Efforts to advance underwater noise management in Canada: Introduction to the Marine Pollution Bulletin Special Issue.

This introduction to a special issue on approaches to managing underwater noise in Canada provides a brief overview of recent efforts to better understand and reduce anthropogenic underwater noise. Recent programs have aimed to increase understanding of anthropogenic noise in the habitats of highly endangered whales and have supported management actions such as vessel slow downs. Technical workshops have advanced the development of quiet ship design and associated technologies. Collaborative research examined noise levels in the St. Lawrence Estuary and the Arctic Ocean. Efforts to better manage noise have gone beyond shipping: enhanced mitigation measures have been put in place for naval exercises near habitats used by southern resident killer whales, while other work has focused on the identification of appropriate metrics for measuring noise. To coordinate and advance these and other efforts, the Government of Canada is developing a national Ocean Noise Strategy.

Repression of Fyn-related kinase in breast cancer cells is associated with promoter site-specific CpG methylation.

The triple-negative breast cancer subtype is highly aggressive and has no defined therapeutic target. Fyn-related kinase (FRK) is a non-receptor tyrosine kinase, reported to be downregulated in breast cancer and gliomas, where it is suggested to have tumor suppressor activity. We examined the expression profile of FRK in a panel of 40 breast cancer cells representing all the major subtypes, as well as in 4 non-malignant mammary epithelial cell lines. We found that FRK expression was significantly repressed in a proportion of basal B breast cancer cell lines. We then determined the mechanism of suppression of FRK in FRK-low or negative cell lines. In silico analyses of the FRK promoter region led to the identification of at least 17 CpG sites. Bisulphite sequencing of the promoter region revealed that two of these sites were consistently methylated in FRK-low/negative cell lines and especially in the basal B breast cancer subtype. We further show that treatment of these cells with histone deacetylase inhibitors, Entinostat and Mocetinostat' promoted re-expression of FRK mRNA and protein. Further, using luciferase reporter assays, we show that both GATA3-binding protein FOG1 and constitutively active STAT5A increased the activity of FRK promoter. Together, our results present the first evidence that site-specific promoter methylation contributes to the repression of FRK more so in basal B breast cancers. Our study also highlights the potential clinical significance of targeting FRK using epigenetic drugs specifically in basal B breast cancers which are usually triple negative and very aggressive.

Attention deficit hyperactivity disorder, combined type, dysthymic disorder and anxiety disorders: differential patterns of neurodevelopmental deficits.

The associations between neurodevelopmental deficits (NDD) and (1) attention deficit hyperactivity disorder, combined type (ADHD-CT) and (2) internalising disorders have been replicated. To date, the specific association between standardized NDD and carefully defined ADHD-CT alone, dysthymic disorder alone and anxiety disorders alone has not been systematically investigated in children of primary school age. A cross-sectional study of NDD in 99 six- to 12-year-old children with categorically and dimensionally defined ADHD-CT alone, dysthymic disorder alone and anxiety disorders alone and 20 age-matched healthy children was undertaken. The ADHD-CT and dysthymic disorder groups had increased total neurological subtle signs, compared to the anxiety disorders group, which, in turn, had increased total neurological subtle signs compared with the healthy children. Interestingly, the dysthymic disorder children had increased conjugate eye gaze difficulties compared with the other three groups. The differences remained after controlling for full scale IQ. These findings suggest a neurobiological underpinning of dysthymic disorder, while confirming that of ADHD-CT in primary school age children. Future studies will explore whether the above more specific neurological subtle signs are developmental phase specific or independent associations.

Cerebrovascular risk factors, executive dysfunction, and depression in older primary care patients.

OBJECTIVE: "Executive" cognitive functions may be of particular clinical importance in geriatric depression and may reflect underlying cerebrovascular disease. This study examined the associations of selected components of executive function with cerebrovascular risk factors, depression, and overall functional status. METHOD: Study measures were completed on 448 primary care patients aged>or=65 years based on patient interviews and medical chart review. Multiple regression techniques determined the presence of specified independent associations. RESULTS: Some but not all study hypotheses were confirmed. Cerebrovascular risk factors were associated with major depression and with some cognitive measures, but their associations with depression and with the most specific measures of executive function were limited and not independent of overall medical burden. Measures of initiation-perseveration and mental set shifting were associated with overall functional disability; these cognitive measures were not associated with depression diagnosis, or with depressive symptoms when also covarying medical burden or excluding patients with dementia. CONCLUSIONS: Clinicians should be aware of the potential functional significance of these components of cognition. Longitudinal risk factor studies and complementary techniques such as neuroimaging may help identify pathogenetically distinct subgroups of later-life depression that might respond preferentially to specific interventions.

