Atrial Fibrillation Clinics in Canada: A Nationwide Project Report

The increased prevalence of atrial fibrillation (AF) has led to specialized AF clinics (AFCs) to facilitate management of AF patients. In this article we report on outpatient AFCs in Canada, which is essential to health policies required to standardize the performance of existing AFCs and help design new AFCs. We surveyed 14 clinics in 5 provinces; 100% provided responses to a detailed questionnaire on clinic processes and care practices. Fourteen care maps were analyzed, and 5 models of care were identified; 4 were specific to AFCs. An online survey with 49 questions included items on: (1) process before visit; (2) process at visit; (3) patient education provided; (4) outreach; and (5) specific clinic information. Clinicians’ advice to patients on self-care items such as: (1) amount of alcohol and (2) caffeine intake; (3) exercise activity; (4) stressful events; (5) “when to go to the emergency department”; and (6) lifestyle changes, were evaluated to assess consistency in practice. There were moderate variances in clinicians’ advice to patients in 5 of 6 self-care items. The 1 item that had 100% consistent practice recommendation was when to go to the emergency department. A guideline-based clinical assessment checklist (CAC) was piloted to obtain feedback on its usability in real-world practice; revisions finalized the “simplified CAC” for AF care encompassing 35 data points with rationale. There was 100% positive feedback on its ability to provide baseline elements in AF care. When validated, a “simplified CAC” can facilitate a standardized clinical assessment tool in clinical practice.     

Expression and characterization of αvβ5 integrin on intestinal macrophages

Macrophages play a crucial role in maintaining homeostasis in the intestine, but the underlying mechanisms have not yet been elucidated fully. Here, we show for the first time that mature intestinal macrophages in mouse intestine express high levels of αvβ5 integrin, which acts as a receptor for the uptake of apoptotic cells and can activate molecules involved in several aspects of tissue homeostasis such as angiogenesis and remodeling of the ECM. αvβ5 is not expressed by other immune cells in the intestine, is already present on intestinal macrophages soon after birth, and its expression is not dependent on the microbiota. In adults, αvβ5 is induced during the differentiation of monocytes in response to the local environment and it confers intestinal macrophages with the ability to promote engulfment of apoptotic cells via engagement of the bridging molecule milk fat globule EGF‐like molecule 8. In the absence of αvβ5, there are fewer monocytes in the mucosa and mature intestinal macrophages have decreased expression of metalloproteases and IL 10. Mice lacking αvβ5 on haematopoietic cells show increased susceptibility to chemical colitis and we conclude that αvβ5 contributes to the tissue repair by regulating the homeostatic properties of intestinal macrophages.     

Blood-Brain Barrier Permeability of Asiaticoside,Madecassoside and Asiatic Acid in Porcine Brain Endothelial Cell Model

Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (P_app) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10^?6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases.     

Effect of sarpogrelate on cardiovascular disorders

The present article, dedicated to Dr NS Dhalla on the occasion of the jubilee of his life’s work, is a brief review of articles based on the authors’ studies of sarpogrelate conducted in collaboration with Dr NS Dhalla. These studies on the effects of sarpogrelate on cardiovascular disorders have been ongoing for more than 10 years, and 10 articles have been published to date.     

The Absence of HIV Mutations in Cerebrospinal Fluid and in Peripheral Blood Mononuclear Cells During a Regimen Containing Trizivir Plus Tenofovir

Abstract

Methotrexate (MTX) is widely used in the treatment of hematological diseases. The typical side-effects of high-dose MTX chemotherapy on the CNS range from asymptomatic white matter changes to severe CNS demyelination. MTX neuro - toxicity has been described to be associated with homocysteine and folate levels as well as genetic variants affecting methionine metabolism. Here we describe a case of severe, acute MTX-induced encephalopathy in a patient who was found to be homozygous for the rare missense variant methionine synthase (MTR) c.2756A>G (D919G), which may have modified the effect of MTX on homocysteine metabolism. This finding encourages further studies to determine to what extent the individual conditions of folate and methionine metabolism influence the effects or side-effects of MTX treatment.     

