A decade ago, hepcidin, an antimicrobial peptide with iron-regulatory properties, was discovered and proposed as playing a significant role in the pathogenesis of anemia of chronic disease. Subsequent studies have demonstrated that hepcidin is the keystone of the linked systems of iron balance and iron transport in health and in ...

Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties ...

N-arachidonoyl 5-HT (NA-5HT) has anti-nociceptive effects reported to be mediated by inhibitory actions at the transient receptor potential vanilloid receptor 1 (TRPV1) and fatty acid amide hydrolase (FAAH). Anandamide and N-arachidonoyl dopamine (NA-DA), endocannabinoids that activate TRPV1 or are metabolized by FAAH, also inhibit T-type calcium channels (I(Ca) ). T-type ...

Betahistine, the main histamine drug prescribed to treat vestibular disorders, is a histamine H(3) receptor antagonist. Here, we explored the potential for modulation of the most recently cloned histamine receptor (H(4) receptor) to influence vestibular system function, using a selective H(4) receptor antagonist JNJ 7777120 and the derivate compound JNJ ...

Candida infections are a leading cause of infectious disease-related death in infants supported with extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics; thus, standard fluconazole dosing in children on ECMO may result in suboptimal drug exposure. This study determined the pharmacokinetics of fluconazole in infants on ECMO. ...

Bendamustine with or without rituximab provides an effective and more tolerable alternative to the polytherapy cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP) in the treatment of haematological tumours and is currently approved for the treatment of many haematological malignancies. Navitoclax (ABT-263) is a potent inhibitor of Bcl-2, Bcl-x(L) and Bcl-w, which has demonstrated efficacy in ...

Pluripotent stem cells offer an abundant and malleable source for the generation of differentiated cells for transplantation as well as for in vitro screens. Patterning and differentiation protocols have been developed to generate neural progeny from human embryonic or induced pluripotent stem cells. However, continued refinement is required to enhance ...

Femoral head fractures may present in various patterns with or without associated fractures around the hip. As a result, the treating orthopaedic surgeon must understand not only the fracture pattern, but also patient-related fractures and the relevant operative exposures and reconstructive options to achieve the best functional outcome while minimizing ...

Estimating disease incidence from cross-sectional surveys, using biomarkers for "recent" infection, has attracted much interest. Despite widespread applications to HIV, there is currently no consensus on the correct handling of biomarker results classifying persons as "recently" infected long after the infections occurred. We derive a general expression for a weighted ...

Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients can be used to model different human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. Here, we analyzed neuronal properties of an iPSC line derived from a patient with ...

The optimal management strategy for femoral neck fractures remains highly debated. The femoral neck is intracapsular and the vascular supply is fragile. Furthermore, the curvature of the proximal femur results in high mechanical stresses through the femoral neck. Poor outcomes of nonunion and avascular necrosis (AVN) are common. This chapter ...

Daptomycin is approved for the treatment of complicated skin and skin-structure infections and Staphylococcus aureus bacteremia. We sought to characterize daptomycin single-dose pharmacokinetics and tolerability in young infants. Subjects < 120 days of age with suspected systemic infections were eligible for inclusion. Each subject was given a single 6 mg/kg ...

Articular cartilage lesions of the glenohumeral joint are an especially difficult clinical problem to manage, particularly in the younger, more active patient. Left untreated, these lesions may progress in the long-term, leading to further pain and disability. While shoulder arthroplasty remains a viable option in older patients with glenohumeral arthritis, ...

Large symptomatic osteochondral defects in a young active population represent a therapeutic challenge for orthopedic surgeons, since standard interventions such as debridement, microfracture and autologous osteochondral transfer are not suitable for the treatment of these larger lesions. Fresh osteochondral allograft transplantation provides a surgical option for these challenging defects, both ...

Major depressive disorder and the use of serotonin reuptake inhibitors (SRIs) in pregnancy have been associated with preterm birth. Studies that have attempted to separate effects of illness from treatment have been inconclusive. We sought to explore the separate effects of SRI use and major depressive episodes in pregnancy on ...

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the Norwegian Childhood Immunization Program in 2006. A substantial effectiveness of PCV7 immunization against invasive pneumococcal disease has been demonstrated, whereas evidence of its impact on respiratory tract infections are less consistent. This study included children participating in the Norwegian Mother ...

Phosphatidylinositol 3-kinase (PI3K) is essential for both G protein-coupled receptor (GPCR)- and receptor tyrosine kinase (RTK)-mediated cancer cell migration. Here, we have shown that maximum migration is achieved by full activation of phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 (P-Rex1) in the presence of Gβγ and PI3K signaling pathways. Lysophosphatidic acid (LPA)- ...

