Global gene expression profiles of hematopoietic stem and progenitor cells from patients with chronic myeloid leukemia: the effect of in vitro culture with or without imatinib

Abstract

In this study, we determined the gene expression profiles of bone marrow-derived cell fractions, obtained from normal subjects and Chronic Myeloid Leukemia (CML) patients, that were highly enriched for hematopoietic stem (HSCs) and progenitor (HPCs) cells. Our results indicate that the profiles of CML HSCs and HPCs were closer to that of normal progenitors, whereas normal HSCs showed the most different expression profile of all. We found that the expression profiles of HSCs and HPCs from CML marrow were closer to each other than those of HSCs and HPCs from normal marrow. The major biologic processes dysregulated in CML cells included DNA repair, cell cycle, chromosome condensation, cell adhesion, and the immune response. We also determined the genomic changes in both normal and CML progenitor cells under culture conditions, and found that several genes involved in cell cycle, steroid biosynthesis, and chromosome segregation were upregulated, whereas genes involved in transcription regulation and apoptosis were downregulated. Interestingly, these changes were the same, regardless of the addition of Imatinib (IM) to the culture. Finally, we identified three genes—PIEZO2, RXFP1, and MAMDC2- that are preferentially expressed by CML primitive cells and that encode for cell membrane proteins; thus, they could be used as biomarkers for CML stem cells.

Gene expression profiles of hematopoietic stem and progenitor cells from CML patients have been obtained. The in vitro effect of Imatinib on such gene expression profiles was assessed. Potential leukemic biomarker genes were identified.

http://ift.tt/2yKkaIa

Phosphorylated ERK is a potential prognostic biomarker for Sorafenib response in hepatocellular carcinoma

Abstract

Sorafenib, the only approved drug for hepatocellular carcinoma, acts as a remarkable inhibitor of Raf serine-threonine kinases. However, Sorafenib is expensive, and clinical experience shows that it is not an effective treatment for many patients. Previous study has demonstrated that phosphorylated ERK (pERK) is a key downstream component in the RAF/MEK/ERK signaling pathway. Here, we investigate whether pERK is a useful biomarker for treating HCC with Sorafenib. In vitro cell viability assays showed that the efficacy of Sorafenib was distinctly different according to the level of pERK. Furthermore, in established patient-derived xenografts from HCC specimens, we found that the growth rate of tumors with high levels of pERK was significantly decreased by Sorafenib treatment. Taken together, pERK is a potential biomarker for the sensitivity to Sorafenib in treating HCC.

In hepatocellular carcinoma (HCC), the efficacy of Sorafenib remains moderate and certain patients display a short period of survival following treatment. Our vitro and in vivo results revealed the relationship between the expression of phosphorylated ERK (pERK) and Sorafenib response in HCC. We confirmed that tumors containing higher levels of pERK are more sensitive to Sorafenib. pERK may be a useful biomarker in treating HCC with Sorafenib.

http://ift.tt/2hGFUcU

The role of general psychosocial factors for the use of cancer screening—Findings of a population-based observational study among older adults in Germany

Abstract

Within the framework of the health-belief model, some studies exist investigating the association between illness-specific psychosocial factors and the use of cancer screenings. However, studies investigating the association between general psychosocial factors and the use of cancer screenings are missing. Thus, this study aimed at examining the association between well-established general psychosocial factors and the use of cancer screenings. Data were gathered from a large, population-based sample of community-dwelling individuals aged 40 and above in Germany (n = 7673; in 2014). Loneliness, cognitive well-being, affective well-being (negative and positive affect), optimism, self-efficacy, self-esteem, self-regulation, perceived autonomy, perceived stress, and perceived social exclusion were used as general psychosocial factors. Furthermore, individuals were asked whether they regularly underwent early cancer screening in the past years (yes; no). A total of 65.6% of the individuals used cancer screening. Adjusting for sociodemographic factors, self-rated health, morbidity and lifestyle factors, multiple logistic regressions revealed that the use of cancer screening is positively associated with decreased loneliness, cognitive well-being, optimism, self-efficacy, self-esteem, self-regulation, perceived autonomy, decreased perceived stress, decreased perceived social exclusion, and positive affect, while it is not associated with negative affect. This study stresses the strong association between general psychosocial factors and the use of cancer screening. This knowledge might be fruitful to address individuals at risk for underuse.

http://ift.tt/2yKk830

Identification and characterization of a metastatic suppressor BRMS1L as a target gene of p53

Summary

The tumor suppressor p53 and its family members, p63 and p73, play a pivotal role in the cell fate determination in response to diverse upstream signals. As transcription factors, p53 family proteins regulate a number of genes that are involved in cell-cycle arrest, apoptosis, senescence, and maintenance of genomic stability. Recent studies revealed that p53 family proteins are important for the regulation of cell invasion and migration. Microarray analysis showed that breast cancer metastasis-suppressor 1- like (BRMS1L) is upregulated by p53 family proteins, specifically p53, TAp63γ, and TAp73β. We identified two responsive elements of p53 family proteins in the first intron and upstream of BRMS1L. These response elements are well conserved among mammals. Functional analysis showed that ectopic expression of BRMS1L inhibited cancer cell invasion and migration; knockdown of BRMS1L by siRNA induced the opposite effect. Importantly, clinical databases revealed that reduced BRMS1L expression correlated with poor prognosis in patients with breast and brain cancer. Altogether, these results strongly indicate that BRMS1L is one of the mediators downstream of the p53 pathway, and inhibits cancer cell invasion and migration, which are essential steps in cancer metastasis. Collectively, our results demonstrate that BRMS1L is involved in cancer cell invasion and migration, and may be a therapeutic target for cancer.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zmKmpa

Halofuginone improves caustic-induced oxidative injury of esophagus in rats

Abstract

Background

The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats.

Materials and methods

Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1 ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100 µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2 cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity.

Results

GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone.

Conclusion

In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.

http://ift.tt/2iayOBe

The Burden of Hospital Readmissions among Pediatric Patients with Inflammatory Bowel Disease

To evaluate the burden and predictors of hospital readmissions among pediatric patients with inflammatory bowel disease using the Nationwide Readmissions Database.

http://ift.tt/2yiFFPT

Salivary Cortisol Levels Predict Therapeutic Response to a Sleep-Promoting Method in Children with Postural Tachycardia Syndrome

To determine the value of salivary cortisol concentrations in predicting the efficacy of sleep-promoting treatment in children with postural tachycardia syndrome (POTS).

http://ift.tt/2g9Fvj7

Ventricular Performance is Associated with Need for Extracorporeal Membrane Oxygenation in Newborns with Congenital Diaphragmatic Hernia

To compare echocardiography (ECHO) findings of patients with congenital diaphragmatic hernia (CDH) who required extracorporeal membrane oxygenation (ECMO) to non-ECMO treated patients.

http://ift.tt/2g7WFNG

Can Multidetector Computed Tomography Rule Out Left Atrial Thrombus in Patients With Atrial Fibrillation?

