%, and 17.6% of studies, respectively. Very few studies considered location of residence (i.e. urban or rural status). CONCLUSIONS: The use of ML in asthma studies has been increasing with most of this focused on the three major topics (>50%). Future research using ML could focus on gaps such as a broader range of study topics and focus on its use in additional populations (e.g. location of residence).Supplemental data for this article is available online at http://dx.doi.org/ .

Providing comparison normal examples alongside pathologic thoracic radiographic cases can improve veterinary students' ability to identify abnormal findings or diagnose disease.

Learning by comparison is a frequently employed education strategy used across many disciplines and levels. Interpreting radiographs requires both skills of perception and pattern recognition, which makes comparison techniques particularly useful in this field. In this randomized, prospective, parallel-group study, students enrolled in second and third-year radiology veterinary courses were given a case-based thoracic radiographic interpretation assignment. A cohort of the participants was given cases with side-by-side comparison normal images while the other cohort only had access to the cases. Twelve cases in total were presented to the students, with 10 cases depicting examples of common thoracic pathologies, while 2 cases were examples of normal. Radiographs of both feline and canine species were represented. Correctness of response to multiple choice questions was tracked, as was year and group (group 1: non compare, Control; group 2: compare, Intervention). Students assigned to group 1 had a lower percentage of correct answers than students assigned to group 2 (45% Control vs. 52% Intervention; P = 0.01). This indicates that side-by-side comparison to a normal example is helpful in identifying disease. No statistical significance was noted for the correctness of responses according to the year of training (P = 0.90). The overall poor performance on the assignment, regardless of group or year, shows that students in the early years of undergraduate veterinary radiology training struggle with the interpretation of common pathologies, likely a result of a lack of exposure to a multitude of cases and normal variants.

Targeting glycogen synthase kinase 3 for therapeutic benefit in lymphoma.

Targeting the B-cell receptor and phosphatidylinositol 3-kinase/mTOR signaling pathways has shown meaningful, but incomplete, antitumor activity in lymphoma. Glycogen synthase kinase 3 (GSK3) α and ß are 2 homologous and functionally overlapping serine/threonine kinases that phosphorylate multiple protein substrates in several key signaling pathways. To date, no agent targeting GSK3 has been approved for lymphoma therapy. We show that lymphoma cells abundantly express GSK3α and GSK3ß compared with normal B and T lymphocytes at the messenger RNA and protein levels. Utilizing a new GSK3 inhibitor 9-ING-41 and by genetic deletion of GSK3α and GSK3ß genes using CRISPR/CAS9 knockout, GSK3 was demonstrated to be functionally important to lymphoma cell growth and proliferation. GSK3ß binds to centrosomes and microtubules, and lymphoma cells treated with 9-ING-41 become arrested in mitotic prophase, supporting the notion that GSK3ß is necessary for the progression of mitosis. By analyzing recently published RNA sequencing data on 234 diffuse large B-cell lymphoma patients, we found that higher expression of GSK3α or GSK3ß correlates well with shorter overall survival. These data provide rationale for testing GSK3 inhibitors in lymphoma patient trials.

Personal and early life factors associated with new-onset asthma, remission, and persistence of asthma in a 2-year follow-up of schoolchildren.

OBJECTIVE: The natural course of childhood asthma, after its onset, is characterized by periods of persistence, relapse and remission. To investigate personal and early life factors associated with new-onset asthma, persistence and remission among children. METHODS: The study was conducted in the province of Saskatchewan, Canada. Children in grades Kindergarten to Grade 8 (ages 5-14 years) participated in a cross-sectional study in 2013. In 2015, we approached those who gave consent in 2013 to be re-contacted, creating a prospective cohort. Data were collected using questionnaires in both years. Participants in 2013 who also had data in 2015 (25%: n = 324/1,348) had their asthma status reclassified and longitudinal descriptors were applied: "no asthma", "new-onset asthma", "persistent" or "remission". Personal and early life factors associations with asthma outcomes in 2015 were evaluated. RESULTS: Among those without asthma in 2013 (n = 245), the incidence of new-onset asthma in 2015 was 7.2%. Among those with asthma in 2013 (n = 79), 47.1% had remission and 52.9% had persistent asthma in 2015. Parental history of asthma (adjusted odds ratio (aOR): 4.99; 95% confidence interval (CI): 1.88-28.27), early life respiratory infection (aOR: 1.92; 95%CI: 1.47-7.88), early life allergy [aOR: 6.39; 95%CI: 1.34-30.58) and early life infection (aOR: 4.99; 95%CI: 1.19-20.93) were associated with new onset asthma. Similarly, while parental history of asthma (aOR: 1.13; 95%CI: 0.29-4.34), early life respiratory infection (aOR: 2.71; 95%CI: 0.70-10.45), and early life ear infection (aOR: 1.34; 95%CI: 0.36-5.05) were also positively association with persistent asthma, the associations were not statistically significant. CONCLUSION: Parental history of asthma, early life respiratory infection and allergy might not only influence the onset of childhood asthma but also be associated with asthma persistence.

