Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation.

Background: Dystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood.

Indications for MARS-MRI in Patients Treated With Articular Surface Replacement XL Total Hip Arthroplasty.

Background: The purpose of this study was to identify which patient and clinical factors are predictive of adverse local tissue reaction (ALTR) and to use these factors to create a highly sensitive algorithm for indicating metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) in Articular Surface Replacement (ASR) XL total hip arthroplasty patients. Our secondary aim was to compare our algorithm to existing national guidelines on when to take MARS-MRI in metal-on-metal total hip arthroplasty patients.

Methods: The study consisted of 137 patients treated with unilateral ASR XL implants from a prospective, multicenter study.

Allogeneic Hematopoietic Cell Transplantation for Chronic Granulomatous Disease: Controversies and State of the Art.

Chronic granulomatous disease (CGD) is a congenital disorder characterized by recurrent life-threatening bacterial and fungal infections and development of severe inflammation secondary to a congenital defect in 1 of the 5 phagocyte oxidase (phox) subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Hematopoietic cell transplant (HCT) is a curative treatment for patients with CGD that provides donor neutrophils with functional NADPH and superoxide anion production. Many characteristics of CGD, including preexisting infection and inflammation and the potential for cure with mixed-donor chimerism, influence the transplant approach and patient outcome.

Tissue stiffening promotes keratinocyte proliferation through activation of epidermal growth factor signaling.

Tissue biomechanics regulate a wide range of cellular functions, but the influences on epidermal homeostasis and repair remain unclear. Here, we examined the role of extracellular matrix stiffness on human keratinocyte behavior using elastomeric substrates with defined mechanical properties. Increased matrix stiffness beyond normal physiologic levels promoted keratinocyte proliferation but did not alter the ability to self-renew or terminally differentiate.

Indications for MARS-MRI in Patients Treated With Metal-on-Metal Hip Resurfacing Arthroplasty.

Background: Currently, there are no universally accepted guidelines on when to obtain metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) in metal-on-metal (MoM) hip resurfacing arthroplasty (HRA) patients. Our primary aims were to identify which patient and clinical factors are predictive of adverse local tissue reaction (ALTR) and create an algorithm for indicating MARS-MRI in patients with Articular Surface Replacement (ASR) HRA. The secondary aim was to compare our algorithm to existing guidelines on when to perform MARS-MRI in MoM HRA patients.

Pumpless arteriovenous extracorporeal membrane oxygenation: A novel mode of respiratory support in a lamb model of congenital diaphragmatic hernia.

Background: Extracorporeal membrane oxygenation (ECMO) is commonly required in neonates with congenital diaphragmatic hernia (CDH) complicated by pulmonary hypertension (PH). ECMO carries significant risk, and is contraindicated in the setting of extreme prematurity or intracranial hemorrhage. Pumpless arteriovenous ECMO (P-ECMO) may represent an alternative for respiratory support.

Identification of novel gene fusion and personalized therapeutic targets through integrative clinical sequencing in secondary acute myeloid leukemia in a patient with severe congenital neutropenia: a case report and literature review.

Severe congenital neutropenia (SCN) is a rare hematologic disorder characterized by defective myelopoiesis and a high incidence of malignant transformation to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). SCN patients who develop MDS/AML have excessive toxicities to traditional chemotherapy, and safer therapies are needed to improve overall survival in this population. In this report, we outline the use of a prospective integrative clinical sequencing trial (PEDS-MIONCOSEQ) in a patient with SCN and AML to help identify oncogenic targets for less toxic agents.

High-dose Chemotherapy is Efficacious and Well Tolerated in a Toddler With Aicardi Syndrome and Malignant Sacrococcygeal Teratoma.

Aicardi syndrome (AS) is a rare neurodevelopmental disorder, predominantly seen in female individuals, which appears to have an increased risk of both benign and malignant neoplasia. We report the case of a child with AS who presented with metastatic malignant sacrococcygeal tumor (with yolk sac elements) which recurred and then was treated with 3 cycles of high-dose chemotherapy with autologous stem cell rescue. The patient tolerated therapy with acceptable toxicity and remains in clinical remission 3 months after the completion of therapy.

Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood.

The neuropeptide oxytocin (OT) has been implicated in a wide range of affiliative processes. OT exerts its functions via OT receptors, which are encoded by the oxytocin receptor gene (OXTR). Epigenetic modification of OXTR through the process of DNA methylation has been associated with individual differences in behavioral phenotypes.

Umbilical cannulation optimizes circuit flows in premature lambs supported by the EXTra-uterine Environment for Neonatal Development (EXTEND).

Key Points: Bronchopulmonary dysplasia is a disease of extreme prematurity that occurs when the immature lung is exposed to gas ventilation. We designed a novel 'artificial womb' system for supporting extreme premature lambs (called EXTEND) that obviates gas ventilation by providing oxygen via a pumpless arteriovenous circuit with the lamb submerged in sterile artificial amniotic fluid. In the present study, we compare different arteriovenous cannulation strategies on EXTEND, including carotid artery/jugular vein (CA/JV), carotid artery/umbilical vein (CA/UV) and umbilical artery/umbilical vein (UA/UV).

Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning: The URTH Trial.

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts.

Acid ceramidase and its inhibitors: a drug target and a new class of drugs for killing glioblastoma cancer stem cells with high efficiency.

Glioblastoma remains the most common, malignant primary cancer of the central nervous system with a low life expectancy and an overall survival of less than 1.5 years. The treatment options are limited and there is no cure.

A Survey of Validation Strategies for CRISPR-Cas9 Editing.