Fifteen prospective studies met inclusion criteria, with a total of 2,540 patients, for whom 8 studies obtained delayed-phase images, 11 studies obtained ECG-gated images, 9 studies achieved pulse rates lower than 70 beats/min, and only 5 studies had a combination of all 3 characteristics: ECG gating, pulse rate control, and delayed-phase imaging. Studies were reported to be of high quality (all included studies having Quality Assessment of Diagnostic Accuracy Studies score >10), and statistical heterogeneity in the delayed-phase imaging group was low.

http://ift.tt/2yKkkiS

A Comparison of Headache Treatment in the Emergency Department: Prochlorperazine Versus Ketamine

Intravenous subdissociative-dose ketamine has been shown to be effective for pain management, but has not been specifically studied for headaches in the emergency department (ED). For this reason, we designed a study to compare standard treatment (prochlorperazine) with ketamine in patients with benign headaches in the ED.

http://ift.tt/2hG2Fhn

Acetaminophen or Nonsteroidal Anti-Inflammatory Drugs in Acute Musculoskeletal Trauma: A Multicenter, Double-Blind, Randomized, Clinical Trial

We determine whether pain treatment with acetaminophen was not inferior to nonsteroidal anti-inflammatory drugs or the combination of both in minor musculoskeletal trauma.

http://ift.tt/2yJoc3A

Pembrolizumab May Be Beneficial in a Subset of Soft-Tissue Sarcomas [Research Watch]

Anti–PD-1 therapy with pembrolizumab achieved responses in 18% of patients with soft-tissue sarcoma.

http://ift.tt/2xEA01Z

Keap1 Loss Drives Kras-Mutant Lung Cancer and Glutaminolysis Dependency [Research Watch]

Loss of Keap1 hyperactivates NRF2 to induce glutaminolysis-dependent Kras-driven lung cancer.

http://ift.tt/2yndY7x

BRCA1-BARD1 Activates RAD51 for DNA Repair by Homologous Recombination [Research Watch]

BRCA1–BARD1 binds to RAD51 to enhance its activity in the promotion of homologous DNA pairing.

http://ift.tt/2xELF0J

EGFR Ligands Have Differential Effects on Dimer Stability and Signaling [Research Watch]

EREG and EPGN induce weak EGFR dimerization but sustained signaling compared with EGF.

http://ift.tt/2ynahPb

Lactate Fuels the TCA Cycle in Non-Small Cell Lung Cancer [Research Watch]

In many patients with NSCLC, lactate is a major fuel source for the tumor TCA cycle.

http://ift.tt/2xEzYan

Cell-cycle and DNA-damage response pathway is involved in leptomeningeal metastasis of non-small cell lung cancer

Purpose: Leptomeningeal metastases (LM) is a detrimental complication of non-small cell lung cancer (NSCLC) and associated with poor prognosis. However, the underlying mechanisms of the metastasis process are still poorly understood. Experimental Design: We performed next-generation panel sequencing of primary tumor tissue, cerebrospinal fluid (CSF) and matched normal controls from epidermal growth factor receptor (EGFR) mutation-positive NSCLC patients with LM. Results: The status of EGFR activating mutations was highly concordant between primary tumor and CSF. PIK3CA aberrations were high in these patients, implicating an association with LM risk. Intriguingly, low overlapping of somatic protein-changing variants was observed between paired CSF and primary lesions, exhibiting tumor heterogeneity and genetic divergence. Moreover, genes with CSF-recurrent genomic alterations were predominantly involved in cell-cycle regulation and DNA damage response (DDR), suggesting a role of the pathway in LM development. Conclusions: Our study has shed light on the genomic variations of NSCLC-LM, demonstrated genetic heterogeneity and divergence, uncovered involvement of cell-cycle and DDR pathway, and paved the way for potential therapeutic approaches to this unmet medical need.

http://ift.tt/2ghMfz2

RAD50 expression is associated with poor clinical outcomes after radiotherapy for resected non-small cell lung cancer

Purpose: Although postoperative radiotherapy is often used to maintain local control after surgical resection and chemotherapy for locally advanced non-small cell lung cancer (NSCLC), both locoregional failure and distant metastasis remain problematic.  The mechanisms of therapeutic resistance remain poorly understood.    Experimental Design: We used reverse-phase protein arrays (RPPAs) to profile the baseline expression of 170 total and phosphorylated proteins in 70 NSCLC cell lines to categorize pathways that may contribute to radiation resistance. Significant markers identified by RPPA were further analyzed in tissue microarrays (TMAs) of specimens from 127 patients with NSCLC who had received surgery before receiving postoperative radiotherapy. Cox regression analysis and log-rank tests were used to identify potential predictive factors. We then validated the biological function of the markers in NSCLC cell lines in vitro. Results: Of the 170 proteins or phospho-proteins profiled, a subset of 12 proteins was found to correlate with radiation response parameters. TMA analysis of the 12 proteins showing the greatest differences in expression in the RPPA analysis demonstrated that RAD50 had the strongest correlation with distant relapse-free survival, locoregional relapse-free survival, and disease-free survival in patients with NSCLC. We confirmed that knockdown of RAD50 sensitized NSCLC cells to radiation and that upregulation of RAD50 increased radioresistance in in vitro experiments. Conclusion: Upregulated RAD50 may be a predictor of radioresistance in patients with lung cancer who received radiotherapy.

http://ift.tt/2ymUn81

Phase 1b/2 Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors

Purpose NC-6004, a novel cisplatin nanoparticle developed using micellar technology exhibits sustained release of cisplatin and selective distribution to tumors. Preclinical data demonstrated a favorable tolerability profile and preserved or improved anti-tumor activity compared to cisplatin across animal models. We evaluated the safety and tolerability of NC-6004 and gemcitabine using a Bayesian continual reassessment model (N-CRM) to determine the optimal dose. Experimental Design Patients with advanced solid tumors received NC-6004 at 60-180mg/m2 on Day 1 and gemcitabine at 1250 mg/m2 on Days 1 and 8 every three weeks. Dose escalation of NC-6004 began with a single patient run-in until a dose limiting toxicity occurred at 180mg/m2. Cohorts of four patients were enrolled at doses predicted by the N-CRM. The maximum tolerated dose (MTD) was defined as having the greatest probability of target toxicity < 25%. Quality of life was assessed using EORTC-QLQ-C30. Results Among 22 patients, the most common Grade 3/4 hematologic adverse events were leukopenia (68%) and thrombocytopenia (59%). Of 20 pretreated patients evaluable for response, half were previously exposed to a platinum agent. The MTD was 135 mg/m2. Nine patients were treated at the MTD with median treatment duration of 15 weeks (range, 3-50). Tumor shrinkage occurred in 11 (55%), partial responses in 3 (15%) and stable disease in 14 (70%). Most patients reported stable or improved EORTC QLQ-C30 scores. Conclusions Greater cisplatin equivalent doses were achieved with no clinically significant neuro-, oto- or nephrotoxicity. These data demonstrate tolerability and promising activity of NC-6004 in combination with gemcitabine.

http://ift.tt/2yiAfBG

APC/CFZR-1 Controls SAS-5 Levels To Regulate Centrosome Duplication in Caenorhabditis elegans

As the primary microtubule-organizing center, centrosomes play a key role in establishing mitotic bipolar spindles that secure correct transmission of genomic content. For the fidelity of cell division, centrosome number must be strictly controlled by duplicating only once per cell cycle. Proper levels of centrosome proteins are shown to be critical for normal centrosome number and function. Overexpressing core centrosome factors leads to extra centrosomes, while depleting these factors results in centrosome duplication failure. In this regard, protein turnover by the ubiquitin-proteasome system provides a vital mechanism for the regulation of centrosome protein levels. Here, we report that FZR-1, the Caenorhabditis elegans homolog of Cdh1/Hct1/Fzr, a co-activator of the anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, functions as a negative regulator of centrosome duplication in the Caenorhabditis elegans embryo. During mitotic cell division in the early embryo, FZR-1 is associated with centrosomes and enriched at nuclei. Loss of fzr-1 function restores centrosome duplication and embryonic viability to the hypomorphic zyg-1(it25) mutant, in part, through elevated levels of SAS-5 at centrosomes. Our data suggest that the APC/C^FZR-1 regulates SAS-5 levels by directly recognizing the conserved KEN-box motif, contributing to proper centrosome duplication. Together, our work shows that FZR-1 plays a conserved role in regulating centrosome duplication in Caenorhabditis elegans.

http://ift.tt/2iaOBAa

Innate sensing of cancer's non-immunologic hallmarks

Ruth Seelige | Stephen Searles | Jack D Bui

http://ift.tt/2yfChVF

Importance of PCR-based Tumor Testing in the Evaluation of Lynch Syndrome–associated Endometrial Cancer

