Neural and physiological responses to a cold pressor challenge in healthy adolescents.

Abnormal autonomic function is common in pediatric diseases. Assessment of central mechanisms underlying autonomic challenges may reveal vulnerabilities antecedent to system failure. Our objective was to characterize central markers and physiological responses to a cold pressor challenge in normal children as a critical step for establishing such screening.

Regional cerebral blood flow alterations in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a condition characterized by upper airway muscle atonia with continued diaphragmatic efforts, resulting in repeated airway obstructions, periods of intermittent hypoxia, large thoracic pressure changes, and substantial shifts in arterial pressure with breathing cessation and resumption. The hypoxic exposure and hemodynamic changes likely induce the structural and functional deficits found in multiple brain areas, as shown by magnetic resonance imaging (MRI) procedures. Altered cerebral blood flow (CBF) may contribute to these localized deficits; thus, we examined regional CBF, using arterial spin labeling procedures, in 11 OSA (age, 49.

Ultrasensitive molecular detection using thermal conductance of a hydrophobic gold-water interface.

The thermal conductance from a hydrophobic gold aqueous interface is measured with increasing solute concentration. A small amount of aqueous solute molecules (1 solute molecule in 550 water molecules) dramatically increases the heat dissipation into the surrounding liquid. This result is consistent with a thermal conductance that is limited by an interface interaction where minority aqueous components significantly alter the surface properties and heat transport through the interface.

The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in Drosophila melanogaster through maintaining a progenitor-like cell state.

The capacity of tumour cells to maintain continual overgrowth potential has been linked to the commandeering of normal self-renewal pathways. Using an epithelial cancer model in Drosophila melanogaster, we carried out an overexpression screen for oncogenes capable of cooperating with the loss of the epithelial apico-basal cell polarity regulator, scribbled (scrib), and identified the cell fate regulator, Abrupt, a BTB-zinc finger protein. Abrupt overexpression alone is insufficient to transform cells, but in cooperation with scrib loss of function, Abrupt promotes the formation of massive tumours in the eye/antennal disc.

Increased risk of breast cancer associated with long-term shift work in Canada.

Objectives: Long-term night work has been suggested as a risk factor for breast cancer; however, additional studies with more comprehensive methods of exposure assessment to capture the diversity of shift patterns are needed. As well, few previous studies have considered the role of hormone receptor subtype.

Methods: Relationships between night shift work and breast cancer were examined among 1134 breast cancer cases and 1179 controls, frequency-matched by age in Vancouver, British Columbia, and Kingston, Ontario.

Nocturnal dipping is preserved in children with sleep disordered breathing regardless of its severity.

Objective: Sleep disordered breathing (SDB) in adults has been associated with a loss of nocturnal dipping in blood pressure (BP) and heart rate, however, there have been limited studies in children. We measured BP non-invasively and continuously overnight in 105 children aged 7-12 with a range of severities of SDB and 36 non-snoring controls to examine nocturnal dipping profiles.

Study Design: Children with SDB were divided into three severity groups according to their obstructive apnea hypopnea index.

Moderate-to-vigorous intensity physical activity across the life course and risk of pre- and post-menopausal breast cancer.

Moderate-to-vigorous intensity physical activity (MVPA) reduces breast cancer risk, although the effects of MVPA in different settings across the life course and how they may differ by menopausal status are unclear. This gap was addressed using data from a case-control study of 1,110 incident breast cancer cases and 1,172 cancer-free controls, frequency matched by age, from Vancouver and Kingston, Canada. In Vancouver, cases were recruited from the British Columbia Cancer Registry and controls from the Screening Mammography Program of British Columbia and in Kingston cases and controls were recruited from a breast assessment center.

Arousal from sleep pathways are affected by the prone sleeping position and preterm birth: preterm birth, prone sleeping and arousal from sleep.

