Occupational Risk Factors for COPD Phenotypes in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study

Introduction: The contribution of occupational exposure to the risk of chronic obstructive pulmonary disease COPD in population-based studies is of interest. We compared the performance of self-reported exposure to a newly developed JEM in exposure-response evaluation. Methods: We used cross-sectional data from Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of 45–84 year olds free of clinical cardiovascular disease at baseline. MESA ascertained the most recent job and employment, and the MESA Lung Study measured spirometry, and occupational exposures for 3686 participants. Associations between health outcomes (spirometry defined airflow limitation and Medical Research Council-defined chronic bronchitis) and occupational exposure [self-reported occupational exposure to vapor-gas, dust, or fumes (VGDF), severity of exposure, and a job-exposure matrix (JEM)-derived score] were evaluated using logistic regression models adjusted for non-occupational risk factors. Results: The prevalence of airflow limitation was associated with self-reported exposure to vapor-gas (OR 2.6, 95%CI 1.1–2.3), severity of VGDF exposure (P-trend < 0.01), and JEM dust exposure (OR 2.4, 95%CI 1.1–5.0), and with organic dust exposure in females; these associations were generally of greater magnitude among never smokers. The prevalence of chronic bronchitis and wheeze was associated with exposure to VGDF. The association between airflow limitation and the combined effect of smoking and VGDF exposure showed an increasing trend. Self-reported vapor-gas, dust, fumes, years and severity of exposure were associated with increased prevalence of chronic bronchitis and wheeze (P < 0.001). Conclusions: Airflow limitation was associated with self-reported VGDF exposure, its severity, and JEM-ascertained dust exposure in smokers and never-smokers in this multiethnic study.     

Healthcare providers’ awareness of the information needs of their cardiac rehabilitation patients throughout the program continuum

Objective

To (1) describe cardiac rehabilitation (CR) participant information needs, (2) investigate whether CR providers are cognizant of patient's information needs and preferred delivery formats, and (3) investigate whether patient information needs change over the course of CR.

Methods

In this cross-sectional study, 306 CR patients and 28 CR providers completed a survey. The survey consisted of the Information Needs in CR (INCR) questionnaire, and items about preferred education delivery formats.

Results

Low-income CR participants had significantly greater information needs than high-income participants. CR providers were cognizant of patient information needs, except patients did desire more information on diagnosis and treatment than providers perceived (p < 0.01). Books, lectures and discussion were identified as the preferred delivery formats by both patients and providers. There were some significant differences in patient information needs over the course of the program, particularly in relation to concerns and risk factors.

Conclusion

CR patients desire information in many areas, particularly regarding emergency/safety and diagnosis/treatment. CR providers were highly cognizant of patient information needs; however, these do change over time.

Practice implications

These findings could inform evaluation and improvement of CR education programming, to ensure programs are meeting patient information needs across all stages of recovery.     

Vagus Nerve Stimulation and Food Intake: Effect of Body Mass Index

Animal research suggests that vagus nerve stimulation (VNS) is associated with weight loss and decreased appetite. Results from human studies are mixed; some suggest that VNS affects weight whereas others do not, and it is unclear how VNS affects eating behaviors. Baseline body mass index (BMI) and VNS device settings may moderate the effects of VNS on caloric intake. This study investigates the association among BMI, VNS device settings, and caloric intake of highly palatable foods during VNS on versus VNS off sessions in 16 adult patients (62.5% female; BMI mean = 29.11 ± 6.65) using VNS therapy for either epilepsy or depression. Participants attended 2 experimental sessions (VNS on versus off) where they were presented with 4 preferred snack foods totaling 1600 calories. At the start of the session, they either had their VNS devices turned off or left on. Caloric intake was calculated by weighing foods before and after each session. BMI category (overweight/obese and lean) was the between group factor in the analysis. After controlling for covariates, an interaction of condition and BMI category (P = .03) was found. There was an interaction of condition and device output current (P = .05) and a trend toward an interaction of condition and device on time (P = .07). Excess weight may impact how neurobiological signals from the vagus nerve affect appetite and eating. Future research is needed to further elucidate this relationship.     