Lynch syndrome (LS) is a hereditary cancer syndrome caused by a germline mutation in a DNA mismatch repair gene, usually MLH1, MSH2, MSH6, or PMS2. The most common cancers associated with LS are colorectal adenocarcinoma and endometrial carcinoma. Identification of women with LS-associated endometrial cancer is important, as these women and their affected siblings and children are at-risk of developing these same cancers. Germline testing of all endometrial cancer patients is not cost effective, and screening using young age of cancer diagnosis and/or presence of family history of syndrome-associated is underutilized and ineffective. Therefore, most groups now advocate for tumor tissue testing to screen for LS, with germline testing targeted to women with abnormal tissue testing results. Immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 is used in many clinical laboratories for this tumor screening step, as immunohistochemistry is relatively inexpensive and is technically more accessible for smaller clinical labs. PCR-based tissue testing, whereas technically more challenging, does play an important role in the identification of these patients. MLH1 methylation analysis identifies women with tumor MLH1 loss who likely have sporadic endometrial cancer and do not need heightened cancer prevention surveillance. High levels of microsatellite instability have been identified in tumors with retained positive expression of mismatch repair proteins. Somatic sequencing of mismatch repair genes from tumor DNA, whereas not currently available in most clinical laboratories, is helpful in resolution of cases in which germline sequencing fails to identify a mutation in a mismatch repair gene. The tumor tissue testing approach can help to identify most women at-risk for germline mutations in a LS gene, but not all patients will be captured using this approach. Clinical suspicion can still play a pivotal role in accurately identifying a subset of these patients.

http://ift.tt/2kNA3rc

Surgical Pathology of Gastrointestinal Stromal Tumors: Practical Implications of Morphologic and Molecular Heterogeneity for Precision Medicine

Gastrointestinal stromal tumor (GIST), the most common mesenchymal neoplasm of the gastrointestinal tract, exhibits diverse histologic and clinical manifestations. With its putative origin in the gastrointestinal pacemaker cell of Cajal, GIST can arise in association with any portion of the tubular gastrointestinal tract. Morphologically, GISTs are classified as spindled or epithelioid, though each of these subtypes encompasses a broad spectrum of microscopic appearances, many of which mimic other histologic entities. Despite this morphologic ambiguity, the diagnosis of GIST is aided in many cases by immunohistochemical detection of KIT (CD117) or DOG1 expression. The natural history of GIST ranges from that of a tumor cured by surgical resection to that of a locally advanced or even widely metastatic, and ultimately fatal, disease. This clinicopathologic heterogeneity is paralleled by an underlying molecular diversity: the majority of GISTs are associated with spontaneous activating mutations in KIT, PDGFRA, or BRAF, while additional subsets are driven by genetic lesions—often inherited—of NF1 or components of the succinate dehydrogenase enzymatic complex. Specific gene mutations correlate with particular anatomic or morphologic characteristics and, in turn, with distinct clinical behaviors. Therefore, prognostication and treatment are increasingly dictated not only by morphologic clues, but also by accompanying molecular genetic features. In this review, we provide a comprehensive description of the heterogenous molecular underpinnings of GIST, including implications for the practicing pathologist with regard to morphologic identification, immunohistochemical diagnosis, and clinical management.

http://ift.tt/2kObdrd

Epigenetic Alterations in Bone and Soft Tissue Tumors

Human malignancies are driven by heritable alterations that lead to unchecked cellular proliferation, invasive growth and distant spread. Heritable changes can arise from changes in DNA sequence, or, alternatively, through altered gene expression rooted in epigenetic mechanisms. In recent years, high-throughput sequencing of tumor genomes has revealed a central role for mutations in epigenetic regulatory complexes in oncogenic processes. Through interactions with or direct modifications of chromatin, these proteins help control the accessibility of genes, and thus the transcriptional profile of a cell. Dysfunction in these proteins can lead to activation of oncogenic pathways or silencing of tumor suppressors. Although epigenetic regulators are altered across a broad spectrum of human malignancies, they play a particularly central role in tumors of mesenchymal and neuroectodermal origin. This review will focus on recent advances in the understanding of the molecular pathogenesis of a subset of tumors in which alterations in the polycomb family of chromatin modifying complexes, the SWI/SNF family of nucleosome remodelers, and histones play a central role in disease pathogenesis. Although this review will focus predominantly on the molecular mechanisms underlying these tumors, each section will also highlight areas in which an understanding of the molecular pathogenesis of these diseases has led to the adoption of novel immunohistochemical and molecular markers.

http://ift.tt/2kNmgAP

Myxoid Mesenchymal Tumors of the Uterus: An Update on Classification, Definitions, and Differential Diagnosis

Tumors with a predominant myxoid stroma are rare in the uterus. When encountered, however, they pose a diagnostic challenge. Traditionally myxoid leiomyosarcoma has been the most important consideration in this category, given its adverse prognosis and deceptively bland morphology. Conventional features of malignancy are variably present; in contrast, an infiltrative tumor border is a consistent pathologic characteristic. More recently, previously under-recognized lesions have been identified, in part due to our growing knowledge of their underlying molecular alterations: uterine inflammatory myofibroblastic tumor frequently harbors ALK rearrangements and a novel ZC3H7B-BCOR gene fusion has been described in a subset of myxoid high-grade endometrial stromal sarcomas. These tumors need to be distinguished from myxoid leiomyosarcoma, as by comparison have a less aggressive course and are amenable to targeted treatments. In addition, uterine mesenchymal tumors with malignant potential need to be distinguished from benign tumors and epithelial and mixed malignancies. This review aims to discuss our current understanding of the most common uterine myxoid neoplasms: their clinical features, their distinguishing histopathologic, immunohistochemical, and molecular features and the clues and pitfalls in their diagnosis.

http://ift.tt/2kNmecb

If it is Not a Glioblastoma, Then What is it? A Differential Diagnostic Review

As its historical name glioblastoma multiforme implies, glioblastoma is a histologically diverse, World Health Organization grade IV astrocytic neoplasm. In spite of its simple definition of presence of vascular proliferation and/or necrosis in a diffuse astrocytoma, the wide variety of cytohistomorphologic appearances overlap with many other neoplastic or non-neoplastic lesions. Here, after a brief review of glioblastoma is provided, the differential diagnostic possibilities with an emphasis on mimics and pitfalls are discussed. To provide an approach applicable to diagnostic practice, these discussions are grouped arbitrarily according to general malignant appearance such as pleomorphic xanthoastrocytoma and ganglioglioma, especially their anaplastic versions, and cellular features such as small cell and epithelioid glioblastoma. Some non-neoplastic lesions that can potentially be mistaken for glioblastoma under certain circumstances are also briefly mentioned. Additional studies, including immunohistochemistry and molecular markers, are included where applicable. Otherwise, exhaustive review of these individual entities, including their epidemiology and molecular biology, is outside the scope of this discussion.

http://ift.tt/2kNmasX

Categorization of species based on their microRNAs employing sequence motifs, information-theoretic sequence feature extraction, and k-mers

Diseases like cancer can manifest themselves through changes in protein abundance, and microRNAs (miRNAs) play a key role in the modulation of protein quantity. MicroRNAs are used throughout all kingdoms and h...

http://ift.tt/2zmYFue

Wavelet coherence analysis: a new approach to distinguish organic and functional tremor types

Tremor is the most common neurological movement disorder (Louis and Ferreira 2010), with Parkinsonian tremor (PT), functional tremor (FT), essential tremor (ET), and enhanced physiological tremor (EPT) as the most common types. Distinguishing tremor types is important as it determines treatment options and prognosis (Gupta and Lang 2009).

http://ift.tt/2xEqrFk

Non–Clostridium difficile Bacterial Infections Are Rare in Patients With Flares of Inflammatory Bowel Disease

Clostridium difficile infection (CDI) causes flares in patients with inflammatory bowel disease (IBD). We investigated the frequency and outcomes of non-CDI bacterial enteric infections in symptomatic patients with IBD.

http://ift.tt/2xEgQt0

Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy

Poorly-differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly-differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports and pathology slides were reviewed for demographics, clinical history and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1 and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas.

