Emergency department (ED) crowding and patient boarding are associated with increased mortality and decreased patient satisfaction. This study uses a positive deviance methodology to identify strategies among high-performing, low-performing, and high-performance improving hospitals to reduce ED crowding.
http://ift.tt/2ge2FrS
Παρασκευή 25 Αυγούστου 2017
Hospital Strategies for Reducing Emergency Department Crowding: A Mixed-Methods Study
Molecular Data and the IPSS-R: How Mutational Burden Can Affect Prognostication in MDS
Abstract
Purpose of Review
The purpose of this study is to review established prognostic models in myelodysplastic syndromes (MDS) and describe how molecular data can be used to improve patient risk stratification.
Recent Findings
Somatic mutations are common in MDS and are associated with disease features including outcomes. Several recurrently mutated genes have prognostic significance independent of risk stratification tools used in practice. However, this prognostic impact can depend on the clinicogenetic context in which mutations occur. Qualitatively, SF3B1 mutations appear favorable only in patients with < 5% bone marrow blasts while mutations of several genes, including ASXL1, SRSF2, U2AF1, NRAS, and IDH2, appear adverse in this context. Mutations of TP53, RUNX1, and EZH2 appear adverse regardless of blast percentage. Consensus on how to best incorporate mutations into risk assessment is still being developed.
Summary
Somatic mutations can refine risk stratification and improve the accuracy of existing prognostic models, often upstaging or downstaging patients across the boundary of higher- and lower-risk MDS.
http://ift.tt/2xkZWkl
Hip fractures and Parkinson’s disease: a case series
Publication date: Available online 25 August 2017
Source:Injury
Author(s): Ross Coomber, Zeiad Alshameeri, Francesco Masia, Federico Mela, Martyn J Parker
There are no specific guidelines for treating Parkinson's disease patients who present with a hip fracture. Here we present a large cohort of patients with Parkinson's disease who suffered hip fractures. Our aim was to assess for differences between a Parkinson's disease population and a non-Parkinson's disease population with hip fractures and make recommendations on management guidelines.We performed a comprehensive analysis of prospectively collected data on all patients with hip fracture who were admitted into our department over a period of 29 years.In total 9225 patients with hip fractures were included in this study, 452 (4.9%) patients had Parkinson's disease. The mobility scores were worse pre- and post-operatively in the Parkinson's group as were mini-mental scores and ASA grade. Post-operative complications were similar between the two groups, with no difference in dislocation rate or wound complications. However, other outcomes including mobility and mortality rate at 1year were worse in the Parkinson's group. These patients also had a longer hospital stay and were more likely to be immobile and discharged to an institution.We recommend that Parkinson's disease patients should be assessed more thoroughly in the peri-operative period and arrangement for rehab and discharge planning should commence as soon as possible following admission. The consent process should reflect longer hospital stays, worse mobility, higher mortality and increased likelihood of discharge to institution but concern over increased complications, specifically dislocation was not evident in our data.
http://ift.tt/2gf4HHV
Re: Mediastinal injury is the strongest predictor of mortality in mounted blast amongst UK deployed forces: Methodological issues
Publication date: Available online 25 August 2017
Source:Injury
Author(s): A. Phillip Pearce, Anthony M.J. Bull, Jonathon C. Clasper
http://ift.tt/2iyv5NS
Letter to Editor: Freestanding Emergency Departments Can Help Fill The Gap in Trauma Care
Publication date: Available online 25 August 2017
Source:Injury
Author(s): Cedric Dark
http://ift.tt/2gf4xjN
Changes in cortical microarchitecture are independent of areal bone mineral density in patients with fragility fractures
Publication date: Available online 25 August 2017
Source:Injury
Author(s): Haider Mussawy, Gero Ferrari, Felix N. Schmidt, Tobias Schmidt, Tim Rolvien, Sandra Hischke, Wolfgang Rüther, Michael Amling
Dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) are commonly used to assess the areal bone mineral density (aBMD) and peripheral microstructure, respectively. While DXA is the standard to diagnose osteoporosis, HR-pQCT provides information about the cortical and trabecular architecture. Many fragility fractures occur in patients who do not meet the osteoporosis criterion (i.e., T-score≤−2.5). We hypothesize that patients with T-score above −2.5 and fragility fracture may have abnormal bone microarchitecture. Therefore, in this retrospective clinical study, HR-pQCT data obtained from patients with fragility fractures and T-scores≥−2.5 (n=71) were compared to corresponding data from patients with fragility fractures and T-scores≤−3.5 (n=56). Types of secondary osteoporosis were excluded from the study. To verify the dependency of alterations in bone microarchitecture and T-score, the association between HR-pQCT values and aBMD as reflected by the T-score at both proximal femora, was assessed. At the distal tibia, cortical thickness was lower (p<0.001), cortical porosity was similar (p=0.61), trabecular number was higher (p<0.001), and bone volume fraction (BV/TV) was higher (p<0.001) in patients with T-scores≥−2.5 than in patients with T-scores≤−3.5. Trabecular number and BV/TV correlated with T-score (r=0.68, p<0.001; r=0.61, p<0.001), whereas the cortical values did not. Our results thus demonstrate the importance of bone structure, as assessed by HR-pQCT, in addition to the standard DXA T-score in the diagnosis of osteoporosis.
http://ift.tt/2iwJQAG
Insulin complexed with cyclodextrins stimulates epithelialization and neovascularization of skin wound healing in rats
Publication date: Available online 25 August 2017
Source:Injury
Author(s): Jean Carlos Fernando Besson, Luzmarina Hernandes, Jéssica Men de Campos, Karina Amélia Morikawa, Ciomar Aparecida Bersani-Amado, Graciette Matioli
IntroductionSkin lesions are a significant public health problem, above all that wounds fail to heal properly and become chronic. Due to its reepithelization action, insulin has the potential to heal skin lesions, by stimulating the proliferation and migration of keratinocytes, angiogenic stimulus, and increasing collagen deposition. In the present study insulin was complexed with with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and its wound healing effect and inclusion complex (HPβCD-I) were evaluated in excisional wounds in the skin of rats.Material and MethodsThree different gel based pharmaceutical forms were created: carbopol 940® base gel, an insulin gel comprising the base gel plus 50 IU of insulin and a gel complex comprising the base gel plus (HPβCD) complexed with insulin (HPβCD-I) were used to verify wound healing in vitro and in vivo assays.ResultsThe wounds in the skin of rats were treated with gel containing HPβCD-I not cytoxically irritating and cytotoxic. Analysis of cell proliferation and measurement of the length and thickness of the epidermis showed that HPβCD-I prolonged the proliferation and migration of keratinocytes. Revascularization analysis of lesions treated with HPβCD-I compared to those treated with insulin found that angiogenic stimulus was less intense, but more constant and prolonged in the modified release process. There was increased deposition of type I and III collagen fibers in accordance with the treatment time.ConclusionTherefore, the slow release of complexed insulin modulated the reepithelialization process by stimulating cell proliferation and migration of keratinocytes, favoring greater concentration of serum insulin, modulating inflammatory response, matrix remodeling and promoting neovascularization. Angiogenesis extended by the steady release of insulin can be effective in the treatment of chronic wounds.
http://ift.tt/2gf4nsH
Anterior subcutaneous internal fixation of the pelvis − what rod-to-bone distance is anatomically optimal?
Publication date: Available online 25 August 2017
Source:Injury
Author(s): Georg Osterhoff, Elisabeth V. Aichner, Julian Scherer, Hans-Peter Simmen, Clément M.L. Werner, Georg C. Feigl
IntroductionAnterior fixation of the pelvis using subcutaneous supra-acetabular pedicle screw internal fixation (INFIX) has proven to be a useful tool by avoiding the downsides of external fixation in patients where open fixation is not suited.The purpose of this study was to find a rod-to-bone distance for the INFIX that allows for minimal hazard to the inguinal neuro-vascular structures and, at the same time, as little as possible interference with the soft tissues of the proximal thigh when the patient is sitting.MethodsAn INFIX was applied to 10 soft-embalmed cadaver pelvises with three different rod-to-bone distances. With each configuration, the relations of the rod to the neuro-vascular and the muscular surroundings were measured in supine and sitting position.ResultsExcept for the femoral artery, vein and nerve, all investigated anatomical structures of the groin were under compression with a rod-to-bone distance of 1cm. With a rod-to-bone distance of 2cm most of the anatomical structures were safe in supine position, although less than with 3cm. With hip flexion some structures got under compression, especially the lateral femoral cutaneous nerve (LFCN, 80%) and the anterior cutaneous branches of the femoral nerve (ACBFN, 35%). With a rod-to-bone distance of 3cm almost all anatomical structures were safe in supine position, while with hip flexion most superficial structures of the proximal thigh got under compression, especially the LFCN (75%) and the ACBFN (60%).ConclusionsAiming for a rod-to-bone distance of 2cm is the safest way with regard to compression of the femoral neuro-vascular bundle and at the same time leads to the least compression of more superficial structures like the LFCN, the ACBFN, or the sartorius and the rectus femoris muscles in sitting position.
http://ift.tt/2ixtiIX
Guide wire insertion for percutaneous LC2 screws in acetabular and pelvic ring fixation using a transpedicular working cannula
Publication date: Available online 25 August 2017
Source:Injury
Author(s): Julian Scherer, Pierre Guy, Kelly A. Lefaivre, Hans-Christoph Pape, Clément M.L. Werner, Georg Osterhoff
Closed reduction and percutaneous screw fixation (CRIF) of iliac crescent fractures and fractures of the anterior column of the acetabulum has become an established method in the treatment of these injuries. After reduction, safe insertion of a guide wire is a key step during this procedure. We present a technique that can facilitate introducing the guide wire under fluoroscopic guidance and allow for decreased radiation exposure.
