Cancers, Vol. 10, Pages 93: The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas

Cancers, Vol. 10, Pages 93: The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas

Cancers doi: 10.3390/cancers10040093

Authors: Ines Garces de los Fayos Alonso Huan-Chang Liang Suzanne D. Turner Sabine Lagger Olaf Merkel Lukas Kenner

The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a variety of members including c-JUN, c-FOS and ATF, is involved in mediating many biological processes such as proliferation, differentiation and cell death. Since their discovery, the role of AP-1 TFs in cancer development has been extensively analysed. Multiple in vitro and in vivo studies have highlighted the complexity of these TFs, mainly due to their cell-type specific homo- or hetero-dimerization resulting in diverse transcriptional response profiles. However, as a result of the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being recognized as promising therapeutic targets for various malignancies. In this review, we focus on the impact of deregulated expression of AP-1 TFs in CD30-positive lymphomas including Classical Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma.

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A phase II, multicenter, single-arm trial of eribulin as first- or second-line chemotherapy for HER2-negative advanced or metastatic breast cancer: evaluation of efficacy, safety, and patient-reported outcomes

Abstract

Purpose

Although eribulin is a suitable option for early-line treatment of metastatic breast cancer (MBC), data on first- or second-line use of eribulin for human epidermal growth factor receptor 2 (HER2)-negative MBC are still limited. Therefore, we conducted a phase II trial to investigate the efficacy and safety of eribulin for first- or second-line chemotherapy for HER2-negative MBC.

Materials and methods

We performed a phase II, open-label, single-arm, multicenter study in Japan. Eligible patients were women with histologically confirmed HER2-negative MBC without chemotherapy or only one chemotherapy line for MBC. The primary endpoint was the overall response rate (ORR) and the secondary endpoints included the clinical benefit rate (ORR + stable disease for 6 months; CBR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and health-related quality of life (HRQoL).

Results

A total of 35 patients with HER2-negative MBC were enrolled between March 2013 and February 2017 (data cut-off July 31, 2017). The ORR was 37.1% (95% CI 21.1–53.2%). The CBR was 54.3% (95% CI 37.8–70.8%). The median PFS was 6.2 months (95% CI 2.7–9.4 months) and median OS was 21.4 months (95% CI 11.5–32.9 months). Common grade 3/4 adverse events were neutropenia (42.9%) but febrile neutropenia (2.9%). Although the majority of non-hematological adverse events were mild in severity, one patient died of pneumonitis. In HRQoL analysis, eribulin appeared to maintain HRQoL of many patients.

Conclusions

Eribulin as first- or second-line chemotherapy is effective and has manageable toxicity for patients with HER2-negative MBC.

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The combination of cardiorespiratory fitness and muscle strength, and mortality risk

Abstract

Little is known about the combined associations of cardiorespiratory fitness (CRF) and hand grip strength (GS) with mortality in general adult populations. The purpose of this study was to compare the relative risk of mortality for CRF, GS, and their combination. In UK Biobank, a prospective cohort of > 0.5 million adults aged 40–69 years, CRF was measured through submaximal bike tests; GS was measured using a hand-dynamometer. This analysis is based on data from 70,913 men and women (832 all-cause, 177 cardiovascular and 503 cancer deaths over 5.7-year follow-up) who provided valid CRF and GS data, and with no history of heart attack/stroke/cancer at baseline. Compared with the lowest CRF category, the hazard ratio (HR) for all-cause mortality was 0.76 [95% confidence interval (CI) 0.64–0.89] and 0.65 (95% CI 0.55–0.78) for the middle and highest CRF categories, respectively, after adjustment for confounders and GS. The highest GS category had an HR of 0.79 (95% CI 0.66–0.95) for all-cause mortality compared with the lowest, after adjustment for confounders and CRF. Similar results were found for cardiovascular and cancer mortality. The HRs for the combination of highest CRF and GS were 0.53 (95% CI 0.39–0.72) for all-cause mortality and 0.31 (95% CI 0.14–0.67) for cardiovascular mortality, compared with the reference category of lowest CRF and GS: no significant association for cancer mortality (HR 0.70; 95% CI 0.48–1.02). CRF and GS are both independent predictors of mortality. Improving both CRF and muscle strength, as opposed to either of the two alone, may be the most effective behavioral strategy to reduce all-cause and cardiovascular mortality risk.

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Surprising origin of two carved bones donated to the Buchenwald Memorial Museum

Abstract

Unidentified bones were donated to the Buchenwald Memorial Museum in Weimar, Germany. The donor thought the bones may have belonged to internees of the concentration camp and had been decoratively carved by camp personnel. Non-destructive forensic anthropological examination was carried out on the bones to identify their possible origin. Comparative human and non-human bones samples were used to determine the provenance of the bones and the anatomical region they may have come from. Literature and internet searches were conducted to trace the origin of the carved motifs on the bones. The bones were determined to belong to the lower limb region of bovids. The carvings were found to correspond with those of existing bone examples found in some museums in the UK. They were traced to German prisoners of war dating to the First World War. An in-depth examination of the donated bones revealed their non-human provenance. It further showed that no link existed between the bones, internees of the concentration camp, and the time of the camp's existence. It was discovered that they belonged to the period 1914–1918 and form an important part of German prisoner of war history in the UK.

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Sedentary behaviour and risk of all-cause, cardiovascular and cancer mortality, and incident type 2 diabetes: a systematic review and dose response meta-analysis

Abstract

Purpose: To estimate the strength and shape of the dose–response relationship between sedentary behaviour and all-cause, cardiovascular disease (CVD) and cancer mortality, and incident type 2 diabetes (T2D), adjusted for physical activity (PA). Data Sources: Pubmed, Web of Knowledge, Medline, Embase, Cochrane Library and Google Scholar (through September-2016); reference lists. Study Selection: Prospective studies reporting associations between total daily sedentary time or TV viewing time, and ≥ one outcome of interest. Data Extraction: Two independent reviewers extracted data, study quality was assessed; corresponding authors were approached where needed. Data Synthesis: Thirty-four studies (1,331,468 unique participants; good study quality) covering 8 exposure-outcome combinations were included. For total sedentary behaviour, the PA-adjusted relationship was non-linear for all-cause mortality (RR per 1 h/day: were 1.01 (1.00–1.01) ≤ 8 h/day; 1.04 (1.03–1.05) > 8 h/day of exposure), and for CVD mortality (1.01 (0.99–1.02) ≤ 6 h/day; 1.04 (1.03–1.04) > 6 h/day). The association was linear (1.01 (1.00–1.01)) with T2D and non-significant with cancer mortality. Stronger PA-adjusted associations were found for TV viewing (h/day); non-linear for all-cause mortality (1.03 (1.01–1.04) ≤ 3.5 h/day; 1.06 (1.05–1.08) > 3.5 h/day) and for CVD mortality (1.02 (0.99–1.04) ≤ 4 h/day; 1.08 (1.05–1.12) > 4 h/day). Associations with cancer mortality (1.03 (1.02–1.04)) and T2D were linear (1.09 (1.07–1.12)). Conclusions: Independent of PA, total sitting and TV viewing time are associated with greater risk for several major chronic disease outcomes. For all-cause and CVD mortality, a threshold of 6–8 h/day of total sitting and 3–4 h/day of TV viewing was identified, above which the risk is increased.

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From Homer and Hippocrates to modern personalized medicine: is there a role for pharmacoepigenomics in the treatment of alcohol addiction?

Pharmacogenomics, Ahead of Print.


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Pharmacogenetics of oral antidiabetic therapy

Pharmacogenomics, Ahead of Print.


https://ift.tt/2GfIrWC

Effect of hydrochlorothiazide on serum uric acid concentration: a genome-wide association study

Pharmacogenomics, Ahead of Print.


https://ift.tt/2Gg2cl6

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design

Future Oncology, Ahead of Print.


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Incisor malalignment and the risk of periodontal disease progression

The objective of this study was to investigate the association between incisor crowding, irregularity, and periodontal disease progression in the anterior teeth.

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Editorial Board

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Comparison of digital intraoral scanners and alginate impressions: Time and patient satisfaction

Recent technological advances have made intraoral scans and digital models a possibility and a promising alternative to conventional alginate impressions. Several factors should be examined when considering an intraoral scanner, including patient acceptance and efficiency. The objectives of this study were to assess and compare patient satisfaction and time required between 2 intraoral scanners and conventional alginate impressions.

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Epidemiologic study of orthodontic retention procedures

The aims of this study were to survey current retention procedures applied by Dutch orthodontists and to examine their acquaintance with "unintentionally active retainers."

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April 2018:153(4)

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Directory: AAO Officers and Organizations

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Orthodontic therapy: Fundamental treatment concepts

The arrival of Orthodontic therapy: Fundamental treatment concepts adds to the lexicon of the Dental Color Atlas series, edited by Herbert F. Wolf and published by Thieme Medical Publishers. Featured on the cover of this heavy hardback volume is the molecular structure of proteins together with maloccluded teeth, hinting at the contained wide encompassment of orthodontic therapy.

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Nonsurgical correction of a severe anterior open bite with mandibular molar intrusion using mini-implants and the multiloop edgewise archwire technique

This article reports the case of a 24-year-old man with a large anterior open bite, mild mandibular crowding, increased overjet, no passive lip sealing, and Angle Class I malocclusion. The treatment results were achieved by mandibular molar intrusion using 1.8 × 8.5-mm mini-implants (C-implants) inserted between the mandibular first and second molars bilaterally. A 2.5-mm molar intrusion and open-bite closure occurred within 8 months. The multiloop edgewise archwire technique helped to intrude the posterior teeth.

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Extraction of maxillary canines

I read the article in the October 2017 issue entitled "Extraction of maxillary canines: Esthetic perceptions of patient smiles among dental professionals and laypeople" with great interest (Thiruvenkatachari B, Javidi H, Griffiths SE, Shah AA, Sandler J. Am J Orthod Denotofacial Orthop 2017;152:509-15).

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Dentoskeletal effects of facemask therapy in skeletal Class III cleft patients with or without bone graft

The association between maxillary protraction and bone graft in patients with cleft lip and palate remains unclear. The purpose of this study was to investigate whether a secondary alveolar bone graft influences dentoskeletal effects of facemask therapy in unilateral cleft lip and palate patients with a skeletal Class III relationship.

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Qualified immunity: Pure heart and empty head

I don't know about you, but lately, over the past 2 or 3 years, we have seen a slight uptick in patient presentations where we must ask ourselves whether we are looking at a possible case of child abuse. The facts of Nelson v Lindaman, No. 13-0719 (Iowa Sup. Ct. April 24, 2015), had the following facts. A child was brought to the emergency room suffering from an arm fracture. The treating emergency room physician doubted the father's account of the injury and reported suspected child abuse to the proper authorities.

