Neighbourhood Walkability and Daily Steps in Adults with Type 2 Diabetes

Introduction

There is evidence that greater neighbourhood walkability (i.e., neighbourhoods with more amenities and well-connected streets) is associated with higher levels of total walking in Europe and in Asia, but it remains unclear if this association holds in the Canadian context and in chronic disease populations. We examined the relationships of different walkability measures to biosensor-assessed total walking (i.e., steps/day) in adults with type 2 diabetes living in Montreal (QC, Canada).

Materials and Methods

Participants (60.5±10.4 years; 48.1% women) were recruited through McGill University-affiliated clinics (June 2006 to May 2008). Steps/day were assessed once per season for one year with pedometers. Neighbourhood walkability was evaluated through participant reports, in-field audits, Geographic Information Systems (GIS)-derived measures, and the Walk Score^®. Relationships between walkability and daily steps were estimated using Bayesian longitudinal hierarchical linear regression models (n = 131).

Results

Participants who reported living in the most compared to the least walkable neighbourhoods completed 1345 more steps/day (95% Credible Interval: 718, 1976; Quartiles 4 versus 1). Those living in the most compared to the least walkable neighbourhoods (based on GIS-derived walkability) completed 606 more steps per day (95% CrI: 8, 1203). No statistically significant associations with steps were observed for audit-assessed walkability or the Walk Score^®.

Conclusions

Adults with type 2 diabetes who perceived their neighbourhoods as more walkable accumulated more daily steps. This suggests that knowledge of local neighborhood features that enhance walking is a meaningful predictor of higher levels of walking and an important component of neighbourhood walkability.     

Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage

High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology.     

Seabird diversity hotspot linked to ocean productivity in the Canary Current Large Marine Ecosystem

Upwelling regions are highly productive habitats targeted by wide-ranging marine predators and industrial fisheries. In this study, we track the migratory movements of eight seabird species from across the Atlantic; quantify overlap with the Canary Current Large Marine Ecosystem (CCLME) and determine the habitat characteristics that drive this association. Our results indicate the CCLME is a biodiversity hotspot for migratory seabirds; all tracked species and more than 70% of individuals used this upwelling region. Relative species richness peaked in areas where sea surface temperature averaged between 15 and 20°C, and correlated positively with chlorophyll a, revealing the optimum conditions driving bottom-up trophic effects for seabirds. Marine vertebrates are not confined by international boundaries, making conservation challenging. However, by linking diversity to ocean productivity, our research reveals the significance of the CCLME for seabird populations from across the Atlantic, making it a priority for conservation action.     

Suppression of the Arboviruses Dengue and Chikungunya Using a Dual-Acting Group-I Intron Coupled with Conditional Expression of the Bax C-Terminal Domain

In portions of South Asia, vectors and patients co-infected with dengue (DENV) and chikungunya (CHIKV) are on the rise, with the potential for this occurrence in other regions of the world, for example the United States. Therefore, we engineered an antiviral approach that suppresses the replication of both arboviruses in mosquito cells using a single antiviral group I intron. We devised unique configurations of internal, external, and guide sequences that permit homologous recognition and splicing with conserved target sequences in the genomes of both viruses using a single trans-splicing Group I intron, and examined their effectiveness to suppress infections of DENV and CHIKV in mosquito cells when coupled with a proapoptotic 3'' exon, ΔN Bax. RT-PCR demonstrated the utility of these introns in trans-splicing the ΔN Bax sequence downstream of either the DENV or CHIKV target site in transformed Aedes albopictus C6/36 cells, independent of the order in which the virus specific targeting sequences were inserted into the construct. This trans-splicing reaction forms DENV or CHIKV ΔN Bax RNA fusions that led to apoptotic cell death as evidenced by annexin V staining, caspase, and DNA fragmentation assays. TCID50-IFA analyses demonstrate effective suppression of DENV and CHIKV infections by our anti-arbovirus group I intron approach. This represents the first report of a dual-acting Group I intron, and demonstrates that we can target DENV and CHIKV RNAs in a sequence specific manner with a single, uniquely configured CHIKV/DENV dual targeting group I intron, leading to replication suppression of both arboviruses, and thus providing a promising single antiviral for the transgenic suppression of multiple arboviruses.     

Secreted HHIP1 interacts with heparan sulfate and regulates Hedgehog ligand localization and function

Vertebrate Hedgehog (HH) signaling is controlled by several ligand-binding antagonists including Patched-1 (PTCH1), PTCH2, and HH-interacting protein 1 (HHIP1), whose collective action is essential for proper HH pathway activity. However, the molecular mechanisms used by these inhibitors remain poorly understood. In this paper, we investigated the mechanisms underlying HHIP1 antagonism of HH signaling. Strikingly, we found evidence that HHIP1 non–cell-autonomously inhibits HH-dependent neural progenitor patterning and proliferation. Furthermore, this non–cell-autonomous antagonism of HH signaling results from the secretion of HHIP1 that is modulated by cell type–specific interactions with heparan sulfate (HS). These interactions are mediated by an HS-binding motif in the cysteine-rich domain of HHIP1 that is required for its localization to the neuroepithelial basement membrane (BM) to effectively antagonize HH pathway function. Our data also suggest that endogenous, secreted HHIP1 localization to HS-containing BMs regulates HH ligand distribution. Overall, the secreted activity of HHIP1 represents a novel mechanism to regulate HH ligand localization and function during embryogenesis.