Detection of mono- and di-hexoses as metabolites of 4-bromoaniline using HPLC-TOF-MS/MS

1. The metabolic fate of 4-bromoaniline (4-BrA) was investigated in rat following intraperitoneal administration at 50?mg kg ? 1 using HPLC-TOF-MS/MS. 2. The sensitivity provided by the use of TOF-MS/MS, aided by the distinctive isotope pattern resulting from the presence of the bromine substituent in the molecule, enabled the detection of many previously uncharacterized metabolites in the samples. 3. Several groups of minor metabolites were detected in the urine that corresponded to a number of isomeric hexose and di-hexose-containing conjugates (possibly glucosides and diglucosides) of 4-BrA. 4. As well as hexose and di-hexose conjugates of 4-BrA, several further groups of metabolites that also contained either a sulphamate or sulphate group in addition to the sugar moieties were also detected.     

APOε2 and education in cognitively normal older subjects with high levels of AD pathology at autopsy: findings from the Nun Study

Asymptomatic Alzheimer''s disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE could be associated with the different clinical outcomes between ASYMAD and MCI subjects despite equivalent AD pathology. A total of 523 brains from the Nun Study were screened for this investigation. The results showed higher APOε2 frequency (p < 0.001) in ASYMAD (19.2%) vs. MCI (0%) and vs. AD (4.7%). Furthermore, higher education in ASYMAD vs. MCI and AD (p < 0.05) was found. These novel autopsy-verified findings support the hypothesis of the beneficial effect of APOε2 and education, both which seem to act as contributing factors in delaying or forestalling the clinical manifestations of AD despite consistent levels of AD pathology.     

An insight into electrical resistivity of white matter and brain tumors

BackgroundThere is a lack of information regarding electrical properties of white matter and brain tumors.ObjectiveTo investigate the feasibility of in-vivo measurement of electrical resistivity during brain surgery and establish a better understanding of the resistivity patterns of brain tumors in correlation to the white matter.MethodsA bipolar probe was used to measure electrical resistivity during surgery in a prospective cohort of patients with brain tumors. For impedance measurement, the probe applied a constant current of 0.7 μA with a frequency of 140 Hz. The measurement was performed in the white matter within and outside peritumoral edema as well as in non-enhancing, enhancing and necrotic tumor areas. Resistivity values expressed in ohmmeter (Ω1m) were compared between different intracranial tissues and brain tumors.ResultsNinety-two patients (gliomas WHO II:16, WHO III:10, WHO IV:33, metastasis:33) were included. White matter outside peritumoral edema had higher resistivity values (13.3 ± 1.7 Ω1m) than within peritumoral edema (8.5 ± 1.6 Ω1m), and both had higher values than brain tumors including non-enhancing (WHO II:6.4 ± 1.3 Ω1m, WHO III:6.3 ± 0.9 Ω1m), enhancing (WHO IV:5 ± 1 Ω1m, metastasis:5.4 ± 1.3 Ω1m) and necrotic tumor areas (WHO IV:3.9 ± 1.1 Ω1m, metastasis:4.3 ± 1.3 Ω1m), p=<0.001. No difference was found between low-grade and anaplastic gliomas, p = 0.808, while resistivity values in both were higher than the highest values found in glioblastomas, p = 0.003 and p = 0.004, respectively.ConclusionsThe technique we applied enabled us to measure electrical resistivity of white matter and brain tumors in-vivo presumably with a significant effect with regard to dielectric polarization. Our results suggest that there are significant differences within different areas and subtypes of brain tumors and that white matter exhibits higher electrical resistivity than brain tumors.     

Stem-Cell-Based Gene Therapy for HIV Infection

Despite the enormous success of combined anti-retroviral therapy, HIV infection is still a lifelong disease and continues to spread rapidly worldwide. There is a pressing need to develop a treatment that will cure HIV infection. Recent progress in stem cell manipulation and advancements in humanized mouse models have allowed rapid developments of gene therapy for HIV treatment. In this review, we will discuss two aspects of HIV gene therapy using human hematopoietic stem cells. The first is to generate immune systems resistant to HIV infection while the second strategy involves enhancing anti-HIV immunity to eliminate HIV infected cells.