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Objective assessment of the contribution of dental esthetics and facial attractiveness in men via eye tracking

Recently, greater emphasis has been placed on smile esthetics in dentistry. Eye tracking has been used to objectively evaluate attention to the dentition (mouth) in female models with different levels of dental esthetics quantified by the aesthetic component of the Index of Orthodontic Treatment Need (IOTN). This has not been accomplished in men. Our objective was to determine the visual attention to the mouth in men with different levels of dental esthetics (IOTN levels) and background facial attractiveness, for both male and female raters, using eye tracking.

https://ift.tt/2uqiD8P

Reliability and validity of mandibular posterior vertical asymmetry index in panoramic radiography compared with cone-beam computed tomography

The purposes of this study were to compare the asymmetry index using panoramic radiography and cone-beam computed tomography for detecting mandibular posterior asymmetry and to evaluate the diagnostic value of the asymmetry index on panoramic radiography.

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Anatomic assessment of the mandibular buccal shelf for miniscrew insertion in white patients

Cortical bone thickness, bone width, insertion depth, and proximity to nerves are important factors when planning and placing orthodontic miniscrews. The objective of this study was to anatomically assess the mandibular buccal shelf in a white patient population as the insertion site for orthodontic miniscrews by investigating these 4 variables.

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Distinguishing Among Evolutionary Forces Acting on Genome-Wide Base Composition: Computer Simulation Analysis of Approximate Methods for Inferring Site Frequency Spectra of Derived Mutations in Recombining Regions

Inferred ancestral nucleotide states are increasingly employed in analyses of within and between species genome variation. Although numerous studies have focused on ancestral inference among distantly related lineages, approaches to infer ancestral states in polymorphism data have received less attention. Recently developed approaches that employ complex transition matrices allow us to infer ancestral nucleotide sequence in several evolutionary scenarios of base composition. However, the requirement of a single gene tree to calculate a likelihood is an important limitation for conducting ancestral inference using within-species variation in recombining genomes. To resolve this problem, and to extend the applicability of ancestral inference in studies of base composition evolution, we first evaluate three previously proposed methods to infer ancestral nucleotide sequences among within- and between-species sequence variation data. The methods employ a single allele, bifurcation tree, or a star tree for within-species variation data. Using simulated nucleotide sequences, we employ ancestral inference to infer fixations and polymorphisms. We find that all three methods show biased inference. We modify the bifurcating tree method to include weights to adjust for an expected site frequency spectrum, "bifurcating tree with weighting" (BTW). Our simulation analysis show that the BTW method can substantially improve the reliability and robustness of ancestral inference in a range of scenarios, including fixation biases and non-stationarity, in base composition evolution.

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The Draft Genome of the Invasive Walking Stick, Medauroidea extradentata, Reveals Extensive Lineage-Specific Gene Family Expansions of Cell Wall Degrading Enzymes in Phasmatodea

Plant cell wall components are the most abundant macromolecules on Earth. The study of the breakdown of these molecules is thus a central question in biology. Surprisingly, plant cell wall breakdown by herbivores is relatively poorly understood, as nearly all early work focused on the mechanisms used by symbiotic microbes to breakdown plant cell walls in insects such as termites. Recently, however, it has been shown that many organisms make endogenous cellulases. Insects, and other arthropods, in particular have been shown to express a variety of plant cell wall degrading enzymes in many gene families with the ability to break down all the major components of the plant cell wall. Here we report the genome of a walking stick, Medauroidea extradentata, an obligate herbivore that makes uses of endogenously produced plant cell wall degrading enzymes. We present a draft of the 3.3Gbp genome along with an official gene set that contains a diversity of plant cell wall degrading enzymes. We show that at least one of the major families of plant cell wall degrading enzymes, the pectinases, have undergone a striking lineage-specific gene family expansion in the Phasmatodea. This genome will be a useful resource for comparative evolutionary studies with herbivores in many other clades and will help elucidate the mechanisms by which metazoans breakdown plant cell wall components.

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A Bayesian Genomic Regression Model with Skew Normal Random Errors

Genomic selection (GS) has become a tool for selecting candidates in plant and animal breeding programs. In the case of quantitative traits, it is common to assume that the distribution of the response variable can be approximated by a normal distribution. However, it is known that the selection process leads to skewed distributions. There is vast statistical literature on skewed distributions, but the skew normal distribution is of particular interest in this research. This distribution includes a third parameter that drives the skewness, so that it generalizes the normal distribution. We propose an extension of the Bayesian whole-genome regression to skew normal distribution data in the context of GS applications, where usually the number of predictors vastly exceeds the sample size. However, it can also be applied when the number of predictors is smaller than the sample size. We used a stochastic representation of a skew normal random variable, which allows the implementation of standard Markov Chain Monte Carlo (MCMC) techniques to efficiently fit the proposed model. The predictive ability and goodness of fit of the proposed model were evaluated using simulated and real data, and the results were compared to those obtained by the Bayesian Ridge Regression model. Results indicate that the proposed model has a better fit and is as good as the conventional Bayesian Ridge Regression model for prediction, based on the DIC criterion and cross-validation, respectively. A computing program coded in the R statistical package and C programming language to fit the proposed model is available as supplementary material.

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QTL Mapping of Genome Regions Controlling Manganese Uptake in Lentil Seed

This study evaluated Mn concentration in the seeds of 120 RILs of lentil developed from the cross "CDC Redberry" x "ILL7502". Micronutrient analysis using atomic absorption spectrometry indicated mean seed manganese (Mn) concentrations ranging from 8.5 to 26.8 mg/kg, based on replicated field trials grown at three locations in Turkey in 2012 and 2013. A linkage map of lentil was constructed and consisted of seven linkage groups with 5,385 DNA markers. The total map length was 973.1 cM, with an average distance between markers of 0.18 cM. A total of 6 QTLs for Mn concentration were identified using composite interval mapping (CIM). All QTLs were statistically significant and explained 15.3 to 24.1% of the phenotypic variation, with LOD scores ranging from 3.00 to 4.42. The high-density genetic map reported in this study will increase fundamental knowledge of the genome structure of lentil, and will be the basis for the development of micronutrient-enriched lentil genotypes to support biofortification efforts.

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A G3BP1-interacting lncRNA promotes ferroptosis and apoptosis in cancer via nuclear sequestration of p53

Long non-coding RNAs (lncRNA) have been associated with various types of cancer, however, the precise role of many lncRNAs in tumorigenesis remains elusive. Here we demonstrate that the cytosolic lncRNA P53RRA is downregulated in cancers and functions as a tumor suppressor by inhibiting cancer progression. Chromatin remodeling proteins LSH and Cfp1 silenced or increased P53RRA expression respectively. P53RRA bound Ras GTPase-activating protein-binding protein 1 (G3BP1) using nucleotides 1 and 871 of P53RRA and the RRM interaction domain of G3BP1 (aa 177-466). The cytosolic P53RRA-G3BP1 interaction displaced p53 from a G3BP1 complex resulting in greater p53 retention in the nucleus which led to cell cycle arrest, apoptosis, and ferroptosis. P53RRA promoted ferroptosis and apoptosis by affecting transcription of several metabolic genes. Low P53RRA expression significantly correlated with poor survival in patients with breast and lung cancers harboring wild-type p53. These data show that lncRNAs can directly interact with the functional domain of signaling proteins in the cytoplasm, thus regulating p53 modulators to suppress cancer progression.

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The circular RNA circPRKCI promotes tumor growth in lung adenocarcinoma

Somatic copy-number variations (CNV) may drive cancer progression through both coding and noncoding transcripts. However, noncoding transcripts resulting from CNV are largely unknown, especially for circular RNAs. By integrating bioinformatics analyses of alerted circRNAs and focal CNV in lung adenocarcinoma (LAC), we identify a proto-oncogenic circular RNA (circPRKCI) from the 3q26.2 amplicon, one of the most frequent genomic aberrations in multiple cancers. circPRKCI was overexpressed in LAC tissues, in part due to amplification of the 3q26.2 locus, and promoted proliferation and tumorigenesis of LAC. circPRKCI functioned as a sponge for both miR-545 and miR-589 and abrogated their suppression of the pro-tumorigenic transcription factor E2F7. Intra-tumor injection of cholesterol-conjugated siRNA specifically targeting circPRKCI inhibited tumor growth in a patient-derived LAC xenograft model. In summary, circPRKCI is crucial for tumorigenesis and may serve as a potential therapeutic target in LAC patients.

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I{kappa}B kinase {alpha} is required for development and progression of KRAS-mutant lung adenocarcinoma.

Although oncogenic activation of nuclear factor (NF)-κΒ has been identified in various tumors, the NF-κΒ-activating kinases (inhibitor of NF-κΒ kinases, IKK) responsible for this are elusive. In this study, we determined the role of IKKα and IKKβ in KRAS-mutant lung adenocarcinomas induced by the carcinogen urethane and by respiratory epithelial expression of oncogenic KRASG12D. Using NF-κB reporter mice and conditional deletions of IKKα and IKKβ, we identified two distinct early and late activation phases of NF-κΒ during chemical and genetic lung adenocarcinoma development, which were characterized by nuclear translocation of RelB, ΙκΒβ, and IKKα in tumor-initiated cells. IKKα was a cardinal tumor promoter in chemical and genetic KRAS-mutant lung adenocarcinoma, and respiratory epithelial IKKα-deficient mice were markedly protected from the disease. IKKα specifically cooperated with mutant KRAS for tumor induction in a cell-autonomous fashion, providing mutant cells with a survival advantage in vitro and in vivo. IKKα was highly expressed in human lung adenocarcinoma, and a heat shock protein 90 inhibitor that blocks IKK function delivered superior effects against KRAS-mutant lung adenocarcinoma compared with a specific IKKβ inhibitor. These results demonstrate an actionable requirement for IKKα in KRAS-mutant lung adenocarcinoma, marking the kinase as a therapeutic target against this disease.

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Intratumoral CpG-B promotes anti-tumoral neutrophil, cDC, and T cell cooperation without reprograming tolerogenic pDC

Cancer immunotherapies utilize distinct mechanisms to harness the power of the immune system to eradicate cancer cells. Therapeutic vaccines, aimed at inducing active immune responses against an existing cancer, are highly dependent on the immunological microenvironment, where many immune cell types display high levels of plasticity and, depending on the context, promote very different immunological outcomes. Among them, plasmacytoid dendritic cells (pDC), known to be highly immunogenic upon inflammation, are maintained in a tolerogenic state by the tumor microenvironment. Here we report that intratumoral (i.t.) injection of established solid tumors with CpG oligonucleotides-B (CpG-B) inhibits tumor growth. Interestingly, control of tumor growth was independent of tumor-associated (TA) pDC, which remained refractory to CpG-B stimulation and whose depletion did not alter the efficacy of the treatment. Instead, tumor growth inhibition subsequent to i.t. CpG-B injection depended on the recruitment of neutrophils into the milieu, resulting in the activation of conventional dendritic cells (cDC), subsequent increased anti-tumor T cell priming in draining lymph nodes, and enhanced effector T cell infiltration in the tumor microenvironment. These results reinforce the concept that intratumoral delivery of TLR9 agonists alters the tumor microenvironment by improving the anti-tumor activity of both innate and adaptive immune cells.

