Pd(II)-Catalyzed Synthesis of Benzocyclobutenes by β-Methylene-Selective C(sp)-H Arylation with a Transient Directing Group.

Methylene-selective C-H functionalization is a significant hurdle that remains to be addressed in the field of Pd(II) catalysis. We report a Pd(II)-catalyzed synthesis of benzocyclobutenes by methylene-selective C(sp)-H arylation of ketones. The reaction utilizes glycine as a transient directing group and a 2-pyridone ligand, which may govern the methylene selectivity by making intimate molecular associations with the substrate during concerted metalation-deprotonation.

Recent applications of C-H functionalization in complex natural product synthesis.

In this review, recent examples featuring C-H functionalization in the synthesis of complex natural products are discussed. A focus is given to the way in which C-H functionalization can influence the logical process of retrosynthesis, and the review is organized by the type and method of C-H functionalization.

Clinical and genetic study of hereditary spastic paraplegia in Canada.

Objective: To describe the clinical, genetic, and epidemiologic features of hereditary spastic paraplegia (HSP) in Canada and to determine which clinical, radiologic, and genetic factors determine functional outcomes for patients with HSP.

Methods: We conducted a multicenter observational study of patients who met clinical criteria for the diagnosis of HSP in the provinces of Alberta, Ontario, and Quebec from 2012 to 2015. Characteristics of the participants were analyzed using descriptive statistics.

Adult and child urinary 2,4-D in cities with and without cosmetic pesticide bylaws: a population-based cross-sectional pilot study.

We evaluated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure in four municipalities with and without cosmetic pesticide bylaws in British Columbia, Canada. We recruited a child (aged 1.5-5 years) and adult from 10 households in each city, who provided urine samples in May and June, 2009.

Replication study of MATR3 in familial and sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by an extensive loss of motor neurons in the primary motor cortex, brainstem, and spinal cord. Genetic studies report a high heritability of ALS. Recently, whole-exome sequencing analysis of familial ALS (FALS) patients allowed the identification of missense variations within the MATR3 gene.

Smoking history is associated to cognitive impairment in Parkinson's disease.

Introduction: Patients with Parkinson's disease (PD) are more likely to suffer from cognitive impairment and dementia than healthy older adults. The aim of this study was to investigate smoking history as a risk factor for cognitive decline in PD.

Method: One hundred thirty-nine PD patients aged 50 years and older (Hoehn and Yahr = 1-3) were recruited from a clinical database.

Synthesis and Performance of a Biomimetic Indicator for Alkylating Agents.

4-(4-Nitrobenzyl)pyridine (NBP) is a colorimetric indicator compound for many types of carcinogenic alkylating agents. Because of the similar reactivity of NBP and guanine in DNA, NBP serves as a DNA model. NBP assays are used in the toxicological screening of pharmaceutical compounds, detection of chemical warfare agents, environmental hygiene technology, preliminary toxicology tests, mutagenicity of medicinal compounds, and other chemical analyses.

Investigation of C9orf72 repeat expansions in Parkinson's disease.

Large repeat expansions in the C9orf72 gene were recently reported to be a major cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Given some of the clinical and pathologic overlap between these 2 diseases and Parkinson's disease, we sought to evaluate the presence of these expansions in a cohort of French-Canadian patients with Parkinson's disease. No pathologic expansion was found in our cohort of patients suggesting that C9orf72 repeat expansions do not play a major role in the pathogenesis of Parkinson's disease.

Clinical validity of the Mattis Dementia Rating Scale-2 in Parkinson disease with MCI and dementia.

The utility of the Mattis Dementia Rating Scale 2 (MDRS-2) in screening for dementia in Parkinson disease (PD) is well documented. However, little is known about its sensitivity to mild cognitive impairment in PD (PD-MCI). This study sought to document the validity of the MDRS-2 for diagnoses of PD-MCI and dementia in PD (PDD).

Mattis Dementia Rating Scale 2: screening for MCI and dementia.

Identifying patients at higher risk of developing dementia is important. The usefulness of the Mattis Dementia Rating scale-Second Edition (MDRS-2) to detect and differentiate between patients with amnestic mild cognitive impairment (A-MCI), Parkinson's disease and MCI (PD-MCI), PD with dementia (PDD), and Alzheimer's disease (AD) was investigated. In all, 22 healthy controls (HC), 22 A-MCI, 22 PD-MCI, 16 PDD, and 22 AD patients were evaluated using an extensive neuropsychological battery, including the MDRS-2.

Association of long ATXN2 CAG repeat sizes with increased risk of amyotrophic lateral sclerosis.

Objective: To analyze the ataxin 2 (ATXN2) CAG repeat size in a cohort of patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Large (CAG)(n) alleles of the ATXN2 gene (27-33 repeats) were recently reported to be associated with an increased risk of ALS.

Design: Case-control study.

LRRK2 is not a significant cause of Parkinson's disease in French-Canadians.

Background: An old founder mutation (G2019S) was found with high frequency in the North African Arabs (30%) and Ashkenazi Jews (18% ).

Objective: Demonstrate if mutations in the LRRK2 gene are a significant cause of Parkinson's disease (PD) in the French-Canadian founder population.

Methods: Cases were recruited through a designated movement disorder clinic in Quebec City.

When passion leads to problematic outcomes: a look at gambling.