G-quadruplex ligands have attracted considerable interest as novel anticancer therapeutics due to their capability to interfere with guanosine-rich DNA/RNA sequences, such as telomeres. Elucidation of the structures of telomeric G-quadruplexes has led, in the past few years, to the rational development of effective G-quadruplex-stabilizing small molecules. In the present study, ...

Lung nodules are commonly encountered in clinical practice, yet little is known about their management in community settings. An automated method for identifying patients with lung nodules would greatly facilitate research in this area. Using members of a large, community-based health plan from 2006 to 2010, we developed a method ...

During embryogenesis, the endothelial and the hematopoietic lineages first appear during gastrulation in the blood island of the yolk sac. We have previously reported that an Ets variant gene 2 (Etv2/ER71) mutant embryo lacks hematopoietic and endothelial lineages; however, the precise roles of Etv2 in yolk sac development remains unclear. ...

To replicate the association of variants in RYR3 gene with common carotid intima-media thickness (cIMT), a surrogate marker of atherosclerosis, we genotyped single nucleotide polymorphisms (SNPs) rs2229116 and rs7177922 in a sub-population of 244 HIV-positive and HIV-negative men. SNP rs2229116 was associated with common cIMT in HIV infected white men ...

Breast cancer research and treatment by different subtypes is an inevitable trend. We investigated the clinicopathologic features and outcomes of different breast cancer subtypes in Southern China. A total of 5809 patients with invasive ductal carcinomas were identified. Immunohistochemical (IHC) markers for estrogen receptor (ER), progesterone receptor (PR), Her2/neu, and ...

A 19-year-old female soccer player presented for evaluation of pain at the base of the right hallux after a recent sports injury. She had a history of 4 operations, 1 each at both knees and both elbows, for the treatment of osteochondritis dissecans (OCD). Examination showed tenderness to palpation and ...

Hematopoietic stem cell (HSC) function is tightly regulated by cytokine signaling. Although phospho-flow cytometry allows us to study signaling in defined populations of cells, there has been tremendous hurdle to carry out this study in rare HSCs due to unrecoverable critical HSC markers, low HSC number, and poor cell recovery ...

To measure reader variability related to the evaluation of screening chest radiographs (CXRs) for findings of primary lung cancer. From the National Lung Screening Trial (NLST), 100 cases were randomly selected from baseline CXR examinations for retrospective interpretation by 9 NLST radiologists; images with noncalcified lung nodules (NCNs) or other ...

We examined the usability of smartphones for accessing a web-based e-Diary for self-monitoring symptoms in children and adolescents with sickle cell disease (SCD). One group of participants (n = 10; mean age, 13.1 ± 2.4 y; 5 M; 5 F) responded to questions using precompleted paper-based measures. A second group ...

Recent research suggests that microtubule-associated protein 1 light chain 3B (LC3B) confers protection against hypoxia-induced pulmonary hypertension (HPH) by inhibiting proliferation of pulmonary artery (PA) wall cells. We recently demonstrated that 17β-estradiol (E2), a sex hormone with known protective properties in HPH, increases lung LC3-II expression in chronically hypoxic male ...

We present a fabrication process to create bifunctional microparticles displaying two distinct proteins that are spatially segregated onto the surface hemispheres. Silica and polystyrene microparticles with 2.0, 4.1, and 4.7 μm diameters are processed with metal deposition to form two chemically distinct and segregated hemispheres. The surface of each hemisphere ...

Protein structure is highly diverse when considering a wide range of protein types, helping to give rise to the multitude of functions that proteins perform. In particular, certain proteins are known to adopt a knotted or slipknotted fold. How such proteins undergo mechanical unfolding was investigated utilizing a combination of ...

Comment on: Rankin EB, et al. Cell 2012; 149:63-74.

Numerous stimuli, including oncogenic signaling, DNA damage or eroded telomeres trigger proliferative arrest, termed cellular senescence. Accumulating evidence suggests that cellular senescence is a potent barrier to tumorigenesis in vivo, however oncogene induced senescence can also promote cellular transformation. Several oncogenes, whose overexpression results in cellular senescence, converge on the ...

The zinc-finger transcription factor, Mxr1 activates methanol utilization and peroxisome biogenesis genes in the methylotrophic yeast, Pichia pastoris. Expression of Mxr1-dependent genes is regulated in response to various carbon sources by an unknown mechanism. We show here that this mechanism involves the highly conserved 14-3-3 proteins. 14-3-3 proteins participate in ...