http://ift.tt/2gdQRFH
Long-term consequences of landmine injury: a survey of civilian survivors in Bosnia-Herzegovina 20 years after the war
Publication date: Available online 25 August 2017
Source:Injury
Author(s): Katherine O. Ryken, Matthew Hogue, J. Lawrence Marsh, Marin Schweizer
IntroductionBosnia-Herzegovina is one of the most landmine-contaminated countries in Europe. Since the beginning of the war in 1992, there have been 7,968 recorded landmine victims, with 1,665 victims since the end of the war in 1995. While many of these explosions result in death, a high proportion of these injuries result in amputation, leading to a large number of disabled individuals.ObjectiveThe purpose of this study is to conduct a survey of civilian landmine victims in Bosnia-Herzegovina in order to assess the effect of landmine injuries on physical, mental, and social well-being.MethodsCivilian survivors of landmine injuries were contacted while obtaining care through local non-governmental organizations (NGOs) throughout Bosnia-Herzegovina to inquire about their current level of independence, details of their injuries, and access to healthcare and public space. The survey was based upon Physicians for Human Rights handbook, "Measuring Landmine Incidents & Injuries and the Capacity to Provide Care."Results42 survivors of landmines completed the survey, with an average follow up period of 22.0 years (±1.7). Of civilians with either upper or lower limb injuries, 83.3% underwent amputations. All respondents had undergone at least one surgery related to their injury: 42.8% had at least three total operations and 23.8% underwent four or more surgeries related to their injury. 26.2% of survivors had been hospitalized four or more times relating to their injury. 57.1% of participants reported they commonly experienced anxiety and 47.6% reported depression within the last year. On average, approximately 35% of out-of-pocket household income went toward paying medical bills, even given governmental and non-governmental assistance. Most survivors relied upon others to take care of them: only 41.5% responded they were capable of caring for themselves. 63.4% of respondents reported their injury had limited their ability to gain training, attend school, and go to work.ConclusionThe majority of civilian landmine survivors report adverse health effects due to their injuries, including anxiety, depression, multiple surgeries, and hospitalizations. The majority also experience loss of independence, either requiring care of family members for activities of daily living, disability, and inability to be employed. Further research is required to determine effective interventions for landmine survivors worldwide.
http://ift.tt/2iyEBAn
First report of sasX -positive methicillin-resistant Staphylococcus aureus in Japan
Abstract
SasX is a known virulence factor of Staphylococcus aureus involved in colonisation and immune evasion of the bacterium. The sasX gene, which is located on the ϕSPβ prophage, is frequently found in the sequence type (ST) 239 S. aureus lineage, which is the predominant healthcare-associated clone in Asian countries. In Japan, ST239 clones have rarely been identified, and sasX-positive strains have not been reported to date. Here, we report the first identification of 18 sasX-positive methicillin-resistant S. aureus (MRSA) strains in Japanese hospitals between 2009 and 2011. All sasX-positive isolates belonged to an ST239-staphylococcal cassette chromosome mec type III (ST239-III) lineage. However, we were unable to identify additional sasX-positive MRSA strains from 2012 to 2016, indicating that the small epidemic of sasX-positive isolates observed in this study was temporary. The sequence surrounding sasX in the strain TOHH628 lacked 51 genes that encode phage packaging and structural proteins, and no bacteriophage was induced by mitomycin C. Additionally, in the TOHH628 strain, the region (64.6 kb) containing sasX showed high identity to the ϕSPβ-like element (71.3 kb) of the Taiwanese MRSA strain Z172. The data strongly suggest that the present sasX-positive isolates found in Japanese hospitals were transmitted incidentally from other countries.http://ift.tt/2udKybn
Characterization of a lactose-responsive promoter of ATP-binding cassette (ABC) transporter gene from Lactobacillus acidophilus 05–172
Abstract
A novel lactose-responsive promoter of the ATP-binding cassette (ABC) transporter gene Lba1680 of Lactobacillus acidophilus strain 05–172 isolated from a traditionally fermented dairy product koumiss was characterized. In L. acidophilus 05–172, expression of Lba1680 was induced by lactose, with lactose-induced transcription of Lba1680 being 6.1-fold higher than that induced by glucose. This is in contrast to L. acidophilus NCFM, a strain isolated from human feces, in which expression of Lba1680 and Lba1679 is induced by glucose. Both gene expression and enzyme activity assays in L. paracasei transformed with a vector containing the inducible Lba1680 promoter (PLba1680) of strain 05–172 and a heme-dependent catalase gene as reporter confirmed that PLba1680 is specifically induced by lactose. Its regulatory expression could not be repressed by glucose, and was independent of cAMP receptor protein. This lactose-responsive promoter might be used in the expression of functional genes in L. paracasei incorporated into a lactose-rich environment, such as dairy products.http://ift.tt/2tYuZA9
Carbon recycling by cyanobacteria: improving CO 2 fixation through chemical production
Abstract
Atmospheric CO2 levels have reached an alarming level due to industrialization and the burning of fossil fuels. In order to lower the level of atmospheric carbon, strategies to sequester excess carbon need to be implemented. The CO2-fixing mechanism in photosynthetic organisms enables integration of atmospheric CO2 into biomass. Additionally, through exogenous metabolic pathways in these photosynthetic organisms, fixed CO2 can be routed to produce various commodity chemicals that are currently produced from petroleum. This review will highlight studies and modifications to different components of cyanobacterial CO2-fixing systems, as well as the application of these systems toward CO2-derived chemical production. 2,3-Butanediol is given particular focus as one of the most thoroughly studied systems for conversion of CO2 to a bioproduct.http://ift.tt/2wwH8AY
Investigation of triclosan contamination on microbial biomass and other soil health indicators
Abstract
Triclosan (TCS) is an antimicrobial compound found in personal care products, and consequently in greywater. After its release to the environment, it continues its antimicrobial action on indigenous microbial communities. Little is known about the environmental impacts of high levels of TCS, which may occur due to accumulation following long-term greywater application to soil. Soil microcosms were established using a silty clay loam and augmented with a range of TCS concentrations ranging from 500 to 7500 mg kg−1. Samples were analysed for substrate-induced respiration, microbial biomass and sulphatase activity. The soil augmented with the lowest concentration of TCS (500 mg kg−1) significantly decreased microbial biomass, with a calculated EC20 of 195 mg kg−1. Substrate-induced respiration indicated that the soil microbial community was impacted for all TCS concentrations; however, the community showed potential to recover over time. Sulphatase activity was less sensitive to TCS and was significantly impacted at high concentrations of TCS (>2500 mg kg−1). It is likely that TCS has selective toxicity for more susceptible microbes when introduced into the soil environment. At high levels, TCS could overwhelm TCS-degrading soil microbes.http://ift.tt/2vmC01x
Diversity and antimicrobial activity of bacteria isolated from different Brazilian coral species
Abstract
Corals harbor a wide diversity of bacteria associated with their mucus. These bacteria can play an important role in nutrient cycling, degradation of xenobiotics and defense against pathogens by producing antimicrobial compounds. However, the diversity of the cultivable heterotrophic bacteria, especially in the Brazilian coral species, remains poorly understood. The present work compares the diversity of cultivable bacteria isolated from the mucus and surrounding environments of four coral species present along the Brazilian coast, and explores the antibacterial activity of these bacteria. Bacteria belonging to the phyla Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes were isolated. The mucus environment presented a significantly different bacteria composition, compared to the water and sediment environments, with high abundance of Alcanivorax, Acinetobacter, Aurantimonas and Erythrobacter. No difference in the inhibition activity was found between the isolates from mucus and from the surrounding environment. Eighty-three per cent of the bacteria isolated from the mucus presented antimicrobial activity against Serratia marcescens, an opportunistic coral pathogen, suggesting that they might play a role in maintaining the health of the host. Most of the bacteria isolates that presented positive antimicrobial activity belonged to the genus Bacillus.http://ift.tt/2vn0aZy
Retention of seed trees fails to lifeboat ectomycorrhizal fungal diversity in harvested Scots pine forests
Abstract
Fennoscandian forestry has in the past decades changed from natural regeneration of forests towards replantation of clear-cuts, which negatively impacts ectomycorrhizal fungal (EMF) diversity. Retention of trees during harvesting enables EMF survival, and we therefore expected EMF communities to be more similar to those in old natural stands after forest regeneration using seed trees compared to full clear-cutting and replanting. We sequenced fungal ITS2 amplicons to assess EMF communities in 10–60 year-old Scots pine stands regenerated either using seed trees or through replanting of clear-cuts with old natural stands as reference. We also investigated local EMF communities around retained old trees. We found that retention of seed trees failed to mitigate the impact of harvesting on EMF community composition and diversity. With increasing stand age EMF communities became increasingly similar to those in old natural stands and permanently retained trees maintained EMF locally. From our observations we conclude that EMF communities, at least common species, post-harvest are more influenced by environmental filtering, resulting from environmental changes induced by harvest, than by the continuity of trees. These results suggest that retention of intact forest patches is a more efficient way to conserve EMF diversity than retaining dispersed single trees.http://ift.tt/2vpVT4S
Genomic characterization of environmental Pseudomonas aeruginosa isolated from dental unit waterlines revealed the insertion sequence IS Pa11 as a chaotropic element
Abstract
The bacterium Pseudomonas aeruginosa is well known to have a remarkable adaptive capacity allowing it to colonize many environments. A recent study on environmental isolates from dental unit waterlines (DUWLs) hinted at a genetic clustering into two groups. Isolates from one of these groups, named cluster III, were shown to have unusual phenotypes for environmental isolates, such as an increased biofilm production. To have a better ecological view, more specifically on isolates from cluster III, the complete genomes of 39 isolates including 16 from DUWLs were sequenced. In addition to an investigation of antibiotic resistance and secretion system gene content, a molecular phylogeny allowed confirmation of the split of the 16 environmental isolates in two groups and also sheds light on a correlation between the phylogenetic positions and the serotypes of the isolates. Isolates from cluster III harboured insertion sequences ISPa11 inserted into the O-specific antigen biosynthesis clusters and the gene lasR, encoding for a master regulator of the quorum sensing. Investigation of key regulators revealed another truncated gene, gacS. Alteration in lasR and gacS genes was consistent with phenotypic assays confirming their inactivation. These results bring new perspectives regarding the ecological adaptive potential of P. aeruginosa.http://ift.tt/2vpv1C1
Histone H3 lysine 9 methyltransferase FvDim5 regulates fungal development, pathogenicity, and osmotic stress responses in Fusarium verticillioides
Abstract
Histone methylation plays important biological roles in eukaryotic cells. Methylation of lysine 9 at histone H3 (H3K9me) is critical for regulating chromatin structure and gene transcription. Dim5 is a lysine histone methyltransferase (KHMTase) enzyme, which is responsible for the methylation of H3K9 in eukaryotes. In the current study, we identified a single ortholog of Neurospora crassa Dim5 in Fusarium verticillioides. In this study, we report that FvDim5 regulates the trimethylation of H3K9 (H3K9me3). The FvDIM5 deletion mutant (ΔFvDim5) showed significant defects in conidiation, perithecium production, and fungal virulence. Unexpectedly, we found that deletion of FvDIM5 resulted in increased tolerance to osmotic stresses and upregulated FvHog1 phosphorylation. These results indicate the importance of FvDim5 for the regulation of fungal development, pathogenicity, and osmotic stress responses in Fusarium verticillioides.http://ift.tt/2vfcsV5
Complete Genome Analysis of Lactobacillus fermentum SK152 from Kimchi Reveals Genes Associated with its Antimicrobial Activity
Abstract
Research findings on probiotics highlight their importance in repressing harmful bacteria, leading to more extensive research on their potential applications. We analysed the genome of Lactobacillus fermentum SK152, which was isolated from the Korean traditional fermented vegetable dish kimchi, to determine the genetic makeup and genetic factors responsible for the antimicrobial activity of L. fermentum SK152 and performed a comparative genome analysis with other L. fermentum strains. The genome of L. fermentum SK152 was found to comprise a complete circular chromosome of 2,092,273 bp, with an estimated GC content of 51.9% and 2,184 open reading frames. It consisted of 2,038 protein-coding genes and 73 RNA-coding genes. Moreover, a gene encoding a putative endolysin was found. A comparative genome analysis with other L. fermentum strains showed that SK152 is closely related to L. fermentum 3872 and F-6. An evolutionary analysis identified five positively selected genes that encode proteins associated with transport, survival and stress resistance. These positively selected genes may be essential for L. fermentum to colonise and survive in the stringent environment of the human gut and exert its beneficial effects. Our findings highlight the potential benefits of SK152.http://ift.tt/2vxZ7m8
Letters to the Editor
Radiation Research, Volume 188, Issue 3, Page 369-371, September 2017.