Serum matrix metalloproteinase-2 as a predictor of level of hypoxemia and severity of obstructive sleep apnea.

PURPOSE: Intermittent hypoxia in obstructive sleep apnea (OSA) resembles ischemia/reperfusion. Oxidative stress during ischemia/reperfusion increases matrix metalloproteinase-2 (MMP-2) activity and leads to adverse cardiovascular consequences in animal models, but there is scarce information about MMP-2 in humans with OSA. The aim of this study was to determine if serum MMP-2 levels of patients with OSA differ from controls and if MMP-2 activity correlates with the severity of OSA and level of hypoxemia. METHODS: Patients with OSA (n = 124) were recruited from the Sleep Disorders Center (Saskatoon City Hospital, Canada) after in-lab polysomnography (PSG). Controls (n = 26) were subjects referred for PSG who did not have OSA. Severity of OSA was categorized according to American Academy of Sleep Medicine criteria. Level of hypoxemia was expressed as oxygen desaturation index (ODI; 3% desaturation). Gelatin zymography was performed to measure serum MMP-2 activity. RESULTS: Serum MMP-2 activity was significantly higher in patients with OSA than in controls (p = 0.029). MMP-2 activity in patients with severe OSA was significantly higher than in those with mild/moderate OSA and controls (p = 0.002). Linear regression showed positive associations with MMP-2 activity in serum for AHI (p < 0.001) and ODI (p = 0.003). The associations persisted after adjustment for multiple confounders, including age, sex, BMI, and cardiovascular disease. CONCLUSIONS: Serum MMP-2 activity was associated with OSA severity, and level of hypoxemia in patients with OSA, suggesting MMP-2 is worth considering as a potential biomarker to be included in future studies on sets of biomarkers for hypoxemic insult in OSA.

Improving hospital safety for patients with chronic kidney disease: a mixed methods study.

BACKGROUND: People living with chronic kidney disease (CKD) require complex medical management and may be frequently hospitalized. Patient safety incidents during hospitalization can result in serious complications which may negatively affect health outcomes. There has been limited examination of how these patients perceive their own safety. OBJECTIVES: This study compared the safety perceptions of patients hospitalized with CKD using two approaches: (a) the Patient Measure of Safety (PMOS) questionnaire and (b) qualitative interviews. The study objectives were to: (1) assess concordance between qualitative and quantitative data on safety perceptions and (2) better understand safety as perceived by study participants. METHODS: A cross-sectional convergent mixed methods design was used. Integration at the reporting level occurred by weaving together patient narratives and survey domains through the use of a joint display. Interview data were merged with results of the PMOS on a case-by-case basis for analysis to assess for concordance or discordance between these approaches to safety data collection. RESULTS: Of the 30 inpatients with CKD, almost one quarter (23.3 %) of participants reported low levels of perceived safety in hospitals. Four major themes emerged from the interviews: receiving safe care; expecting to be taken care of; expecting to be cared for; and reporting safety concerns. Suboptimal communication, delays in care and concerns about technical aspects of care were common to both forms of data collection. Concordance was noted between qualitative and quantitative data with respect to communication/teamwork, respect and dignity, staff roles, and ward type/lay-out. While interviews allowed for participants to share specific concerns related to safety about quality of interpersonal interactions, use of the questionnaire alone did not capture this concern. CONCLUSIONS: Safety issues are a concern for in-patients with CKD. Both quantitative and qualitative approaches provided important and complementary insights into these issues. Narratives were mostly concordant with questionnaire scores. Findings from this mixed methods study suggest that communication, interpersonal interactions, and delays in care were more concerning for participants than technical aspects of care. Eliciting the concerns of people with CKD in a systematic fashion, either through interviews or a survey, ensures that hospital safety improvement efforts focus on issues important to patients.