http://ift.tt/2hFaB2k

DNA-methylation profiling discloses significant advantages over NanoString method for molecular classification of medulloblastoma

http://ift.tt/2ynoImT

Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis

Abstract

In search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi–Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequencing, we identified novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the germline of familial glioma patients as well as in test and validation cohorts of glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby rare RNASEH2B variants were significantly more frequent in familial glioma patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS, such as calcification and increased type I interferon expression. Patients carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG expression was also induced by ADAR and RNASEH2B variants in tumor cells and was blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development.

http://ift.tt/2gfvunU

Balneotherapeutic effects of high mineral spring water on the atopic dermatitis-like inflammation in hairless mice via immunomodulation and redox balance

Atopic dermatitis (AD) is a chronic relapsing allergic inflammatory skin disease that currently affects millions of children and adults worldwide. Drugs used to treat these inflammatory diseases include anti-h...

http://ift.tt/2yg3DLB

Potential impact of global climate change on benthic deep-sea microbes

Abstract

Benthic deep-sea environments are the largest ecosystem on Earth, covering approximately 65% of the Earth surface. Microbes inhabiting this huge biome at all water depths represent the most abundant biological components and a relevant portion of the biomass of the biosphere, and play a crucial role in global biogeochemical cycles. Increasing evidence suggests that global climate changes are affecting also deep-sea ecosystems, both directly (causing shifts in bottom-water temperature, oxygen concentration and pH), and indirectly (through changes in surface oceans' productivity and in the consequent export of organic matter to the seafloor). However, the responses of the benthic deep-sea biota to such shifts remain largely unknown. This applies particularly to deep-sea microbes, which include bacteria, archaea, micro-eukaryotes and their viruses. Understanding the potential impacts of global change on the benthic deep-sea microbial assemblages and the consequences on the functioning of the ocean interior is a priority to better forecast the potential consequences at global scale. Here we explore the potential changes in the benthic deep-sea microbiology expected in the coming decades using case studies on specific systems used as test models.

http://ift.tt/2ymnEzx

Resonance Fluorescence of an InGaAs Quantum Dot in a Planar Cavity Using Orthogonal Excitation and Detection

Resonant excitation of a single self-assembled quantum dot can be achieved using an excitation mode orthogonal to the fluorescence collection mode. We demonstrate a method using the waveguide and Fabry-Perot modes of a planar microcavity surrounding the quantum dots. The method allows complete freedom in the detection polarization.

http://ift.tt/2ylUMay

Correlation of Lung Clearance Index with Hyperpolarized 129Xe Magnetic Resonance Imaging in Pediatric Subjects with Cystic Fibrosis

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1073-1075, October 15, 2017.


http://ift.tt/2ghWkfi

Tracheal Foreign Body Removal Using Flexible Bronchoscope in a Pediatric Patient. A Novel Approach

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1071-1072, October 15, 2017.


http://ift.tt/2ghbXDU

Biomarkers in Critical Illness: New Insights and Challenges for the Future

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 944-945, October 15, 2017.


http://ift.tt/2ymNgw8

Health Disparities in Patients with Pulmonary Arterial Hypertension: A Blueprint for Action. An Official American Thoracic Society Statement

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page e32-e47, October 15, 2017.


http://ift.tt/2ggLyWM

Reply: Carbon Monoxide Exposure in Workplaces, Including Coffee Processing Facilities

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1081-1082, October 15, 2017.


http://ift.tt/2ym0lWF

Recovery from Critical Illness: Physical Rehabilitation in the Intensive Care Unit, Timing of Persistent Critical Illness, and Caregiver Outcomes

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1068-1070, October 15, 2017.


http://ift.tt/2ggLwOE

Bringing Lung Function Prediction Equations to Diverse Populations

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 942-944, October 15, 2017.


http://ift.tt/2ghaxZV

Right Ventricle Vasculature in Human Pulmonary Hypertension Assessed by Stereology

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1075-1077, October 15, 2017.


http://ift.tt/2ymDKsQ

Recognizing Workplace Factors Contributing to Interstitial Lung Disease

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 949-951, October 15, 2017.


http://ift.tt/2ylmuV4

Accounting for Patient Preferences Regarding Life-Sustaining Treatment in Evaluations of Medical Effectiveness and Quality

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 958-963, October 15, 2017.


http://ift.tt/2ghbWQm

Pulmonary Hypertension in Children

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page P15-P16, October 15, 2017.


http://ift.tt/2ylyjdS

Fifty Years of Physiology in Obstructive Sleep Apnea

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 954-957, October 15, 2017.


http://ift.tt/2gienSH

Triple Therapy in Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1082-1083, October 15, 2017.


http://ift.tt/2ymnO9Z

Labor Market Outcomes: Expanding the List of Patient-centered Outcomes in Critical Care

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 946-947, October 15, 2017.


http://ift.tt/2ggPCpK

Fifty Years of Research in ARDS.; Gas Exchange in Acute Respiratory Distress Syndrome

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 964-984, October 15, 2017.


http://ift.tt/2ylf8ks

Identification of Infants at Risk for Chronic Lung Disease at Birth. Potential for a Personalized Approach to Disease Prevention

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 951-952, October 15, 2017.


http://ift.tt/2giecqv

Occupational Exposures and Subclinical Interstitial Lung Disease. The MESA (Multi-Ethnic Study of Atherosclerosis) Air and Lung Studies

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1031-1039, October 15, 2017.


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Reply: “FULFIL an Unmet Need in Chronic Obstructive Pulmonary Disease” and “Triple Therapy in Chronic Obstructive Pulmonary Disease”

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page 1083-1084, October 15, 2017.


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Plexiform Vasculopathy in Chronic Thromboembolic Pulmonary Hypertension

American Journal of Respiratory and Critical Care Medicine, Volume 196, Issue 8, Page e48-e51, October 15, 2017.


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Routine treatment and outcome of breast cancer in younger versus elderly patients: results from the SENORA project of the prospective German TMK cohort study

Abstract

Purpose

There is an ongoing discussion about 'undertreatment' of breast cancer in elderly patients. Due to low accrual into clinical trials, level 1 evidence is scarce. We report prospective data of elderly patients with breast cancer treated by medical oncologists in Germany.

Methods

The SENORA project within the prospective cohort study TMK (Tumour Registry Breast Cancer) was conducted in 82 centres from 2007–2015. Among 2316 patients, half were enrolled with curative and half with palliative treatment intention. Overall, 478 patients (21%) were aged ≥ 70.

Results

In the adjuvant setting, elderly patients aged ≥ 70 had more advanced tumour stages at diagnosis and a higher prevalence of comorbidities than younger patients. Elderly patients received adjuvant chemotherapy less frequently, yet the 3-year disease-free survival was similar (86% vs. 88%). In the palliative setting, elderly patients more frequently received endocrine therapy and less frequently chemotherapy. Their median overall survival [24.9 months, 95% CI (confidence interval) 20.0–30.2] was significantly shorter than that of younger patients (39.7 months, 95% CI 34.9–44.2). A Cox proportional hazards model showed a significantly increased risk of mortality for: age ≥ 70 at start of therapy, negative HR- or HER2-status, higher number of metastatic sites, more comorbidities and high tumour grading at diagnosis.

Conclusions

Our results shed light on the routine treatment of elderly patients with breast cancer. A regression model demonstrated that age is but one of various prognostic factors determining the shorter overall survival of elderly patients.

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The Other End of the Leash: An Experimental Test to Analyze How Owners Interact with Their Pet Dogs

This article presents eight different experimental tasks, mirroring the everyday life of dogs and owners, used to analyze how owners interact with their dogs in a standardized way. The tasks included both positive (e.g. play) and negative (potentially stressful) situations (e.g. physical restriction).

http://ift.tt/2ymti4a

Bead Based Multiplex Assay for Analysis of Tear Cytokine Profiles

Analysis of tear film cytokines helps in studying various ocular diseases. Bead based multiplex assays are simple and sensitive and enable the testing of multiple targets in samples with small volumes. Here we describe a protocol for tear film cytokine profiling a using bead based multiplex assay.