Vallerand et al. (2003) have proposed that individuals can have two distinct types of passion toward an activity. Harmonious passion, an internal force leading one to choose to engage in the activity, is proposed to be associated with positive consequences.

Passion and gambling: on the validation of the Gambling Passion Scale (GPS).

Vallerand and his colleagues (Vallerand & Blanchard, 1999; Vallerand, Blanchard, Koestner, & Gagné, 2001) have recently proposed a new concept of passion. According to these authors, passion refers to a strong inclination toward an activity that we like, find important, and in which we invest time. Vallerand et al.

Glucocorticoids decrease endothelin-A- and -B-receptor expression in the kidney.

Glucocorticoids play an important role in circulatory homeostasis and in excess they cause hypertension. These corticosteroids affect the expression of many genes involved in blood pressure control including preproendothelin-1 (PPET-1), the precursor of endothelin-1 (ET-1), a potent vasoactive peptide. We have previously shown that glucocorticoids increase PPET-1 mRNA levels in rat aorta.

Glucocorticoids increase preproendothelin-1 expression in rat aorta.

Glucocorticoids play an important role in circulatory homeostasis. They modulate peripheral resistance by their direct action on blood vessels. We have previously shown that glucocorticoids increase preproendothelin-1 gene transcription rate in vascular smooth muscle cells (Morin C et al.

Transcriptional regulation of pre-pro-endothelin-1 gene by glucocorticoids in vascular smooth muscle cells.

Endothelin is a potent vasoactive peptide involved in the maintenance of vascular tone and in pathophysiological states. Endothelin-1 synthesis is controlled at the transcriptional level. We report that glucocorticoids increase the pre-pro-endothelin-1 gene transcription rate in vascular smooth muscle cells.

Glucocorticoids but not mineralocorticoids modulate endothelin-1 and angiotensin II binding in SHR vascular smooth muscle cells.

Both glucocorticoids and mineralocorticoids are involved in circulatory homoeostasis and blood pressure control. In recent years direct effects of both steroid classes on vascular smooth muscle cells (VSMC) have been reported. We have thus examined the effects of RU 28362, a pure glucocorticoid agonist, and aldosterone, the physiologic mineralocorticoid, on the binding to VSMC from spontaneously hypertensive rats (SHR) of two key vasoactive peptides, endothelin-1 and angiotensin II.

Regulation of 21-hydroxylase activity by steroids.

In this study, we investigated the effect of steroids on guinea pig and bovine adrenal steroidogenesis, especially 21-hydroxylase activity. Analysis of guinea pig adrenal steroids indicated the presence of high concentrations of androstenedione in the guinea pig adrenal; furthermore, in vitro studies using guinea pig adrenal cortex cells in primary culture confirmed that androstenedione is one of the major C19 steroids produced and secreted. The direct action of steroids on steroid production by adrenal cells was investigated.

Isozymes of 11 beta-hydroxysteroid dehydrogenase: which enzyme endows mineralocorticoid specificity?

Intracellular enzymes which interconvert circulating hormones between active and inactive forms aid in regulating the biological activity of the ligand in a cell-specific manner. This is particularly important in mineralocorticoid target tissues where glucocorticoids and mineralocorticoids have equivalent affinity for the mineralocorticoid receptor. Inactivation of glucocorticoids at the 11-hydroxyl position by the action of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) permits the occupation of the mineralocorticoid receptor by aldosterone in the presence of much higher levels of circulating cortisol.

Comparison of quinapril and atenolol as single drugs or in combination with hydrochlorothiazide in moderate to severe hypertensives, using automated ambulatory monitoring.

1. Forty patients with moderate to severe hypertension and daytime ambulatory diastolic blood pressure > or = 90 mm Hg were randomized double-blind to once-daily treatment with either quinapril up to 20 mg (n = 20) or atenolol up to 100 mg (n = 20) as single drugs or in combination with hydrochlorothiazide 25 mg over a period of 12 weeks. 2.

Comparison of amlodipine and captopril in hypertension based on 24-hour ambulatory monitoring.

The efficacy and toleration of once-daily amlodipine (5-10 mg o.d.) and captopril (25-50 mg b.

Steroidogenesis in guinea pig adrenal cortex: effects of ACTH on steroid secretion and steroidogenic enzyme activities and expression.

In this study, we investigated guinea pig adrenal steroidogenesis, specially, C19 steroid production. Analysis of adrenal steroids by high performance liquid chromatography and gas chromatography indicated the presence of androstenedione and 11β-hydroxyandrostenedione. Adrenal androstenedione and 11β-hydroxyandrostenedione levels were stimulated by ACTH administration while only 11β-hydroxyandrostenedione was increased in plasma.

Comparison of the effects of amlodipine and captopril on clinic and ambulatory blood pressure.

Forty-one patients with mild to moderate essential hypertension (sitting diastolic blood pressure (DBP) 95-114 mmHg) were randomised in a double-blind fashion to treatment with either amlodipine 5-10 mg once daily (n = 21) or captopril 25-50 mg twice daily (n = 20) over a period of 8 weeks. Office BP, heart rate and side effects were assessed during the run-in period on placebo, and after 2, 4 and 8 weeks' treatment. Blood pressure and heart rate were measured at the same time at each visit, 12 hours after the last captopril dose and 24 hours after the last amlodipine dose.