Embryonal tumors in Canadian children less than 36 months of age: results from the Canadian Pediatric Brain Tumor Consortium (CPBTC).

Embryonal tumors are a heterogeneous group of central nervous system (CNS) tumors whose subgroups have varying incidence and outcome. Despite these differences, they are often grouped as a single entity for study purposes. To date, there are no Canadian multi-institutional studies examining the incidence and outcome of all embryonal subtypes.

Cell Adhesion Molecule CD166/ALCAM Functions Within the Crypt to Orchestrate Murine Intestinal Stem Cell Homeostasis.

Background & Aims: Intestinal epithelial homeostasis is maintained by active-cycling and slow-cycling stem cells confined within an instructive crypt-based niche. Exquisite regulating of these stem cell populations along the proliferation-to-differentiation axis maintains a homeostatic balance to prevent hyperproliferation and cancer. Although recent studies focus on how secreted ligands from mesenchymal and epithelial populations regulate intestinal stem cells (ISCs), it remains unclear what role cell adhesion plays in shaping the regulatory niche.

Novel Model of Tendon Regeneration Reveals Distinct Cell Mechanisms Underlying Regenerative and Fibrotic Tendon Healing.

To date, the cell and molecular mechanisms regulating tendon healing are poorly understood. Here, we establish a novel model of tendon regeneration using neonatal mice and show that neonates heal via formation of a 'neo-tendon' that differentiates along the tendon specific lineage with functional restoration of gait and mechanical properties. In contrast, adults heal via fibrovascular scar, aberrant differentiation toward cartilage and bone, with persistently impaired function.

A qualitative analysis of multi-level barriers to HIV testing among women in Lebanon.

While the number of HIV cases in the Middle East and North Africa region is low compared to other regions, recent studies show that incidence is increasing especially among high-risk populations; in particular, little is known about women and HIV in the region. Through semi-structured interviews with sexual healthcare providers and staff at non-governmental organisations, we sought to understand barriers to HIV testing among women in Lebanon. Using snowball sampling, key informants were recruited from greater Beirut (12 physicians, 9 non-governmental organisation staff).

Antegrade sclerotherapy in adolescent varicocele patients.

Introduction: In the 1970s, Tauber described the antegrade sclerotherapy technique to treat varicoceles, and reported a 10% recurrence rate. The present study aimed to evaluate paediatric success rates and the effect of modifications to the surgical technique.

Methods: A prospective study was performed of all adolescent patients undergoing antegrade sclerotherapy surgery.

Fkbp10 Deletion in Osteoblasts Leads to Qualitative Defects in Bone.

Osteogenesis imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures, and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65-kDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon, and ligaments in postnatal tissues.

ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development.

Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed.

Mucosectomy impairs ileal microcirculation and results in flap contraction after experimental ileocystoplasty.

Introduction: Bladder augmentation with demucosalized ileal flap is a promising alternative approach for mucus free bladder augmentation; however, the contraction of the flap is still a major concern. It has been hypothesized that mucosectomy causes ischemic damage, but no direct histological evidence has been found and attention is now focused on the urothelium cover to prevent the exposure of the denuded surface to urine or the use of balloons to keep the flaps distended.

Objective: Our aim was to study the effect of mucosectomy on the microcirculation of ileal flaps during reverse clam ileocystoplasty using direct intraoperative imaging of the ileum.

EMILIN3, an extracellular matrix molecule with restricted distribution in skin.

EMILIN3 is an extracellular matrix glycoprotein that displays a dynamic and restricted expression pattern in connective tissues during post-natal life. In this study, we report the characterization of EMILIN3 deposition in the skin. In addition, to unravel the functions of this protein in skin homeostasis, we generated Emilin3 null mice and provide evidence that EMILIN3 is dispensable for hair follicle growth and maintenance throughout adult life.

"You Can't Just Walk Down the Street and Meet Someone": The Intersection of Social-Sexual Networking Technology, Stigma, and Health Among Gay and Bisexual Men in the Small City.

