Biological Impacts of Thermal Extremes: Mechanisms and Costs of Functional Responses Matter.

Thermal performance curves enable physiological constraints to be incorporated in predictions of biological responses to shifts in mean temperature. But do thermal performance curves adequately capture the biological impacts of thermal extremes? Organisms incur physiological damage during exposure to extremes, and also mount active compensatory responses leading to acclimatization, both of which alter thermal performance curves and determine the impact that current and future extremes have on organismal performance and fitness. Thus, these sub-lethal responses to extreme temperatures potentially shape evolution of thermal performance curves.

A new structural relaxation pathway of low-density amorphous ice.

Low-density amorphous (LDA) ice is involved in critical cosmological processes and has gained prominence as one of the at least two distinct amorphous forms of ice. Despite these accolades, we still have an incomplete understanding of the structural diversity that is encompassed within the LDA state and the dynamic processes that take place upon heating LDA. Heating the high-pressure ice VIII phase at ambient pressure is a remarkable example of temperature-induced amorphisation yielding LDA.

Leukocyte Ig-Like receptor B1 restrains dendritic cell function through increased expression of the NF-κB regulator ABIN1/TNIP1.

Inhibitory receptors of the human leukocyte immunoglobulin-like receptor family are constitutively expressed on all myeloid cell types and regulate their functional activity. We demonstrate that ligation of the human leukocyte antigen class I-specific receptor LILRB1, during the differentiation of monocytes to dendritic cells in vitro, results in increased expression of the nuclear factor κB inhibitor protein ABIN1 (also known as TNIP1). Similarly increased expression of ABIN1/TNIP1 was observed in the "immunosuppressive" monocyte populations of patients with non-Hodgkin lymphoma ex vivo.

The establishment of DOHaD working groups in Australia and New Zealand.

The evidence underpinning the developmental origins of health and disease (DOHaD) is overwhelming. As the emphasis shifts more towards interventions and the translational strategies for disease prevention, it is important to capitalize on collaboration and knowledge sharing to maximize opportunities for discovery and replication. DOHaD meetings are facilitating this interaction.

Fine-Scale Microclimatic Variation Can Shape the Responses of Organisms to Global Change in Both Natural and Urban Environments.

When predicting the response of organisms to global change, models use measures of climate at a coarse resolution from general circulation models or from downscaled regional models. Organisms, however, do not experience climate at such large scales. The climate heterogeneity over a landscape and how much of that landscape an organism can sample will determine ultimately the microclimates experienced by organisms.

A Random Walk in the Park: An Individual-Based Null Model for Behavioral Thermoregulation.

Behavioral thermoregulators leverage environmental temperature to control their body temperature. Habitat thermal quality therefore dictates the difficulty and necessity of precise thermoregulation, and the quality of behavioral thermoregulation in turn impacts organism fitness via the thermal dependence of performance. Comparing the body temperature of a thermoregulator with a null (non-thermoregulating) model allows us to estimate habitat thermal quality and the effect of behavioral thermoregulation on body temperature.

Diet-induced obesity and prenatal undernutrition lead to differential neuroendocrine gene expression in the hypothalamic arcuate nuclei.

Previously we reported that prenatal undernutrition (UN) leads to a dysregulation of appetite suppression through alterations in hypothalamic neuropeptide gene expression. In the current study, we expand our observations and investigate neuroendocrine transcriptional responses and central leptin sensitivity within the arcuate nucleus of rats exposed to prenatal UN or a postnatal high-fat diet (HF). Pregnant Wistar rats were fed a standard chow diet either ad libitum (AD) or at 30 % of AD intake throughout gestation (UN) resulting in either control or intrauterine growth-restricted female offspring.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

PROSPECT Eligibility and Clinical Outcomes: Results From the Pan-Canadian Rectal Cancer Consortium.

Background: The PROSPECT trial (N1048) is evaluating the selective use of chemoradiation in patients with cT2N1 and cT3N0-1 rectal cancer undergoing sphincter-sparing low anterior resection. We evaluated outcomes of PROSPECT-eligible and -ineligible patients from a multi-institutional database.

Patients And Methods: Data from patients with locally advanced rectal cancer who received chemoradiation and low anterior resection from 2005 to 2014 were retrospectively collected from 5 Canadian centers.

Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring.

Maternal obesity predisposes offspring to metabolic and reproductive dysfunction. We have shown previously that female rat offspring born to mothers fed a high-fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. The mechanisms driving this reproductive phenotype are currently unknown thus we investigated whether changes in ovarian function were involved.

Management of Epidermal Growth Factor Receptor Inhibitor-Induced Hypomagnesemia: A Systematic Review.

Background: Despite occurring in 30% of patients, there are no evidence-based guidelines on the management of epidermal growth factor receptor inhibitor (EGFRI)-induced hypomagnesemia. Based on expert opinion, severe hypomagnesemia should be treated by intravenous magnesium replacement. A systematic review of published data of intervention on EGFRI-induced hypomagnesemia was performed.

Media Reporting of Practice-Changing Clinical Trials in Oncology: A North American Perspective.

Introduction: Media reporting of clinical trials impacts patient-oncologist interactions. We sought to characterize the accuracy of media and Internet reporting of practice-changing clinical trials in oncology.