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Magnetic Resonance Neurography

Abstract

Purpose

To establish normal values and to identify demographic determinants of quantitative biomarkers in magnetic resonance neurography (MRN).

Methods

In this study 60 healthy individuals (5 men and 5 women of every decade between 20 and 80 years) were examined according to a standardized MRN protocol at 3 T, including multiecho T2 relaxometry. Nerve cross-sectional area (CSA), transverse relaxation time (T2), and proton spin density (PSD) were assessed for the sciatic, tibial, median, ulnar, and radial nerves. Correlation with demographic variables, such as height, weight, body mass index (BMI), and age was expressed by Pearson coefficients and t‑tests were used to compare MRN biomarkers between men and women with and without normalization to body weight and BMI by linear regression.

Results

The average nerve CSA correlated moderately with height (r = 0.28, p = 0.04), weight (r = 0.40, p = 0.002), and BMI (r = 0.35, p = 0.008), but not with age (r = 0.23, p = 0.09). While T2 did not correlate with demographic parameters, PSD was strongly inversely associated with BMI (r = −0.64, p < 0.001) and weight (r = −0.557, p < 0.001). Sex-dependent differences in imaging marker values were found for CSA but became negligible after normalization to body weight.

Conclusion

Quantitative biomarkers of MRN co-vary with demographic variables. As particularly important determinants, we identified body weight for nerve CSA and BMI for PSD. The presented normal values and demographic determinants may assist investigations into the potential of MRN biomarkers in further disease-specific studies.

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PRIMUM NON NOCERE : now and again an echo of DPD with capecitabine

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Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual

Abstract

Answer questions and earn CME/CNE

To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8-1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors "microscopic" and "macroscopic" for regional node metastasis are redefined as "clinically occult" and "clinically apparent"; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA-IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA Cancer J Clin 2017;000:000-000. © 2017 American Cancer Society.

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Transcanalicular Diode Laser-assisted Dacryocystorhinostomy for the Treatment of Primary Acquired Nasolacrimal Duct Obstruction

The goal of this protocol is to present transcanalicular laser-assisted dacryocystorhinostomy as a minimally invasive approach in the treatment of primary acquired nasolacrimal duct obstruction.

http://ift.tt/2wSwiCd

Faecal microbiota transplantation donor stools need screening for poliovirus

We read with interest the recent report describing faecal microbiota transplantation (FMT) as an effective treatment for certain gastrointestinal diseases, such as Clostridium difficile infection,1 with its high burden and increasing frequency.2 In FMT, donor stools are screened for infectious diseases prior to use.3 Screening protocols are still developing. The protocol of Cammarota et al recognises as risky 'recent (<6 months) history of vaccination with a live attenuated virus, if there is a possible risk of transmission'.1 We contend that this precaution needs extension to include donors who are chronic poliovirus excreters.

Many countries used live attenuated oral poliovirus vaccine (OPV).4 In the USA, the OPV recommendation for routine immunisation ended 1 January 2000.5 A small proportion of OPV recipients, those with primary immune deficiencies (PIDs), are chronic faecal excreters of virulent vaccine-derived poliovirus. There were 73 described cases between...

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Rosuvastatin promotes the differentiation of peripheral blood monocytes into M2 macrophages in patients with atherosclerosis by activating PPAR-γ

OBJECTIVE: To evaluate M2 marker changes in human circulating monocytes before and after rosuvastatin treatment, and to investigate the effects of rosuvastatin on the differentiation of monocytes into M2 macrophages by activating peroxisome proliferator-activated receptor-γ (PPAR-γ).

PATIENTS AND METHODS: A total of 20 patients was administrated with rosuvastatin. The human peripheral blood mononuclear cells (PBMCs) were extracted by Ficoll-Hypaque density gradient centrifugation method. PPAR-γ, CD206 and CD163 mRNA levels were detected by Real-time polymerase chain reaction (RT-PCR). The total content of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), PPAR-γ, extracellular signal-regulated kinase (ERK) and p38 Mitogen-activated protein kinase (MAPK) and the contents of phosphorylated ERK and p38 MAPK were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS: The expression levels of CD206, Interleukin 10 (IL-10), and chemokine (C-C motif) ligand 18 (CCL18) were significantly improved by rosuvastatin. The expression level of PPAR-γ in circulating monocytes was also distinctly up-regulated through the treatment with rosuvastatin. After rosuvastatin therapy, PPAR-γ mRNA expression was unceasingly increased with time prolonging. The tendency of mRNA level of aP2 was the same as that of PPAR-γ. In vitro experiments indicated that in M2 macrophages, rosuvastatin could enhance the decrease of CD163 expression level induced by interleukin 4 (IL-4). M1 macrophages cultured by supernatant that was used to culture M2 macrophages could significantly inhibit TNF-α and MCP-1 expressions. Rosuvastatin could remarkably induce the phosphorylation of p38 MAPK, but the effect on ERK1/2 was not obvious.

CONCLUSIONS: Our results confirmed expressions of M2 markers in human circulating peripheral blood monocytes after rosuvastatin therapy. Both in vivo and in vitro experiments proved that rosuvastatin can induce the expression and activation of PPAR-γ in human monocytes, resulting in the differentiation of monocytes into M2 macrophages.

L'articolo Rosuvastatin promotes the differentiation of peripheral blood monocytes into M2 macrophages in patients with atherosclerosis by activating PPAR-γ sembra essere il primo su European Review.

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Patients Get Health Care at Home

Telehealth is an aspect of healthcare whose potential scope and impact have yet to be determined. However, we are beginning to see more programs experiment and validate various implementations of telehealth with promising results.

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Oral Anticoagulation and Functional Outcome after Intracerebral Hemorrhage

ABSTRACT

Objective: Oral Anticoagulation Treatment (OAT) resumption is a therapeutic dilemma in Intracerebral Hemorrhage (ICH) care, particularly for lobar hemorrhages related to amyloid angiopathy. We sought to determine whether OAT resumption after ICH is associated with long-term outcome, accounting for ICH location (i.e. lobar vs. non-lobar).

Methods: We meta-analyzed individual patient data from: 1) the multi-center RETRACE study (n=542); 2) a US-based single-center ICH study (n=261); 3) the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study (n=209). We determined whether, within one year from ICH, OAT resumption was associated with: 1) mortality; 2) favorable functional outcome (modified Rankin Scale [mRS] 0-3); stroke incidence. We separately analyzed non-lobar and lobar ICH cases using propensity score matching and Cox regression models.

Results: We included 1012 OAT-related ICH survivors (633 non-lobar and 379 lobar). Among non-lobar ICH survivors 178/633 (28%) resumed OAT, while 86/379 (23%) lobar ICH survivors did. In multivariable analyses OAT resumption after non-lobar ICH was associated with decreased mortality (Hazard Ratio [HR]=0.25, 95% Confidence Interval [CI]=0.14-0.44, p<0.0001) and improved functional outcome (HR=4.22, 95% CI=2.57-6.94, p<0.0001). OAT resumption after lobar ICH was also associated with decreased mortality (HR=0.29, 95% CI=0.17-0.45, p<0.0001) and favorable functional outcome (HR=4.08, 95% CI=2.48-6.72, p<0.0001). Furthermore, OAT resumption was associated with decreased all-cause stroke incidence in both lobar and non-lobar ICH (both p<0.01).

Interpretation: These results suggest novel evidence of an association between OAT resumption and outcome following ICH, regardless of hematoma location. These findings support conducting randomized trials to explore risks and benefits of OAT resumption after ICH. This article is protected by copyright. All rights reserved.