Social-sexual networking technologies have been reported to yield both psychosocial benefits and sexual risks for gay and bisexual men, yet little research has explored how technology interacts with the social-geographical environment to shape the health of gay and bisexual men in the relatively understudied environment of small cities. This article draws on 29 semistructured interviews examining the use of social-sexual networking technologies among racially diverse gay and bisexual men in two small cities. Questions probed participants' use of technology to meet sexual partners, engagement in the gay community, and the role of virtual and nonvirtual spaces in relation to health.

Safety and Wound Outcomes Following Genetically Corrected Autologous Epidermal Grafts in Patients With Recessive Dystrophic Epidermolysis Bullosa.

Importance: Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating, often fatal, inherited blistering disorder caused by mutations in the COL7A1 gene encoding type VII collagen. Support and palliation are the only current therapies.

Objective: To evaluate the safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with RDEB.

The Ankle Injury Management (AIM) trial: a pragmatic, multicentre, equivalence randomised controlled trial and economic evaluation comparing close contact casting with open surgical reduction and internal fixation in the treatment of unstable ankle fractures in patients aged over 60 years.

Background: Close contact casting (CCC) may offer an alternative to open reduction and internal fixation (ORIF) surgery for unstable ankle fractures in older adults.

Objectives: We aimed to (1) determine if CCC for unstable ankle fractures in adults aged over 60 years resulted in equivalent clinical outcome compared with ORIF, (2) estimate cost-effectiveness to the NHS and society and (3) explore participant experiences.

Design: A pragmatic, multicentre, equivalence randomised controlled trial incorporating health economic evaluation and qualitative study.

Close Contact Casting vs Surgery for Initial Treatment of Unstable Ankle Fractures in Older Adults: A Randomized Clinical Trial.

Importance: Ankle fractures cause substantial morbidity in older persons. Surgical fixation is the contemporary intervention but is associated with infection and other healing complications.

Objective: To determine whether initial fracture treatment with close contact casting, a molded below-knee cast with minimal padding, offers outcome equivalent to that with immediate surgery, with fewer complications and less health resource use.

“There's a Difference—I Own This”: Negotiating Social and Financial Services under Threat of Mortgage Foreclosure.

Although national housing markets have recovered from the Great Recession, communities hardest hit by the foreclosure crisis remain immersed in mortgage trouble. Nineteen percent of homeowners are underwater on their mortgages and communities of color are overrepresented among zip codes still experiencing default in rising numbers. The social services needs of homeowners at risk of foreclosure show few signs of abating.

Determinants of perceived insufficient milk among new mothers in León, Nicaragua.

Breastfeeding has been shown to improve maternal and child health. In Nicaragua, the primary risk of death and disability-adjusted life years among children under 5 years of age is suboptimal breastfeeding. Although the Nicaraguan Ministry of Health promotes exclusive breastfeeding from within the first half hour through the first 6 months of life, less than a third of children in the country under 6 months of age are exclusively breastfed.

Unique Footprint in the scl1.3 Locus Affects Adhesion and Biofilm Formation of the Invasive M3-Type Group A Streptococcus.

The streptococcal collagen-like proteins 1 and 2 (Scl1 and Scl2) are major surface adhesins that are ubiquitous among group A Streptococcus (GAS). Invasive M3-type strains, however, have evolved two unique conserved features in the scl1 locus: (i) an IS1548 element insertion in the scl1 promoter region and (ii) a nonsense mutation within the scl1 coding sequence. The scl1 transcript is drastically reduced in M3-type GAS, contrasting with a high transcription level of scl1 allele in invasive M1-type GAS.

'The big ole gay express': sexual minority stigma, mobility and health in the small city.

Recent research has examined how gay and bisexual men experience and navigate the variations in sexual minority stigma that exist across geographic contexts, with implications for their health. We extend this literature on stigma, mobility, and health by considering the unique and understudied setting of the small city. Drawing on semi-structured interviews (n = 29) conducted in two small US cities (New Haven and Hartford), we find that these small cities serve as both destinations and points of departure for gay and bisexual men in the context of stigma.