Are Dietary Factors Associated with Lung Function in Canadian Adults?

Purpose: The purpose of this study was to explore the impact of dietary factors and biomarkers on lung function among Canadian adults (18-79 years). Methods: Our data source was the Canadian Health Measures Survey Cycle-3, which included 3397 adults. The household and clinic questionnaires and physical measures were used to assess individual dietary factors, modified Mediterranean Diet Scores, and biomarkers. Results: The overall mean percent predicted values for FVC and FEV1 were 97% and 95%, respectively. While somewhat inconsistent between outcomes, higher lung function was associated with bean, grain, milk, fruit, and vegetable consumption, whereas lower lung function was associated with egg and potato consumption. Among the biomarkers, vitamin D, chloride, total serum protein, and red blood cell folate were associated with higher lung function, whereas C-reactive protein and vitamin B12 was associated with lower lung function. Conclusion: Our study provides support for an association between some dietary factors and lung function, though not entirely consistent between a specific dietary factor and the outcomes studied (FVC, FEV1, FVC/FEV1, and FEF25%-75%). The associations between a specific biomarker and lung function were more consistent (i.e., observed with a larger number of lung function outcomes) than were the dietary factors.

Depression and binge drinking in farm and non-farm rural adults in Saskatchewan, Canada.

INTRODUCTION: Despite some attention paid to farm stress in the popular press, recent Canadian research examining the mental wellbeing of farming populations relative to other rural dwellers is sparse. International research on the topic has shown inconsistent findings and has mainly focused on men. The objective of the present study was to examine the correlates of mental health among rural Saskatchewan women and men, positioning farm/non-farm residence as a main explanatory variable, and depression and binge drinking as measures of mental health. METHODS: The cross-sectional sample consisted of 1701 women (47.8% farm) and 1700 men (53.3% farm) who participated in the 2014 phase of the Saskatchewan Rural Health Study, a prospective cohort study primarily examining the respiratory health of rural people in the southern part of the province of Saskatchewan, Canada. Data were collected using mailed self-report questionnaires and included measures of mental health assessing health professional diagnosed depression and binge drinking, in addition to a broad array of demographic characteristics, stressors and resources. Multiple logistic regression was the primary method of analysis; generalized estimating equations were utilized to account for household clustering. All analyses were conducted separately for women and men and by mental health indicator. RESULTS: Farm/non-farm residence was related to depression but only under particular circumstances, which in turn differed by gender. In women, non-farm residents with two or more chronic conditions reported more depression than their farm counterparts (odds ratio (OR)=2.62; 95% confidence interval (CI) 1.28-5.36); non-farm men with secondary school education reported greater depression than farm-dwelling men (OR=2.93; 95%CI 1.31-6.59). The remaining correlates of depression were generally consistent with previous research in rural populations, including younger age, being non-partnered (men only), higher stress, greater financial strain (women only) and lower social support (women only). Binge drinking was significantly elevated in non-farm women (OR=1.68; 95%CI 1.21-2.33) and non-farm men (OR=1.70; 95%CI 1.33-2.17) compared to the farming population. Among women only, not having access to a regular family doctor/nurse practitioner was associated with an increased likelihood of binge drinking (OR=2.05; 95%CI 1.13-3.71) compared to women perceiving better access. CONCLUSION: The present study is one of very few recently published quantitative studies of the correlates of mental health among farm and non-farm adults in rural Canada. The findings suggest that non-farm dwellers in rural Saskatchewan may be more vulnerable to compromised mental health than their farming counterparts. Additional research employing a longitudinal design and enhanced measurement is required to confirm or refute these findings.

Prevalence and Risk of Obstructive Sleep Apnea and Arterial Hypertension in the Adult Population in Poland: An Observational Subset of the International Prospective Urban Rural Epidemiology (PURE) Study.

