The genomic landscape of two Burkitt lymphoma cases and derived cell lines: comparison between primary and relapse samples.

Relapse occurs in 10-40% of Burkitt lymphoma (BL) patients that have completed intensive chemotherapy regimens and is typically fatal. While treatment-naive BL has been characterized, the genomic landscape of BL at the time of relapse (rBL) has never been reported. Here, we present a genomic characterization of two rBL patients.

Current methodological approaches in conditioned pain modulation assessment in pediatrics.

Conditioned pain modulation (CPM) paradigms have been used in various studies with healthy and non-healthy adult populations in an attempt to elucidate the mechanisms of pain processing. However, only a few studies so far have applied CPM in pediatric populations. Studies finding associations with chronic pain conditions suggest that deficiencies in underlying descending pain pathways may play an important role in the development and persistence of pain early in life.

Sleep and quality of life of patients with glycogen storage disease on standard and modified uncooked cornstarch.

Background: Glycemic control in hepatic glycogen storage diseases (GSDs) relies on specific nutritional recommendations, including strict avoidance of a fasting period. Uncooked cornstarch (UCCS) is an important therapeutic component. A new modified UCCS, Glycosade™, was created with the objective of prolonging euglycemia.

Methacholine challenge test: Comparison of tidal breathing and dosimeter methods in children.

Introduction: Methacholine Challenge Test (MCT) is used to confirm, assess the severity and/or rule out asthma. Two MCT methods are described as equivalent by the American Thoracic Society (ATS), the tidal breathing and the dosimeter methods. However, the majority of adult studies suggest that individuals with asthma do not react at the same PC between the two methods.

Beyond HIV-serodiscordance: Partnership communication dynamics that affect engagement in safer conception care.

Introduction: We explored acceptability and feasibility of safer conception methods among HIV-affected couples in Uganda.

Methods: We recruited HIV-positive men and women on antiretroviral therapy (ART) ('index') from the Uganda Antiretroviral Rural Treatment Outcomes cohort who reported an HIV-negative or unknown-serostatus partner ('partner'), HIV-serostatus disclosure to partner, and personal or partner desire for a child within two years. We conducted in-depth interviews with 40 individuals from 20 couples, using a narrative approach with tailored images to assess acceptability of five safer conception strategies: ART for the infected partner, pre-exposure prophylaxis (PrEP) for the uninfected partner, condomless sex timed to peak fertility, manual insemination, and male circumcision.

A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer.

Biallelic inactivation of BRCA1 or BRCA2 is associated with a pattern of genome-wide mutations known as signature 3. By analyzing ∼1,000 breast cancer samples, we confirmed this association and established that germline nonsense and frameshift variants in PALB2, but not in ATM or CHEK2, can also give rise to the same signature. We were able to accurately classify missense BRCA1 or BRCA2 variants known to impair homologous recombination (HR) on the basis of this signature.

Hypoxia Biomimicry to Enhance Monetite Bone Defect Repair.

Tissue hypoxia is a critical driving force for angiogenic and osteogenic responses in bone regeneration and is, at least partly, under the control of the Hypoxia Inducible Factor-1α (HIF-1α) pathway. Recently, the widely used iron chelator deferoxamine (DFO) has been found to elevate HIF-1α levels independent of oxygen concentrations, thereby, creating an otherwise normal environment that mimics the hypoxic state. This has the potential to augment the biological properties of inorganic scaffolds without the need of recombinant growth factors.

Understanding coping strategies during pregnancy and the postpartum period: a qualitative study of women living with HIV in rural Uganda.

Background: In sub-Saharan Africa, 58% of adults living with HIV are women. In Uganda, HIV prevalence is 8.3% for women compared to 6.

Prediction of behavioural and cognitive deficits in patients with traumatic brain injury at an acute rehabilitation setting.

Objective: The goal of this study was to identify factors that would predict short-term neuropsychological outcome in patients with traumatic brain injury (TBI) hospitalized in an acute rehabilitation setting.

Methods: Data was collected in the context of an acute early rehabilitation setting of a trauma centre. A brief neuropsychological assessment was carried out for 348 patients within a month following their trauma.

Defective bone repair in mast cell-deficient Cpa3Cre/+ mice.

In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic.

Diet diversity, growth and adiposity in healthy breastfed infants fed homemade complementary foods.

Background/objectives: Infant complementary feeding is important for establishing food preferences. Few studies exist on the effects of infant complementary feeding choices (food preparation methods) on dietary intake, growth or adiposity. We examined whether provision of homemade complementary food is associated with the development of dietary diversity, nutrient intakes and quality of infant growth.

Defective Bone Repair in C57Bl6 Mice With Acute Systemic Inflammation.

Background: Bone repair is initiated with a local inflammatory response to injury. The presence of systemic inflammation impairs bone healing and often leads to malunion, although the underlying mechanisms remain poorly defined. Our research objective was to use a mouse model of cortical bone repair to determine the effect of systemic inflammation on cells in the bone healing microenvironment.

Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor associated with intractable drug-resistant epilepsy. In order to identify underlying genetic alterations and molecular mechanisms, we examined three family members affected by multinodular DNETs as well as 100 sporadic tumors from 96 patients, which had been referred to us as DNETs. We performed whole-exome sequencing on 46 tumors and targeted sequencing for hotspot FGFR1 mutations and BRAF p.

Extracorporeal resuscitation for refractory out-of-hospital cardiac arrest in adults: A systematic review of international practices and outcomes.