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Cancers, Vol. 9, Pages 136: Radiation-Induced Changes of microRNA Expression Profiles in Radiosensitive and Radioresistant Leukemia Cell Lines with Different Levels of Chromosome Abnormalities

Cancers, Vol. 9, Pages 136: Radiation-Induced Changes of microRNA Expression Profiles in Radiosensitive and Radioresistant Leukemia Cell Lines with Different Levels of Chromosome Abnormalities

Cancers doi: 10.3390/cancers9100136

Authors: Daria Liamina Wladimir Sibirnyj Anna Khokhlova Viacheslav Saenko Eugenia Rastorgueva Aleksandr Fomin Yury Saenko

In our study, we estimate an effect from chromosome aberrations and genome mutations on changes in microRNA expression profiles in cancer cell lines demonstrating different radiosensitivity. Here, cell viability and microRNA spectrum have been estimated 1, 4, and 24 h after irradiation. MiSeq high-throughput sequencing system (Illumina, San Diego, CA, USA) is employed to perform microRNA spectrum estimation. In the K562 cell line, the number of expressed microRNAs in chromosomes demonstrates a more pronounced variation. An analysis of microRNA effects on signaling pathway activity demonstrates differences in post-transcriptional regulation of the expression of genes included into 40 signaling pathways. In the K562 cell line, microRNA dynamics analyzed for their dependence on chromosome localization show a wider scattering of microRNA expression values for a pair of chromosomes compared to the HL-60 cell line. An analysis of microRNAs expression in the K562 and HL-60 cell lines after irradiation has shown that chromosome abnormalities can affect microRNA expression changes. A study of radiation-induced changes of microRNA expression profiles in the K562 and HL-60 cell lines has revealed a dependence of microRNA expression changes on the number of chromosome aberrations and genome mutations.

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Ledipasvir and Tenofovir drug interaction in HIV-HCV co-infected patients: Impact on Tenofovir Ctrough and Renal Safety

Abstract

We evaluate the impact of ledipasvir on both tenofovir plasma trough concentration (C_trough) and estimated glomerular renal function (eGFR) in HIV-HCV co-infected patients receiving a tenofovir(TDF)-based antiretroviral regimen and treated with ledipasvir/sofosbuvir.

Twenty-six patients [81% male, median age: 51years; HCV genotype 1(75%)/4(15%)] were included. Tenofovir C_trough (interquartile:IQR) increased from 78ng/mL (53-110) at baseline to 141ng/mL (72-176) at M1 (p=0.003). No significant difference on eGFR using both Cockroft-Gault and MDRD formula, respectively [median(IQR)] was observed between baseline [101.3ml/min (91.1-114.1); 95.6ml/min (86.5-111.2)], M1 [102.4ml/min (89.8-112.9), p=0.26; 92.5ml/min (88.1-114.3), p=0.27], end-of-treatment [96.5ml/min (82.4-115.4), p=0.39; 95.4ml/min (84.2-105.4), p=0.16] and 12-weeks after the end of treatment [100.5ml/min (83.3-111.9), p=0.24; 93.4ml/min (82.2-103.5), p=0.16]. Three patients progressed from CKD stage 1 to stage 2 at PT12.

A significant increase in tenofovir exposure through P-gp inhibition by ledipasvir was confirmed without significant impact on glomerular renal function in our population with normal renal function or mild renal impairment.

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N - tert -butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic activity of heparin-binding growth factors

Abstract

The peptides N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) and BOC-Met-Leu-Phe (BOC1) are widely used antagonists of formyl peptide receptors (FPRs), BOC2 acting as an FPR1/FPR2 antagonist whereas BOC1 inhibits FPR1 only. Extensive investigations have been performed by using these FPR antagonists as a tool to assess the role of FPRs in physiological and pathological conditions. Based on previous observations from our laboratory, we assessed the possibility that BOC2 may exert also a direct inhibitory effect on the angiogenic activity of vascular endothelial growth factor-A (VEGF-A). Our data demonstrate that BOC2, but not BOC1, inhibits the angiogenic activity of heparin-binding VEGF-A₁₆₅ with no effect on the activity of the non-heparin-binding VEGF-A₁₂₁ isoform. Endothelial cell-based bioassays, surface plasmon resonance analysis, and computer modeling indicate that BOC2 may interact with the heparin-binding domain of VEGF-A₁₆₅, thus competing for heparin interaction and preventing the binding of VEGF-A₁₆₅ to tyrosine kinase receptor VEGFR2, its phosphorylation and downstream signaling. In addition, BOC2 inhibits the interaction of a variety of heparin-binding angiogenic growth factors with heparin, including fibroblast growth factor 2 (FGF2) whose angiogenic activity is blocked by the compound. Accordingly, BOC2 suppresses the angiogenic potential of human tumor cell lines that co-express VEGF-A and FGF2. Thus, BOC2 appears to act as a novel multi-heparin-binding growth factor antagonist. These findings caution about the interpretation of FPR-focusing experimental data obtained with this compound and set the basis for the design of novel BOC2-derived, FPR independent multi-target angiogenesis inhibitors.

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Comment on “Long-Term Survival Benefit and Potential for Cure after R1 Resection for Colorectal Liver Metastases”: A Reply

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Survival Analysis in a Randomized Trial of HIPEC in Ovarian Cancer

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Diagnostic Accuracy of Magnetic Resonance Imaging Hepatic Proton Density Fat Fraction in Pediatric Nonalcoholic Fatty Liver Disease

ABSTRACT

We assessed the performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in children to stratify hepatic steatosis grade before and after treatment in the Cysteamine Bitartrate Delayed-Release for the Treatment of Nonalcoholic Fatty Liver Disease in Children (CyNCh) trial, using centrally-scored histology as reference. Participants had multi-echo 1.5T or 3T MRI on scanners from three manufacturers. Of 169 enrolled children, 110 (65%) and 83 (49%) had MRI and liver biopsy at baseline and at end-of-treatment (EOT; 52-weeks), respectively. At baseline, 17% (19/110), 28% (31/110), and 55% (60/110) of liver biopsies showed grades 1, 2, and 3 histologic steatosis; corresponding PDFF (mean ± standard deviation) values were 10.9 ± 4.1%, 18.4 ± 6.2%, and 25.7 ± 9.7%, respectively. PDFF classified grade 1 vs. 2-3 and 1-2 vs. 3 steatosis with areas under receiving operator characteristic curves (AUROCs) of 0.87 (95% confidence interval [CI]: 0.80, 0.94) and 0.79 (0.70, 0.87), respectively. PDFF cut-offs at 90% specificity were 17.5% for grades 2-3 steatosis, and 23.3% for grade 3 steatosis. At EOT, 47% (39/83), 41% (34/83), and 12% (10/83) of biopsies showed improved, unchanged, and worsened steatosis grade, respectively, with corresponding PDFF (mean ± standard deviation) changes of -7.8 ± 6.3%, -1.2 ± 7.8% and 4.9 ± 5.0%, respectively. PDFF change classified steatosis grade improvement and worsening with AUROCs (95% CIs) of 0.76 (0.66, 0.87) and 0.83 (0.73, 0.92), respectively. PDFF change cut-off values at 90% specificity were -11.0% and +5.5% for improvement and worsening. Conclusion: MRI-estimated PDFF has high diagnostic accuracy to both classify and predict histologic steatosis grade, and change in histologic steatosis grade in children with NAFLD. This article is protected by copyright. All rights reserved.

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The Warburg effect: persistence of stem cell metabolism in cancers as a failure of differentiation

Abstract

Background: Two recent observations regarding the Warburg effect are that (i) the metabolism of stem cells is constitutive ('aerobic') glycolysis while normal cellular differentiation involves a transition to oxidative phosphorylation and (ii) the degree of glucose uptake of a malignancy as imaged by ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) is associated with histologic measures of tumor differentiation. Combining these observations, we hypothesized that the high levels of glucose uptake observed in poorly differentiated cancers may reflect persistence of the glycolytic metabolism of stem cells in malignant cells that fail to fully differentiate.Patients and Methods: Tumor glucose uptake was measured by FDG-PET in 552 patients with histologically diverse cancers. We used normal mixture modeling to explore FDG-PET standardized uptake value (SUV) distributions and tested for associations between glucose uptake and histological differentiation, risk of lymph node metastasis, and survival. Using RNA-seq data, we performed pathway and transcription factor analyses to compare tumors with high and low levels of glucose uptake.Results: We found that well-differentiated tumors had low FDG uptake, while moderately and poorly differentiated tumors had higher uptake. The distribution of SUV for each histology was bimodal, with a low peak around SUV 2-5 and a high peak at SUV 8-14. The cancers in the two modes were clinically distinct in terms of the risk of nodal metastases and death. Carbohydrate metabolism and the pentose-related pathway were elevated in the poorly differentiated/high SUV clusters. Embryonic stem cell-related signatures were activated in poorly differentiated/high SUV clusters.Conclusions: Our findings support the hypothesis that the biological basis for the Warburg effect is a persistence of stem cell metabolism (i.e. aerobic glycolysis) in cancers as a failure to transition from glycolysis-utilizing undifferentiated cells to oxidative phosphorylation-utilizing differentiated cells. We found that cancers cluster along the differentiation pathway into two groups, utilizing either glycolysis or oxidative phosphorylation. Our results have implications for multiple areas of clinical oncology.