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Exome sequencing of plasma DNA portrays the mutation landscape of colorectal cancer and discovers mutated VEGFR2 receptors as modulators of anti-angiogenic therapies

Background:Despite the wide use of antiangiogenic drugs in the clinical setting, predictive biomarkers of response to these drugs are still unknown.Experimental design: We applied whole-exome sequencing of matched germline and basal plasma cell-free DNA samples (WES-cfDNA) on a RAS/BRAF/PIK3CA wild-type metastatic colorectal cancer patient with primary resistance to standard treatment regimens, including inhibitors to the VEGF:VEGFR2 pathway. We performed extensive functional experiments, including ectopic expression of VEGFR2 mutants in different cell lines, kinase and drug sensitivity assays, and cell- and patient-derived xenografts. Results: WES-cfDNA yielded a 77% concordance rate with tumor exome sequencing and enabled the identification of the KDR/VEGFR2 L840F clonal, somatic mutation as the cause of therapy refractoriness in our patient. Additionally, we found that 1-3% of samples from cancer sequencing projects harbor KDR somatic mutations located in protein residues frequently mutated in other cancer-relevant kinases, such as EGFR, ABL1, and ALK. Our in vitro and in vivo functional assays confirmed that L840F causes strong resistance to anti-angiogenic drugs, whereas the KDR hot-spot mutant R1032Q confers sensitivity to strong VEGFR2 inhibitors. Moreover, we showed that the D717V, G800D, G800R, L840F, G843D, S925F, R1022Q, R1032Q, and S1100F VEGFR2 mutants promote tumor growth in mice. Conclusions: Our study supports WES-cfDNA as a powerful platform for portraying the somatic mutation landscape of cancer and discovery of new resistance mechanisms to cancer therapies. Importantly, we discovered that VEGFR2 is somatically mutated across tumor types and that VEGFR2 mutants can be oncogenic and control sensitivity/resistance to antiangiogenic drugs.

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Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes

Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes

Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes, Published online: 28 March 2018; doi:10.1038/s41416-018-0041-x

Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes

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Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer

Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer

Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer, Published online: 28 March 2018; doi:10.1038/s41416-018-0027-8

Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer

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The purinergic P2X7 ion channel receptor—a ‘repair’ receptor in bone

Niklas Rye Jørgensen

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EHR Usability Contributes to Possible Patient Harm Events

TUESDAY, March 27, 2018 -- Electronic health record (EHR) usability may contribute to possible patient harm events, according to a research letter published in the March 27 issue of the Journal of the American Medical Association. Jessica L. Howe,...

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Parent-Child Book Reading Tied to Psychosocial Benefits

TUESDAY, March 27, 2018 -- Reading books together is associated with psychosocial benefits in both children and parents, according to a review published online March 27 in Pediatrics. Qian-Wen Xie, from the University of Hong Kong, and colleagues...

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1980 to 2014 Saw Decrease in U.S. Mortality From Infectious Diseases

TUESDAY, March 27, 2018 -- There were declines in mortality from most categories of infectious diseases between 1980 and 2014 in the United States, according to a study published in the March 27 issue of the Journal of the American Medical...

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Condition Readmission Measures Don't Reflect Overall Quality

TUESDAY, March 27, 2018 -- Current publicly reported measures may not be good surrogates for overall hospital quality related to 30-day readmissions, according to a study published online March 27 in the Annals of Internal Medicine. Neel M. Butala,...

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Cervical Cancer Frequently Diagnosed After Age 65

TUESDAY, March 27, 2018 -- A considerable proportion of women are diagnosed with cervical cancer after age 65, according to a study presented at the Society of Gynecologic Oncology's Annual Meeting on Women's Cancer, held from March 24 to 27 in New...

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Cost-Effectiveness of Biomarker Tests for Irritable Bowel Syndrome with Diarrhea – A Framework for Payers

Diagnosis of diarrhea-predominant irritable bowel syndrome (IBS-D) relies on the Rome IV symptom-based criteria, which are imperfect for separating functional vs organic disease. Biomarker tests for IBS-D might be added to symptom data to allow clinicians to make more accurate and precise diagnoses in a cost-effective manner. We tested the economic consequences of using a range of hypothetical IBS-D biomarkers, and explored at what cost and level of accuracy a biomarker becomes cost effective. We produced a framework for payers to evaluate the return on an investment of implementing IBS-D biomarkers of varying accuracy and cost.

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Dyspepsia

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Rethinking What We Know About Hemorrhoids

Although hemorrhoids are responsible for considerable economic cost and personal suffering, they have received surprisingly little research attention. In the United States, hemorrhoids are the third most common outpatient gastrointestinal diagnosis with nearly 4 million office and emergency department visits annually. The etiology of hemorrhoids is speculative. A low-fiber diet and constipation have historically been thought to increase the risk for hemorrhoids, but not proven. Symptoms commonly attributed to hemorrhoids include bleeding, pain, pruritus, fecal seepage, prolapse and mucus discharge.

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Endoscopic drainage of pancreatic fluid collections

Endoscopy has emerged as a mainstay in the management of pancreatic fluid collections (PFCs), representing an important advance in clinical medicine that has significantly improved the risk-benefit ratio of treating this complex patient population. While endoscopic pseudocyst drainage has generally supplanted surgical and percutaneous approaches, the optimal strategy for walled-off necrosis remains variable and multi-disciplinary despite an emerging trend from randomized trials favoring endoscopy.

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Vedolizumab treatment may reduce steroid burden and improve histology in patients with eosinophilic gastroenteritis

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Is modest drinking good for the liver?

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A New Method for Monitoring Abnormal Muscle Response in Hemifacial Spasm: A Prospective Study

Hemifacial spasm (HFS) is a neurovascular compression syndrome and microvascular decompression (MVD) is the only curative treatment. An intraoperative abnormal muscle response (AMR) has been a reliable diagnostic tool and indicator of complete facial nerve decompression. An AMR is elicited by stimulation of a facial nerve branch and is recorded from facial muscles innervated by other nerve branches. Typically, it is instantly eliminated on intraoperative facial nerve electromyography (EMG) when the facial nerve is decompressed.

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Intratumoral and Peritumoral Lymphovascular Invasion Detected by D2–40 Immunohistochemistry Correlates with Metastasis in Primary Cutaneous Merkel Cell Carcinoma

Primary cutaneous Merkel cell carcinoma (MCC) is an aggressive neuroendocrine malignancy in which lymphovascular invasion (LVI) correlates with more aggressive phenotype. The prognostic significance of LVI detected by D2–40 immunohistochemistry (IHC) in MCC remains controversial. We aimed to determine how LVI detected by D2–40 IHC compares with LVI detected by hematoxylin–eosin (H&E) staining in predicting MCC metastasis. Clinical and histopathologic features of MCCs diagnosed and treated during 2002–2015 were assembled and included 58 MCC tumors from 58 patients.

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Intratumoral Heterogeneity of ERBB2 Amplification and HER2 Expression in Micropapillary Urothelial Carcinoma

Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. MPUC has been shown to commonly exhibit ERBB2 amplification and HER2 protein overexpression, but the frequency and distribution of these findings within micropapillary (MP) and not otherwise specified (NOS) components of tumors have not been addressed. Therefore, we evaluated ERBB2 amplification and HER2 expression in 43 MPUC cases by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC).

https://ift.tt/2I5NWrC

Complete Genome Sequence Can Be ID'd From Amniotic Fluid

TUESDAY, March 27, 2018 -- The complete genome sequence of fetuses can be elucidated from amniotic fluid, according to a study published online March 15 in Clinical Chemistry. Qing Mao, from Complete Genomics Inc., in San Jose, Calif., and...

https://ift.tt/2J0e4VN

Concern for Employer, Insurance Discrimination for Alzheimer's Patients

TUESDAY, March 27, 2018 -- U.S. adults express concerns about discrimination by employers and insurance for patients with Alzheimer's disease dementia, according to a study published online March 27 in Alzheimer's & Dementia. Shana D. Stites,...

https://ift.tt/2J0edsj

Educational Attainment Down With In Utero Exposure to AEDs

TUESDAY, March 27, 2018 -- Exposure to sodium valproate or a combination of antiepileptic drugs (AEDs) in utero is associated with worse attainment on national educational tests for 7-year-olds, according to a study published online March 26 in the...

https://ift.tt/2J0e9sz

Social Isolation, Loneliness May Increase AMI, Stroke Risk

TUESDAY, March 27, 2018 -- Isolation and loneliness may be associated with increased risk of acute myocardial infarction (AMI) and stroke, according to a study published online March 27 in Heart. Christian Hakulinen, Ph.D., from the University of...

https://ift.tt/2IYdeZG

Hepatitis C Screening Increasing Among Baby Boomers

TUESDAY, March 27, 2018 -- For baby boomers, born between 1945 and 1965, the odds of hepatitis C virus (HCV) screening increase over time, although the rates of screening are low, according to a study published online March 27 in Cancer...

https://ift.tt/2GdJsyn

Inactivity, Prolonged Sitting Tied to Urinary Tract Infections in Men

TUESDAY, March 27, 2018 -- Prolonged sitting time and low physical activity levels are tied to higher incidence of lower urinary tract symptoms (LUTS) in men, according to a study published online March 20 in BJU International. Heung Jae Park, from...

https://ift.tt/2pI0JJ4

Children's Hoverboard, Skateboard Injuries Are Similar

TUESDAY, March 27, 2018 -- Injury characteristics among hoverboard riders and skateboarders are similar, according to a study published online March 26 in Pediatrics. Sean Bandzar, M.D., from New York-Presbyterian Hospital in New York City, and...