Obstructive sleep apnea (OSA) is a common breathing disorder affecting millions of people worldwide. The disorder is connected with serious consequences including hypertension, myocardial infarction, arrhythmias, coronary disease, cardiac insufficiency, stroke, transient ischemic attack, and cognitive decline. Epidemiological data assessing the prevalence of OSA in different countries vary in methodology, size, and characteristics of population chosen and thus are hardly comparable. There are very few reports on the prevalence of OSA and on the diagnostic accuracy of sleep questionnaires available in Poland. In this report we present the analysis of the prevalence of, and risk factors for OSA in the Polish adult population consisting of 613 community-based subjects (227 men and 386 women). The study was based on the STOP-BANG questionnaire, a validated Screening Tool for OSA in primary care. It is a part of Polish subset of the Prospective Urban Rural Epidemiology (PURE) study, an ongoing population cohort study of individuals from urban and rural communities from 21 countries. We took into account age, gender, body mass index (BMI), and antihypertensive treatment. The findings are that over one half of the Polish population investigated had a moderate to high risk of OSA (66.5% of men and 60.1% of women). After the adjustments for age, gender, and BMI we noticed a dose-response relationship between arterial blood pressure behavior and OSA. The association was significant among women, but not men. Based on previous studies we can assume that one half of this high risk group would be further diagnosed for OSA. This study, the first large scale screening for OSA in Poland, shows a substantial, much higher than previously appreciated, prevalence of risk for OSA in the population at large.

Consequences of Changing the GOLD Reports (2007-2011-2017) on the Treatment Regimen of Patients with COPD.

Detailed treatment regimens for patients with chronic obstructive pulmonary disease (COPD) were developed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Every few years the method of classification of COPD severity and the treatment recommendations are significantly revised. The aim of this study was to determine the clinical implications of changing GOLD reports (2007-2011-2017) and the impact that these changes would have on pharmacological treatment regimens of patients with COPD. A group of 500 randomly chosen primary care physicians in Poland each provided information on 10 consecutive patients diagnosed with COPD. This data was used to simulate the therapeutic consequences of the update of the GOLD 2007 report to GOLD 2011 and GOLD 2017. Pharmacological treatment algorithms from the GOLD 2007 report prefer the use of inhaled corticosteroids (ICS) and short-acting bronchodilators (60.2% and 50%, respectively). Compared to the GOLD 2007 report, there would be an almost eightfold reduction in the frequency of short-acting bronchodilator using the GOLD 2011 report and over fourfold decrease using the GOLD 2017 report. With each subsequent update of the GOLD report, the frequency of use of ICS would be significantly (p < 0.001) reduced. Pharmacological treatment by the GOLD 2011 and 2017 reports would be dominated by the use of long-acting bronchodilators from the group ß2-agonists and muscarinic antagonist groups. Updates from the GOLD 2007 COPD report to GOLD 2011 and 2017 would have a significant impact on everyday clinical practice. Changes would result in a reduction of treatment intensity.

Childhood asthma in Batumi, Georgia: Prevalence and environmental correlates.

OBJECTIVE: A relative lack of data for Eastern Europe and unknown epidemiology of childhood asthma in Batumi (Georgia) justified a study aimed at determining the prevalence of physician-diagnosed asthma and related respiratory conditions, a comparison of the prevalence of these conditions between urban and rural children, and identification of their environmental correlates. METHODS: Subjects of the cross-sectional population-based study were 3238 urban and 2081 rural children aged 5-17 years whose respiratory status was assessed using the ISAAC questionnaire. RESULTS: The overall prevalence of asthma was larger in rural children than in urban children (2.8% vs. 1.8%, respectively; p = 0.01). Spastic bronchitis occurred with similar frequency in urban (7.8%) and rural children (6.5%). Compared with urban children, rural subjects had dry cough at night (13.1 vs 8.2%, p < 0.001) and attacks of dyspnea (4.7 vs 2.4%, p < 0.001) more often. The prevalence of other symptoms did not differ significantly between urban and rural subjects. Results of multivariate analyses showed that both asthma and spastic bronchitis were associated (p < 0.05) with parental history of asthma, dampness in the house, and poor financial standing of the family. In addition, asthma was related to coal/wood-based heating whereas spastic bronchitis was associated with passive smoking and lower parental education. CONCLUSIONS: The findings show a low prevalence of ever-diagnosed asthma in the examined population. Nosological tradition and similar correlates of asthma and spastic bronchitis suggest that some cases of asthma might be included in the diagnostic category of spastic bronchitis.

Asthma diagnosis among children along an urban-rural gradient.