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Asymmetric Phosphatidylethanolamine Distribution Controls Fusion Pore Lifetime and Probability

Little attention has been given to how the asymmetric lipid distribution of the plasma membrane might facilitate fusion pore formation during exocytosis. Phosphatidylethanolamine (PE), a cone-shaped phospholipid, is predominantly located in the inner leaflet of the plasma membrane and has been proposed to promote membrane deformation and stabilize fusion pores during exocytotic events. To explore this possibility, we modeled exocytosis using plasma membrane SNARE-containing planar-supported bilayers and purified neuroendocrine dense core vesicles (DCVs) as fusion partners, and we examined how different PE distributions between the two leaflets of the supported bilayers affected SNARE-mediated fusion.

http://ift.tt/2ylpalD

Asymmetric Phosphatidylethanolamine Distribution Controls Fusion Pore Lifetime and Probability

Little attention has been given to how the asymmetric lipid distribution of the plasma membrane might facilitate fusion pore formation during exocytosis. Phosphatidylethanolamine (PE), a cone-shaped phospholipid, is predominantly located in the inner leaflet of the plasma membrane and has been proposed to promote membrane deformation and stabilize fusion pores during exocytotic events. To explore this possibility, we modeled exocytosis using plasma membrane SNARE-containing planar-supported bilayers and purified neuroendocrine dense core vesicles (DCVs) as fusion partners, and we examined how different PE distributions between the two leaflets of the supported bilayers affected SNARE-mediated fusion.

http://ift.tt/2ylpalD

Study on the effect of different doses of rosuvastatin on ventricular remodeling in patients with acute coronary syndrome after emergency percutaneous coronary intervention

OBJECTIVE: The objective of the present study was to observe the effects of different doses of rosuvastatin on cardiac protection in patients with acute coronary syndrome (ACS) after stent implantation.

PATIENTS AND METHODS: A total of 137 patients with ACS were selected from March 2014 to January 2015 and randomly divided into: 1. The conventional treatment group: 45 patients were treated with conventional drugs such as aspirin, clopidogrel, nitrates, and a β-blocker; 2. The conventional rosuvastatin dose group: 45 patients received 10 mg/d rosuvastatin before sleep in addition to routine therapy; 3. The large rosuvastatin dose group: 47 patients received 20 mg/d rosuvastatin before sleep in addition to routine therapy. The course of treatment was 12 weeks. At 1, 6, and 12 week, ultrasound echocardiography, electrocardiogram (ECG), high-sensitivity C-reactive protein (hs-CRP), and pro-brain natriuretic peptide (pro-BNP) levels were tested to evaluate the therapeutic effects. The ultrasonic imaging criteria included left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), and left ventricular ejection fraction (LVEF).

RESULTS: After 1 week, hs-CRP, pro-BNP, and echocardiography of the patients in the three groups showed no significant differences (p>0.05); after 6 and 12 weeks, the levels of hs-CRP, MMP-9, and pro-BNP in the large rosuvastatin dose group were significantly lower than in the conventional rosuvastatin dose group and conventional treatment group (p<0.05), and ultrasonic indexes changed significantly after 12 weeks (p<0.05). There were no significant differences in ultrasonic indexes after 6 weeks (p>0.05). No thrombosis or restenosis occurred during the follow-up period in each group.

CONCLUSIONS: Three months after emergency percutaneous coronary intervention, a high-dose of rosuvastatin can delay ventricular remodeling, effectively inhibit malignant remodeling of the heart, improve left ventricular systolic function, reduce the prevalence of adverse events, and significantly improve the long-term prognosis.

L'articolo Study on the effect of different doses of rosuvastatin on ventricular remodeling in patients with acute coronary syndrome after emergency percutaneous coronary intervention sembra essere il primo su European Review.

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Melatonin promotes osteoblast differentiation of bone marrow mesenchymal stem cells in aged rats

OBJECTIVE: The current study was to explore the effect of melatonin on osteoporosis and relevant mechanisms.

MATERIALS AND METHODS: We performed micro-CT to detect bone microstructure and ELISA to detect the contents of osteocalcin (OCN) and bone alkaline phosphatase (BAP) in serum. Double fluorescence labeling of calcein and tetracycline and toluidine blue staining were used to determine morphological indexes of bone tissues. Alizarin red staining and Oil Red O staining were performed to recognize bone cells and adipocytes. RT-PCR was performed to determine the expression of osteoblast differentiation related genes.

RESULTS: In the current study, data from micro-CT indicated that melatonin significantly increased the bone mass density (BMD), bone volume/tissue volume (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th), and decreased the Structure Model Index (SMI) and trabecular Separation/Spacing (Tb.Sp) in elderly rats. Melatonin reduced calcium and phosphorus losses in urine and increased BAP and OCN levels in serum in elderly rats and increased bone formation rate (BFR) and bone mineralization rate (MAR) in elderly rats. Melatonin increased the number of osteoblasts in bone marrow and reduced the number of adipocytes in elderly rats. Melatonin also promoted the expression of osteogenic differentiation genes and suppressed the expression of adipogenic differentiation genes.

CONCLUSIONS: WE suggest that melatonin could alleviate osteoporosis in aged rats' models probably by promoting osteoblast differentiation.

L'articolo Melatonin promotes osteoblast differentiation of bone marrow mesenchymal stem cells in aged rats sembra essere il primo su European Review.

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The effect of saikosaponin D on doxorubicin pharmacokinetics and its MDR reversal in MCF-7/adr cell xenografts

OBJECTIVE: Multidrug resistance (MDR) is a major cause of chemotherapy failure in the treatment of cancer patients. This study aimed to determine whether saikosaponin D (SSd) can enhance the efficacy of the anticancer drug doxorubicin (Dox) both in vitro and in vivo and whether SSd can alter Dox pharmacokinetics in the serum of mice.

MATERIALS AND METHODS: MCF-7/adr cells were used to investigate the effect of SSd on reversing MDR. Cell viability was assessed by MTT assay. Pharmacokinetic tests were used to evaluate the effects of SSd on serum Dox disposition. An MCF-7/adr cell xenograft model was established to investigate the effect of SSd on reversing MDR in vivo. Tumor growth and weights were measured. Immunohistochemistry staining was used to detect the expression of P-gp (P-glycoprotein), an ATP-dependent efflux pump that mediates MDR in xenograft tumor tissues.

RESULTS: SSd could effectively reverse MDR in MCF-7/adr cells in vitro and had no cytotoxic effects on human amniotic epithelial cells (hAEC). There was no significant difference between the Dox pharmacokinetic parameters obtained in the mice that received Dox only and Dox combined with SSd, indicating that SSd did not alter the pharmacokinetic profiles of Dox. Furthermore, the combination of Dox and SSd had a stronger anticancer effect than Dox alone or SSd alone by inhibiting tumor growth and P-gp expression.

CONCLUSIONS: Our results suggest that SSd could effectively reverse MDR in vitro and in vivo and could be a potential MDR reversal agent for P-gp-mediated MDR in breast cancer therapy.

L'articolo The effect of saikosaponin D on doxorubicin pharmacokinetics and its MDR reversal in MCF-7/adr cell xenografts sembra essere il primo su European Review.