http://ift.tt/2gdgZRc
Identifying Voxels at Risk for Progression in Glioblastoma Based on Dosimetry, Physiologic and Metabolic MRI
Radiation Research, Volume 188, Issue 3, Page 303-313, September 2017.
http://ift.tt/2iwpWpz
Cancer Incidence after In Utero Exposure to Ionizing Radiation in Techa River Residents
Radiation Research, Volume 188, Issue 3, Page 314-324, September 2017.
http://ift.tt/2gdVHD3
The Development of Technology for Effective Respiratory-Gated Irradiation Using an Image-Guided Small Animal Irradiator
Radiation Research, Volume 188, Issue 3, Page 247-263, September 2017.
http://ift.tt/2iwpEyZ
Mortality from Circulatory Diseases and other Non-Cancer Outcomes among Nuclear Workers in France, the United Kingdom and the United States (INWORKS)
Radiation Research, Volume 188, Issue 3, Page 276-290, September 2017.
http://ift.tt/2gcMElC
Impact of Co-Culturing with Fractionated Carbon-Ion-Irradiated Cancer Cells on Bystander Normal Cells and Their Progeny
Radiation Research, Volume 188, Issue 3, Page 335-341, September 2017.
http://ift.tt/2iwpwQ1
Microenvironment and Dose-Delivery-Dependent Response after Exposure to Ionizing Radiation in Human Colorectal Cancer Cell Lines
Radiation Research, Volume 188, Issue 3, Page 291-302, September 2017.
http://ift.tt/2gdgCWO
Synthesis and Characterization of a Rosmarinic Acid Derivative that Targets Mitochondria and Protects against Radiation-Induced Damage In Vitro
Radiation Research, Volume 188, Issue 3, Page 264-275, September 2017.
http://ift.tt/2iwps2J
Urine Interleukin-18 (IL-18) as a Biomarker of Total-Body Irradiation: A Preliminary Study in Nonhuman Primates
Radiation Research, Volume 188, Issue 3, Page 325-334, September 2017.
http://ift.tt/2gdDV2B
Monte Carlo Electron Track Structure Calculations in Liquid Water Using a New Model Dielectric Response Function
Radiation Research, Volume 188, Issue 3, Page 355-368, September 2017.
http://ift.tt/2gdFAp2
Serum microRNAs as Early Indicators for Estimation of Exposure Degree in Response to Ionizing Irradiation
Radiation Research, Volume 188, Issue 3, Page 342-354, September 2017.
http://ift.tt/2iy3KLT
Pharmacoepigenomics of opiates and methadone maintenance treatment: current data and perspectives
Pharmacogenomics, Ahead of Print.
http://ift.tt/2vpBjkX
Mesonephric adenocarcinoma of the uterine corpus with intracystic growth completely confined to the myometrium: a case report and literature review
Mesonephric adenocarcinoma (MA) is a rare tumor believed to arise from mesonephric remnants occurring mostly in the uterine cervix and, to a lesser extent, the corpus. Since the first case report of MA in the ...
http://ift.tt/2ixUwze
A case of intravascular large B cell lymphoma presenting as nodular goiter
Intravascular large B-cell lymphoma (IVLBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that is rare and highly aggressive and that may progressively involve many organs. CNS (central nervous system...
http://ift.tt/2gdyMYl
Impact of therapy on genomics and transcriptomics in high-risk prostate cancer treated with neoadjuvant docetaxel and androgen deprivation therapy
Background: The combination of docetaxel chemotherapy and androgen deprivation therapy (ADT) has become a standard treatment for patients with metastatic prostate cancer. The recently accrued Phase III CALGB 90203 trial was designed to investigate the clinical effectiveness of this treatment approach earlier in the disease. Specimens from this trial offer a unique opportunity to interrogate the acute molecular response to docetaxel and ADT and identify predictive biomarkers. Methods: We evaluated baseline clinical data, needle biopsies and radical prostatectomy (RP) specimens from 52 (of 788) patients enrolled on CALGB 90203 at one high volume center. Pathology review, tumor and germline targeted DNA sequencing (n=72 genes), and expression profiling using Nanostring platform (n=163 genes) were performed to explore changes in critical prostate cancer pathways linked to aggression and resistance. Results: 3/52 patients had only microfocal residual cancer at prostatectomy. The most common alterations included TMPRSS2-ERG fusion (n=32), TP53 mutation or deletion (n=11), PTEN deletion (n=6), FOXA1 (n=6), SPOP (n=4) mutation, with no significant enrichment in post-treated specimens. We did not observe AR amplification or mutations. The degree of AR signaling suppression varied among treated tumors and there was up-regulation of both AR and AR-V7 expression as well as a subset of neuroendocrine and plasticity genes. Conclusions: These data support the feasibility of targeted and temporal genomic and transcriptome profiling of neoadjuvant-treated prostate cancer with limited formalin-fixed paraffin embedded tissue requirement. Characterization of the heterogeneity of treatment response and molecular outliers that arise post-treatment provides new insight into potential early markers of resistance.
http://ift.tt/2geS0x7
Duration of colonization with and risk factors for prolonged carriage of multidrug resistant organisms among residents in long-term care facilities
Residents of long-term care facilities (LTCFs) colonized with multidrug resistant organisms (MDROs) are often placed under contact isolation to ensure appropriate infection control. This isolation may reduce o...
http://ift.tt/2vxaiLR
Neural Precursors Drive Glioma Invasion of the Subventricular Zone [Research Watch]
A NPC-derived pleiotrophin promotes glioma invasion into the subventricular zone.
http://ift.tt/2vp9vNC
Vitamin C Restores TET2 Activity in TET2-Deficient Leukemia [Research Watch]
TET2 restoration promotes DNA demethylation and differentiation to suppress leukemic progression.
http://ift.tt/2wOYetJ
CMTM6 Regulates PD-L1 Expression and Antitumor Immunity [Research Watch]
CMTM6 binds to PD-L1 on the plasma membrane to promote its stability and inhibitory activity.
http://ift.tt/2voP9nN
TERT Promoter Mutations Promote Immortalization and Genomic Instability [Research Watch]
TERT promoter mutations may induce early and late tumorigenesis by separate mechanisms.
http://ift.tt/2wOZFbx
MAGE-A3-Targeted Autologous CD4+ T Cells May Target Metastatic Cancer [Research Watch]
Adoptive transfer of MAGE-A3–targeted CD4+ T cells is safe and achieves responses in several tumor types.
http://ift.tt/2vp9b1v
Benefits of Dominance over Additive Models for the Estimation of Average Effects in the Presence of Dominance
In quantitative genetics, the average effect at a single locus can be estimated by an additive (A) model, or additive plus dominance (AD) model. In the presence of dominance, the AD-model is expected to be more accurate, because the A-model falsely assumes that residuals are independent and identically distributed. Our objective was to investigate accuracy of an estimated average effect (α ) in the presence of dominance, using either a single locus A-model or AD-model. Estimation was based on a finite sample from a large population in Hardy-Weinberg equilibrium (HWE), and root mean squared error of α was calculated for several broad sense heritabilities, sample sizes, and sizes of the dominance effect. Results show that with the A-model, both sampling deviations of genotype frequencies from HWE frequencies and sampling deviations of allele frequencies contributed to the error. With the AD-model, only sampling deviations of allele frequencies contributed to the error, provided that all three genotype classes were sampled. In the presence of dominance, the root mean squared error of α with the AD-model was always smaller than with the A-model, even when the heritability was smaller than one. Remarkably, in the absence of dominance, there was no disadvantage of fitting dominance. In conclusion, the AD-model yields more accurate estimates of average effects from a finite sample, because it is more robust against sampling deviations from HWE frequencies than the A-model. Genetic models that include dominance, therefore, yield higher accuracies of estimated average effects than purely additive models when dominance is present.
http://ift.tt/2vwETJy
Prevalence and risk factors for Staphylococcus aureus nasopharyngeal carriage during a PCV trial
We conducted an ancillary study among individuals who had participated in a cluster-randomized PCV-7 trial in rural Gambia (some clusters were wholly-vaccinated while in others only young children had been vac...
http://ift.tt/2xkpm1D
The associations between socioeconomic status and risk of Staphylococcus aureus bacteremia and subsequent endocarditis – a Danish nationwide cohort study
Staphylococcus aureus bacteremia (SAB) is the leading cause of infective endocarditis in several countries. Since socioeconomic status (SES) is known to influence the risk of infectiou...
http://ift.tt/2w5HYDK
Distribution of Streptococcus pneumoniae serotypes in the northeast macro-region of São Paulo state/Brazil after the introduction of conjugate vaccine
Infections caused by Streptococcus pneumoniae (Spn) still challenge health systems around the world, even with advances in vaccination programs. The present study evaluated the frequency of various Spn serotypes ...
http://ift.tt/2xkI6hx
Accuracy of different diagnostic tests for early, delayed and late prosthetic joint infection
A combination of laboratory, histopathological and microbiological tests for diagnosis of prosthetic joint infection (PJI) have been strongly recommended. This study aims to characterize the accuracy of indivi...
http://ift.tt/2w5Ohr6
The contribution of respiratory pathogens to fatal and non-fatal respiratory hospitalizations: a pilot study of Taqman Array Cards (TAC) in Kenya
Respiratory diseases cause substantial morbidity and mortality worldwide, with sub-Saharan Africa bearing the greatest burden. Identifying etiologies of respiratory disease is important to inform cost effectiv...
http://ift.tt/2xkOPI4
The Cause of the Aimless Convoy
Never has a biomarker with so much evidence demonstrating its disutility, enjoyed such a long reign of prosperity as BNP and its natriuretic analogs. And while evidence discrediting BNP's use for the diagnosis and inpatient management of acute exacerbations of heart failure (HF) is well documented, its utility to guide outpatient therapy in patients […]
EMCrit by Rory Spiegel.