OBJECTIVE: Studies have reported lower asthma prevalence in rural compared to urban areas. While environmental factors have mostly been implicated for these differences, the lower asthma prevalence could also be linked to asthma under-diagnosis in rural children. We investigate if rural children experience under-diagnosis of asthma more compared to urban children. METHODS: In 2013, we conducted a cross-sectional survey of schoolchildren across an urban-rural gradient in Saskatchewan, Canada. The participants formed sampling frame for future studies. In 2015, we approached those who gave consent in 2013 for further testing, repeated the survey, and conducted clinical testing. Based on survey responses, children were classified into "no asthma," "at-risk-for-asthma," and "diagnosed asthma." We then classified asthma status as either "no asthma" or "probable asthma" based on a validated asthma algorithm. RESULTS: The study population of 335 schoolchildren (aged 7-17 years) comprised of 73.4% from large urban, 13.7% from small urban, and 12.8% from rural areas. Proportion with report of physician-diagnosed asthma was 28.5% (Large urban), 34.8% (Small urban), and 20.9% (Rural). Mean percent predicted FEV1 and FEF25%-75% were lower in rural compared to small urban and large urban children (p < 0.05). Among those not classified as with "diagnosed asthma" by the survey, the algorithm further identified presence of asthma in 5.5% large urban, 8.1% small urban, and 18.8% rural children (p = 0.03). CONCLUSION: The study revealed evidence of asthma underdiagnosis in rural areas and further supports the use of objective measures in addition to symptoms history when investigating asthma across urban-rural gradients.

The association between endotoxin in house dust with atopy and exercise-induced bronchospasm in children with asthma.

BACKGROUND: Studies have reported protective and adverse associations between microbial exposure and childhood asthma. However, among children with asthma the relationships between endotoxin and exercise-induced bronchospasm (EIB) is less clear. OBJECTIVE: We investigated the association between exposure to endotoxin in house dust with atopy and EIB in children with asthma. METHODS: A cross-sectional survey was conducted among schoolchildren (aged 7-17 years) in the province of Saskatchewan, Canada. A subpopulation with asthma (n = 116) were identified from 335 participants using a validated asthma algorithm. We determined atopy among the asthma subpopulation by skin prick testing (SPT) while EIB was evaluated using exercise challenge testing (ECT). Dust samples were collected from mattress and play area floors, and endotoxin was measured in dust extracts. Logistic regression analyses were used to explore associations between endotoxin with atopy and EIB. RESULTS: Among the 116 children with asthma, 99 completed SPT and all had completed ECT. Of these, 71/99 (71.7%) were atopic and 26/116 (22.4%) had EIB. Exposure to high play area endotoxin concentration [adjusted odds ratio (aOR) = 0.15, 95% CI: 0.03-0.85] and load (aOR = 0.11, 95% CI: 0.02-0.73) were negatively associated with atopy. In contrast, EIB was positively associated with high mattress endotoxin concentration (aOR = 6.01, 95% CI: 1.20-30.13). CONCLUSION: Indoor microbial endotoxin exposure has varied associations with atopy and exercise-induced bronchospasm among children with asthma.

Predictors of Physical Activity Levels in Community-Dwelling Older Adults: A Multivariate Approach Based on a Socio-Ecological Framework.

The purpose of this study was to explore cross-sectional relationships between self-reported physical activity (PA) and personal, social, and environmental factors in community-dwelling adults aged 50 years and older. Accounting for clustering by neighborhood, generalized estimating equations were used to examine associations between selected correlates and the Physical Activity Scale for the Elderly (PASE) score while adjusting for confounders. Data for 601 participants were analyzed: 79% female, 37% married, mean age 76.8 (± 8.7) years, mean PASE score 112.6 (± 64.8). Age, living in seniors' housing, using nursing/home care services, receiving encouragement to be active, and having benches available in the neighborhood were inversely associated with PASE. Self-efficacy, SF-12 score, PA barriers, social support, and the presence of trails showed positive associations. Several personal, social, and environmental factors associated with PA were identified. The inverse association between PA and living in seniors' housing units should be considered when developing PA programs for older adults.

Exposure to agricultural hazards among children who visit farms.