Aim: Extracorporeal resuscitation during cardiopulmonary resuscitation (ECPR) deploys rapid cardiopulmonary bypass to sustain oxygenated circulation until the return of spontaneous circulation (ROSC). The purpose of this systematic review is to address the defining elements and outcomes (quality survival and organ donation) of currently active protocols for ECPR in refractory out-of-hospital cardiac arrest (OHCA) of cardiac origin in adult patients. The results may inform policy and practices for ECPR and help clarify the corrresponding intersection with deceased organ donation.

Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients.

Background: We previously reported an association between tryptophan (Trp) catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is associated with more rapid evolution of hepatitis C virus (HCV)-associated liver disease despite antiretroviral therapy (ART), possibly due to immune dysregulation. We hypothesized that liver fibrosis in HIV/HCV coinfection would be associated with immune dysfunction and alterations in Trp metabolism.

Epigenetic inheritance through the female germ-line: The known, the unknown, and the possible.

Although genetic mutations have long been known to influence gene expression and individual phenotype, studies emerging over the past decade indicate that such changes can also be induced in the absence of alterations in base-sequence. Epigenetically driven changes in gene expression or phenotype, when they are transmitted to succeeding generations, represent an entirely new mechanism that could generate heritable variation in a population. To understand the mechanistic basis of epigenetic inheritance, it is essential to learn how these changes may be transmitted through the germ-line to the next generation.

In Brief: Picturing the complex world of chromatin remodelling families.

Over the past decade, chromatin remodelling emerged as one of the most important causes of both abnormal development and cancer. Although much has been written about one or another of the complexes, no recent concise summary of the chromatin remodelling families as a whole is available. In this short review, we introduce the family members, briefly summarize their role in developmental abnormalities and neoplasia, and outline the different ways in which these families remodel chromatin.

Protocols for uncontrolled donation after circulatory death: a systematic review of international guidelines, practices and transplant outcomes.

Introduction: A chronic shortage of organs remains the main factor limiting organ transplantation. Many countries have explored the option of uncontrolled donation after circulatory death (uDCD) in order to expand the donor pool. Little is known regarding the variability of practices and outcomes between existing protocols.

Characterization of a Pre-Clinical Mini-Pig Model of Scaphoid Non-Union.

A fractured scaphoid is a common disabling injury that is frequently complicated by non-union. The treatment of non-union remains challenging because of the scaphoid's small size and delicate blood supply. Large animal models are the most reliable method to evaluate the efficacy of new treatment modalities before their translation into clinical practice.

Fibroblast-epithelial cell interactions drive epithelial-mesenchymal transition differently in cells from normal and COPD patients.

Background: Epithelial-to-mesenchymal transition (EMT), which involves changes in cellular morphology of highly polarized epithelial cells and the gain of mesenchymal cell phenotype with migratory and invasive capacities, is implicated in smoking-related chronic obstructive pulmonary disease (COPD). However, the interactions of fibroblasts and epithelial cells and the participation of fibroblasts in the EMT processes in COPD are poorly understood. Here, we investigated the hypothesis that EMT is active in human bronchial epithelial (HBE) cells of COPD patients, and that mediators secreted by lung fibroblasts from COPD patients induce EMT.

High density infill in cracks and protrusions from the articular calcified cartilage in osteoarthritis in standardbred horse carpal bones.

We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC mineralizing (tidemark) front (MF) into hyaline articular cartilage (HAC).

Micro CT Analysis of Spine Architecture in a Mouse Model of Scoliosis.

Objective: Mice homozygous for targeted deletion of the gene encoding fibroblast growth factor receptor 3 (FGFR3(-/-)) develop kyphoscoliosis by 2 months of age. The first objective of this study was to use high resolution X-ray to characterize curve progression in vivo and micro CT to quantify spine architecture ex vivo in FGFR3(-/-) mice. The second objective was to determine if slow release of the bone anabolic peptide parathyroid hormone related protein (PTHrP-1-34) from a pellet placed adjacent to the thoracic spine could inhibit progressive kyphoscoliosis.

Follicle-stimulating hormone regulates expression and activity of epidermal growth factor receptor in the murine ovarian follicle.

Fertility depends on the precise coordination of multiple events within the ovarian follicle to ensure ovulation of a fertilizable egg. FSH promotes late follicular development, including expression of luteinizing hormone (LH) receptor by the granulosa cells. Expression of its receptor permits the subsequent LH surge to trigger the release of ligands that activate EGF receptors (EGFR) on the granulosa, thereby initiating the ovulatory events.

Defective bone repair in mast cell deficient mice with c-Kit loss of function.

KitW-sh mice carry an inactivating mutation in the gene encoding the receptor for stem cell factor, which is expressed at high levels on the surface of haematopoietic precursor cells. The mutation results in mast cell deficiency, a variety of defects in innate immunity and poorly defined abnormalities in bone. The present study was designed to characterise healing of a cortical window defect in skeletally mature KitW-sh mice using high-resolution micro computed tomographic imaging and histological analyses.

MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects.

The functional repair of large skeletal defects remains a significant challenge to orthopaedic surgeons due to the lack of effective strategies to promote bone regeneration, particularly in the elderly. This study investigated the potential use of bone marrow derived mesenchymal stromal cells (MSC) in a dense collagen scaffold with a bolus dose of vascular endothelial growth factor (VEGF) to repair a defect in the femoral diaphysis of mice. MSC isolated from bone marrow of 4-month-old donor mice were seeded in type I collagen gels that were then compressed to form scaffolds with a fibrillar density similar to osteoid.