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Cutaneous leishmaniasis in a severely immunocompromised HIV patient in Kumbo, Northwest region of Cameroon: case report
Leishmaniasis is a rising opportunistic infection in individuals with human immunodeficiency virus (HIV). Cases of leishmania and HIV co-infection have been documented in several countries in the world with mo...
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Two promoters in the esx-3 gene cluster of Mycobacterium smegmatis respond inversely to different iron concentrations in vitro
The ESX secretion system, also known as the Type VII secretion system, is mostly found in mycobacteria and plays important roles in nutrient acquisition and host pathogenicity. One of the five ESXs, ESX-3, is ...
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A Standard Methodology to Examine On-site Mutagenicity As a Function of Point Mutation Repair Catalyzed by CRISPR/Cas9 and SsODN in Human Cells
http://ift.tt/2w554u9
Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure
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Heart Attack, Stroke Risk May Be Elevated Following Cancer Diagnosis
A diagnosis of cancer can come with an increased risk of a heart attack or stroke in the months after beginning treatment, a new study suggests. Within 6 months of a diagnosis, the risk of either event was more than twice that seen in people without cancer.
http://ift.tt/2vobPEL
Methods and Tips for Intravenous Administration of Adeno-associated Virus to Rats and Evaluation of Central Nervous System Transduction
Methods for a wide-scale central nervous system gene delivery in the rat are covered. In this example, the purpose is to mimic a disease that affects the entire spinal cord. The widespread transduction can be used to deliver a therapeutic protein to the CNS from a one-time, peripheral administration.
http://ift.tt/2vdF40Q
Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study)
Abstract
Background
The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months.
We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses.
Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients.
Methods
This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon's optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy.
Discussion
Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA.
Trial registration
NCT02402842, EudraCT: 2014–001789-81.
http://ift.tt/2vd2Mu5
The social and behavioral influences (SBI) study: study design and rationale for studying the effects of race and activation on cancer pain management
Abstract
Background
Racial disparities exist in the care provided to advanced cancer patients. This article describes an investigation designed to advance the science of healthcare disparities by isolating the effects of patient race and patient activation on physician behavior using novel standardized patient (SP) methodology.
Methods/design
The Social and Behavioral Influences (SBI) Study is a National Cancer Institute sponsored trial conducted in Western New York State, Northern/Central Indiana, and lower Michigan. The trial uses an incomplete randomized block design, randomizing physicians to see patients who are either black or white and who are "typical" or "activated" (e.g., ask questions, express opinions, ask for clarification, etc.). The study will enroll 91 physicians.
Discussion
The SBI study addresses important gaps in our knowledge about racial disparities and methods to reduce them in patients with advanced cancer by using standardized patient methodology. This study is innovative in aims, design, and methodology and will point the way to interventions that can reduce racial disparities and discrimination and draw links between implicit attitudes and physician behaviors.
Trial registration
http://ift.tt/1pydFNc, #NCT01501006, November 30, 2011.
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An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus
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Introduction of Nature's Complexity in Engineered Blood-compatible Biomaterials
Biomaterials with excellent blood-compatibility are needed for applications in vascular replacement therapies, such as vascular grafts, heart valves and stents, and in extracorporeal devices such as hemodialysis machines and blood-storage bags. The modification of materials that are being used for blood-contacting devices has advanced from passive surface modifications to the design of more complex, smart biomaterials that respond to relevant stimuli from blood to counteract coagulation. Logically, the main source of inspiration for the design of new biomaterials has been the endogenous endothelium. Endothelial regulation of hemostasis is complex and involves a delicate interplay of structural components and feedback mechanisms. Thus, challenges to develop new strategies for blood-compatible biomaterials now lie in incorporating true feedback controlled mechanisms that can regulate blood compatibility in a dynamic way. Here, supramolecular material systems are highlighted as they provide a promising platform to introduce dynamic reciprocity, due to their inherent dynamic nature.
Blood-compatible biomaterial development moves towards complex and smart biomaterials that are able to respond to and influence stimuli in a similar fashion as nature's blood-contacting surfaces. Here, the progress from passive surface modifications to functionalization with feedback controlled systems that can regulate blood compatibility in a dynamic way is highlighted, with a special interest for strategies based on supramolecular chemistry.
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Synthetic Biomaterials to Rival Nature's Complexity—a Path Forward with Combinatorics, High-Throughput Discovery, and High-Content Analysis
Cells in tissue receive a host of soluble and insoluble signals in a context-dependent fashion, where integration of these cues through a complex network of signal transduction cascades will define a particular outcome. Biomaterials scientists and engineers are tasked with designing materials that can at least partially recreate this complex signaling milieu towards new materials for biomedical applications. In this progress report, recent advances in high throughput techniques and high content imaging approaches that are facilitating the discovery of efficacious biomaterials are described. From microarrays of synthetic polymers, peptides and full-length proteins, to designer cell culture systems that present multiple biophysical and biochemical cues in tandem, it is discussed how the integration of combinatorics with high content imaging and analysis is essential to extracting biologically meaningful information from large scale cellular screens to inform the design of next generation biomaterials.
Recent advances in biomaterials discovery aided by combinatorics, high-throughput arraying, and high content analysis are discussed. Synthetic polymer libraries, extracellular matrix protein and peptide microarrays are explored, and new tools for multivariate systems that are guiding the development of 3D model tissues towards next-generation assays for biomedicine and biotechnology are discussed.
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Cholera Toxin Subunit B Enabled Multifunctional Glioma-Targeted Drug Delivery
Glioma is among the most formidable brain cancers due to location in the brain. Cholera toxin subunit B (CTB) is investigated to facilitate multifunctional glioma-targeted drug delivery by targeting the glycosphingolipid GM1 expressed in the blood–brain barrier (BBB), neovasulature, and glioma cells. When modified on the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (CTB-NPs), CTB fully retains its bioactivity after 24 h incubation in the fresh mouse plasma. The formed protein corona (PC) of CTB-NP and plain PLGA nanoparticles (NP) after incubation in plasma is analyzed using liquid chromatography tandem massspectrometry (nano-LC-MS/MS). CTB modification does not alter the protein components of the formed PC, macrophage phagocytosis, or pharmacokinetic profiles. CTB-NP can efficiently penetrate the in vitro BBB model and target glioma cells and human umbilical vascular endothelial cells. Paclitaxel is loaded in NP (NP/PTX) and CTB-NP (CTB-NP/PTX), and their antiglioma effects are assessed in nude mice bearing intracranial glioma. CTB-NP/PTX can efficiently induce apoptosis of intracranial glioma cells and ablate neovasulature in vivo, resulting in significant prolongation of survival of nude mice bearing intracranial glioma (34 d) in comparison to those treated with NP/PTX (29 d), Taxol (24 d), and saline (21 d). The present study suggests a potential multifunctional glioma-targeted drug delivery system enabled by cholera toxin subunit B.
Cholera toxin subunit B (CTB), the nontoxic moiety of cholera toxin, is able to circumvent the blood–brain barrier, and to target neovasculature and glioma cells. CTB modification on the surface of polymeric nanoparticles does not significantly alter components of the formed protein corona. CTB retains bioactivity during blood circulation, presenting a promising ligand for multifunctional targeting of glioma.
http://ift.tt/2vdSkCV
Rational Design of Glucose-Responsive Insulin Using Pharmacokinetic Modeling
A glucose responsive insulin (GRI) is a therapeutic that modulates its potency, concentration, or dosing of insulin in relation to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. Current GRI design lacks a theoretical basis on which to base fundamental design parameters such as glucose reactivity, dissociation constant or potency, and in vivo efficacy. In this work, an approach to mathematically model the relevant parameter space for effective GRIs is induced, and design rules for linking GRI performance to therapeutic benefit are developed. Well-developed pharmacokinetic models of human glucose and insulin metabolism coupled to a kinetic model representation of a freely circulating GRI are used to determine the desired kinetic parameters and dosing for optimal glycemic control. The model examines a subcutaneous dose of GRI with kinetic parameters in an optimal range that results in successful glycemic control within prescribed constraints over a 24 h period. Additionally, it is demonstrated that the modeling approach can find GRI parameters that enable stable glucose levels that persist through a skipped meal. The results provide a framework for exploring the parameter space of GRIs, potentially without extensive, iterative in vivo animal testing.
This paper combines pharmacokinetic models of glucose–insulin metabolism with mathematical models of glucose-responsive insulins to explore the effective parameter space of these new types of therapeutics. The model reveals that there is a range of parameter values that can maintain glycemic control over a 24 h period, from a single bolus over a wide range of conditions.
http://ift.tt/2gb0dCo
Paramedics roll child down sidewalk to ER after ambulance breaks down
The paramedics pushed the child with cardiac problems on a gurney for two blocks to the hospital
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Motion Manipulation of Micro- and Nanomotors
Inspired by the self-migration of microorganisms in nature, artificial micro- and nanomotors can mimic this fantastic behavior by converting chemical fuel or external energy into mechanical motion. These self-propelled micro- and nanomotors, designed either by top-down or bottom-up approaches, are able to achieve different applications, such as environmental remediation, sensing, cargo/sperm transportation, drug delivery, and even precision micro-/nanosurgery. For these various applications, especially biomedical applications, regulating on-demand the motion of micro- and nanomotors is quite essential. However, it remains a continuing challenge to increase the controllability over motors themselves. Here, we will discuss the recent advancements regarding the motion manipulation of micro- and nanomotors by different approaches.