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Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes

https://ift.tt/2I5cmkI

Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer

https://ift.tt/2GA0kTy

Dilemmas for the pathologist in the oncologic assessment of pancreatoduodenectomy specimens

Abstract

A pancreatoduodenectomy specimen is complex, and there is much debate on how it is best approached by the pathologist. In this review, we provide an overview of topics relevant for current clinical practice in terms of gross dissection, and macro- and microscopic assessment of the pancreatoduodenectomy specimen with a suspicion of suspected pancreatic cancer. Tumor origin, tumor size, degree of differentiation, lymph node status, and resection margin status are universally accepted as prognostic for survival. However, different guidelines diverge on important issues, such as the diagnostic criteria for evaluating the completeness of resection. The macroscopic assessment of the site of origin in periampullary tumors and cystic lesions is influenced by the grossing method. Bi-sectioning of the head of the pancreas may offer an advantage in this respect, as this method allows for optimal visualization of the periampullary area. However, a head-to-head comparison of the assessment of clinically relevant parameters, using axial slicing versus bi-sectioning, is not available yet and the gold standard to compare both techniques prospectively might be subject of debate. Further studies are required to validate the various dissection protocols used for pancreatoduodenectomy specimens and their specific value in the assessment of pathological parameters relevant for prognosis.

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314 Harder to Breathe: An Unusual Case of Severe Hyperphosphaturic Hypophosphatemia and Normal FGF-23 Levels in a Young Female Patient

https://ift.tt/2IZMWGv

242 Pharmacokinetics of Ferric Pyrophosphate Citrate (Triferic®) in Pediatric CKD-5HD Patients Administered IV and via Dialysate

https://ift.tt/2GjDr39

Pre-injury Depression and Anxiety in Patients with Orthopedic Trauma and their Treatment

Publication date: Available online 27 March 2018
Source:Injury
Author(s): Edward Haupt, Heather K. Vincent, Andrew Harris, Terrie Vasilopoulos, Robert Guenther, Sharareh Sharififar, Jennifer E. Hagen
PurposeDepressive symptoms have a known negative impact on outcomes following musculoskeletal injury. This study determined the pre-injury prevalence of psychiatric diagnoses of depression and anxiety, medication lapses and psychiatric consult services among patients admitted for orthopaedic trauma.MethodsThis is a retrospective study of data from our Level-1 trauma center. Patients admitted to the orthopaedic trauma service during 2010-2015 were included (N = 4,053). Demographics, Injury Severity Scores (ISS), mental health diagnoses, psychotropic medications, medication type and delay, psychiatric consultation use, intensive care unit (ICU) stay and total hospital length of stay (LOS) were abstracted from medical records and the institutional trauma registry.ResultsThe 12-month prevalence of a major depressive episode is 6.6%-8.6% in adults in the United States. In our database, only 152/4053 (3.8%) of the patients had documented medical history of depression (80%) or anxiety (30%), and these patients had a 32% longer LOS (p < 0.016). Nearly two-thirds of patients who used psychotropic medications prior to injury experienced a delay in receiving these medications in the hospital (median = 1.0 day, range 0-14 days). Sixteen percent of patients also received a new psychotropic medication while hospitalized: an antipsychotic (8/16 patients, to treat delirium), an anxiolytic (3/16 patients for acute anxiety), or an antidepressant (1/16). Among patients with depression or anxiety, 16.7% received a psychiatric consult. Patients with psychiatric consults had higher ISS, were more likely to have longer ICU LOS and had longer hospital LOS than those without consults (all p<0.05).ConclusionThe prevalence of depression and anxiety is grossly under-reported in our registry compared to national prevalence data. Patients with pre-existing disease had longer LOS and a higher rate of extended ICU care. Further studies are needed to characterize the true prevalence of disease in this patient population and its effect on patient outcomes after traumatic orthopaedic injury.



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Characterization of disability following traumatic through knee and transfemoral amputations

Publication date: Available online 27 March 2018
Source:Injury
Author(s): David J. Tennent, Elizabeth M. Polfer, Nicole M. Sgromolo, Chad A. Krueger, Benjamin M. Potter
IntroductionThe purpose of this study is to characterize through knee and transfemoral amputations following severe traumatic injuries.MethodsA retrospective review of all transfemoral and through knee amputations sustained by United States military service members from 1 October 2001 to 30 July 2011 was conducted. Data from the Department of Defense Trauma Registry, the Armed Forces Health Longitudinal Technology Application, inpatient medical records and the Physical Evaluation Board Liaison Offices were queried in order to obtain characteristics related to injury sustained, demographics, treatment, and disability/mental health outcome data.ResultsA total of 1631 amputations in 1315 patients were identified. Of these there were 37 through knee and 296 were transfemoral amputations. Adequate records for detailed analysis were available on 140 and 25 transfemoral and through knee amputations respectively. There were no significant differences in demographic information, injury mechanism, initial injury severity score, or associated injuries, to include contralateral amputations. There was no significant difference in average disability rating (67.9% vs 78.3%, p = 0.46) or number of service members determined to be fully disabled (42.2% vs 28.6% p = 0.33) between the transfemoral and through knee amputation groups. Whereas there was no difference between groups preoperatively, the knee disarticulation group displayed a higher rate of mental health diagnoses post-amputation (96% vs 72%, p < 0.001) and a higher preponderance of anxiety related disorders than the transfemoral amputees (26.92% vs 12.96%, p = 0.0129).Discussion/conclusionAmong this military amputee through knee and transfemoral amputees displayed similar physical disability profiles. However, the through knee amputees displayed a higher level of anxiety related disorders and mental health diagnosis overall. While we don't believe this relationship to be causal in nature, this finding reflects the importance of paying particular attention to mental health in the final disposition of traumatic lower extremity amputees.



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The use of Arteriovenous Anastomosis for Venous Drainage During Tamai Zone I Fingertip Replantation

Publication date: Available online 27 March 2018
Source:Injury
Author(s): Fei Wu, Xiaofang Shen, Kyle R. Eberlin, Zhibo Sun, Xiao Zhou, Mingyu Xue
PurposeThe purpose of this study was to evaluate outcomes for patients sustaining a distal fingertip amputation who underwent replantation witharteriovenous anastomosis for venous drainage over a one year period at our institution. This technique has been utilized when insufficient veins are identified in the amputated part for standard veno-venous anastomosis.MethodsA retrospective study was performed on patients presenting from 2013–2014. Guillotine, crush, and avulsion/degloving injuries were included if they underwent fingertip (Tamai Zone I) replantation with arterial anastomosis for vascular inflow and arteriovenous anastomosis for venous drainage. The cases were further classified as Ishikawa subzone I and subzone II.ResultsArteriovenous anastomosis for venous drainage during replantation was used in 45 digits in 35 patients. 41 of the 45 digits underwent successful replantation using this technique (91%). The mean active ROM in the DIP joint of the fingers and in the IP joint of thumbs was 65 degrees and 57 degrees, respectively. Sensory evaluation demonstrated a mean of 6.9 mm s2PD in digits where the digital nerves could be repaired. 11 replanted digits without nerve repair regained some sensory recovery with a mean of 9.6 mm s2PD. 91% of patients were highly satisfied with the appearance of the replanted digits based on Tamai criteria.ConclusionsArteriovenous anastomosis for venous outflow should be considered during zone I fingertip replantation if sufficient veins are not identified in the amputated part. This technique may allow for more routine and successful distal replantation.



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Modified Stoppa approach for operative treatment of acetabular fractures: 10-year experience and mid-term follow-up

Publication date: Available online 27 March 2018
Source:Injury
Author(s): Diederik O. Verbeek, Kornelis J. Ponsen, Mark van Heijl, J. Carel Goslings
IntroductionThe (modified) Stoppa approach for acetabular fracture surgery has gained significant popularity and early results have been encouraging but clinical outcome at extensive follow-up is scarce. The purpose of this study is to provide an update on our experience with this approach for operative treatment of acetabular fractures and to assess clinical outcome at mid-term follow-up.MethodsIn this retrospective study, all patients treated operatively for an acetabular fracture using the Stoppa approach over a 10-year period were included. Surgery details were reviewed and patients were contacted and requested to return for follow-up. Primary outcome was native hip survivorship, secondary outcome measures included; functional outcome (Merle d'Aubiginé, Harris hip) scores, health-related quality of life (short-form 36) and radiographic outcome (heterotopic ossification, hip osteoarthritis).ResultsForty-five patients received operative fixation for 47 acetabular fractures using the Stoppa approach. Complications requiring surgical intervention were found in one patient (with a vascular lesion) intra-operatively and 3 patients (with wound infections (2) and diffuse bleeding (1)) post-operatively. Follow-up was 83% and 29/39 (74%) native hips survived at mean 59 months (SD 49) postoperatively. Excellent-good functional scores were found in 88% (Merle d'Aubiginé) and 76% (Harris hip) of patients who had retained their native hip. Most (6/8) short-form 36 indices in these patients were comparable to population norms. Of 29 native hips with radiographic follow-up (mean 59 months (SD 49), 4 (86%) had no-minimal radiographic abnormalities.ConclusionThis study confirms that the Stoppa approach is a safe and effective technique for acetabular fracture fixation. Moreover, at mid-term follow-up, this approach is associated with satisfactory results in terms of hip survivorship as well as functional and radiographic outcome. As such, our findings reinforce the notion that this less invasive technique presents a valuable alternative to the ilioinguinal approach for the surgical treatment of acetabular fractures.



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Fixed Angle Plate Fixation of Comminuted Patellar Fractures

Publication date: Available online 27 March 2018
Source:Injury
Author(s): Tyler B. Moore, Bharat R. Sampathi, David P. Zamorano, Martin C. Tynan, John A. Scolaro
IntroductionComminuted patella fractures are uncommon and difficult fractures to manage. Multiple treatment modalities have been suggested, with little clinical data to support practice. Recent biomechanical and technical investigations have described successful plate fixation of comminuted patella fractures. The purpose of this study was to evaluate radiographic, clinical and functional outcome of comminuted patella fractures treated with a fixed angle locking plates. We believe stable fixation, which results in successful fracture union and functional recovery, can be achieved with this technique.Materials and MethodsA retrospective review was performed at a single regional academic Level 1 trauma hospital. All comminuted patella fractures treated with a fixed angle locking plate (AO/OTA 34C2 and C3) over a six-year period were evaluated. Thirty-six patients were identified. Average length of follow up was 154 weeks (range 12–297 weeks). Twenty patients were available for functional outcome scoring. Primary outcome measures were: Knee Outcome Score (KOS), Lower Extremity Functional Scale (LES) and goniometer measured knee range of motion. Secondary outcomes evaluated the need for additional screw or cerclage fixation, reoperation for any reason, bothersome hardware, infection and nonunion.ResultsAverage KOS = 57.2 (20-74), average LES = 58.9 (15-80). Median extension = 0 degrees (full extension), median flexion = 130 degrees. Supplemental screws were used in 17/36 cases; cerclage used in 2/36 cases. Hardware irritation was noted in 4/20 patients, no patient requested elective hardware removal, one patient had failure of fixation and no nonunions were identified.ConclusionFixed angle plate stabilization of comminuted patella fractures is a viable technique for fracture fixation. Good to excellent return of knee function and low complication rates, including need for hardware removal, can be expected.