Assessment and monitoring of glycemic control in primary diabetes care: monitoring techniques, record keeping, meter downloads, tests of average glycemia, and point-of-care evaluation.

PURPOSE: To present a review of glucose monitoring methods useful in primary care. DATA SOURCES: Pertinent publications in the literature, printed materials and resources, and the clinical experience of the authors as a referral center for care of patients with diabetes. CONCLUSIONS: Regular monitoring of glucose control is an integral and important aspect of diabetes care. It allows the advanced practice nurse (APN) to assess whether diabetes goals are being met or not, involves patients in the care of their disease, and assists in making informed treatment decisions. IMPLICATIONS FOR PRACTICE: A working knowledge of glucose monitoring methods, monitors, testing devices, and laboratory tests is extremely beneficial for the APN in attaining standards of care for patients with diabetes.

Dysthymic disorder contributes to oppositional defiant behaviour in children with Attention Deficit Hyperactivity Disorder, combined type (ADHD-CT).

BACKGROUND: The specific relationships between oppositional defiant disorder (ODD), ADHD-CT, dysthymic disorder (DD) and anxiety disorders symptoms have not been studied in children with ADHD-CT. The relationship to DD is important because DD is common, has an earlier age of onset, is associated with significant morbidity and with increased rates of treatment non-responsiveness when comorbid with major depressive disorder and/or ADHD-CT. METHODS: 200 clinically referred children with ADHD-CT, without comorbid major depressive disorder, were identified. "ODD", "ADHD-CT", "DD" and "anxiety disorders" symptoms were defined by composite measures of (1) semi-structured clinical interview and (2) parent and/or child standardized questionnaires. Standard multiple regression was used to examine how well "ADHD-CT", "DD" and "anxiety disorders" symptoms predict "ODD" symptoms. RESULTS: Only "ADHD-CT" (15% of the variance) and "DD" (8% of the variance) symptoms made independent significant contributions to the prediction of "ODD" symptoms. LIMITATIONS: The study's sample size did not allow "ODD" and "conduct disorder" symptoms to be analysed separately. CONCLUSIONS: The association of DD with ODD may reflect a unique contribution of DD to ODD in children, whether ADHD-CT is present or not, or only when ADHD-CT is present.

Characteristics of internalizing and externalizing disorders in medication-naive, clinically referred children with attention deficit hyperactivity disorder, combined type and dysthymic disorder.

OBJECTIVE: Internalizing and externalizing disorders are frequently comorbid with attention deficit hyperactivity disorder, combined type (ADHD-CT) and dysthymic disorder (DD) in referred primary school-age children, yet there has been relatively little systematic research of the nature of these comorbid disorders. We describe the characteristics of parent- and child-reported internalizing and externalizing disorders in primary school-age children with ADHD-CT and DD. METHOD: A cross-sectional study of 45 clinically referred medication naive children with ADHD-CT and DD, examining parent and child reports of internalizing and externalizing disorders, defined categorically and dimensionally. RESULTS: Generalized anxiety disorder and separation anxiety disorder were increased in the DD groups, whether ADHD-CT was present or not. Major depressive disorder was increased in the ADHD-CT and DD group compared to the ADHD-CT alone and the DD alone groups. Conduct disorder was increased in the ADHD-CT alone group compared to the DD with and without ADHD-CT groups. Verbal and fullscale IQ were increased in the DD groups, whether ADHD-CT was present or not, compared to the ADHD-CT alone group. CONCLUSIONS: There is emerging evidence that DD and anxiety may represent a different phenotypic expression of a common underlying aetiological process, while the co-occurrence of ADHD-CT and anxiety disorders remains unclear. Only the ADHD-CT and DD group is significantly associated with major depressive disorder, which suggests an additive effect. In contrast, conduct disorder and decreased verbal and fullscale IQ are only associated with the ADHD-CT group, which may suggest a protective effect of DD when comorbid with ADHD-CT. From a research perspective, it is important to confirm these found associations in larger samples derived from epidemiological populations.