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.     

The relationship of major depressive disorder and gender to changes in smoking for current and former smokers: longitudinal evaluation in the US population

Aims Although depression and smoking are correlated highly, the relationship of major depressive disorder (MDD) to smoking cessation and relapse remains unclear. This study compared changes in smoking for current and former smokers with and without current and life‐time MDD over a 3‐year period. Design Analysis of two waves of longitudinal data from the National Institute on Alcohol Abuse and Alcoholism's National Epidemiologic Survey on Alcohol and Related Conditions (wave 1, 2001–02; wave 2, 2004–05). Setting Data were collected through face‐to‐face interviews from non‐institutionalized United States civilians, aged 18 years and older, in 50 states and the District of Columbia. Participants A total of 11 973 adults (54% male) classified as current or former daily smokers at wave 1 and completed wave 2. Measurements Classification as current or former smokers at wave 1 and wave 2. Findings Smoking status remained stable for most participants. Wave 1 current daily smokers with current MDD [odds ratio (OR) = 1.38, 95% confidence interval (CI): 1.03, 1.85] and life‐time MDD (OR = 1.52, 95% CI: 1.15, 2.01) were more likely than those without the respective diagnosis to report continued smoking at wave 2. Wave 1 former daily smokers with current MDD (OR = 0.44, 95% CI: 0.26, 0.76) were less likely to report continued abstinence at wave 2. None of the gender × MDD diagnosis interactions were significant. Patterns of results remained similar when analyses were limited to smokers with nicotine dependence. Conclusions Current and life‐time major depressive disorders are associated with a lower likelihood of quitting smoking and current major depressive disorder is associated with greater likelihood of smoking relapse.     

Innervation of the feline eyelids

Abstract

The innervation of the eyelids is incompletely understood. This is a particular problem for those who wish to develop animal models of eyelid dysfunction in humans. Blepharospasm, for example, is a disease of uncontrolled eyelid spasm that is difficult to manage clinically because the aetiology is not understood. The anatomical literature on eyelid innervation is sparse and even conflicting. We attempted to study eyelid innervation, both sensory and motor*, with injection of horseradish peroxidase (HRP) into the superior eyelidinferior eyelidand bulbar conjunctiva. We used 13 anaesthetized weanling cats. Shape and structure of the facial nucleus varied along its rostrocaudal extent, but there was a clear demarcation of lateral and medial division. HRP-filled facial nucleus cells were ipsilateral to the injection site, and label appeared throughout the rostrocaudal length. All injection sites, including bulbar conjunctiva, labelled facial nucleus neurons located with overlapping distribution, predominantly in the dorsal part of the lateral division. Likewise, heavy labelling occurred throughout the entire ipsilateral cranial cervical ganglion and the trigeminal ganglion in all kittens. Injection of upper or lower eyelids caused some labelling in the second through the fourth cervical spinal ganglia. [Neurol Res 1992; 14. 000-000]