On-demand regulation of the motion of artificial micro- and nanomotors is essential for diverse applications. The recent progress made during the last decade to manipulate the motional behavior of micro- and nanomotors by various approaches (such as light, magnetic fields, ultrasound, electric fields, temperature, pH, chemotaxis, and the addition of chemicals) is discussed.
http://ift.tt/2gbIBGi
Superior Photocatalytic H2 Production with Cocatalytic Co/Ni Species Anchored on Sulfide Semiconductor
Downsizing transition metal-based cocatalysts on semiconductors to promote photocatalytic efficiency is important for research and industrial applications. This study presents a novel and facile strategy for anchoring well-dispersed metal species on CdS surface through controlled decarboxylation of the ethylenediaminetetraacetate (EDTA) ligand in the metal–EDTA (M–EDTA) complex and CdS mixture precursor to function as a cocatalyst in the photocatalytic H2 evolution. Microstructure characterization and performance evaluation reveal that under visible light the resulting pentacoordinated Co(II) and hexacoordinated Ni(II) on CdS exhibits a high activity of 3.1 mmol h−1 (with turnover frequency (TOF) of 626 h−1 and apparent quantum efficiency (AQE) of 56.2% at 420 nm) and 4.3 mmol h−1 (with TOF of 864 h−1 and AQE of 67.5% at 420 nm), respectively, toward cocatalytic hydrogen evolution, and the cocatalytic activity of such a hexacoordinated Ni(II) even exceeds that of platinum. Further mechanistic study and theoretical modeling indicate that the fully utilized Co(II)/Ni(II) active sites, efficient charge transfer, and favorable kinetics guarantee the efficient activities. This work introduces a promising precursor, i.e., M–EDTA for planting well-dispersed transition metal species on the sulfide supports by a facile wet-chemistry approach, providing new opportunities for photocatalytic H2 production at the atomic/molecular scale.
Well-dispersed Co(II) species with pentacoordination and Ni(II) species with hexacoordination are anchored on CdS surface by using metal–ethylenediaminetetraacetate complex as precursor, both of which function as efficient cocatalysts in the photocatalytic H2 evolution, even the activity of Ni(II) species exceeding that of platinum with apparent quantum efficiency of 67.5% at 420 nm.
http://ift.tt/2vvRsVd
Reprogrammable Phononic Metasurfaces
Phononic metamaterials rely on the presence of resonances in a structured medium to control the propagation of elastic waves. Their response depends on the geometry of their fundamental building blocks. A major challenge in metamaterials design is the realization of basic building blocks that can be tuned dynamically. Here, a metamaterial plate is realized that can be dynamically tuned by harnessing geometric and magnetic nonlinearities in the individual unit cells. The proposed tuning mechanism allows a stiffness variability of the individual unit cells and can control the amplitude of transmitted excitation through the plate over three orders of magnitude. The concepts can be extended to metamaterials at different scales, and they can be applied in a broad range of engineering applications, from seismic shielding at low frequency to ultrasonic cloaking at higher frequency ranges.
"On-the-fly" steering of mechanical waves in time and space is realized. By harnessing geometric and magnetic nonlinearities, 3D-printed phononic metamaterials change their shape from 2D to 3D. This shape change shifts its dynamical characteristics from attenuating waves to permitting their propagation. Such change is dynamic, element-wise, noninvasive, and reversible; therefore it is referred to as reprogramming of matter.
http://ift.tt/2vdi7uW
Synthetic Control of Kinetic Reaction Pathway and Cationic Ordering in High-Ni Layered Oxide Cathodes
Nickel-rich layered transition metal oxides, LiNi1−x(MnCo)xO2 (1−x ≥ 0.5), are appealing candidates for cathodes in next-generation lithium-ion batteries (LIBs) for electric vehicles and other large-scale applications, due to their high capacity and low cost. However, synthetic control of the structural ordering in such a complex quaternary system has been a great challenge, especially in the presence of high Ni content. Herein, synthesis reactions for preparing layered LiNi0.7Mn0.15Co0.15O2 (NMC71515) by solid-state methods are investigated through a combination of time-resolved in situ high-energy X-ray diffraction and absorption spectroscopy measurements. The real-time observation reveals a strong temperature dependence of the kinetics of cationic ordering in NMC71515 as a result of thermal-driven oxidation of transition metals and lithium/oxygen loss that concomitantly occur during heat treatment. Through synthetic control of the kinetic reaction pathway, a layered NMC71515 with low cationic disordering and a high reversible capacity is prepared in air. The findings may help to pave the way for designing high-Ni layered oxide cathodes for LIBs.
High-nickel layered oxides are promising high-capacity cathodes for next-generation lithium-ion batteries; however, synthetic control of cationic ordering in this type of material has been challenging. Herein, in situ studies are carried out on synthesis reactions for preparing LiNi0.7Mn0.15Co0.15O2 under real synthesis conditions, providing insights into thermodynamic and kinetic parameters governing cationic ordering in high-Ni layered oxides.
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Outcome of colon cancer initially presenting as colon perforation and obstruction
Abstract
Background
Emergency complications of colon cancer include perforation and obstruction which were recognized as poor prognostic factors. Few studies have directly compared the outcomes of these two groups. In this study, we evaluated mortality and morbidity in patients with colon cancer initially presenting as perforation and obstruction.
Methods
Newly diagnosed colon cancer cases initially presenting with perforation or obstruction at Tzu Chi General Hospital, Hualien, Taiwan, between 2009 and 2015 were included. Cases of iatrogenic perforation or perforation sites far away from the tumor sites and rectal (< 15 cm from the anal verge) cancer were excluded. Progression-free survival, local recurrence rate, distant metastasis rate, and overall survival were the evaluated outcomes.
Results
Eighty-one patients met the selection criteria; 23 and 58 patients had perforation and obstruction, respectively, as the initial symptom. The median age was 72 years. The median tumor stage was stage IIIB. The 1-year and 3-year survival rates were 83.7 and 59.7%, respectively. The perforation group (PRG) and obstruction group (OBG) did not differ significantly in intensive care unit (ICU) stay rate (p = 0.147), sex (p = 0.45), comorbidities (heart, liver, and renal diseases and diabetes mellitus), median stage (p = 0.198), and overall survival (p = 0.328). However, PRG had a higher age at diagnosis (74 vs. 64 years, p = 0.037), a higher APACHE II score (12 vs. 7, p = 0.002), lower disease-free survival (p = 0.001), a higher recurrence rate (56.5 vs. 19%, p = 0.002), a higher distant metastasis rate (39.1 vs. 13.8%, p = 0.015), and a higher local recurrence rate (43.5 vs. 5.2%, p < 0.001) than did OBG. OBG had a higher two-stage operation rate (46.6 vs. 17.4%, p = 0.022). After adjustment for the tumor stage, comorbidity (chronic renal disease), body mass index (BMI), and adjuvant chemotherapy or radiotherapy in multivariate statistics, PRG had lower disease-free survival (p = 0.005) than OBG but overall survival was identical.
Conclusion
For colon cancer initially presenting as perforation or obstruction, the PRG had poorer progression-free survival, a higher local recurrence rate, and a higher distant metastasis rate than did OBG. Overall survival did not differ between these two groups.
http://ift.tt/2wNfejZ
Heavy alcohol drinking downregulates ALDH2 gene expression but heavy smoking up-regulates SOD2 gene expression in head and neck squamous cell carcinoma
Abstract
Background
This study aims to determine the relationship between expression levels of ALDH2 and SOD2 genes and clinical parameters such as alcohol drinking, tobacco smoking, primary site of HNSCC, and human papilloma virus (HPV) state.
Methods
Gene expression data were obtained from gene expression omnibus (GEO accession number: GSE65858). Clinical data (N = 270) including survival result, gender, age, TNM stage, primary site of HNSCC, HPV status, alcohol drinking, and tobacco smoking habit were analyzed according to gene expression pattern.
Results
ALDH2 gene was expressed in low levels in patients with heavy alcohol consumption. It was expressed in high (p = 0.01) levels in patients with no or light alcohol consumption. ALDH2 gene was also expressed in low levels in patients with oral cavity cancers or hypopharynx cancers. However, ALDH2 gene was expressed in high (p = 0.03) levels in patients with oropharyngeal cancers or laryngeal cancers. HPV-positive patients were found to have high (p = 0.02) expression levels of ALDH2. SOD2 gene was expressed in high (p = 0.005) levels in patients who had greater mean pack-year of tobacco smoking. Based on log rank test, the group of patients with high expression of ALDH2 showed better (p = 0.002) clinical results than those with low expression of ALDH2. Difference of survival results between ALDH2 high-expressed group and ALDH2 low-expressed group was validated in another cohort (GSE39368, N = 138).
Conclusions
Heavy alcohol drinking downregulates ALDH2 gene expression level. Heavy smoking up-regulates SOD2 gene expression level in patients with head and neck squamous cell carcinoma. The group of patients with low expression levels of ALDH2 showed significantly poorer survival results compared to those with high expression levels of ALDH2.
http://ift.tt/2vnrswe
Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1
Abstract
Background
To overcome the hostile hypoxic microenvironment of solid tumors, tumor cells secrete a large number of non-coding RNA-containing exosomes that facilitate tumor development and metastasis. However, the precise mechanisms of tumor cell-derived exosomes during hypoxia are unknown. Here, we aim to clarify whether hypoxia affects tumor growth and progression by transferring long non-coding RNA-urothelial cancer-associated 1 (lncRNA-UCA1) enriched exosomes secreted from bladder cancer cells.
Methods
We used bladder cancer 5637 cells with high expression of lncRNA-UCA1 as exosome-generating cells and bladder cancer UMUC2 cells with low expression of lncRNA-UCA1 as recipient cells. Exosomes derived from 5637 cells cultured under normoxic or hypoxic conditions were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting analysis. These exosomes were co-cultured with UMUC2 cells to evaluate cell proliferation, migration and invasion. We further investigated the roles of exosomal lncRNA-UCA1 derived from hypoxic 5637 cells by xenograft models. The availability of lncRNA-UCA1 in serum-derived exosomes as a biomarker for bladder cancer was also assessed.
Results
We found that hypoxic exosomes derived from 5637 cells promoted cell proliferation, migration and invasion, and hypoxic exosomal RNAs could be internalized by three bladder cancer cell lines. Importantly, lncRNA-UCA1 was secreted in hypoxic 5637 cell-derived exosomes. Compared with normoxic exosomes, hypoxic exosomes derived from 5637 cells showed the higher expression levels of lncRNA-UCA1. Moreover, Hypoxic exosomal lncRNA-UCA1 could promote tumor growth and progression though epithelial-mesenchymal transition, in vitro and in vivo. In addition, the expression levels of lncRNA-UCA1 in the human serum-derived exosomes of bladder cancer patients were higher than that in the healthy controls.
Conclusion
Together, our results demonstrate that hypoxic bladder cancer cells remodel tumor microenvironment to facilitate tumor growth and development though secreting the oncogenic lncRNA-UCA1-enriched exosomes and exosomal lncRNA-UCA1 in human serum has the possibility as a diagnostic biomarker for bladder cancer.
http://ift.tt/2vvN0pH
Non-cholestatic acute hepatitis following Candesartan administration.
