Molecular principles for heparin oligosaccharide-based inhibition of neutrophil elastase in cystic fibrosis.

Cystic fibrosis (CF) is a multifactorial disease in which dysfunction of protease-antiprotease balance plays a key role. The current CF therapy relies on dornase α, hypertonic saline, and antibiotics and does not address the high neutrophil elastase (NE) activity observed in the lung and sputum of CF patients. Our hypothesis is that variants of heparin, which potently inhibit NE but are not anticoagulant, would help restore the protease-antiprotease balance in CF.

Fathers with Childhood ADHD, Parenting, and Their Young Children's Behavior: Offspring of the Pittsburgh ADHD Longitudinal Study (PALS).

Despite high heritability, no research has followed children with ADHD to parenthood to study their offspring and parenting behaviors. Given greater prevalence of ADHD in males and lack of research involving fathers, this study evaluated offspring of fathers with and without ADHD histories for ADHD and disruptive behavior and compared fathers' parenting behaviors. Male fathers (N = 29) from the Pittsburgh ADHD Longitudinal Study (PALS) participated with their preschool-aged offspring.

Anaesthesia: what a surgeon needs to know.

Surgeons and anaesthetists work closely together, sometimes in challenging circumstances. To help surgeons cooperate with anaesthetists to deliver high quality care for patients, a working knowledge of modern anaesthetic practice is useful. The specialty of anaesthetics is developing rapidly, and periodic updating of this knowledge is likely to be required.

ACR Appropriateness Criteria Orbits Vision and Visual Loss.

Visual loss can be the result of an abnormality anywhere along the visual pathway including the globe, optic nerve, optic chiasm, optic tract, thalamus, optic radiations or primary visual cortex. Appropriate imaging analysis of visual loss is facilitated by a compartmental approach that establishes a differential diagnosis on the basis of suspected lesion location and specific clinical features. CT and MRI are the primary imaging modalities used to evaluate patients with visual loss and are often complementary in evaluating these patients.

Two case reports of zoledronic acid-induced uveitis.

Zoledronic acid (zoledronate) is a bisphosphonate used predominantly as a second-line treatment for post-menopausal osteoporosis. Its administration is associated with an acute phase reaction. Here, we present two cases of anterior uveitis following initial administration of zoledronate.

2-O, 3-O desulfated heparin mitigates murine chemotherapy- and radiation-induced thrombocytopenia.

Thrombocytopenia is a significant complication of chemotherapy and radiation therapy. Platelet factor 4 (PF4; CXCL4) is a negative paracrine of megakaryopoiesis. We have shown that PF4 levels are inversely related to steady-state platelet counts, and to the duration and severity of chemotherapy- and radiation-induced thrombocytopenia (CIT and RIT, respectively).

Immunology of oligodendrocyte precursor cells in vivo and in vitro.

Remyelination following myelin/oligodendrocyte injury in the central nervous system (CNS) is dependent on oligodendrocyte progenitor cells (OPCs) migrating into lesion sites, differentiating into myelinating oligodendrocytes (OLs), and ensheathing axons. Experimental models indicate that robust OPC-dependent remyelination can occur in the CNS; in contrast, histologic and imaging studies of lesions in the human disease multiple sclerosis (MS) indicate the variable extent of this response, which is particularly limited in more chronic MS lesions. Immune-mediated mechanisms can contribute either positively or negatively to the presence and functional responses of OPCs.

Silk Fibroin Films Facilitate Single-Step Targeted Expression of Optogenetic Proteins.

Optical methods of interrogating neural circuits have emerged as powerful tools for understanding how the brain drives behaviors. Optogenetic proteins are widely used to control neuronal activity, while genetically encoded fluorescent reporters are used to monitor activity. These proteins are often expressed by injecting viruses, which frequently leads to inconsistent experiments due to misalignment of expression and optical components.

Cigarette Smoking Progression Among Young Adults Diagnosed With ADHD in Childhood: A 16-year Longitudinal Study of Children With and Without ADHD.

Introduction: Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for smoking cigarettes, but there is little longitudinal research on the array of smoking characteristics known to be prognostic of long-term smoking outcomes into adulthood. These variables were studied into early adulthood in a multisite sample diagnosed with ADHD combined type at ages 7-9.9 and followed prospectively alongside an age- and sex-matched local normative comparison group (LNCG).

Layers and Multilayers of Self-Assembled Polymers: Tunable Engineered Extracellular Matrix Coatings for Neural Cell Growth.

Growing primary cells and tissue in long-term cultures, such as primary neural cell culture, presents many challenges. A critical component of any environment that supports neural cell growth in vivo is an appropriate 2-D surface or 3-D scaffold, typically in the form of a thin polymer layer that coats an underlying plastic or glass substrate and aims to mimic critical aspects of the extracellular matrix. A fundamental challenge to mimicking a hydrophilic, soft natural cell environment is that materials with these properties are typically fragile and are difficult to adhere to and stabilize on an underlying plastic or glass cell culture substrate.

Combination of the low anticoagulant heparin CX-01 with chemotherapy for the treatment of acute myeloid leukemia.