BACKGROUND: Children are commonly injured on farms, yet no studies provide evidence about exposures that leave rural children visiting farms at risk. OBJECTIVES: The objectives of this study were to study (a) how frequently rural nonfarm children are exposed to farms, farm work and associated activities; and (b) the safety conditions and practices on farms being visited. METHODS: A cross-sectional survey was administered in Saskatchewan, Canada to rural parents during 2014. Participation included reports on 458 farms visited by rural children, and then 549 children from 312 families who had been exposed to a farm in the past year. Child-level indicators included age, sex, farm safety education and training, engagement in farm work and play activities and exposure to specific farm safety hazards. Farm-level indicators included self-perceived safety conditions, and child supervision practices. RESULTS: One-third of the children sampled (n=549) had been exposed to a farm in the past year. Safety conditions, practices and supervision varied by demographic subgroup. Farm safety education and agriculture training were most common in the oldest age group (13 to 17 years; 24.7% and 9.2%, respectively) of which 40.8% had worked on a farm previously, averaging 10 hours/week (interquartile range 3 to 20) during summer months. Mechanized and nonmechanized work was observed for children of both sexes and rose with age. Physical hazards were reported both proximally (≤100 yards) and distally (>300 yards) to farm homes. CONCLUSIONS: Children who visit farms are potentially exposed to risk, and these risks increase with age as children take on formal work roles, leaving them vulnerable to farm injury.

Comparison of spirometric results obtained from the sitting and standing position in children participating in an epidemiological study.

INTRODUCTION: It is recommended that spirometric testing in children be completed while sitting. Our experience indicates that children prefer standing during spirometry. AIM: We sought to compare spirometric results obtained from the sitting (SIP) and standing (STP) positions. MATERIAL AND METHODS: Two testing sessions were performed in random order (SIP vs. STP: 30-45 min apart) in 118 children (7-13 years), attending one, randomly selected, primary school (response rate: 92%). RESULTS: Acceptable quality was found in 77.9% of STP and 77.1% of SIP maneuvers. Higher values of spirometric variables on STP, compared to SIP, were obtained for forced vital capacity (FVC) (2.12 ±0.41 l vs. 2.11 ±0.39 l) and forced expiratory volume in 1 s (FEV1) (1.78 ±0.36 l vs. 1.77 ±0.35 l) but the differences were not statistically significant. Relative between-position differences (RBPD) ≤ 5% were found with the following frequencies: FVC: 56.4%, FEV1: 69.2%, PEF: 21.7%, and FEF25-75: 24.3%. Similar patterns were found for FEF25, FEF50, and FEF75. Relative between-position differences were related to age in the case of FEV1 (p = 0.005), FEF25 (p = 0.02), and FEF25-75 (p = 0.01) where older children had smaller RBPD. Forced vital capacity RBPD was lower (p = 0.01) in subjects with current wheeze; PEF RBPD were lower (p = 0.02) in children with asthma. CONCLUSIONS: In epidemiological studies, the position of spirometric testing does not affect the results of lung function assessment.

Drugs with anti-oxidant properties can interfere with cell viability measurements by assays that rely on the reducing property of viable cells.

Cell viability assays such as Cell Titer Blue and Alamar Blue rely on the reducing property of viable cells to reduce the reagent dye to a product which gives a fluorescent signal. The current manufacture-recommended protocols do not take into account the possibility of the reagent substrate being reduced directly to the fluorescent product by drugs with an anti-oxidant property. After suspecting spurious results while determining the cytotoxic potential of a drug of interest (DOI) with known anti-oxidant property against a renal cell cancer (RCC) cell line, we aimed to establish that drugs with anti-oxidant property can indeed cause false-negative results with the current protocols of these assays by direct reduction of the reagent substrate. We also aimed to counter the same with a simple modification added to the protocol. Through our experiments, we conclusively demonstrate that drugs with anti-oxidant properties can indeed interfere with cell viability measurements by assays that rely on the reducing property of viable cells. A simple modification in the protocol, as elaborated in the manuscript, can prevent spurious results with these otherwise convenient assays.Laboratory Investigation advance online publication, 27 February 2017; doi:10.1038/labinvest.2017.18.

Clinical efficacy and safety of surface imaging guided radiosurgery (SIG-RS) in the treatment of benign skull base tumors.

