Abstract-Surface electrode recordings cannot delineate the activation within the human or canine sinoatrial node (SAN) because they are intramural structures. Thus, the site of origin of excitation and conduction pathway(s) within the SAN of these mammals remains unknown. Canine right atrial preparations (nϭ7) were optically mapped. The SAN 3D structure and protein expression were mapped using immunohistochemistry. SAN optical action potentials had diastolic depolarization and multiple upstroke components that corresponded to the separate excitations of the node and surface atrial layers. Pacing-induced SAN exit block eliminated atrial optical action potential components but retained SAN optical action potential components. Excitation originated in the SAN (cycle length, 557Ϯ72 ms) and slowly spread (1.2 to 14 cm/sec) within the SAN, failing to directly excite the crista terminalis and intraatrial septum. After a 49Ϯ22 ms conduction delay within the SAN, excitation reached the atrial myocardium via superior and/or inferior sinoatrial exit pathways 8.8Ϯ3.2 mm from the leading pacemaker site. The ellipsoidal 13.7Ϯ2.8/4.9Ϯ0.6 mm SAN structure was functionally insulated from the atrium. This insulation coincided with connexin43-negative regions at the borders of the node, connective tissue, and coronary arteries. During normal sinus rhythm, the canine SAN is functionally insulated from the surrounding atrial myocardium except for 2 (or more) narrow superior and inferior sinoatrial exit pathways separated by 12.8Ϯ4.1 mm. Conduction failure in these sinoatrial exit pathways leads to SAN exit block and is a modulator of heart rate. The clinical signs of SAN dysfunction include bradycardia, sinus pauses, sinus arrest, sinus exit block, and reentrant arrhythmias. 3,4 Although the syndrome may have many causes and commonly affects elderly persons, it usually is idiopathic. 5 Studies of human SAN function are complicated by the inability of epior endocardial mapping to detect the origin and slow propagation of action potentials (APs) within the SAN before it activates adjacent atrial myocardium. 6,7 Sinus rhythm (SR) is physiologically controlled by autonomic modulation of pacemaker ion channels, 8 calcium handling, 9 and shifts of the leading pacemaker site. 10 -12 Anatomic structure and electrophysiological heterogeneity play important roles in SAN excitation under various conditions. 6 Recently, we investigated activation patterns in the rabbit SAN using optical mapping, 13 which is the only available technology that allows the resolution of simultaneous changes in the activation pattern and AP morphology from multiple sites. In that study, we demonstrated that the rabbit SAN is functionally insulated from the atrial septum. 13 However, the rabbit SAN is essentially a 2D structure 14 in contrast to the 3D structure of the canine 7,15,16 and human 17,18 SANs. Bromberg et al 7 suggested that the canine SAN may be functionally insulated from the surrounding atrial myocytes, except for a limited number of exit si...

Malignancy in cancer is associated with aerobic glycolysis (Warburg effect) evidenced by increased trapping of [(18)F]deoxyglucose (FdG) in patients imaged by positron emission tomography (PET). [(18)F]deoxyglucose uptake correlates with glucose transporter (GLUT-1) expression, which can be regulated by hypoxia-inducible factor 1 alpha (HIF-1alpha). We have previously reported in established breast lines that HIF-1alpha levels in the presence of oxygen leads to the Warburg effect. However, glycolysis and GLUT-1 can also be induced independent of HIF-1alpha by other factors, such as c-Myc and phosphorylated Akt (pAkt). This study investigates HIF-1alpha, c-Myc, pAkt, and aerobic glycolysis in low-passage breast cancer cells under the assumption that these represent the in vivo condition better than established lines. Similar to in vivo FdG-PET or primary breast cancers, rates of glycolysis were diverse, being higher in cells expressing both c-Myc and HIF-1alpha and lower in cell lines low or negative in both transcription factors. No correlations were observed between glycolytic rates and pAkt levels. Two of 12 cell lines formed xenografts in mice. Both were positive for HIF-1alpha and phosphorylated c-Myc, and only one was positive for pAkt. Glycolysis was affected by pharmacological regulation of c-Myc and HIF-1alpha. These findings suggest that c-Myc and/or HIF-1alpha activities are both involved in the regulation of glycolysis in breast cancers.

The goal of this systematic review was to examine the effect of exercise on quality of life (QOL) in women living with breast cancer. Data bases searched were MEDLINE, EMBASE, CINAHL, PubMed, and PEDro. Keywords were "breast cancer and quality of life" in combination with "exercise" or "physical activity" (with associated Mesh terms). Limits were English or French language. Included studies were independently reviewed for methodological quality (van Tulder et al.) and assigned a level of evidence (Centre for Evidence-Based Medicine). Nine relevant randomized controlled trials were included: four of moderate methodological quality and five of high methodological quality. There was strong evidence that exercise positively influences QOL in women living with breast cancer. Exercise can be an effective strategy to improve QOL in women living with breast cancer. Future research is necessary to determine optimal exercise types and parameters.

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Hepatic iron overload is a serious complication of chronic transfusion therapy in patients with sickle cell disease (SCD). No firm consensus has been reached with regard to correlation between hepatic iron content (HIC) and variables including age, number of transfusions, and serum iron makers. Also, the role of HIC in determining hepatic injury is not well established. There is scarcity of data on chronically transfused children with SCD and no other confounding liver pathology. We aimed to further explore relationships between these variables in a cohort of children with SCD on chronic transfusion therapy naive to chelation. Liver biopsies obtained before starting chelation therapy from 27 children with sickle cell anemia receiving chronic transfusion therapy were evaluated for histologic scoring and determination of HIC. Average serum ferritin and iron saturation values were determined for 6 months before biopsy. Duration and total volume of transfusion were obtained from the medical records. All children were negative for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infections. Mean age at biopsy was 10.95+/-3.34 years. Mean duration and total volume of transfusions were 50.0+/-26.6 months and 17.4+/-9.6 L, respectively. Pearson product-moment bivariate correlation coefficients indicated significant correlations between HIC and histologic iron score, serum ferritin, iron saturation, age, and transfusion volume. After adjusting for transfusion volume, a significant correlation was only seen between HIC and transfusion volume. Mean HIC was 21.8+/-10.4 mg/g dry weight, with fibrosis observed in 10 patients and lobular inflammation in 9. HIC was higher in biopsies with fibrosis (28.2+/-3.8 mg/g) than biopsies without fibrosis (17.6+/-18.3 mg/g; P=0.012). HIC did not differ between biopsies with lobular inflammation (25.5+/-4.0 mg/g) and biopsies without inflammation (19.9+/-2.5 mg/g; P=0.22). These findings show that transfusion volume provides more insight on hepatic iron overload than serum iron markers.