Objectives: Preterm infants exhibit depressed arousability from sleep when compared with term infants. As the final cortical element of the arousal process may be the most critical for survival, we hypothesized that the increased vulnerability of preterm infants to the Sudden Infant Death Syndrome (SIDS) could be explained by depressed cortical arousal (CA) responses. We evaluated the effects of preterm birth on stimulus-induced arousal processes in both the prone and supine sleeping positions.

Shift work, circadian gene variants and risk of breast cancer.

Circadian (clock) genes have been linked with several functions relevant to cancer, and epidemiologic research has suggested relationships with breast cancer risk for variants in NPAS2, CLOCK, CRY2 and TIMELESS. Increased breast cancer risk has also been observed among shift workers, suggesting potential interactions in relationships of circadian genes with breast cancer. Relationships with breast cancer of 100 SNPs in 14 clock-related genes, as well as potential interactions with shift work history, were investigated in a case-control study (1042 cases, 1051 controls).

Adolescent drinking targets corticotropin-releasing factor peptide-labeled cells in the central amygdala of male and female rats.

Adolescence is a developmental period when many teenagers first drink alcohol and often engage in binge drinking. Early onset of alcohol is linked to increased risk of stress-related disorders in adulthood in humans, suggesting that alcohol may interfere with development of the stress regulatory system. We investigated the effect of voluntary alcohol exposure on corticotropin-releasing factor (CRF) peptide-producing cells in the central nucleus of the amygdala (CeA) in adolescent male and female rats.

A randomized controlled trial of peripheral blood mononuclear cell depletion in experimental human lung inflammation.

Rationale: Depletion of monocytes reduces LPS-induced lung inflammation in mice, suggesting monocytes as potential therapeutic targets in acute lung injury.

Objectives: To investigate whether depletion of circulating blood monocytes has beneficial effects on markers of systemic and pulmonary inflammation in a human model of acute lung inflammation.

Methods: A total of 30 healthy volunteers were enrolled in a randomized controlled trial.

Medical emergency team involvement in patients hospitalized with acute myeloid leukemia.

Patients with acute myeloid leukemia (AML) are at risk for sudden clinical deterioration. We aimed to describe the incidence of medical emergency team (MET) activation, intensive care unit (ICU) admissions and outcomes for patients with AML. We performed a 5-year retrospective cohort study of patients hospitalized with AML.

In Drosophila, RhoGEF2 cooperates with activated Ras in tumorigenesis through a pathway involving Rho1-Rok-Myosin-II and JNK signalling.

The Ras oncogene contributes to ≈ 30% of human cancers, but alone is not sufficient for tumorigenesis. In a Drosophila screen for oncogenes that cooperate with an activated allele of Ras (Ras(ACT)) to promote tissue overgrowth and invasion, we identified the GTP exchange factor RhoGEF2, an activator of Rho-family signalling. Here, we show that RhoGEF2 also cooperates with an activated allele of a downstream effector of Ras, Raf (Raf(GOF)).

"When You're Sitting on the Fence, Hope's the Hardest Part": Challenges and Experiences of Heterosexual and Same-Sex Couples Adopting Through the Child Welfare System.

Foster-to-adopt families can be viewed as systems that are influenced by many other systems (e.g., the legal system, the social service agency, and the birth family).

Marked reductions in visual evoked responses but not γ-aminobutyric acid concentrations or γ-band measures in remitted depression.

Background: Magnetic resonance spectroscopy (MRS) studies have consistently demonstrated reduced cortical γ-aminobutyric acid (GABA) concentrations in individuals with major depression. However, evidence for a persistent deficit during remission, which would suggest that GABA dysfunction is a possible trait marker of depression, is equivocal. Although MRS measures total concentration of GABA, magneto-encephalography provides direct measures of neural activity, with cortical γ oscillations shaped by the activity of GABAergic inhibitory interneurons.

Risk of selected cancers due to occupational exposure to chlorinated solvents in a case-control study in Montreal.