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The burden of gunshot wounding of UK military personnel in Iraq and Afghanistan from 2003-14

Publication date: Available online 27 March 2018
Source:Injury
Author(s): T. Stevenson, D.J. Carr, J.G. Penn-Barwell, T.J. Ringrose, S.A. Stapley
IntroductionGunshot wounding (GSW) is the second most common mechanism of injury in warfare after explosive injury. The aim of this study was to define the clinical burden of GSW placed on UK forces throughout the recent Iraq and Afghanistan conflicts.MethodsThis study was a retrospective review of data from the UK Military Joint Theatre Trauma Registry (JTTR). A JTTR search identified records within the 12 year period of conflict between 19 Mar 2003 and 27 Oct 2014 of all UK military GSW casualties sustained during the complete timelines of both conflicts. Included cases had their clinical timelines and treatment further examined from time of injury up until discharge from hospital or death.ResultsThere were 723 casualties identified (177 fatalities, 546 survivors). Median age at the time of injury was 24 years (range 18-46 years), with 99.6% of casualties being male. Most common anatomical locations for injury were the extremities, with 52% of all casualties sustaining extremity GSW, followed by 16% GSW to the head, 15% to the thorax, and 7% to the abdomen. In survivors, the rate of extremity injury was higher at 69%, with head, thorax and abdomen injuries relatively lower at 5%, 11% and 6% respectively. All GSW casualties had a total of 2,827 separate injuries catalogued. A total of 545 casualties (523 survivors, 22 fatalities) underwent 2,357 recorded surgical procedures, which were carried out over 1,455 surgical episodes between admission to a deployed medical facility and subsequent transfer to the Royal Centre for Defence Medicine (RCDM) in the UK. This gave a median of 3 (IQR 2-5) surgical procedures within a median of 2 (IQR 2-3) surgical episodes per casualty. Casualties had a combined length of stay (LoS) of 25 years within a medical facility, with a mean LoS in a deployed facility of 1.9 days and 14 days in RCDM.ConclusionThese findings define the massive burden of injury associated with battlefield GSW and underscore the need for further research to both reduce wound incidence and severity of these complex injuries.



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Are the current guidelines for surgical delay in hip fractures too rigid? A single center assessment of mortality and economics

Publication date: Available online 27 March 2018
Source:Injury
Author(s): Kristof Kempenaers, Ben Van Calster, Cindy Vandoren, An Sermon, Willem-Jan Metsemakers, Paul Vanderschot, Dominique Misselyn, Stefaan Nijs, Harm Hoekstra
PurposeControversy remains around acceptable surgical delay of acute hip fractures with current guidelines ranging from 24 to 48 hours. Increasing healthcare costs force us to consider the economic burden as well. We aimed to evaluate the adjusted effect of surgical delay for hip fracture surgery on early mortality, healthcare costs and readmission rate. We hypothesized that shorter delays resulted in lower early mortality and costs.MethodsIn this retrospective cohort study 2573 consecutive patients aged ≥50 years were included, who underwent surgery for acute hip fractures between 2009 and 2017. Main endpoints were thirty- and ninety-day mortality, total cost, and readmission rate. Multivariable regression included sex, age and ASA score as covariates.ResultsThirty-day mortality was 5% (n = 133), ninety-day mortality 12% (n = 304). Average total cost was €11960, dominated by hospitalization (59%) and honoraria (23%). Per 24 hours delay, the adjusted odds ratio was 1.07 (95% CI 0.98–1.18) for thirty-day mortality, 1.12 (95% CI 1.04–1.19) for ninety-day mortality, and 0.99 (95% CI = 0.88–1.12) for readmission. Per 24 hours delay, costs increased with 7% (95% CI 6–8%). For mortality, delay was a weaker predictor than sex, age, and ASA score. For costs, delay was the strongest predictor. We did not find clear cut-points for surgical delay after which mortality or costs increased abruptly. The adjusted odds ratio was 0.99 (95% CI = 0.88–1.12) for readmission.ConclusionsDespite only modest associations with mortality, we observed a steady increase in healthcare costs when delaying surgery. Hence, a more pragmatic approach with surgery as soon as medically and organizationally possible seems justifiable over rigorous implementation of the current guidelines.



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Myeloid sarcoma of the nasal septum following invasive fungal sinusitis: report of a case and review of the relevant literature

Abstract

Myeloid sarcoma is an uncommon extramedullary manifestation of myeloproliferative malignancies, such as acute myeloid leukemia (AML). This sarcoma most often involves structures such as subperiosteal bone, peritoneum, or pericardium, and has only rarely been reported in the nose and paranasal sinuses. The signs and symptoms of myeloid sarcoma can overlap with those of acute invasive fungal sinusitis (AIFS), a life-threatening surgical emergency. This report describes a 75-year-old male with a known history of AML who developed both AIFS and myeloid sarcoma. Several months after successful treatment for biopsy proven AIFS, this patient developed a new soft tissue mass of the nasal septum. A new biopsy was obtained which revealed infiltrating blast cells with evidence of monocytic differentiation diagnostic of myeloid sarcoma. Given symptoms of severe nasal obstruction, this patient received palliative radiotherapy to the nasal septum, which provided temporary improvement prior to the patient succumbing to his underlying malignancy. We review the existing reports of mucosal myeloid sarcomas, diagnostic overlap of myeloid sarcoma and AIFS, as well as currently available treatment strategies.

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Bluetongue virus seropositivity and some risk factors affecting bluetongue virus infection in sheep flocks

Abstract

Bluetongue (BT) is an insect-transmitted, viral, and non-contagious disease in several species of domestic and wild ruminants. Sheep is the most susceptible host for bluetongue virus (BTV) in ruminants. In current study, 556 serum samples of ewes were assessed by competitive ELISA to investigate the serum status of BTV antibodies and risk factors affecting its seroprevalence in sheep flocks of Hamedan province, west part of Iran. In total, 256 out of 556 (46%) samples were found seropositive against BTV in all examined counties with different prevalence (ranging from 23.9 to 85%). The mean of age in positive and negative groups (2.87 ± 0.83 and 2.94 ± 0.83, respectively) was not significantly different but the seroprevalence rates showed a reduction by increasing of age in sheep herds (P < 0.05). The analyzed data showed that 67.8% of abortions occurred in the second half of pregnancy and 25.0% of abortions happened in the first half of pregnancy period, and only 7.2% of lamb wastage occurred in the first day after labor. An association was found between seropositivity to BTV and abortion history, so that the seropositivity rates in ewes with abortion and non-abortion history were 41.7 and 4.3%, respectively (df = 4, χ² = 6.73, P = 0.0001). The present study demonstrated the seroprevalence of BT in sheep is considerable in this region, so isolation and identification of involved serotypes of BTV and preparation of a precise control program with emphasis on vaccination and eradication of carriers are suggested for controlling of the BT.

https://ift.tt/2I7P4L3

Identification of Dopamine D1-Alpha Receptor Within Rodent Nucleus Accumbens by an Innovative RNA In Situ Detection Technology

Identification of dopamine D1-alpha receptor in the nucleus accumbens is critical for clarifying D1 receptor dysfunction during a central nervous system disease. We performed a novel RNA in situ hybridization assay to visualize single RNA molecules in a specific brain area.

https://ift.tt/2uqRNgW

Chemical Synthesis of Porous Barium Titanate Thin Film and Thermal Stabilization of Ferroelectric Phase by Porosity-Induced Strain

Here, we present a protocol for the synthesis of porous barium titanate (BaTiO3) thin film by a surfactant-assisted sol-gel method, in which self-assembled amphipathic surfactant micelles are used as an organic template.

https://ift.tt/2pJEnrv

Microdissection of Primary Renal Tissue Segments and Incorporation with Novel Scaffold-free Construct Technology

Tissue-engineered renal constructs provide a solution for the organ shortage and deleterious effects of dialysis. Here, we describe a protocol to micro dissect murine kidneys for isolation of cortico-medullary segments. These segments are implanted into scaffold-free cellular constructs, forming renal organoids.

https://ift.tt/2GvWo6e

Matrix Metalloproteinase 8: Could it Benefit the CAR-T Cell Therapy of Solid Tumors?- a- Commentary on Therapeutic Potential

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Benefits of caseload midwifery to prevent fetal alcohol spectrum disorder: A discussion paper

Publication date: Available online 27 March 2018
Source:Women and Birth
Author(s): Natasha Reid, Jenny Gamble, Debra K. Creedy, Amy Finlay-Jones
BackgroundExposure to alcohol prenatally can result in a child being diagnosed with fetal alcohol spectrum disorder. Affected infants experience lifelong impairments that can involve, physical, cognitive, behavioural and emotional difficulties that impact on their functional capacity. Effective prevention of fetal alcohol spectrum disorder is critically needed in Australia. Reduction in the prevalence of this disorder will only be possible if we prevent alcohol consumption during pregnancy.AimThis paper provides an overview of fetal alcohol spectrum disorder and discusses the role of caseload midwifery as part of a multi-level prevention approach.FindingsDrawing on previous research, caseload midwifery has potential to support the prevention of fetal alcohol spectrum disorder through continuity of care.ConclusionPrevention of fetal alcohol spectrum disorder will be more likely if women experience a supportive relationship with a known midwife, who has received appropriate training and can enable women to feel comfortable in discussing and addressing alcohol use.



https://ift.tt/2pLBaaI

Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary Artery Bypass Graft Surgery

This protocol presents a surgical large animal model of chronic, single vessel ischemia that results in regional abnormalities but does not create infarct, known as hibernating myocardium. Following establishment of chronic ischemia, animals are treated with off-pump LIMA-LAD coronary artery bypass graft surgery to revascularize the ischemic tissue.

https://ift.tt/2Ge8aTm

A Burrowing/Tunneling Assay for Detection of Hypoxia in Drosophila melanogaster Larvae

The protocol describes a simple assay to identify Drosophila melanogaster larvae that are experiencing hypoxia under normal atmospheric oxygen levels. This protocol allows hypoxic larvae to be distinguished from other mutants that show overlapping phenotypes such as sluggishness or slow growth.

https://ift.tt/2uoMsGP

Ossifying Fibromyxoid tumor of soft parts in head and neck: case report and literature review

Ossifying fibromyxoid tumor of soft parts (OFMT), is a rare but morphologically distinctive neoplasm of uncertain histogenesis that most frequently affects middle-aged male adults. Clinically, it usually prese...

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Proceedings of the Annual Meeting of the Austrian Society of Haematology and Medical Oncology

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How do you treat this diversion ileitis and pouchitis?