Abstract
Arterial hypertension is nowadays a highly manageable disorder due to a variety of drugs available for its treatment. Since the late 1990's, angiotensin II receptor blockers have been widely prescribed, achieving appropriate control in patients' blood pressure. Few cases of serious adverse effects have been reported to date. Here we present a case of acute hepatocellular injury secondary to candesartan administration. Further studies should be performed in patients who present this effect in order to prevent more serious outcomes.
http://ift.tt/2waSvff
Effect of time to initiation of postoperative radiation therapy on survival in surgically managed head and neck cancer
BACKGROUND
The objective of this study was to determine the effects of National Comprehensive Cancer Network (NCCN) guideline–adherent initiation of postoperative radiation therapy (PORT) and different time-to-PORT intervals on the overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC).
METHODS
The National Cancer Data Base was reviewed for the period of 2006-2014, and patients with HNSCC undergoing surgery and PORT were identified. Kaplan-Meier survival estimates, Cox regression analysis, and propensity score matching were used to determine the effects of initiating PORT within 6 weeks of surgery and different time-to-PORT intervals on survival.
RESULTS
This study included 41,291 patients. After adjustments for covariates, starting PORT >6 weeks postoperatively was associated with decreased OS (adjusted hazard ratio [aHR], 1.13; 99% confidence interval [CI], 1.08-1.19). This finding remained in the propensity score–matched subset (hazard ratio, 1.21; 99% CI, 1.15-1.28). In comparison with starting PORT 5 to 6 weeks postoperatively, initiating PORT earlier was not associated with improved survival (aHR for ≤ 4 weeks, 0.93; 99% CI, 0.85-1.02; aHR for 4-5 weeks, 0.92; 99% CI, 0.84-1.01). Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements (aHR, 1.09, 1.10, and 1.12 for 7-8, 8-10, and >10 weeks, respectively).
CONCLUSIONS
Nonadherence to NCCN guidelines for initiating PORT within 6 weeks of surgery was associated with decreased survival. There was no survival benefit to initiating PORT earlier within the recommended 6-week timeframe. Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements. Cancer 2017. © 2017 American Cancer Society.
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Phase 1 dose escalation multicenter trial of pracinostat alone and in combination with azacitidine in patients with advanced hematologic malignancies
BACKGROUND
Pracinostat is a potent histone deacetylase inhibitor with antitumor activity in both solid tumor and acute myeloid leukemia (AML) cell lines. Pracinostat is reported to have modest clinical activity in patients with advanced solid tumors. Given the higher preclinical sensitivity of hematologic malignancies to pracinostat, the authors conducted a phase 1 study to assess the safety, maximum tolerated dose, recommended phase 2 dose, efficacy, pharmacokinetics, and pharmacodynamics of pracinostat in patients with advanced hematological malignancies.
METHODS
Pracinostat was administered orally 3 times a week for 3 weeks on a 28-day cycle. Patients were assigned to 7 dose levels using a 3 + 3 dose escalation design.
RESULTS
A total of 44 patients were enrolled, 25 of whom had AML and 14 of whom had myelodysplastic syndrome. The maximum tolerated dose was 120 mg and the recommended phase 2 dose was 60 mg. Two patients with AML achieved a response: 1 complete remission (CR) and 1 complete cytogenetic response. Despite a dose-dependent increase in the plasma concentration of pracinostat, a similar increase in histone acetylation was not observed. As an extension, 10 additional patients with myelodysplastic syndrome were enrolled to assess the safety and efficacy of pracinostat in combination with azacitidine. Six patients achieved a CR and 3 achieved a CR without platelet recovery with no added toxicity.
CONCLUSIONS
The results of the current study demonstrate that pracinostat is safe, with modest single-agent activity in patients with hematological malignancies. Cancer 2017. © 2017 American Cancer Society.
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Long-term weight loss after colorectal cancer diagnosis is associated with lower survival: The Colon Cancer Family Registry
BACKGROUND
Body weight is associated with colorectal cancer (CRC) risk and survival, but to the authors' knowledge, the impact of long-term postdiagnostic weight change is unclear. Herein, the authors investigated whether weight change over the 5 years after a diagnosis of CRC is associated with survival.
METHODS
CRC cases diagnosed from 1997 to 2008 were identified through 4 population-based cancer registry sites. Participants enrolled within 2 years of diagnosis and reported their height and weight 2 years prior. Follow-up questionnaires were administered approximately 5 years after diagnosis. Associations between change in weight (in kg) or body mass index (BMI) with overall and CRC-specific survival were estimated using Cox regression analysis adjusted for age, sex, American Joint Committee on Cancer stage of disease, baseline BMI, nonsteroidal anti-inflammatory drug use, smoking, time between diagnosis and enrollment, and study site.
RESULTS
At the 5-year postdiagnostic survey, 2049 participants reported higher (53%; median plus 5 kg), unchanged (12%), or lower (35%; median -4 kg) weight. Over a median of 5.1 years of subsequent follow-up (range, 0.3-9.9 years), 344 participants died (91 of CRC). Long-term weight loss (per 5 kg) was found to be associated with poorer overall survival (hazard ratio, 1.13; 95% confidence interval, 1.07-1.21) and CRC-specific survival (hazard ratio, 1.25; 95% confidence interval, 1.13-1.39). Significantly lower survival was similarly observed for relative weight loss (>5% vs ≤5% change), BMI reduction (per 1 unit), or BMI category change (overweight to normal vs remaining overweight).
CONCLUSIONS
Weight loss 5 years after a diagnosis of CRC was found to be significantly associated with decreased long-term survival, suggesting the importance of avoiding weight loss in survivors of CRC. Future research should attempt to further evaluate this association, accounting for whether this weight change was intentional or represents a marker of declining health. Cancer 2017. © 2017 American Cancer Society.
http://ift.tt/2gcBUUy
Inhibiting heat shock protein 90 and the ubiquitin-proteasome pathway impairs metabolic homeostasis and leads to cell death in human pancreatic cancer cells
BACKGROUND
Heat shock protein 90 (HSP90) and the ubiquitin-proteasome pathway play crucial roles in the homeostasis of pancreatic cancer cells. This study combined for the first time the HSP90 inhibitor ganetespib (Gan) and the proteasome inhibitor carfilzomib (Carf) to target key mechanisms of homeostasis in pancreatic cancer. It was hypothesized that Gan plus Carf would elicit potent antitumor activity by modulating complementary homeostatic processes.
METHODS
In vitro and in vivo effects of this combination on mechanisms of cell growth and viability were evaluated with human pancreatic cancer cell lines (MIA PaCa-2 and HPAC).
RESULTS
Combined treatment with Gan and Carf significantly decreased cell viability. The mechanism varied by cell line and involved G2-M cell-cycle arrest accompanied by a consistent reduction in key cell-cycle regulatory proteins and concomitant upregulation of p27. Further studies revealed increased autophagy markers, including the upregulation of autophagy related 7 and light chain 3 cleavage, and evidence of apoptosis (increased Bax expression and processing of caspase 3). Immunoblot analyses confirmed the modulation of other pathways that influence cell viability, including phosphoinositide 3-kinase/Akt and nuclear factor κB. Finally, the treatment of athymic mice bearing HPAC tumors with Gan and Carf significantly reduced tumor growth in vivo. An immunoblot analysis of freshly isolated tumors from animals at the end of the study confirmed in vivo modulation of key signaling pathways.
CONCLUSIONS
The results reveal Gan plus Carf to be a promising combination with synergistic antiproliferative, apoptotic, and pro-autophagy effects in preclinical studies of pancreatic cancer and will further the exploration of the utility of this treatment combination in clinical trials. Cancer 2017. © 2017 American Cancer Society.
http://ift.tt/2ixdA0w
The role of surgery and adjuvant therapy in lymph node-positive cancers of the gallbladder and intrahepatic bile ducts
BACKGROUND
Lymph node metastasis is a poor prognostic factor for biliary tract cancers (BTCs). The optimal management of patients who have BTC with positive regional lymph nodes, including the impact of surgery and adjuvant therapy (AT), is unclear.
METHODS
This was a retrospective cohort study of patients who had T1-T3N1M0 gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHC) in the National Cancer Database (2004-2012). Patients were classified by treatment approach (nonoperative, surgery, surgery plus AT). Associations between the overall risk of death and treatment strategy were evaluated with multivariable Cox regression.
RESULTS
Rates of surgical resection were 84.1% for patients with GBC (n = 1335) and 36.6% for those with IHC (n = 1009). The median overall survival of patients in the nonoperative, surgery, and surgery plus AT group was 11.6, 13.3, and 19.6 months, respectively, for those with GBC (log-rank P < .001), and 12.7, 16.2, and 22.6 months, respectively, for those with IHC (log-rank P < .001), respectively. Compared with nonoperative therapy, surgery with or without AT was associated with a lower risk of death from GBC (surgery with AT: hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.48-0.73; surgery without AT: HR, 0.71; 95% CI, 0.56-0.89) and from IHC (surgery with AT: HR, 0.52; 95% CI, 0.42-0.63; surgery without AT: HR, 0.70; 95% CI, 0.56-0.87). AT that included radiation was associated with a lower risk of death relative to surgery alone for patients with GBC regardless of margin status (margin-negative resection: HR, 0.66; 95% CI, 0.52-0.84; margin-positive resection: HR, 0.54; 95% CI, 0.39-0.75), but adjuvant chemotherapy alone was not. For patients with IHC, no survival benefit was detected with adjuvant chemotherapy or radiation for those who underwent either margin-positive or margin-negative resection.
CONCLUSIONS
The best outcomes for patients who have lymph node-positive BTCs are associated with margin-negative resection and, in those who have GBC, the inclusion of adjuvant chemotherapy with radiation regardless of margin status. Cancer 2017. © 2017 American Cancer Society.
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Childhood cancer incidence by ethnic group in England, 2001–2007: a descriptive epidemiological study
Abstract
Background
After the first year of life, cancers are the commonest cause of death in children. Incidence rates vary between ethnic groups, and recent advances in data linkage allow for a more accurate estimation of these variations. Identifying such differences may help identify potential risk or protective factors for certain childhood cancers. This study thus aims to ascertain whether such differences do indeed exist using nationwide data across seven years, as have previously been described in adult cancers.