Objective: To evaluate the association between exposure to chlorinated solvents and cancer.

Methods: We conducted a case-control study of occupational exposures and cancer in Montreal, Quebec, Canada, including 3730 cancer cases and 533 population controls. Occupational exposures were derived using a combination of subject-reported job history and expert assessment.

Nasal and bronchial airway epithelial cell mediator release in children.

Objective: The present study was designed to test the hypothesis that airway epithelial cell (AEC) mediator release is similar in upper and lower airway AEC in children.

Methods: Nasal and bronchial AEC were collected by brushings from children scheduled for general anesthetic. AEC release of the following mediators was measured: interleukin (IL)-6, IL-8, Granulocyte Colony Stimulating Factor (G-CSF), regulated on activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), matrix metallo proteinase (MMP)-9, and tissue inhibitor of metalloproteinases (TIMP)-1.

Human papillomavirus type 52 polymorphism and high-grade lesions of the uterine cervix.

The association between polymorphism of human papillomavirus type 52 (HPV52) and high-grade cervical intraepithelial neoplasia (CIN2,3) was investigated in Canadian women. HPV-52-positive endocervical specimens collected from 216 women selected from a total of 3,614 participants recruited in two case-control and two cohort studies conducted in Canada, were further analyzed by PCR-sequencing of the LCR and E6 gene. Overall, the HPV52 LCR prototype was detected more frequently in Caucasian women (69 of 132, 52.

Relying on experts as we reason together.

In various contexts, it is thought to be important that we reason together. For instance, an attractive conception of democracy requires that citizens reach lawmaking decisions by reasoning with one another. Reasoning requires that reasoners survey the considerations that they take to be reasons, proceed by a coherent train of thought, and reach conclusions freely.

An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discovery.

Anti-cancer drug development involves enormous expenditure and risk. For rapid and economical identification of novel, bioavailable anti-tumour chemicals, the use of appropriate in vivo tumour models suitable for large-scale screening is key. Using a Drosophila Ras-driven tumour model, we demonstrate that tumour overgrowth can be curtailed by feeding larvae with chemicals that have the in vivo pharmacokinetics essential for drug development and known efficacy against human tumour cells.

The Scribble-Dlg-Lgl polarity module in development and cancer: from flies to man.

The Scribble, Par and Crumbs modules were originally identified in the vinegar (fruit) fly, Drosophila melanogaster, as being critical regulators of apico-basal cell polarity. In the present chapter we focus on the Scribble polarity module, composed of Scribble, discs large and lethal giant larvae. Since the discovery of the role of the Scribble polarity module in apico-basal cell polarity, these proteins have also been recognized as having important roles in other forms of polarity, as well as regulation of the actin cytoskeleton, cell signalling and vesicular trafficking.

The Goldilocks mastectomy.

Objective: To reconstruct a breast mound from cutaneous mastectomy flap tissue alone, obviating the need for additional flap or implant techniques.

Summary Background Data: With growing numbers of obese and elderly women facing breast cancer, options outside of simple mastectomy without reconstruction and formal breast reconstruction using complex autologous flap harvesting techniques or artificial implants need to be explored.

Methods: Patients who declined traditional methods of breast reconstruction were offered standard skin sparing mastectomy with closure utilizing a standard Wise pattern.

Functional neuroanatomy and sleep-disordered breathing: implications for autonomic regulation.

A major concern with sleep-disordered breathing conditions, which include obstructive sleep apnea (OSA), central apnea, and congenital central hypoventilation syndrome (CCHS), is the high incidence of accompanying autonomic dysfunction and metabolic disorders. Patients with OSA show exaggerated sympathetic tone, leading to hypertension, cardiac arrhythmia, profuse sweating, impaired cerebral perfusion, and stroke. In addition, OSA appears in 86% of obese Type II diabetic patients, suggesting common deleterious processes.