Cardiac Rehabilitation Series: Canada

Cardiovascular disease is among the leading causes of mortality and morbidity in Canada. Cardiac rehabilitation (CR) has a long robust history here, and there are established clinical practice guidelines. While the effectiveness of CR in the Canadian context is clear, only 34% of eligible patients participate, and strategies to increase access for under-represented groups (e.g., women, ethnic minority groups) are not yet universally applied. Identified CR barriers include lack of referral and physician recommendation, travel and distance, and low perceived need. Indeed there is now a national policy position recommending systematic inpatient referral to CR in Canada. Recent development of 30 CR quality indicators and the burgeoning national CR registry will enable further measurement and improvement of the quality of CR care in Canada. Finally, the Canadian Association of CR is one of the founding members of the International Council of Cardiovascular Prevention and Rehabilitation, to promote CR globally.     

Monomeric site-specific nucleases for genome editing

Targeted manipulation of complex genomes often requires the introduction of a double-strand break at defined locations by site-specific DNA endonucleases. Here, we describe a monomeric nuclease domain derived from GIY-YIG homing endonucleases for genome-editing applications. Fusion of the GIY-YIG nuclease domain to three-member zinc-finger DNA binding domains generated chimeric GIY-zinc finger endonucleases (GIY-ZFEs). Significantly, the I-TevI-derived fusions (Tev-ZFEs) function in vitro as monomers to introduce a double-strand break, and discriminate in vitro and in bacterial and yeast assays against substrates lacking a preferred 5'-CNNNG-3' cleavage motif. The Tev-ZFEs function to induce recombination in a yeast-based assay with activity on par with a homodimeric Zif268 zinc-finger nuclease. We also fused the I-TevI nuclease domain to a catalytically inactive LADGLIDADG homing endonuclease (LHE) scaffold. The monomeric Tev-LHEs are active in vivo and similarly discriminate against substrates lacking the 5'-CNNNG-3' motif. The monomeric Tev-ZFEs and Tev-LHEs are distinct from the FokI-derived zinc-finger nuclease and TAL effector nuclease platforms as the GIY-YIG domain alleviates the requirement to design two nuclease fusions to target a given sequence, highlighting the diversity of nuclease domains with distinctive biochemical properties suitable for genome-editing applications.     

Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance

Background

The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome.

Design and Methods

Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A-producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence.

Results

The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two “non-Th17” interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells.

Conclusions

Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study.     

How Frequently are Words used on Naming Tests used in Spoken Conversation?

Naming, or word-finding ability, is typically assessed using measures that require a patient to name a pictured object. Words used less frequently tend to be more difficult to find when speaking; thus word frequency can be used as a measure of item difficulty on such tests. However, frequency data for words on naming measures has either not been used in the creation of these tests or has been derived from data on how frequently words have been used in written materials. The present study determined how frequently words on the Boston Naming Test (BNT), the Neuropsychological Assessment Battery (NAB) naming subtest, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) naming subtest, and auditory naming measures developed by Hamberger and Seidel (2003, Journal of the International Neuropsychological Society, 9, 479) and Brandt et al. (2010, The Clinical Neuropsychologist, 24, 1326) are used in spoken language. Items on the auditory naming measures had the highest mean frequency, and the BNT items 30–60 had the lowest mean frequency. Furthermore, item frequency on the full BNT, NAB naming forms 1 and 2, and RBANS forms A correlated with item number, indicating items increase in difficulty on these tests, with trends in the same direction found for RBANS form B and Hamberger and Seidel’s auditory naming measure. Finally, differences in mean word frequency between tests underscore how interpretation of change in naming ability based on different measures should be made with caution.