Frameless, surface imaging guided radiosurgery (SIG-RS) is a novel platform for stereotactic radiosurgery (SRS) wherein patient positioning is monitored in real-time through infra-red camera tracking of facial topography. Here we describe our initial clinical experience with SIG-RS for the treatment of benign neoplasms of the skull base. We identified 48 patients with benign skull base tumors consecutively treated with SIG-RS at a single institution between 2009 and 2011. Patients were diagnosed with meningioma (n = 22), vestibular schwannoma (n = 20), or nonfunctional pituitary adenoma (n = 6). Local control and treatment-related toxicity were retrospectively assessed. Median follow-up was 65 months (range 61-72 months). Prescription doses were 12-13 Gy in a single fraction (n = 18), 8 Gy × 3 fractions (n = 6), and 5 Gy × 5 fractions (n = 24). Actuarial tumor control rate at 5 years was 98%. No grade ≥3 treatment-related toxicity was observed. Grade ≤2 toxicity was associated with symptomatic lesions (p = 0.049) and single fraction treatment (p = 0.005). SIG-RS for benign skull base tumors produces clinical outcomes comparable to conventional frame-based SRS techniques while enhancing patient comfort.

Prevalence, risk factors, and clinical outcomes of atopic and nonatopic asthma among rural children.

BACKGROUND: Because of time and cost constraints, objective classification of atopic and nonatopic asthma has been limited in large epidemiologic studies. However, as we try to better understand exposure-outcome associations and ensure appropriate treatment of asthma, it is important to focus on phenotype-defined asthma classification. OBJECTIVE: To compare atopic and nonatopic asthma in rural children with regard to risk factors and clinical outcomes. METHODS: We conducted a cross-sectional study in rural Saskatchewan, Canada, in 2011. Parents of 6- to 14-year-old children completed a health and exposure survey. Skin prick tests were completed in a subsample of 529 children. Asthma was based physician diagnosis. Asthma status was defined as no asthma, nonatopic asthma, and atopic asthma. RESULTS: Asthma prevalence was 14.7% of which 32.1% of cases were atopic. After adjustment, early respiratory illness and a family history of asthma were predictors of childhood asthma, regardless of atopic status (P < .05). Being overweight and having a dog in the home were associated with an increased risk of nonatopic asthma (P < .05). A mother with a history of smoking increased the risk of atopic asthma (P = .01). Compared with those with nonatopic asthma, in the past 12 months, children with atopic asthma were more likely to report a sneezy, runny, or blocked nose or have shortness of breath (odds ratio >2), whereas those with nonatopic asthma were more likely to have parents who missed work (odd ratio >3). Those with nonatopic asthma had significantly lower forced expiratory volume in 1 second compared w2ith those with atopic asthma. CONCLUSION: Exposures may contribute differentially to atopic and nonatopic asthma and result in differential clinical presentation or burden. The study of these characteristics is important for etiologic understanding and management decisions.

Lung function in relation to farm dwelling and farming activities in rural dwelling children.

BACKGROUND AND OBJECTIVE: The relationship between farming exposures and pulmonary function in a rural paediatric population was evaluated. METHODS: Baseline data collection records of the Saskatchewan Rural Health Study (SRHS), a population-based study, were used. A subset of children (6-14 years old) participated in clinical testing, including anthropometric measures and pulmonary function testing (PFT), using spirometry (n = 584). PFTs followed ATS criteria and all statistical analyses were controlled for age, sex and height. RESULTS: Among clinical testing participants, 47.5% were females and 54.5% were farm dwelling. Of those living on farms, 77.5% were livestock farms. Mean percent predicted value (PPV) for forced expiratory volume in 1 s (FEV1 ) and forced vital capacity (FVC) among children living on a farm were 104.8% and 105.4%, respectively. Mean PPV for FEV1 and FVC among children not living on a farm were 102.7% and 101.4%, respectively. After adjustment, higher FEV1 (=0.079, SE = 0.033, P = 0.03) and FVC (=0.110, SE = 0.039, P = 0.006) were seen among children living on a farm. A trend towards lower FEV1 /FVC ratio (-0.013, SE = 0.008, P = 0.09) among children living on a farm was seen compared with children not living on a farm. Higher FVC and lower FEV1 /FVC ratio were seen in children who regularly emptied grain bins (P < 0.05). Trends towards higher FEV1 (P = 0.14) and FVC (P = 0.08) were also seen with children living on a farm in the first year of life. Since the majority of the population was Caucasian (91%), the results were not race-corrected. CONCLUSION: We addressed the lack of knowledge regarding the association between lung function and rural exposures, and found that differences in lung function were seen between children living on a farm and not living on a farm in rural areas and certain farming activities, specifically emptying grain bins, where lung function was generally better in those living on a farm.