Relapses in acute myelogenous leukemia (AML) are a result of quiescent leukemic stem cells (LSCs) in marrow stromal niches, where they resist chemotherapy. LSCs employ CXCL12/CXCR4 to home toward protective marrow niches. Heparin disrupts CXCL12-mediated sequestration of cells in the marrow.

Delayed Presentation of Submucosal Retained Toothbrush from Self-Inflicted Injury in Patient with Schizophrenia.

Foreign body ingestion occurs in not only children but also adults, particularly those with history of neurologic disease, alcohol use, or psychiatric disease. We present the case of a 40-year-old male with schizophrenia who presented to the emergency room with a long history of pharyngeal foreign body sensation which had recently progressed to include trismus, odynophagia, and dyspnea. Flexible laryngoscopy demonstrated fullness of the right posterior pharyngeal wall and computed tomography (CT) showed a linear opaque foreign body extending from the level of the oropharynx to the thyroid ala.

Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma.

Purpose: Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity.

Methods: The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM.

Substance use through adolescence into early adulthood after childhood-diagnosed ADHD: findings from the MTA longitudinal study.

Background: Inconsistent findings exist regarding long-term substance use (SU) risk for children diagnosed with attention-deficit/hyperactivity disorder (ADHD). The observational follow-up of the Multimodal Treatment Study of Children with ADHD (MTA) provides an opportunity to assess long-term outcomes in a large, diverse sample.

Methods: Five hundred forty-seven children, mean age 8.

Incidental Findings on FDG PET/CT in Head and Neck Cancer.

Objective 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG PET/CT) imaging is common in head and neck cancer and often identifies incidental findings that necessitate additional patient evaluations. Our goal was to assess the frequency and nature of these incidental imaging findings on FDG-PET/CT. Study Design Retrospective cohort study.

Longitudinal Evaluation of Chronic Rhinosinusitis Symptoms in a Population-Based Sample.

Background: Chronic rhinosinusitis (CRS) is a prevalent and disabling condition of the nose and sinuses. The natural history of CRS symptoms in a general population sample has not been previously studied.

Objective: In a general population-based sample from Pennsylvania, we used 2 questionnaires mailed 6 months apart to estimate the prevalence of, and identify predictors for, stability or change in symptoms over time.

ACR Appropriateness Criteria Penetrating Neck Injury.

In patients with penetrating neck injuries with clinical soft injury signs, and patients with hard signs of injury who do not require immediate surgery, CT angiography of the neck is the preferred imaging procedure to evaluate extent of injury. Other modalities, such as radiography and fluoroscopy, catheter-based angiography, ultrasound, and MR angiography have their place in the evaluation of the patient, depending on the specific clinical situation and question at hand. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel.

ACR Appropriateness Criteria Cranial Neuropathy.

Evaluation of cranial neuropathy can be complex given the different pathway of each cranial nerve as well as the associated anatomic landmarks. Radiological evaluation requires imaging of the entire course of the nerve from its nucleus to the end organ. MRI is the modality of choice with CT playing a complementary role, particularly in the evaluation of the bone anatomy.

Utrophin influences mitochondrial pathology and oxidative stress in dystrophic muscle.

Background: Duchenne muscular dystrophy (DMD) is a lethal X-linked muscle wasting disorder caused by the absence of dystrophin, a large cytoskeletal muscle protein. Increasing the levels of the dystrophin-related-protein utrophin is a highly promising therapy for DMD and has been shown to improve pathology in dystrophin-deficient mice. One contributing factor to muscle wasting in DMD is mitochondrial pathology that contributes to oxidative stress and propagates muscle damage.

Late-Onset ADHD Reconsidered With Comprehensive Repeated Assessments Between Ages 10 and 25.

Objective: Adolescents and young adults without childhood attention deficit hyperactivity disorder (ADHD) often present to clinics seeking stimulant medication for late-onset ADHD symptoms. Recent birth-cohort studies support the notion of late-onset ADHD, but these investigations are limited by relying on screening instruments to assess ADHD, not considering alternative causes of symptoms, or failing to obtain complete psychiatric histories. The authors address these limitations by examining psychiatric assessments administered longitudinally to the local normative comparison group of the Multimodal Treatment Study of ADHD.

Stereotactic radiotherapy in oligometastatic cancer.

Oligometastatic cancer describes a disease state somewhere between localized and metastatic cancer. Proposed definitions of oligometastatic disease have typically used a cut-off of five or fewer sites of disease. Treatment of oligometastatic disease should have the goal of long-term local control, and in selected cases, disease remission.

Direct Synthesis of Alloyed SiGe Nanowires for Performance-Tunable Lithium Ion Battery Anodes.

Here we report the formation of high capacity Li-ion battery anodes from SiGe alloy nanowire arrays that are grown directly on stainless steel current collectors, in a single-step synthesis. The direct formation of these SiGe nanowires (ranging from SiGe to SiGe) represents a simple and efficient processing route for the production of Li-ion battery anodes possessing the benefits of both Si (high capacity) and Ge (improved rate performance and capacity retention). The nanowires were characterized through SEM, TEM, XRD and ex situ HRSEM/HRTEM.