Introduction

A 43-year-old woman was admitted due to tenesmus and perianal pain caused by a severe perianal skin ulcer (figure 1A). Fifteen years previously, she underwent a total proctocolectomy with ileal pouch–anal anastomosis due to pancolitis-type UC. Three years prior, she had two episodes of pouchitis responding to antibiotic therapy. Her laboratory tests revealed anaemia (haemoglobin level, 96 g/L), elevated C reactive protein level (11.9 mg/dL) and decreased serum albumin level (25 g/L).

While the perianal skin ulcer finally improved after multidisciplinary treatment including ileostomy, severe diversion ileitis and pouchitis became obvious about 13 months after the ileostomy (figure 1B-D). Biopsies from pouch and efferent ileal loop revealed acute and chronic severe inflammation with cryptitis, consistent with diversion pouchitis and ileitis. Antibiotics (metronidazole and ciprofloxacin), corticosteroids and immunosuppressive agents (azathioprine) were not effective for diversion ileitis and pouchitis. There was a significant difference between the intestinal microbiota of the ileal pouch...

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When a transfusion in an emergency service is not really urgent: hyperhaemolysis syndrome in a child with sickle cell disease

A 13-month-old boy with sickle cell disease (SCD) from Equatorial Guinea, who had recently arrived in Spain, presented with fever. He had suffered from malaria and had received a blood transfusion. Following physical examination and complementary tests, intravenous antibiotics and a red blood cell (RBC) transfusion were administered. Soon after a second transfusion 5 days later, the haemoglobin level fell below pretransfusion levels, together with reticulocytopenia, and haematuria—the so-called hyperhaemolysis syndrome—requiring intensive care and treatment with intravenous immunoglobulins and corticosteroids, with resolution of the complication. We want to emphasise the importance of suspecting this rare, though severe complication that can appear after any RBC transfusion especially in patients with SCD, as the clinical syndrome can simulate other more common complications of these patients and a further transfusion is contraindicated. There is no standardised treatment, but intravenous immunoglobulin and corticosteroids are usually effective.

https://ift.tt/2I4KCNl

Brucellosis accompanied by haemophagocytic lymphohistiocytosis and multiple splenic abscesses in a patient with depression

A 39-year-old woman was being treated for depression in our clinic. She subsequently developed a fever and was diagnosed with pancytopenia and moderate splenomegaly. Laboratory and bone marrow results, including markedly increased serum ferritin levels, suggested haemophagocytic lymphohistiocytosis. CT showed multiple splenic abscesses and ovarian vein thrombosis. All laboratory values returned to normal after treatment for culture-positive brucellosis.

https://ift.tt/2IVBFag

Development of a Nursing Electronic Medical Record Usability Protocol

Assessing usability of an electronic medical record is useful for organizations wishing to customize their electronic medical record and determine the impact on usability. The purpose of this article is to describe the development of a protocol to measure electronic medical record usability from a nursing perspective and to develop a scoring methodology. The Technical Evaluation, Testing, and Validation of the Usability of Electronic Health Records (NISTIR 7804), published by the National Institute of Standards and Technology, guided protocol development. Usability was determined by measuring effectiveness, efficiency, and satisfaction. Satisfaction was measured by the System Usability Scale, while effectiveness and efficiency were measured via performance testing by participants, who completed one of three scenarios. A protocol and scoring formula were developed and used to assess nursing usability, resulting in an overall "C" grade for the electronic medical record. Protocol implementation and the scoring/grading calculations can be replicated to assess electronic medical record usability. The three scenarios used in this protocol will be made available upon request from the primary author to promote the use of electronic medical record usability assessment. Using and expanding upon the government's recommended usability assessment guidelines, we were successful in measuring nursing electronic medical record usability and rating an electronic medical record. This study was funded by the Missouri Baptist Medical Center Collaborative Faculty-Staff Grant (a $15 000.00 grant) from the Missouri Baptist Medical Center in St. Louis, Missouri. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Corresponding author: Frank Lyerla, PhD, RN, Southern Illinois University Edwardsville, Alumni Hall, Box 1066, Edwardsville, IL 62026 (flyerla@siue.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The Relationship Between Acceptance Intention Toward a Smartphone Healthcare Application and Health-Promoting Behaviors Among Nursing Students

The purpose of this study was to identify the relationship between acceptance intention toward a smartphone healthcare application and health-promoting behaviors among nursing students in order to propose a method to encourage nursing students' personal health management. Data were collected from June to July 2015 in two cities located in South Korea, targeting 450 nursing students. There was a weak positive relationship between acceptance intention toward a smartphone healthcare application and health-promoting behaviors (r = 0.281, P

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Automated Deterioration Detection Using Electronic Medical Record Data in Intensive Care Unit Patients: A Systematic Review

Timely detection of deterioration in status for intensive care unit patients can be problematic due to variation in data availability and the necessity of integrating data from multiple sources. This can lead to opaqueness of clinical trends and failure to rescue. Automated deterioration detection using electronic medical record data can reduce the risk of failure to rescue. This review describes the automated use of electronic medical record data in identifying deterioration in intensive care unit patients. PubMed and Google Scholar were used to retrieve publications between January 1, 2006, and March 31, 2016. Six studies met inclusion criteria: intensive care unit patient focus, description of electronic medical record data use in automated patient deterioration detection, and presence of predictive, sensitivity, and/or specificity values. Detection focused on specific clinical events such as infection; data sources were electronic medical record–populated databases. Detection algorithms incorporated laboratory results, vital signs, medication orders, and respiratory therapy and radiology documentation. Positive and negative predictive values and sensitivity and specificity measures varied across studies. Three systems generated clinician alerts. Automated deterioration detection using electronic medical record data may be an important aid in caring for intensive care unit patients, but its usefulness is limited by variable electronic medical record detection approaches and performance. The author has disclosed that she has no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Corresponding author: Laurel A. Despins, PhD, RN, Sinclair School of Nursing, University of Missouri, 1 Hospital Drive, Columbia, MO 65211 (despinsl@missouri.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Identification and characterization of inorganic-phosphate-solubilizing bacteria from agricultural fields with a rapid isolation method

The ability to solubilize fixed inorganic phosphorus (P) for plant growth is important for increasing crop yield. More P can be released by inoculating soil with inorganic-phosphate-solubilizing bacteria (iPSB...

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Video: Self-flying drones could serve as emergency responders

"Swarm drones" can navigate themselves and coordinate with each other, making them potentially useful for high-level rescue missions and more

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Progressive Neurological Decline with Deep Bilateral Imaging Changes: A Protean Presentation of Dural Arteriovenous Fistulae

Intracranial dural arteriovenous fistulae (DAVF) within the deep cerebral vasculature are diagnostically challenging because of their variable clinical presentation and typical bilateral neuroimaging findings mimicking inflammatory, infectious, and metabolic processes. Increasingly, reports have emerged highlighting the diagnostic and treatment challenges of these lesions and their associated high morbidity and rapid clinical deterioration when untreated. We describe here a case series of 4 patients with deep cerebral DAVF who presented with impaired arousal or memory and behavioral changes. In all patients, the initial differential diagnosis included metabolic, inflammatory, infectious, or neoplastic disease, with an eventual correct diagnosis obtained after catheter angiography had demonstrated arterialization of the deep venous structures, including the vein of Galen. All patients were successfully treated with endovascular embolization, with 1 patient requiring additional surgical treatment. We review the contemporary diagnostic evaluation and management of DAVF within the deep cerebral vasculature. With rapid diagnosis and treatment, a favorable outcome is possible.
Intervent Neurol 2018;7:256–264

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Tiny architects: biogenesis of intracellular replicative niches by bacterial pathogens

Abstract

Co-evolution of bacterial pathogens with their hosts led to the emergence of a stunning variety of strategies aiming at the evasion of host defences, colonisation of host cells and tissues and, ultimately, the establishment of a successful infection. Pathogenic bacteria are typically classified as extracellular and intracellular, however intracellular lifestyle comes in many different flavours: some microbes rapidly escape to the cytosol whereas, other microbes remain within vacuolar compartments and harness membrane trafficking pathways to generate their host-derived, pathogen-specific replicative niche. Here we review the current knowledge on a variety of vacuolar lifestyles, the effector proteins used by bacteria as tools to take control of the host cell and the main membrane trafficking signalling pathways targeted by vacuolar pathogens as source of membranes and nutrients. Finally, we will also discuss how host cells have developed countermeasures to sense the biogenesis of the aberrant organelles harbouring bacteria. Understanding the dialogue between bacterial and eukaryotic proteins is the key to unravel the molecular mechanisms of infection and in turn, this may lead to the identification of new targets for the development of new antimicrobials.

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Expression and Purification of Biologically Active Recombinant Rabbit Monocyte Chemoattractant Protein1 in Escherichia coli

Abstract

Monocyte chemoattractant protein 1 (MCP1) with recruiting monocytes is an important factor at the beginning of inflammatory disorders such as atherosclerosis which seems its blocking preclude this process and help improvement of related diseases. To perform clinical research in this field, MCP1 protein is required but firstly, animal studies should be done. As the rabbit is a suitable model for many inflammatory disorders, and Escherichia coli BL21(DE3) (BL21) cell is a high-efficiency host for protein expression, we decided to produce recombinant rabbit MCP1 (rRMCP1) in BL21/pET28a system.After codon usage, a construct containing RMCP1 sequence was synthesized, cloned into the pET28a plasmid, and overexpressed in BL21 cells. Followed that, with changing expression condition such as cell concentration before the induction, time period, temperature, shaking rate and inducer concentration (IPTG), rRMCP1 expression was optimized, and purified by Ni-NTA. The biological activity of the expressed protein was verified using monocyte migration assay. Using this expression system, nearly 28 mg/mL rRMCP1 was produced at 26°C/180 rpm for 24 h in LB broth medium with 1 mM IPTG. Therefore, we were succeeded to express the intermediate level of rRMCP1 with this method. This amount of protein is sufficient for biological researches in the laboratory.

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Making point mutations in Escherichia coli BL21 genome using the CRISPR-Cas9 System

Abstract

The CRISPR-Cas9 system is an efficient and rapid tool for genome editing. However, its utilization in bacteria suffers challenges such as the risk of repeated recognition and cutting by Cas9. Here we established a two-step genome editing strategy using Streptococcus pyogenes CRISPR-Cas9 system to achieve a clean mutation with only the target sites into Escherichia coli genome. This strategy can avoid the risk of repeated cutting by gRNA/Cas9 without altering the PAM or inserting additional silent mutations into the genome. The principles and approaches we developed in this study can be applied to modify coding and non-coding sequences in essential and non-essential genes and can also be used for precise genome editing in other microorganisms.