Methods
We obtained data for all cancer registrations for children (aged 0–14) in England from January 2001 to December 2007. Ethnicity (self-assigned) was established through record linkage to the Hospital Episodes Statistics database or cancer registry data. Cancers were classified morphologically according to the International Classification of Childhood Cancer into four groups – leukaemias; lymphomas; central nervous system; and other solid tumours. Age standardised incidence rates were estimated for each ethnic group, as well as incidence rate ratios comparing each individual ethnic group (Indian, Pakistani, Bangladeshi, Black African, Black Carribean, Chinese) to Whites, adjusting for sex, age and deprivation.
Results
The majority of children in the study are UK born. Black children (RR = 1.18, 99% CI: 1.01–1.39), and amongst South Asians, Pakistani children (RR = 1.19, 99% CI: 1.02–1.39) appear to have an increased risk of all cancers. There is an increased risk of leukaemia in South Asians (RR = 1.31, 99% CI: 1.08–1.58), and of lymphoma in Black (RR = 1.72, 99% CI: 1.13–2.63) and South Asian children (RR = 1.51, 99% CI: 1.10–2.06). South Asians appear to have a decreased risk of CNS cancers (RR = 0.71, 99% CI: 0.54–0.95).
Conclusions
In the tradition of past migrant studies, such descriptive studies within ethnic minority groups permit a better understanding of disease incidence within the population, but also allow for the generation of hypotheses to begin to understand why such differences might exist. Though a major cause of mortality in this age group, childhood cancer remains a relatively rare disease; however, the methods used here have permitted the first nationwide estimation of childhood cancer by individual ethnic group.
http://ift.tt/2wMOaS0
Urokinase-type plasminogen activator receptor (uPAR), tissue factor (TF) and epidermal growth factor receptor (EGFR): tumor expression patterns and prognostic value in oral cancer
Abstract
Background
Tumor-specific biomarkers are a prerequisite for the development of targeted imaging and therapy in oral squamous cell carcinoma (OSCC). urokinase-type Plasminogen Activator Receptor (uPAR), Tissue Factor (TF) and Epidermal Growth Factor Receptor (EGFR) are three biomarkers that exhibit enhanced expression in many types of cancers, and have been investigated as potential biomarkers for targeted strategies and prognostication. The aim of the study was to investigate the expression patterns of uPAR, TF and EGFR and their potential prognostic value in OSCC.
Methods
Immunohistochemical expression of uPAR, TF and EGFR in tumor resection specimens from 191 patients with primary OSCC was analyzed. Overall (OS) and disease-free survival (DFS) was calculated. Associations between biomarker expression, clinicopathological factors and patient survival was analyzed using the Cox proportional hazards model for univariate and multivariate analysis, log rank and Kaplan-Meier statistics.
Results
uPAR and TF exhibited a highly tumor-specific expression pattern while EGFR also showed expression in normal tissues outside the tumor compartment. The overall positive expression rate of uPAR, TF and EGFR was 95%, 58% and 98%, respectively. High uPAR expression across the entire cohort was negatively associated with OS (p = 0.031, HR = 1.595 (95%CI 1.044–2.439)) in univariate analysis. The 5-year OS for high and low uPAR expression was 39% and 56%, respectively. The expression of TF and EGFR was not associated with survival outcome.
Conclusions
This study may suggest that uPAR and TF could potentially be attractive targets for molecular imaging and therapy in OSCC due to high positive expression rates and tumor-specific expression patterns. High uPAR expression was significantly associated with a reduced survival. uPAR seems to be a prognostic biomarker in oral cancer.
http://ift.tt/2gbfGSZ
Skeletal muscle depletion during chemotherapy has a large impact on physical function in elderly Japanese patients with advanced non–small-cell lung cancer
Abstract
Background
Elderly patient with advanced cancer is one of the most vulnerable populations. Skeletal muscle depletion during chemotherapy may have substantial impact on their physical function. However, there is little information about a direct relationship between quantity of muscle and physical function. We sought to explore the quantitative association between skeletal muscle depletion, and muscle strength and walking capacity in elderly patients with advanced non–small cell lung cancer (NSCLC).
Methods
Thirty patients aged ≥70 years with advanced NSCLC (stage III-IV) scheduled to initiate first-line chemotherapy were prospectively enrolled between January 2013 and November 2014. Lumbar skeletal muscle index (LSMI, cm2/m2), incremental shuttle walking distance (ISWD, m), and hand-grip strength (HGS, kg) were assessed at baseline, and 6 ± 2 weeks (T2) and 12 ± 4 weeks (T3) after study enrollment. Associations were analyzed using linear regression.
Results
Altogether, 11 women and 19 men with a median age of 74 (range, 70–82) years were included in the study; 24 received cytotoxic chemotherapy and 6, gefitinib. Mean ± standard deviation of LSMI, ISWD and HGS were 41.2 ± 7.8 cm2/m2, 326.0 ± 127.9 m, and 29.3 ± 8.5 kg, respectively. LSMI and ISWD significantly declined from baseline to T2 and T3. HGS significantly declined from baseline to T2 and T3 only in men. Change in LSMI was significantly associated with change in HGS (β = 0.3 ± 0.1, p = 0.0127) and ISWD (β = 8.8 ± 2.4, p = 0.0005).
Conclusions
Skeletal muscle depletion accompanied with physical functional decline started in the early phase of the chemotherapy in elderly patients with advanced NSCLC. Our results suggest that there may be a need for early supportive care in these patients to prevent functional decline during chemotherapy.
Trial registration
Trial registration number: UMIN000009768
Name of registry: UMIN (University hospital Medical Information Network).
URL of registry: Date of registration: 14 January 2013.
Date of enrolment of the first participant to the trial: 23 January 2013.
http://ift.tt/2wN3xcZ
Comparison of PSA value at last follow-up of patients who underwent low-dose rate brachytherapy and intensity-modulated radiation therapy for prostate cancer
Abstract
Background
To compare the PSA value at the last follow-up of patients who underwent prostate low-dose rate brachytherapy (LDR-BT) with that of patients who underwent intensity-modulated radiation therapy (IMRT).
Methods
A total of 610 prostate cancer patients (cT1c-3bN0M0) were enrolled, and 445 of them underwent LDR-BT, while 165 received IMRT (74–76 Gy). The median follow-up period of these two groups was 75 months (LDR-BT) and 78 months (IMRT), respectively. We also evaluated the biochemical recurrence (BCR)-free rate using two definitions (Phoenix definition and PSA ≥ 0.2 ng/mL).
Results
The percentage of patients who achieved PSA < 0.2 ng/mL at the last follow-up was 77.5% in the LDR-BT group and 49.7% in the IMRT group (p < 0.001). Among patients with a normal testosterone level at the last follow-up, the percentage of those who achieved PSA < 0.2 ng/mL at the last follow-up was 79.2% in the LDR-BT group and 32.1% in the IMRT group (p < 0.001). The 5-year BCR-free rate by the Phoenix definition in the IMRT and LDR-BT groups was 89.5 and 95.0% (p < 0.001), respectively. On the other hand, the 5-year BCR-free rate using the definition of PSA ≥ 0.2 ng/mL was 59.1 and 80.1% in the IMRT and LDR-BT groups, respectively (p < 0.001).
Conclusions
The PSA value at the last follow-up of LDR-BT was significantly lower than that of IMRT, and this result was particularly marked in patients with a normal testosterone level at the last follow-up.
http://ift.tt/2wN8nqU
Commissioners order audit of Pa. 911 center
Dispatchers were unable to page fire and EMS for more than a week after a malfunction caused the county's software to revert back to 1997
http://ift.tt/2w45Yam
Utilization of cytocentrifugation slides in flow cytometry laboratory: a tool for correlation of morphology and immunonophenotype
Abstract
Cytocentrifuge slide ("cytospin") is a simple and rapid technique that is mainly used in the cytology laboratory. We have routinely used the technique in flow cytometry (FCM) laboratory at Montefiore Medical Center for more than 15 years. Our aim is to illustrate the contribution of cytospin in direct cellular morphologic visualization in FCM immunophenotyping, in result interpretation, and additionally as a quality control tool. Four thousand two hundred forty-eight cases sent to our FCM Laboratory in the past 21 months were studied retrospectively. The clinical history, cytospins, immunophenotyping panels, FCM contour plots, final FCM reports, and pathology reports were reviewed. Morphologic examination of the cytospin is a cost-effective tool for sample quality screening. Of the 4248 immunophenotyping cases, 359 (8.4%) cases were canceled, according to laboratory protocol based on cytospin review. Morphologic analysis of the cytospin provides extra information that guides both selection of the FCM immunophenotype panel and gating the cells of interest. Additionally, morphologic analysis of cytospin can yield early diagnosis when cohesive benign or malignant non-hematologic cells are present or even infectious organisms such as parasites are identified. Finally, the cytospin is a convenient tool for morphology-phenotype correlation. Cytospin is cost-effective and provides important morphologic information that facilitates FCM immunophenotyping panel selection and result interpretation.
http://ift.tt/2iy2jx1
Heart-bound adiponectin, not serum adiponectin, inversely correlates with cardiac hypertrophy in stroke-prone spontaneously hypertensive rats
Abstract
The inverse correlation between circulating adiponectin concentration and hypertension or cardiac hypertrophy is still controversial. In addition to circulating adiponectin, adiponectin is also bound to tissues such as the heart and skeletal muscle. In this study, we investigated the relationship of serum adiponectin and heart-bound adiponectin to hypertension and cardiac hypertrophy. Four types of hypertensive rats presenting different blood pressure levels were used at different ages: normotensive Wistar-Kyoto rats (WKY); two sub-strains (strains C and B2, having low and high blood pressure, respectively) of spontaneously hypertensive rats (SHR); and stroke-prone SHR (SHRSP). Blood pressure, heart/body weight ratio, serum adiponectin, and heart-bound adiponectin were determined. Histopathological analysis of the heart was carried out to evaluate the relationship with heart-bound adiponectin. Serum adiponectin concentration did not inversely correlate with blood pressure or heart/body weight ratio. In contrast, heart-bound adiponectin levels were significantly lower in SHRSP than in other strains at respective ages. This resulted from a decrease in T-cadherin expression, which induced adiponectin binding to tissues. No significant difference in heart-bound adiponectin among WKY and SHR (C and B2) was detected, indicating that heart-bound adiponectin is not related to hypertension. In addition, differences in heart-bound adiponectin did not affect AMP-activated protein kinase in the traditional adiponectin activation cascade. Histopathological analysis revealed that heart-bound adiponectin inversely correlated with cardiomyocyte hypertrophy and left ventricular wall thickness, and partially with cardiac fibrosis. These results suggest that the decreased level of heart-bound adiponectin in SHRSP is more related to their cardiac hypertrophy than circulating adiponectin.
