Radiofrequency Ablation of the Costotransverse Joint in a Case of Chronic Thoracic Back Pain.

The source of thoracic back pain is often challenging to diagnose and manage, as there exist multiple potential etiologies and treatment strategies. Costotransverse joints are small synovial joints that may be prevalent and overlooked pain generators in the thoracic spine. Intra-articular steroid injections are commonly utilized as non-surgical therapeutic interventions for costotransverse joint pain; however, they have variable efficacy.

Retrospective Cohort Evaluating the Comparative Effectiveness of Ceftaroline and Daptomycin as First-Line Therapies for Inpatient Treatment of Diabetic Foot Infection in the United States Veterans Health Care System.

Background: Both ceftaroline and daptomycin are possible therapeutic options for diabetic foot infection (DFI) and both are active against methicillin-resistant Staphylococcus aureus (MRSA) infection; however, no previous studies have evaluated their effectiveness head-to-head.

Objective: This study compared hospital readmission and mortality proportions among patients receiving ceftaroline fosamil or daptomycin for DFI.

Patients And Methods: This was a retrospective cohort, comparative effectiveness study of adults (aged ≥ 18 years) admitted to United States Veterans Health Care System hospitals with a diagnosis code for DFI between 1 October 2010 and 30 September 2014 with an electronic order for ceftaroline or daptomycin as first-line therapy within 14 days of admission.

Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs.

Airway organoids are polarized 3D epithelial structures that recapitulate the organization and many of the key functions of the in vivo tissue. They present an attractive model that can overcome some of the limitations of traditional 2D and Air-Liquid Interface (ALI) models, yet the limited accessibility of the organoids' apical side has hindered their applications in studies focusing on host-pathogen interactions. Here, we describe a scalable, fast and efficient way to generate airway organoids with the apical side externally exposed.

Culture Methods to Study Apical-Specific Interactions using Intestinal Organoid Models.

The lining of the gut epithelium is made up of a simple layer of specialized epithelial cells that expose their apical side to the lumen and respond to external cues. Recent optimization of in vitro culture conditions allows for the re-creation of the intestinal stem cell niche and the development of advanced 3-dimensional (3D) culture systems that recapitulate the cell composition and the organization of the epithelium. Intestinal organoids embedded in an extracellular matrix (ECM) can be maintained for long-term and self-organize to generate a well-defined, polarized epithelium that encompasses an internal lumen and an external exposed basal side.

Feeder-free and serum-free in vitro assay for measuring the effect of drugs on acute and chronic myeloid leukemia stem/progenitor cells.

Research on chronic and acute myeloid leukemia (CML/AML) is focused on the development of novel therapeutic strategies to eliminate leukemic stem/progenitor cells that are responsible for drug resistance and disease relapse. Methods to culture hematopoietic stem/progenitor cells (HSPCs) from blood or bone marrow samples are indispensable for investigating disease pathogenesis and delineating drug responses in individual patients. A key challenge in this area is that primary leukemic cells grow poorly in culture or rapidly differentiate and lose their hematopoietic potential.

Occurrence of the parasitic copepod Ergasilus labracis on Threespine Sticklebacks from the south coast of Newfoundland.

A study conducted from August to October 2013 surveyed Threespine Sticklebacks Gasterosteus aculeatus (n = 822) for the presence of parasitic copepods in the vicinity of large sea-cage salmonid farms in Bay d'Espoir, Newfoundland. The majority of parasitic copepods surveyed were Ergasilus labracis (n = 4,684). Other parasitic copepods observed on Threespine Sticklebacks during the survey included chalimus-stage Lepeophtheirus spp.

Targeting primitive chronic myeloid leukemia cells by effective inhibition of a new AHI-1-BCR-ABL-JAK2 complex.

Background: Imatinib mesylate (IM) induces clinical remission of chronic myeloid leukemia (CML). The Abelson helper integration site 1 (AHI-1) oncoprotein interacts with BCR-ABL and Janus kinase 2 (JAK2) to mediate IM response of primitive CML cells, but the effect of the interaction complex on the response to ABL and JAK2 inhibitors is unknown.

Methods: The AHI-1-BCR-ABL-JAK2 interaction complex was analyzed by mutational analysis and coimmunoprecipitation.