Many small molecules, including bioactive molecules and approved drugs, spontaneously form colloidal aggregates in aqueous solution at micromolar concentrations. Though it is widely accepted that aggregation leads to artifacts in screens for ligands of soluble proteins, the effects of colloid formation in cell-based assays have not been studied. Here, seven ...

Many analytical techniques benefit greatly from the use of affinity reagent pairs, wherein each reagent recognizes a discrete binding site on a target. For example, antibody pairs have been widely used to dramatically increase the specificity of enzyme linked immunosorbent assays (ELISA). Nucleic acid-based aptamers offer many advantageous features relative ...

We present our early experience of arthroscopic reduction of the dislocated hip in very young infants with developmental dysplasia of the hip (DDH). Eight dislocated hips, which had failed attempts at closed reduction, were treated by arthroscopy of the hip in five children with a mean age of 5.8 months ...

Increasing use of cross-sectional studies has resulted in a concomitant increase in the number of intravascular and perivascular masses found in patients being studied for a multitude of thoracic conditions. As a consequence, there needs to be an awareness of the imaging findings of certain unusual abnormalities that will help ...

Scaphoid nonunions are challenging cases that first must be identified and then treated based on stability, collapse, and vascularity. Unstable nonunions are identified on the basis of collapse of the scaphoid into the "humpback" deformity with an increased intrascaphoid and scapholunate angles. The importance of restoring normal scaphoid alignment has ...

There have been many positive changes in combat casualty care since Desert Storm. The Air Force has made a major change and significant improvement in combat casualty care, which is aided by the United States Army and Navy. The current care is second to none, including rehabilitation. This improvement in ...

Diabetes mellitus is recognised as a risk factor for carpal tunnel syndrome. The response to treatment is unclear, and may be poorer than in non-diabetic patients. Previous randomised studies of interventions for carpal tunnel syndrome have specifically excluded diabetic patients. The aim of this study was to investigate the epidemiology ...

We found a highly divergent circovirus in serum samples from several dogs. Phylogenetic analysis indicates that canine circovirus genotype 1 (CaCV-1) represents the first circovirus reported in dogs and is genetically most closely related to the only known mammalian circovirus, porcine circovirus. Here we report the complete genome sequence of ...

The triangular fibrocartilage complex (TFCC) is an anatomically and biomechanically important structure. Repair of radial-sided TFCC tear has previously been challenging. We designed a new method of radial-sided TFCC tear repair and found that it was also applicable for ulnar-sided TFCC tear repair. From October 2006 to December 2010, 10 ...

Medical Education 2012: 46:613-624 Context  Longitudinal integrated clerkships (LICs) are established, rapidly growing models of education designed to improve the core clinical year of medical school using guiding principles about workplace learning and continuity. This study is the first to report data from direct observations of workplace learning experiences of ...

Hospital admission rates were lower and time to ED discharge was shorter.

Pasteurella multocida is an important etiological agent that can cause many economically important diseases in a wide range of mammals and birds. Here, we report the complete genome sequence of P. multocida HN06, a toxigenic serogroup D strain isolated from a diseased pig in China.

To assess feasibility, complications, local tumor recurrences, overall survival (OS), and estimates of cost effectiveness for multisite cryoablation (MCA) of oligometastatic non-small-cell lung cancer (NSCLC). A total of 49 computed tomography- and/or ultrasound-guided percutaneous MCA procedures were performed on 60 tumors in 31 patients (19 women and 12 men) with ...

ERCP in Roux-en-Y gastric bypass (RYGB) patients is challenging. Balloon-assisted enteroscopy (BAE) allows access to the excluded stomach with creation of a percutaneous endoscopic gastrostomy (PEG). Transgastric self-expandable metal stent (SEMS) placement may allow antegrade ERCP in 1 session. To determine the feasibility of transgastric endoscopy and ERCP through a ...

OBJECTIVES: A young person with many risk factors may have the same level of risk as an older person with no risk factors. Thus a high-risk 40-year-old may have a risk age of 60 years or more. The aim of the study was to derive a generic equation for risk ...

Revascularization of immature necrotic teeth is a reliable treatment alternative to conventional apexogenesis or apexification. In case 1, a 12-year-old boy had his necrotic, immature mandibular left second premolar treated with a revascularization technique. At a24-month follow-up, periapical radiolucency had disappeared and thickening of the root wall was observed. In ...

A child's chronic illness may be impossible to control, but there's still a choice to make.

A major focus of the American College of Epidemiology's Policy Committee has been to review the translation of epidemiologic evidence into policy by developing case studies. This article summarizes crosscutting policy process lessons across the eight cases developed to date through two workshops held in 2009 and 2011. A framework ...