Phase II Weekly Vinblastine for Chemotherapy-Naïve Children With Progressive Low-Grade Glioma: A Canadian Pediatric Brain Tumor Consortium Study.

Purpose Vinblastine monotherapy has shown promising activity and a low-toxicity profile in patients with pediatric low-grade glioma (PLGG) who experienced treatment failure after initial treatment with chemotherapy and/or radiation. The aim of this study was to assess the activity of vinblastine in therapy-naïve children. Patients and Methods Patients < 18 years old with unresectable and/or progressive therapy-naïve PLGG were eligible.

Neonatal death: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data.

More than 40% of all deaths in children under 5 years of age occur during the neonatal period: the first month of life. Immunization of pregnant women has proven beneficial to both mother and infant by decreasing morbidity and mortality. With an increasing number of immunization trials being conducted in pregnant women, as well as roll-out of recommended vaccines to pregnant women, there is a need to clarify details of a neonatal death.

Resolving the paradox of randomised controlled trials and observational studies comparing multi-vessel angioplasty and culprit only angioplasty at the time of STEMI.

Background: Patients presenting with ST-elevation myocardial infarction commonly have multi-vessel coronary artery disease. After the culprit artery is treated, the optimal treatment strategy for the residual disease is not yet defined. Large observational studies suggest that treatment of residual disease should be deferred but smaller randomised controlled trials (RCTs) suggest multi-vessel primary percutaneous coronary intervention (MV-PPCI) at the time of STEMI is safe.

FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders.

FBN1 encodes the gene for fibrillin-1, a structural macromolecule that polymerizes into microfibrils. Fibrillin microfibrils are morphologically distinctive fibrils, present in all connective tissues and assembled into tissue-specific architectural frameworks. FBN1 is the causative gene for Marfan syndrome, an inherited disorder of connective tissue whose major features include tall stature and arachnodactyly, ectopia lentis, and thoracic aortic aneurysm and dissection.

BMP1-like proteinases are essential to the structure and wound healing of skin.

Closely related extracellular metalloproteinases bone morphogenetic protein 1 (BMP1) and mammalian Tolloid-like 1 (mTLL1) are co-expressed in various tissues and have been suggested to have overlapping roles in the biosynthetic processing of extracellular matrix components. Early lethality of mice null for the BMP1 gene Bmp1 or the mTLL1 gene Tll1 has impaired in vivo studies of these proteinases. To overcome issues of early lethality and functional redundancy we developed the novel BT mouse strain, with floxed Bmp1 and Tll1 alleles, for induction of postnatal, simultaneous ablation of the two genes.

Targeting of EMILIN-1 and EMILIN-2 to Fibrillin Microfibrils Facilitates their Incorporation into the Extracellular Matrix.

Elastin microfibril interface-located proteins (EMILINs) 1 and 2 belong to a family of structurally related extracellular glycoproteins with unique functions in the extracellular space, such as modulation of pro-transforming growth factor-β processing, activation of the extrinsic apoptotic pathway, and regulation of Hedgehog and Wnt ligand bioavailability. However, little is known about how EMILINs may exert their extracellular functions. We therefore investigated the spatiotemporal localization and deposition of EMILIN-1 and -2 within the extracellular space.

Ageing, Muscle Power and Physical Function: A Systematic Review and Implications for Pragmatic Training Interventions.

Background: The physiological impairments most strongly associated with functional performance in older people are logically the most efficient therapeutic targets for exercise training interventions aimed at improving function and maintaining independence in later life.

Objectives: The objectives of this review were to (1) systematically review the relationship between muscle power and functional performance in older people; (2) systematically review the effect of power training (PT) interventions on functional performance in older people; and (3) identify components of successful PT interventions relevant to pragmatic trials by scoping the literature.

Methods: Our approach involved three stages.