Substrate utilization during submaximal exercise in children with a severely obese parent.

Background: We have reported a reduction in fatty acid oxidation (FAO) at the whole-body level and in skeletal muscle in severely obese (BMI ≥ 40 kg/m2) individuals; this defect is retained in cell culture suggesting an inherent component. The purpose of the current study was to determine if an impairment in whole-body fatty acid oxidation (FAO) was also evident in children with a severely obese parent.

Methods: Substrate utilization during submaximal exercise (cycle ergometer) was determined in children ages 8-12 y with a severely obese parent (OP, n = 13) or two lean/non-obese (BMI range of 18 to 28 kg/m2) parents (LP, n = 13).

Effects of griseofulvin on apoptosis through caspase-3- and caspase-9-dependent pathways in K562 leukemia cells: An in vitro study.

Background: Griseofulvin, an oral nontoxic antifungal drug, has been reported to possess anticancer effect in human cancer cells, while the mechanisms are not completely understood.

Objective: The aim of this study was to investigate the cytotoxic effect of griseofulvin on K562 cells and to understand its underlying molecular pathways.

Methods: K562 cells were treated with griseofulvin at different concentrations for 24 hours, and the inhibition effect of griseofulvin on K562 cell proliferation was assessed by tetrazolium salt colorimetric assay.

Insights into the stem cells of chronic myeloid leukemia.

Chronic myeloid leukemia (CML) has long served as a paradigm for generating new insights into the cellular origin, pathogenesis and improved approaches to treating many types of human cancer. Early studies of the cellular phenotypes and genotypes represented in leukemic populations obtained from CML patients established the concept of an evolving clonal disorder originating in and initially sustained by a rare, multipotent, self-maintaining hematopoietic stem cell (HSC). More recent investigations continue to support this model, while also revealing new insights into the cellular and molecular mechanisms that explain how knowledge of CML stem cells and their early differentiating progeny can predict the differing and variable features of chronic phase and blast crisis.

Recent salmon declines: a result of lost feeding opportunities due to bad timing?

As the timing of spring productivity blooms in near-shore areas advances due to warming trends in global climate, the selection pressures on out-migrating salmon smolts are shifting. Species and stocks that leave natal streams earlier may be favoured over later-migrating fish. The low post-release survival of hatchery fish during recent years may be in part due to static release times that do not take the timing of plankton blooms into account.

Properties of CD34+ CML stem/progenitor cells that correlate with different clinical responses to imatinib mesylate.

Imatinib mesylate (IM) induces clinical remissions in chronic-phase chronic myeloid leukemia (CML) patients but IM resistance remains a problem. We recently identified several features of CML CD34(+) stem/progenitor cells expected to confer resistance to BCR-ABL-targeted therapeutics. From a study of 25 initially chronic-phase patients, we now demonstrate that some, but not all, of these parameters correlate with subsequent clinical response to IM therapy.

Reduction in multi-lineage and erythroid progenitors distinguishes myelodysplastic syndromes from non-malignant cytopenias.

We studied the diagnostic role of CFC assays in myelodysplastic syndromes (MDS) using CFC data from bone marrow (BM) and peripheral blood (PB) of 221 MDS patients, 51 patients with non-malignant causes of cytopenia and/or dysplasia and 50 normal controls. A consistent decrease in BM but not PB multi-lineage and erythroid progenitor frequencies was seen in patients with MDS compared to controls (P<0.05).

High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival.

Myelodysplastic syndromes (MDSs) pose an important diagnostic and treatment challenge because of the genetic heterogeneity and poorly understood biology of the disease. To investigate initiating genomic alterations and the potential prognostic significance of cryptic genomic changes in low-risk MDS, we performed whole genome tiling path array comparative genomic hybridization (aCGH) on CD34(+) cells from 44 patients with an International Prognostic Scoring System score less than or equal to 1.0.