This article is protected by copyright. All rights reserved
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Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise
Abstract
Manipulating the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to simultaneously assess leg and respiratory muscle blood flow during intense exercise while manipulating WOB. We hypothesized that: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow, and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 m, n = 3 W) performed a maximal cycle test (Day 1) and a series of constant-load exercise trials at 90% of peak work rate (Day 2). On Day 2, WOB was assessed with oesophageal balloon catheters and was: increased (via resistors), decreased (via proportional assist ventilation), or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous indocyanine green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the WOB increased locomotor blood flow. Oxygen uptake was not different during the control and resistor trials (3.8 ± 0.9 vs. 3.7 ± 0.8 l min−1, P > 0.05), but was lower on the PAV trial (3.4 ± 0.7 l min−1, P < 0.05) compared to control. Our findings support the concept that respiratory muscle work significantly influences the distribution of blood flow to both respiratory and locomotor muscles.
This article is protected by copyright. All rights reserved
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Functional capacity in a rat model of heart failure: impact of myocardial infarction size
Abstract
Oxygen uptake (VO2) and exercise tolerance in rats classified by myocardial infarction (MI) size are underexplored. The aim of this study was to evaluate VO2/carbon dioxide production (VCO2) and exercise tolerance in rats that have undergone MI. Fourteen weeks after MI or sham surgery, rats underwent an integrated approach to left ventricular function and VO2/VCO2, exercise tolerance and skeletal muscle weight evaluation. Based on MI size determination, rats were assigned to sham operated controls (Sham, n = 12), small myocardial infarction (SMI, n = 8), and large myocardial infarction (LMI, n = 5) groups. LMI rats showed lower systolic (ejection fraction and fractional shortening) and diastolic (E/A ratio) left ventricular function compared with SMI. VO2max (∼24%, P < 0.05), VO2reserve (∼30%, P < 0.05), time to exhaustion (∼36%, P < 0.05) and maximal velocity (∼30%, P < 0.05) was lower in LMI compared with sham operated controls, with no difference between SMI rats and sham operated controls. VCO2max and respiratory exchange ratio (RER) showed no significant difference between MI rats and sham operated control rats. LMI rats demonstrated lower gastrocnemius weight (∼12%, P < 0.05) and soleus weight (∼19%, P = 0.07) compared with sham operated control rats. Significant correlations between MI size, left ventricular end-diastolic pressure, right ventricle hypertrophy, pulmonary congestion, ejection fraction, and fractional shortening with VO2max and run distance were observed. O2 uptake and exercise intolerance are MI size dependent.
This article is protected by copyright. All rights reserved
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SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting
SELECT-3: a phase I study of selumetinib in combination with platinum-doublet chemotherapy for advanced NSCLC in the first-line setting
British Journal of Cancer advance online publication, August 24 2017. doi:10.1038/bjc.2017.271
Authors: Alastair Greystoke, Nicola Steele, Hendrik-Tobias Arkenau, Fiona Blackhall, Noor Md Haris, Colin R Lindsay, Raffaele Califano, Mark Voskoboynik, Yvonne Summers, Karen So, Dana Ghiorghiu, Angela W Dymond, Stuart Hossack, Ruth Plummer & Emma Dean
http://ift.tt/2xhlj6f
Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients
Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients
British Journal of Cancer advance online publication, August 24 2017. doi:10.1038/bjc.2017.289
Authors: A Ruzzo, F Graziano, Fabio Galli, Francesca Galli, E Rulli, S Lonardi, M Ronzoni, B Massidda, V Zagonel, N Pella, C Mucciarini, R Labianca, M T Ionta, I Bagaloni, E Veltri, P Sozzi, S Barni, V Ricci, L Foltran, M Nicolini, E Biondi, A Bramati, D Turci, S Lazzarelli, C Verusio, F Bergamo, A Sobrero, L Frontini, M Menghi & M Magnani
http://ift.tt/2w2IT89
Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers
Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers
British Journal of Cancer advance online publication, August 24 2017. doi:10.1038/bjc.2017.274
Authors: Ashley M Hopkins, Andrew Rowland, Ganessan Kichenadasse, Michael D Wiese, Howard Gurney, Ross A McKinnon, Chris S Karapetis & Michael J Sorich
http://ift.tt/2xgWp6u
Targeting apoptosis in acute myeloid leukaemia
Targeting apoptosis in acute myeloid leukaemia
British Journal of Cancer advance online publication, August 24 2017. doi:10.1038/bjc.2017.281
Authors: Philippe A Cassier, Marie Castets, Amine Belhabri & Norbert Vey
http://ift.tt/2w23o4z
Cardiovascular disease risk and androgen deprivation therapy in patients with localised prostate cancer: a prospective cohort study
Cardiovascular disease risk and androgen deprivation therapy in patients with localised prostate cancer: a prospective cohort study
British Journal of Cancer advance online publication, August 24 2017. doi:10.1038/bjc.2017.280
Authors: Reina Haque, Marianne UlcickasYood, Xiaoqing Xu, Andrea E Cassidy-Bushrow, Huei-Ting Tsai, Nancy L Keating, Stephen K Van Den Eeden & Arnold L Potosky
http://ift.tt/2xgS4QV
Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis
Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis
British Journal of Cancer advance online publication, August 24 2017. doi:10.1038/bjc.2017.291
Authors: Tomohiro Murakami, Hirotoshi Kikuchi, Hisato Ishimatsu, Ichirota Iino, Amane Hirotsu, Tomohiro Matsumoto, Yusuke Ozaki, Toshiki Kawabata, Yoshihiro Hiramatsu, Manabu Ohta, Kinji Kamiya, Mayu Fukushima, Satoshi Baba, Kyoko Kitagawa, Masatoshi Kitagawa & Hiroyuki Konno
http://ift.tt/2w22uFg
SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway
SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway
British Journal of Cancer advance online publication, August 24 2017. doi:10.1038/bjc.2017.293
Authors: Weiwei Liu, Xuchu Wang, Zhenping Liu, Yiyun Wang, Binbin Yin, Pan Yu, Xiuzhi Duan, Zhaoping Liao, Yuhua Chen, Chunhua Liu, Xiang Li, Yibei Dai & Zhihua Tao
http://ift.tt/2xh77Km
Comparison of Different Sources of Mesenchymal Stem Cells: Palatal versus Lipoaspirated Adipose Tissue
Objectives: The purpose of this study was to compare the proliferation and differentiation potential of mesenchymal stem cells (MSCs) derived from palatal adipose tissue (PAT) and lipoaspirated adipose tissue (LAT). Materials and Methods: PATs were obtained from 2 healthy female patients undergoing surgery for gingival recession, and LATs were obtained from 2 healthy female patients undergoing plastic surgery. LAT- and PAT-derived MSCs were confirmed by flow cytometry using MSC-specific surface markers. The multilineage differentiation capacity of the MSCs was analyzed. The expression of immunophenotyping, embryonic, and differentiation markers was compared between both MSC lines. The proliferation of PAT- and LAT-MSCs was evaluated using a real-time cell analyzer, and telomerase activity was determined using an ELISA-based TRAP assay. Stem cells isolated from PAT and LAT were analyzed by real-time PCR and whole genome array analysis. Results: The cells isolated from PAT had MSC characteristics. In addition, PAT-MSCs had significantly higher alkaline phosphatase activity and osteogenic potential than LAT-MSCs. Although the proliferation and telomerase activities of LAT-MSCs were higher than those of PAT-MSCs, the difference was not statistically significant. The level of embryonic stem cell markers (Oct4 and Nanog) was higher in LAT-MSCs than in PAT-MSCs. The whole genome array analysis demonstrated that 255 gene sequences were differentially expressed, with more than a twofold change in expression. Conclusions: This is the first comparative analysis of the isolation and characterization of MSCs from PAT and LAT. PAT is an accessible source of MSCs, which could be used in periodontal and craniofacial tissue engineering.
Cells Tissues Organs
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Cells Tissues Organs
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Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer
Background/Aims: Palliative chemotherapy is the main treatment for advanced biliary tract cancer (BTC). However, there is a lack of established second-line chemotherapy to treat disease progression after first-line chemotherapy. We examined combination therapy with capecitabine and cisplatin for advanced BTC as a second-line regimen. Methods: We analyzed the medical records of 40 patients diagnosed with BTC who received palliative second-line chemotherapy with capecitabine and cisplatin. Results: The median overall survival from the start of second-line chemotherapy was 6.3 months. The median overall survival from diagnosis was 17.9 months. The median progression-free survival during second-line chemotherapy was 2.3 months. Nine (30%) patients experienced adverse events of grade ≥3. Eastern Cooperative Oncology Group performance score was an independent predictor of adverse events. Conclusions: Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC.
Chemotherapy 2017;62:361-366
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Chemotherapy 2017;62:361-366
http://ift.tt/2w3PqPS
Immobilization of Candida antarctica lipase B onto ECR1030 resin and its application in the synthesis of n-3 PUFA-rich triacylglycerols
Abstract
In this study, Candida antarctica lipase B (CALB) was immobilized onto ECR1030 resin and the obtained immobilized preparation was used for the synthesis of n-3 polyunsaturated fatty acids (PUFA)-rich triacylglycerols (TAG). The immobilization process was systematically studied. Under the optimized conditions, the immobilized preparation of ECR1030-CALB with an esterification activity of 10058 U/g was obtained, which was comparable with the commercially available Novozym 435. Confocal microscopy images showed that CALB diffused from the surface to the center of carrier during immobilization. The basic properties of ECR1030-CALB were also investigated and it was found that the thermostability, acidic and alkaline stability, and organic solvent tolerance of ECR1030-CALB were comparable with Novozym 435. Interestingly, ECR1030-CALB showed significantly higher specificity towards EPA and DHA compared with Novozym 435, which made it suitable for the synthesis of n-3 PUFA-rich TAG. The TAG content of 74.05% was obtained under the optimized conditions, which was slightly higher than that (73.68%) obtained by Novozym 435. This is the first study for systematically studying the immobilization process of lipase using ECR1030 resin as carrier. Overall, the prepared ECR1030-CALB with excellent esterification activity, basic properties, and catalytic performance might be a promising alternative to commercial Novozym 435.
Practical applications: A previous study found that ECR1030 resin was a robust and promising carrier for the immobilization of CALB. However, the detailed immobilization conditions, the basic properties, and catalytic performance of the immobilized preparations using ECR1030 resin as carrier are still unknown. Consequently, knowledge of the above unknown information for the immobilization of CALB using ECR1030 resin as carrier is of great importance for their further practical applications in lipid chemistry.
http://ift.tt/2gaN8Jh
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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