Materials And Methods: The first media articles referencing 17 practice-changing clinical trials were collected from 4 media outlets: newspapers, cable news, cancer websites, and industry websites.

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes.

Background: Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers.

Early life nutrition and the opportunity to influence long-term health: an Australasian perspective.

There are now significant data to support the hypothesis that early life nutrition in the fetus, infant and young child can have profound effects on long-term health. This review considers some of this evidence with specific reference to the current burden of disease in Australia and New Zealand. As the findings of further research become available, recommendations on optimizing early life nutrition should be formulated and made widely available as part of the preventative health policy agenda in both Australia and New Zealand.

The Information Technology Infrastructure for the Translational Genomics Core and the Partners Biobank at Partners Personalized Medicine.

The Biobank and Translational Genomics core at Partners Personalized Medicine requires robust software and hardware. This Information Technology (IT) infrastructure enables the storage and transfer of large amounts of data, drives efficiencies in the laboratory, maintains data integrity from the time of consent to the time that genomic data is distributed for research, and enables the management of complex genetic data. Here, we describe the functional components of the research IT infrastructure at Partners Personalized Medicine and how they integrate with existing clinical and research systems, review some of the ways in which this IT infrastructure maintains data integrity and security, and discuss some of the challenges inherent to building and maintaining such infrastructure.

The Placental Variant of Human Growth Hormone Reduces Maternal Insulin Sensitivity in a Dose-Dependent Manner in C57BL/6J Mice.

The human placental GH variant (GH-V) is secreted continuously from the syncytiotrophoblast layer of the placenta during pregnancy and is thought to play a key role in the maternal adaptation to pregnancy. Maternal GH-V concentrations are closely related to fetal growth in humans. GH-V has also been proposed as a potential candidate to mediate insulin resistance observed later in pregnancy.

Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring.

Palliative chemotherapy for patients 70 years of age and older with metastatic colorectal cancer: a single-centre experience.

Background: Metastatic colorectal cancer (mcrc) commonly affects elderly people, an understudied subset of patients. We analyzed the survival impact of the first and subsequent lines of chemotherapy in eligible non-trial patients 70 years of age and older with mcrc treated between 2004 and 2012.

Methods: This single-centre retrospective analysis estimated overall survival (os) and progression-free survival (pfs) using the Kaplan-Meier method.

Early Life Exposure to Fructose Alters Maternal, Fetal and Neonatal Hepatic Gene Expression and Leads to Sex-Dependent Changes in Lipid Metabolism in Rat Offspring.

Aim: Fructose consumption is associated with altered hepatic function and metabolic compromise and not surprisingly has become a focus for perinatal studies. We have previously shown that maternal fructose intake results in sex specific changes in fetal, placental and neonatal outcomes. In this follow-up study we investigated effects on maternal, fetal and neonatal hepatic fatty acid metabolism and immune modulation.

Magnesium sulfate has sex-specific, dose-dependent vasodilator effects on preterm placental vessels.

Background: Women at risk of preterm delivery receive magnesium sulfate (MgSO4) in the pre-delivery phase to reduce their child's risk of neurodevelopmental complications associated with preterm birth. However, the mechanisms underpinning its placental vascular role remain uncertain.

Methods: The aim of this study was to examine MgSO4 action on vascular tone in male and female human placental vessels from term and preterm deliveries.

Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation.

Consumption of a high-fat (HF) diet during pregnancy and lactation influences later life predisposition to obesity and cardiometabolic disease in offspring. The mechanisms underlying this phenomenon remain poorly defined, but one potential target that has received scant attention and is likely pivotal to disease progression is that of the gut. The present study examined the effects of maternal supplementation with the anti-inflammatory lipid, conjugated linoleic acid (CLA), on offspring metabolic profile and gut expression of taste receptors and inflammatory markers.

Different exercise modalities have distinct effects on the integrin-linked kinase (ILK) and Ca2+ signaling pathways in the male rat bone.

Mechanical loading is essential to maintain optimal skeletal health. Despite the fact that early-life exercise has positive, long-lasting effects on the musculo-skeletal system, the response of the musculo-skeletal system to spontaneous low-impact exercise has been poorly studied. Previously, we identified subtle morphological changes in the femoral diaphysis of exercised animals compared to nonexercised controls.

Acute liver failure and seizures as a consequence of regorafenib exposure in advanced rectal cancer.

Background: Regorafenib is a multi-targeted tyrosine kinase inhibitor approved for use in refractory colorectal cancer. We report the first case of seizures secondary to acute liver failure, shortly after initiation of regorafenib in a patient with advanced rectal carcinoma.

Case Presentation: A 64 year-old Caucasian female presented with confusion and generalized tonic-clonic seizures, 5 days after initiation of regorafenib for advanced rectal cancer.

Predictors of Pathologic Complete Response After Neoadjuvant Treatment for Rectal Cancer: A Multicenter Study.

Background: Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) for rectal cancer is associated with better long-term outcomes, and is used as an early indicator of response to novel agents. To assess the rate and predictors of pCR, we performed a retrospective multicenter study involving 5 Canadian cancer centers.

Patients And Methods: Cancer registries identified consecutive patients with locally advanced rectal adenocarcinoma from the Tom Baker Cancer Centre, Cross Cancer Institute, British Columbia Cancer Agency, Ottawa Hospital Cancer Centre, and the Dr H.