The T7 endonuclease 1 (T7E1) mismatch detection assay is a widely used method for evaluating the activity of site-specific nucleases, such as the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system. To determine the accuracy and sensitivity of this assay, we compared the editing estimates derived by the T7E1 assay with that of targeted next-generation sequencing (NGS) in pools of edited mammalian cells. Here, we report that estimates of nuclease activity determined by T7E1 most often do not accurately reflect the activity observed in edited cells.

Highly Stable RNA Capture by Dense Cationic Polymer Brushes for the Design of Cytocompatible, Serum-Stable SiRNA Delivery Vectors.

The high density of polymer brushes confers to these coatings unique physicochemical properties, in particular for the regulation of biomolecular interaction and the design of highly selective coatings for biosensors and protein patterning. Here, we show that high density poly(dimethylaminoethyl methacrylate) cationic polymer brushes enable the stable uptake of high levels of oligonucleotides. This is proposed to result from the high degree of crowding and associated increase in entropic driving force for the binding of polyelectrolytes such as nucleic acid molecules.

Special equipment considerations for neonatal ECMO.

Extracorporeal membrane oxygenation (ECMO) for neonates is applied routinely at major children's hospitals around the world. While the practice seems routine, the peculiar physiology of the small human imposes particular constraints on selection of equipment, performance of the circuit, and risks to the child. The physiology of small patients and physics of circuit elements leave many areas opaque and far from optimal, but still allow assembly of a set of useful heuristics for good practice.

Short-Term Neurodevelopmental Outcome in Congenital Diaphragmatic Hernia: The Impact of Extracorporeal Membrane Oxygenation and Timing of Repair.

Objectives: The purpose of this study was to assess the need and timing of extracorporeal membrane oxygenation in relation to congenital diaphragmatic hernia repair as modifiers of short-term neurodevelopmental outcomes.

Design: Retrospective study.

Setting: A specialized tertiary care center.

Subpopulations of dermal skin fibroblasts secrete distinct extracellular matrix: implications for using skin substitutes in the clinic.

Background: While several commercial dermoepidermal scaffolds can promote wound healing of the skin, the achievement of complete skin regeneration still represents a major challenge.

Objectives: To perform biological characterization of self-assembled extracellular matrices (ECMs) from three different subpopulations of fibroblasts found in human skin: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi).

Methods: Fibroblast subpopulations were cultured with ascorbic acid to promote cell-assembled matrix production for 10 days.

Handheld isothermal amplification and electrochemical detection of DNA in resource-limited settings.

This paper demonstrates a new method for electrochemical detection of specific sequences of DNA present in trace amounts in serum or blood. This method is designed for use at the point-of-care (particularly in resource-limited settings). By combining recombinase polymerase amplification (RPA)- an isothermal alternative to the polymerase chain reaction - with an electroactive mediator, this electrochemical methodology enables accurate detection of DNA in the field using a low-cost, portable electrochemical analyzer (specifically designed for this type of analysis).

Ataxia Telangiectasia and Cancer Predisposition: Challenges in Management.

Immune dysregulation and predisposition to malignancies are critical comorbidities in children affected with ataxia telangiectasia. In addition, these children exhibit increased toxicity to conventional cancer therapy and dose reductions have been proposed to prevent life threatening adverse effects. These modifications to the treatment regimen may result in suboptimal outcomes for these patients.

Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers.

We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we show how nonmalignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define, for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, while also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases.

Oxytocin receptor genotype and low economic privilege reverses ventral striatum-social anxiety association.

Oxytocin receptor gene (OXTR) polymorphisms, lower ventral striatum (VS) response to social stimuli, and lower economic privilege have been independently associated with depression and anxiety. However, the interactions between these risk factors are unknown. One hundred and fifty-seven healthy adult participants genotyped for OXTR rs237915 completed a common emotion-matching task during functional magnetic resonance imaging.

Knowledge, beliefs, and attitudes of the Quebec population toward chronic pain: Where are we now?

: Many chronic pain (CP) awareness and educational initiatives have been achieved, but it is time to take stock of where we are today. : The aim of this study was to describe and identify determinants of knowledge, beliefs, and attitudes of different subgroups of the Quebec population regarding CP and especially toward people suffering from this condition. : A web-based, cross-sectional study was conducted between May and June 2014.

Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study.

The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patients with typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history.

Inferior Radiographic and Functional Outcomes With Modular Stem in Metal-on-Metal Total Hip Arthroplasty.

Background: Data on the association between stem type and metal-on-metal (MoM) total hip arthroplasty (THA) performance are limited. The aim of this study is to investigate the effect of stem type on the prevalence of osteolysis and radiolucency, blood metal ion levels, and functional outcomes in patients with Articular Surface Replacement THA (ASR XL), a type of MoM THA.

Methods: We analyzed 539 unilateral MoM THAs coupled with Summit (48%), Corail (35%), or S-ROM (17%) hip stems at a mean follow-up of 6.

Spatial discrimination of glioblastoma and treatment effect with histologically-validated perfusion and diffusion magnetic resonance imaging metrics.

The goal of this study is to spatially discriminate tumor from treatment effect (TE), within the contrast-enhancing lesion, for brain tumor patients at all stages of treatment. To this end, the diagnostic accuracy of MRI-derived diffusion and perfusion parameters to distinguish pure TE from pure glioblastoma (GBM) was determined utilizing spatially-correlated biopsy samples. From July 2010 through June 2015, brain tumor patients who underwent pre-operative DWI and DSC-MRI and stereotactic image-guided biopsy were considered for inclusion in this IRB-approved study.