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Hyperchloraemia in sepsis

Chloride represents—quantitatively—the most prevalent, negatively charged, strong plasma electrolyte. Control of chloride concentration is a probable major mechanism for regulating the body's acid–base balance...

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Nucleated red blood cells as predictors of mortality in patients with acute respiratory distress syndrome (ARDS): an observational study

Nucleated red blood cells (NRBCs) in critically ill patients are associated with increased mortality and poor outcome. The aim of the present study was to evaluate the predictive value of NRBCs in patients wit...

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In-hospital and day-120 survival of critically ill solid cancer patients after discharge of the intensive care units: results of a retrospective multicenter study—A Groupe de recherche respiratoire en réanimation en Onco–Hématologie (Grrr-OH) study

To assess outcomes at hospital discharge and day-120 after intensive care unit (ICU) discharge among patients with solid cancer admitted to ICU and to identify characteristics associated with in-hospital and d...

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Mullerianosis of the Urinary Bladder: A Case Report

Mullerianosis is a rare entity consisting of an admixture of 2 or more of the following tissues: endometriosis, endocervicosis, and endosalpingiosis. It most commonly affects the urinary bladder and affects females of fertile age. It presents clinically as hematuria, dysuria, and pelvic pain which may be associated with menstruation. Radiologically and macroscopically, it typically presents as a polypoid mass in the dome or posterior wall of the bladder. Histologically, it consists of glands of varying size lined by endometrial, endocervical, or tubal epithelium. Mullerianosis clinically and histologically mimics other benign and malignant lesions. Herein we report a case of mullerianosis of the urinary bladder. This is a rare lesion with less than 20 cases reported in the literature thus far. We believe raising awareness of this poorly recognized entity is of utmost significance in order to avoid misdiagnosis and the following unnecessary radical procedures.
Case Rep Oncol 2018;11:206–211

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Gemcitabine-Induced Radiation Recall Myositis: Case Report and Review of the Literature

Gemcitabine-induced radiation recall (GIRR) is a phenomenon wherein the administration of gemcitabine induces an inflammatory reaction within an area of prior radiation. We present the case of a 39-year-old female patient with metastatic breast cancer who experienced GIRR myositis 3 months following postoperative radiotherapy, with additional potential paraspinal myositis following ablative radiotherapy to the thoracic spine. A review of previously published cases of GIRR myositis was performed. The case and literature review describe the clinical course and presentation of GIRR, and highlight the importance of including radiation recall as part of a differential diagnosis when a patient undergoing chemotherapy experiences an inflammatory reaction at a prior site of radiation.
Case Rep Oncol 2018;11:168–178

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Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors

Mitotic counts in the World Health Organization (WHO) grading system have narrow cutoff values. True mitotic figures, however, are not always distinguishable from apoptotic bodies and darkly stained nuclei, complicating the ability of the WHO grading system to diagnose well-differentiated neuroendocrine tumors (NETs). The mitosis-specific marker phosphohistone H3 (PHH3) can identify true mitoses and grade tumors reliably. The aim of this study was to investigate the correspondence of tumor grades, as determined by PHH3 mitotic index (MI) and mitotic counts according to WHO criteria, and to determine the clinically relevant cutoffs of PHH3 MI in rectal and nonrectal gastrointestinal NETs. Mitotic counts correlated with both the Ki-67 labeling index and PHH3 MI, but the correlation with PHH3 MI was slightly higher. The PHH3 MI cutoff ≥4 correlated most closely with original WHO grades for both rectal NETs. A PHH3 MI cutoff ≥4, which could distinguish between G1 and G2 tumors, was associated with disease-free survival in patients with rectal NETs, whereas that cutoff value showed marginal significance for overall survival in patient with rectal NETs. In conclusion, the use of PHH3 ≥4 correlated most closely with original WHO grades.

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The Effect of C-Arm Mobility and Field of Vision on Radiation Exposure in the Treatment of Proximal Femoral Fractures: A Randomized Clinical Trial

Objectives. To examine the effect of fluoroscopy devices with different sizes of image intensifier and C-arm maneuverability on operating time, fluoroscopy time, radiation dose and reduction, and fixation quality at intertrochanteric femoral fractures. Design. Single-center, randomized, prospective study. Setting. Academic Level I trauma hospital. Patients and Intervention. 34 patients treated with cephalomedullary nailing for a stable, intertrochanteric proximal femur fracture (OTA A1). Main Outcome Measurement. The total working time of the fluoroscopy device, the dose-area product (DAP), operating time, reduction quality (cortical continuity, symmetrical collodiaphyseal angle, and shortness), and fixation quality (Bosworth quadrants, the tip-apex distance, TAD). Results. There were no cases of poor reduction; also the placement of the blade was optimal for 14 patients and suboptimal in 3 patients in each group. Superior-posterior placement of the blade or TAD > 25 mm was not seen in any patient. Total operating time was significantly shorter when using device A compared to the use of device B ( mins versus  mins, ). Total radiation time was significantly shorter with device A compared to the use of device B ( secs versus  secs, ). The measured radiation dose was lower with the use of device A compared to device B ( Gy·cm2 versus  Gy·cm2, ). Conclusion. Physical properties of fluoroscopy devices used during the fixation of intertrochanteric fractures could yield significant differences in operating times and the radiation dose while having comparable clinical results.

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Healthcare-associated fungal outbreaks: New and uncommon species, New molecular tools for investigation and prevention

Outbreaks of healthcare-associated fungal infections have repeatedly been described over recent years, often caused by new or uncommon species. Candida auris, a recently described multidrug-resistant yeast specie...

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Forging Military Partnerships to Empower the Cancer Research Enterprise

Partnerships and collaborations are an important component of NCI's success. NCI Director Dr. Norman Sharpless describes three efforts made possible by a memorandum of agreement with three US military institutions: the APOLLO network, NAVIGATE, and BD-STEP.

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Clinical characteristics and management of gastric tube cancer after esophagectomy

Abstract

Background

Gastric cancer is the second most common malignancy, overlapping with thoracic esophageal cancer (TEC). Among them, metachronous gastric tube cancers after TEC surgery have been increasing. The aims of this study were to examine the clinicopathological factors and treatment outcomes of gastric tube cancer (GTC) after TEC surgery.

Methods

Thirty-three GTCs in 30 cases after TEC treated between 1997 and 2016 were investigated retrospectively.

Results

Most cases were males. The median interval from TEC surgery to GTC occurrence was 57 (6.5–107.5) months. Almost 2/3 lesions occurred in the lower third of the gastric tube (21/33); 29 lesions (in 26 cases) were superficial cancers, and 4 lesions were advanced cancers. Twenty-two lesions of superficial cancer were differentiated type, and the remaining seven lesions were undifferentiated type. Treatment for superficial cancer had previously been performed with partial gastric tube resection (10 lesions), and the number of cases undergoing endoscopic submucosal dissection (ESD) had increased recently (19 lesions). Most cases with superficial cancer survived without relapse. Four lesions of advanced cancer were found after a relatively long interval following TEC surgery. Most lesions of advanced cancer were scirrhous, undifferentiated type, and they died due to GTC.

Conclusion

GTCs may occur late in the postoperative course following TEC surgery. If they are discovered at an early stage, these lesions can be cured with ESD. Long-term periodic endoscopic examinations after TEC surgery are important.

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Cancers, Vol. 10, Pages 92: Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene

Cancers, Vol. 10, Pages 92: Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene

Cancers doi: 10.3390/cancers10040092

Authors: Mario Monaco Giuseppe Palma Michela Vitiello Anna Capiluongo Barbara D'Andrea Emilia Vuttariello Antonio Luciano Laura Cerchia Gennaro Chiappetta Claudio Arra Alfredo Fusco Monica Fedele

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is an emerging cancer-related gene that is downregulated in different human malignancies, including thyroid cancer, where its levels gradually decrease going from papillary thyroid carcinomas (PTC) to poorly differentiated and undifferentiated highly aggressive anaplastic carcinomas (ATC). The restoration of PATZ1 expression in thyroid cancer cells reverted their malignant phenotype by inducing mesenchymal-to-epithelial transition, thus validating a tumor suppressor role for PATZ1 and suggesting its involvement in thyroid cancer progression. Here, we investigated the consequences of the homozygous and heterozygous loss of PATZ1 in the context of a mouse modeling of PTC, represented by mice carrying the RET/PTC1 oncogene under the thyroid specific control of the thyroglobulin promoter RET/PTC1 (RET/PTC1TG). The phenotypic analysis of RET/PTC1TG mice intercrossed with Patz1-knockout mice revealed that deficiency of both Patz1 alleles enhanced thyroid cancer incidence in RET/PTC1TG mice, but not the heterozygous knockout of the Patz1 gene. However, both RET/PTC1TG;Patz1+/− and RET/PTC1TG;Patz1−/− mice developed a more aggressive thyroid cancer phenotype—characterized by higher Ki-67 expression, presence of ATCs, and increased incidence of solid variants of PTC—than that shown by RET/PTC1TG; Patz1+/+ compound mice. These results confirm that PATZ1 downregulation has a critical role in thyroid carcinogenesis, showing that it cooperates with RET/PTC1 in thyroid cancer progression.

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Backtracking-based dynamic programming for resolving transmit ambiguities in WSN localization

The complexity of agent localization increases significantly when unique identification of the agents is not possible. Corresponding application cases include multiple-source localization, in which the agents ...

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Pediatric Langerhans cell histiocytosis of the temporal bone: clinical and imaging studies of 27 cases

Abstract

Background

We aimed to evaluate the clinical and imaging presentations of Langerhans cell histiocytosis (LCH) in the pediatric temporal bone.

Methods

This retrospective study included 27 pediatric cases with pathological confirmed LCH of the temporal bone. The clinical and imaging features of the cases were analyzed. The involvement of ossicular chain and otic capsule was also evaluated.

Results

A total of 38 lesions (27 cases) with 11 bilateral involvement were identified. For the 27 cases, the most common complaint was periauricular swelling (12/27, 44.4%), followed by otorrhea (9/27, 33.3%) and otalgia (5/27, 18.2%). The mastoid process was the most common involved subsite (31/38, 81.6%) among the 38 lesions. Ten (26.3%, 10/38) lesions belonged to the group of the diffuse involvement, 22 (57.9%, 22/38) were divided into the group of partial involvement and six (15.8%,6/38) localized lesions with punched-out appearance. Erosion of ossicular chains and otic capsule were found in three and seven lesions respectively.

Conclusion

The results indicate that the most common subsite for LCH of the pediatric temporal bone was the mastoid process. The location and extent of pediatric LCH of the temporal bone varied a lot between each other. The ossicular chains usually remain intact and the erosion of otic capsule can occur in some lesions.