Stem cell biomarkers in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a clonal multi-step myeloproliferative disease that is initially produced and ultimately sustained by a rare subpopulation of BCR-ABL+ cells with multi-lineage stem cell properties. These BCR-ABL+ CML stem cells are phenotypically similar to normal hematopoietic stem cells which are also maintained throughout the course of the disease at varying levels in different patients. Defining the unique properties of the leukemic stem cells that produce the chronic phase of CML has therefore had to rely heavily on access to samples from rare patients in which the stem cell compartment is dominated by leukemic elements.

Enumeration of neural stem and progenitor cells in the neural colony-forming cell assay.

Advancement in our understanding of the biology of adult stem cells and their therapeutic potential relies heavily on meaningful functional assays that can identify and measure stem cell activity in vivo and in vitro. In the mammalian nervous system, neural stem cells (NSCs) are often studied using a culture system referred to as the neurosphere assay. We previously challenged a central tenet of this assay, that all neurospheres are derived from a NSC, and provided evidence that it overestimates NSC frequency, rendering it inappropriate for quantitation of NSC frequency in relation to NSC regulation.

Toxicity testing using hematopoietic stem cell assays.

For over 40 years, in vitro assays have been used to understand the complex system of hematopoiesis. Now, several of these assays are undergoing resurgence as scientists in academia and industry are discovering how these assays can be utilized in drug discovery and development. These assays use primary cells from various hematopoietic tissues in multiple species to provide high content information.

Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity.

Background And Objectives: Primitive human hematopoietic cells contain higher levels of aldehyde dehydrogenase (ALDH) activity than their terminally differentiating progeny but the particular stages when ALDH levels change have not been well defined. The objective of this study was to compare ALDH levels among the earliest stages of hematopoietic cell differentiation and to determine whether these could be exploited to obtain improved purity of human cord blood cells with long-term lympho-myeloid repopulating activity in vivo.

Design And Methods: ALDEFLUOR-stained human cord blood cells displaying different levels of ALDH activity were first analyzed for co-expression of various surface markers.

Instability of BCR-ABL gene in primary and cultured chronic myeloid leukemia stem cells.

Background: Imatinib mesylate treatment causes remissions in a majority of patients with chronic myeloid leukemia (CML), but relapses are an increasing problem. We hypothesized that imatinib-resistant leukemic cells emerge from CML stem cells that acquire BCR-ABL gene mutations even before exposure to BCR-ABL-targeted agents such as imatinib.

Methods: Lineage-negative (i.

The challenges of targeting chronic myeloid leukemia stem cells.

Chronic myeloid leukemia (CML) is sustained by a clonally amplified population of Bcr Abl-positive pluripotent stem cells. Persistence of a large, functionally intact yet suppressed residual normal hematopoietic stem cell population in most patients with CML has made it possible to aim at the development of curative therapies. However, achieving this goal requires the identification of agents that will eradicate the leukemic stem cell population.

Chronic myeloid leukemia stem cells possess multiple unique features of resistance to BCR-ABL targeted therapies.

The leukemic stem cells in patients with chronic myeloid leukemia (CML) are well known to be clinically resistant to conventional chemotherapy and may also be relatively resistant to BCR-ABL-targeted drugs. Here we show that the lesser effect of imatinib mesylate (IM) on the 3-week output of cells produced in vitro from lin(-)CD34(+)CD38(-) CML (stem) cells compared with cultures initiated with the CD38(+) subset of lin(-)CD34(+) cells is markedly enhanced (>10-fold) when conditions of reduced growth factor stimulation are used. Quantitative analysis of genes expressed in these different CML subsets revealed a differentiation-associated decrease in IL-3 and G-CSF transcripts, a much more profound decrease in expression of BCR-ABL than predicted by changes in BCR expression, decreasing expression of ABCB1/MDR and ABCG2 and increasing expression of OCT1.

A novel triple purge strategy for eliminating chronic myelogenous leukemia (CML) cells from autografts.

Imatinib-refractory chronic myelogenous leukemia (CML) patients can experience long-term disease-free survival with myeloablative therapy and allogeneic hematopoietic cell transplantation; however, associated complications carry a significant risk of mortality. Transplantation of autologous hematopoietic cells has a reduced risk of complications, but residual tumor cells in the autograft may contribute to relapse. Development of methods for purging tumor cells that do not compromise the engraftment potential of the normal hematopoietic cells in the autograft has been a long-standing goal.