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Prevalence and reasons for intentional use of complementary and alternative medicine as an adjunct to future visits to a medical doctor for chronic disease

Intentional use of complementary and alternative medicine (CAM) has previously only been researched in small, possibly biased, samples. There seems to be a lack of scientific information regarding healthy indi...

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Highly water pressurized brown rice improves cognitive dysfunction in senescence-accelerated mouse prone 8 and reduces amyloid beta in the brain

Alzheimer's disease (AD) is the most common form of dementia and the number of AD patients continues to increase worldwide. Components of the germ layer and bran of Brown rice (BR) help maintain good health an...

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South African medicinal plant extracts active against influenza A virus

Influenza infection remains a major health threat for animals and humans which crucially requires effective antiviral remedies. The usage of herbal medications as readily available alternatives for their compa...

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Species identification approach for both raw materials and end products of herbal supplements from Tinospora species

Nowadays herbal products used in traditional medicine are sold in processed forms and thus morphological authentication is almost impossible. With herbal industry rapidly growing size, consumer safety becomes ...

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Updated frequency analysis of spinocerebellar ataxia in China

Sir,

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The anti-tumor efficacy of CDK4/6 inhibition is enhanced by the combination with PI3K/AKT/mTOR inhibitors through impairment of glucose metabolism in TNBC cells

Abstract

Background

Cell cycle regulators have gain attention as potential targets for anticancer therapy. Palbociclib is a selective inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6), which coordinate the G1-S transition. Palbociclib is currently approved for the treatment of hormone receptor positive, HER2-negative advanced breast cancer (BC) in association with letrozole or fulvestrant. In contrast, its efficacy in triple negative BC (TNBC), either alone or in combined therapies, has not been fully investigated to date.

Methods

Here we evaluated the potential of combining palbociclib with PI3K/mTOR inhibitors in Rb-proficient TNBC cells comparing different schedules of treatment: simultaneous, sequential, or sequential combined treatment (pre-incubation with palbociclib followed by exposure to both palbociclib and PI3K/mTOR inhibitors). We assessed the effects on cell proliferation, cell death, and cell cycle distribution, and looked at the impact of such treatments on glucose metabolism.

Results

Palbociclib exerted cytostatic effects in Rb-positive TNBC cells, inducing a reversible blockade in G0/G1 cell cycle phase associated with down-regulation of CDK6, Rb, and c-myc expression and/or activity. Palbociclib treatment induced AKT signaling, providing a rationale for its combination with PI3K/mTOR inhibitors. The simultaneous or sequential treatment resulted in an additive inhibition of cell proliferation. On the other hand, the sequential combined treatment in which palbociclib was maintained also during exposure to PI3K/mTOR inhibitors gave rise to synergistic anti-proliferative and pro-apoptotic effects, by inhibiting both CDK4/6/Rb/myc and PI3K/mTOR signaling. Interestingly, the inhibition of the Rb/E2F/myc axis mediated by palbociclib resulted in a significant down-regulation of glucose metabolism; most importantly, these inhibitory effects were enhanced by the combination of palbociclib with BYL719 (specific inhibitor of the p110α PI3K-subunit), which promoted a stronger inhibition of GLUT-1 glucose transporter expression, glucose uptake and consumption in comparison with individual treatments, under both normoxic and hypoxic conditions.

Conclusions

Combination of palbociclib with PI3K/mTOR inhibitors may represent a promising therapeutic option for the treatment of Rb-proficient TNBC, with the sequential combined schedule showing a superior efficacy over the other schedules. In addition our results demonstrate that the impairment of glucose metabolism may contribute to the anti-tumor activity of such drug combinations.

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miR-148b-3p inhibits gastric cancer metastasis by inhibiting the Dock6/Rac1/Cdc42 axis

Abstract

Background

Our previous work showed that some Rho GTPases, including Rho, Rac1 and Cdc42, play critical roles in gastric cancer (GC); however, how they are regulated in GC remains largely unknown. In this study, we aimed to investigate the roles and molecular mechanisms of Dock6, an atypical Rho guanine nucleotide exchange factor (GEF), in GC metastasis.

Methods

The expression levels of Dock6 and miR-148b-3p in GC tissues and paired nontumor tissues were determined by immunohistochemistry (IHC) and in situ hybridization (ISH), respectively. The correlation between Dock6/miR-148b-3p expression and the overall survival of GC patients was calculated by the Kaplan-Meier method and log-rank test. The roles of Dock6 and miR-148b-3p in GC were investigated by in vitro and in vivo functional studies. Rac1 and Cdc42 activation was investigated by GST pull-down assays. The inhibition of Dock6 transcription by miR-148b-3p was determined by luciferase reporter assays.

Results

A significant increase in Dock6 expression was found in GC tissues compared with nontumor tissues, and its positive expression was associated with lymph node metastasis and a higher TNM stage. Patients with positive Dock6 expression exhibited shorter overall survival periods than patients with negative Dock6 expression. Dock6 promoted GC migration and invasion by increasing the activation of Rac1 and Cdc42. miR-148b-3p expression was negatively correlated with Dock6 expression in GC, and it decreased the motility of GC cells by inhibiting the Dock6/Rac1/Cdc42 axis.

Conclusions

Dock6 was over-expressed in GC tissues, and its positive expression was associated with GC metastasis and indicated poor prognosis of GC patients. Targeting of Dock6 by miR-148b-3p could activate Rac1 and Cdc42, directly affecting the motility of GC cells. Targeting the Dock6-Rac1/Cdc42 axis could serve as a new therapeutic strategy for GC treatment.

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The Crus exhibits stronger functional connectivity with executive network nodes than with the default mode network

Sir,

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Reply: The Crus exhibits stronger functional connectivity with executive network nodes than with the default mode network

Sir,

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From the Archives

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The value of oligoclonal bands in the multiple sclerosis diagnostic criteria

Abstract

The presence of oligoclonal bands in clinically isolated syndromes is an independent risk factor for developing multiple sclerosis and has been largely excluded from the more recent multiple sclerosis diagnostic criteria. Therefore, our objective was to explore the value of oligoclonal bands in the context of the 2010 McDonald criteria, especially in patients fulfilling exclusively dissemination in space at baseline. For this purpose, we selected 566 patients from a clinically isolated syndrome inception cohort who had IgG oligoclonal bands determination and sufficient data on baseline brain MRI to assess dissemination in space and time. We excluded the cases already fulfilling both dissemination in space and time and divided the remaining 398 into 'no dissemination in space and time' (n = 218), 'dissemination in space' (n = 164) and 'dissemination in time' (n = 16). We assessed Cox proportional hazards regression models with 2010 McDonald as the outcome, using 'no dissemination in space and time' with 0 lesions and negative oligoclonal bands as the reference for different subgroups according to oligoclonal bands status (positive/negative). To assess the diagnostic properties, we selected cases with a follow-up ≥3 years or fulfilling 2010 McDonald within 3 years of the clinically isolated syndrome (n = 314), and compared the performance of all 'dissemination in space' cases (n = 137) versus patients with 'dissemination in space' and positive oligoclonal bands (n = 101). The remaining patients classified as fulfilling 'dissemination in time' or 'no dissemination in space and time' were taken into account to calculate the diagnostic properties. The respective adjusted hazard ratios (95% confidence interval) were 1.5 (0.4–5.7) for 'no dissemination in space and time' with 0 lesions and positive oligoclonal bands, 3.1 (1.4–7.2) for 'no dissemination in space and time' with ≥1 lesions and negative oligoclonal bands, 7.4 (3.5–15.7) for 'no dissemination in space and time' with ≥1 lesions and positive oligoclonal bands, 10.4 (4.8–22.6) for 'dissemination in space' with negative oligoclonal bands, 15.3 (7.5–31.3) for 'dissemination in space' with positive oligoclonal bands, and 9.1 (3.5–23.4) for 'dissemination in time' (not subdivided due to the sample size). The specificity for all cases with 'dissemination in space' was 80.6 and increased to 88.1 after selecting those with positive oligoclonal bands. According to these results, we propose radiological dissemination in space at any time plus positive oligoclonal bands as an additional criterion for diagnosing multiple sclerosis.

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Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer’s disease

Abstract

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.

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Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome

Abstract

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

https://ift.tt/2pKzTjl

Condition-dependent generation of aquaporin-4 antibodies from circulating B cells in neuromyelitis optica

Abstract

Autoantibodies to aquaporin-4 (AQP4) are pathogenic in neuromyelitis optica spectrum disorder (NMOSD). However, it is not known which B cells are the major contributors to circulating AQP4 antibodies nor which conditions promote their generation. Our experiments showed CD19⁺CD27⁺⁺CD38⁺⁺ circulating ex vivo antibody-secreting cells did not produce AQP4 antibodies under several culture conditions. To question whether other cells in circulation were capable of AQP4 antibody production, B cells were differentiated into antibody-secreting cells in vitro. Unfractionated peripheral blood mononuclear cells, isolated from 12 patients with NMOSD and a wide range of serum AQP4 antibody levels (91–26 610 units), were cultured with factors that mimicked established associations of NMOSD including T cell help, concurrent infections and cytokines reported to be elevated in NMOSD. Overall, the in vitro generation of CD19⁺CD27⁺⁺CD38⁺⁺ cells across several culture conditions correlated closely with the total IgG secreted (P < 0.0001, r = 0.71), but not the amount of AQP4 antibody. AQP4 antibody production was enhanced by CD40-ligand (P = 0.005), and by interleukin-2 plus toll-like receptor stimulation versus interleukin-21-predominant conditions (P < 0.0001), and did not require antigen. Across NMOSD patients, this in vitro generation of AQP4 antibodies correlated well with serum AQP4 antibody levels (P = 0.0023, r = 0.81). To understand how early within B cell lineages this AQP4 specificity was generated, purified B cell subsets were activated under these optimized conditions. Naïve pre-germinal centre B cells (CD19⁺CD27⁻IgD⁺) differentiated to secrete AQP4 antibodies as frequently as post-germinal centre cells (CD19⁺CD27⁺). Taken together, these human cell-culture experiments demonstrate that preformed B cells, rather than ex vivo circulating antibody-secreting cells, possess AQP4 reactivity. Their differentiation and AQP4 antibody secretion is preferentially driven by select cytokines and these cells may make the dominant contribution to serum AQP4 antibodies. Furthermore, as AQP4-specific B cells can derive from likely autoreactive naïve populations an early, pre-germinal centre loss of immunological tolerance appears present in some patients with NMOSD. This study has implications for understanding mechanisms of disease perpetuation and for rational choice of immunotherapies in NMOSD. Furthermore, the in vitro model presents an opportunity to apply condition-specific approaches to patients with NMOSD and may be a paradigm to study other antibody-mediated diseases.awy010media15732448284001

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