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Department of Rheumatism, the Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu Province, China. 5331646@qq.com

OBJECTIVE: To observe the curative effect of dl-3-n-Butylphthalide (NBP) on patients with acute cerebral infarction (ACI) and its effects on levels of serum vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).

PATIENTS AND METHODS: A total of 160 ACI patients treated in our hospital who met the criteria were selected and randomly divided into treatment group (n=80, including 42 males and 38 females) and control group (n=80, including 40 males and 40 females). The control group was treated with routine drug therapy, while the treatment group was treated with butylphthalide on this basis. The curative effect was evaluated using the National Institute of Health Stroke Scale (NIHSS) and the Activity of Daily Life Scale (ADL Scale). The levels of the two factors in serum were measured using enzyme-linked immunosorbent assay (ELISA), and the changes in the levels of the two factors in serum at different time points before and after treatment were compared between the two groups.

RESULTS: After treatment, the levels of the two factors in serum in both groups were significantly increased compared with those before treatment (p<0.05), and the increase in treatment group was more significant than that in control group (p<0.05). The scores of ADL scale in both groups were significantly increased after treatment compared with those before treatment, and the increase in treatment group was more significant than that in control group (p<0.05). The scores of NIHSS in both groups were significantly decreased compared with those before treatment, and the decrease in treatment group was more significant than that in control group (p<0.05).

CONCLUSIONS: NBP can improve the expressions of VEGF and bFGF in serum of ACI patients, and its effect is superior to that of conventional drugs.

L'articolo Department of Rheumatism, the Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu Province, China. 5331646@qq.com sembra essere il primo su European Review.

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Analysis of changes in joint function and peripheral blood mononuclear cells in patients with systemic lupus erythematosus and intervention effects of different drugs

OBJECTIVE: To investigate the therapeutic effect of drug therapy with cyclophosphamide and leflunomide on the joint function damage of patients with systemic lupus erythematosus (SLE) and its regulatory effects on expression levels of programmed death receptor 1, Notch signaling pathway genes and interferon-inducible protein 10 in peripheral blood mononuclear cells.

PATIENTS AND METHODS: A total of 60 patients with SLE were randomly divided into two groups. They were treated with cyclophosphamide and leflunomide, respectively. The number of painful joints, joint tenderness index, joint swelling index and erythrocyte sedimentation rate of patients before and after treatment were evaluated, and the peripheral blood was collected from patients in the two groups; the peripheral blood mononuclear cells were extracted.

RESULTS: We observed that the number of painful joints, joint tenderness index and joint swelling index in cyclophosphamide group were decreased after treatment (p<0.05), and the erythrocyte sedimentation rate was significantly decreased (p<0.05). The number of painful joints, joint tenderness index and joint swelling index in leflunomide group were decreased after treatment (p<0.05), and the erythrocyte sedimentation rate was significantly decreased (p<0.05). The comparisons of changes in joint functions and erythrocyte sedimentation rates between cyclophosphamide group and leflunomide group after drug therapy showed that the curative effect in leflunomide group was superior to that in cyclophosphamide group (p<0.05). The positive expression rate of peripheral blood mononuclear cell Notch1 in leflunomide group after treatment was significantly decreased, and the curative effect was superior to that in cyclophosphamide group (p<0.05). The comparisons of changes in programmed death receptor 1 of lymphocytes and interferon-inducible protein 10 between cyclophosphamide group and leflunomide group after drug therapy showed that the curative effect in leflunomide group was superior to that in cyclophosphamide group (p<0.05). The comparison of positive expression rate of nuclear factor-κB (NF-κB) in peripheral blood mononuclear cells between the two groups after treatment showed that the curative effect in leflunomide group was superior to that in cyclophosphamide group (p<0.05). There were positive correlations of the expression level of programmed death receptor 1 of peripheral blood lymphocytes in SLE patients with double-stranded DNA (ds-DNA) and SLE disease activity index (p<0.05). There were positive correlations of the expression level of peripheral interferon-inducible protein 10 in SLE patients with ds-DNA and SLE disease activity index (p<0.05).

CONCLUSIONS: This study proved that both leflunomide and cyclophosphamide have therapeutic effects on the joint functions and immune dysfunction of peripheral blood mononuclear cells of SLE patients; however, and the effect of leflunomide is better. There are positive correlations of SLE disease activity index with the Notch signaling pathway genes, programmed death receptor 1 and interferon-inducible protein 10 in peripheral blood mononuclear cells, suggesting that these factors are related to the immune dysfunction of peripheral blood mononuclear cells.

L'articolo Analysis of changes in joint function and peripheral blood mononuclear cells in patients with systemic lupus erythematosus and intervention effects of different drugs sembra essere il primo su European Review.

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Relationship between blood remifentanil concentration and stress hormone levels during pneumoperitoneum in patients undergoing laparoscopic cholecystectomy

OBJECTIVE: The effect of remifentanil on stress response to surgery is unclear. However, there are not clinical studies investigating the relationship between blood remifentanil concentrations and stress hormones. Therefore, the aim of the present study was to assess the association between blood remifentanil concentrations measured after pneumoperitoneum and cortisol (CORT) or prolactin (PRL) ratio (intraoperative/preoperative value), in patients undergoing laparoscopic cholecystectomy.

PATIENTS AND METHODS: Patients did not receive any pre-anesthetic medication. Anesthesia induction was standardized. Anesthesia maintenance was performed with inhaled sevoflurane at age-adjusted 1.0 minimum alveolar concentration and intravenous remifentanil at infusion rate ranging from 0.1 to 0.4 mcg/kg/min. Blood samples were withdrawn before anesthesia induction and 5 min after achieving a pneumoperitoneum pressure of 12 mmHg. Correlation analyses were performed to evaluate the relationship between measured blood remifentanil concentrations, CORT or PRL ratio (intraoperative/preoperative value) and remifentanil dose delivered by the pump.

RESULTS: A significant inverse correlation was found between CORT ratio and measured blood remifentanil concentration (p=0.03) or planned remifentanil dose (p=0.04). No correlations were found between blood remifentanil concentration and PRL ratio (p=0.83).

CONCLUSIONS: Our data suggest that the CORT response to surgical stress is more efficiently counteracted by increased blood remifentanil concentration.

L'articolo Relationship between blood remifentanil concentration and stress hormone levels during pneumoperitoneum in patients undergoing laparoscopic cholecystectomy sembra essere il primo su European Review.

http://ift.tt/2wSxO7j

Pathological and cytological changes of the nasal mucosa in acute rhinosinusitis: the role of hyaluronic acid as supportive therapy

OBJECTIVE: The aim of this study was to evaluate the reparative role of hyaluronic acid in acute rhinosinusitis (ARS).

PATIENTS AND METHODS: 48 patients affected by ARS were submitted to nasal endoscopy, nasal cytology, mucociliary transport evaluation (MCTt) and visual analogue scale questionnaire (VAS) at T0, after 14-18 days (T1) and after 30-35 days (T2). The patients were randomized into two groups, A and B, and received Levofloxacin and Prednisone. Moreover, using a nebulizer ampoule for nasal douche, Group A received high molecular weight Sodium Hyaluronate (3%) plus saline solution (NaCl 0.9%) twice a day for 30 days; Group B received saline solution twice a day for 30 days.

RESULTS: At T0 only the VAS score showed differences regarding nasal discharge and post-nasal drip. At T1, in Group A MCTt and the number of bacteria were significantly lower than in Group B. The VAS score showed improvement in Group A. At T2 in Group A, MCTt and number of neutrophils were significantly lower than in Group B. The VAS score showed statistically significant differences between the two groups regarding nasal discharge.

CONCLUSIONS: In ARS patients sodium hyaluronate plus saline solution significantly improved symptoms, MCT time and reduced neutrophil count on nasal cytology.

L'articolo Pathological and cytological changes of the nasal mucosa in acute rhinosinusitis: the role of hyaluronic acid as supportive therapy sembra essere il primo su European Review.

http://ift.tt/2yhRIdx

Research on clinical value of galectin-3 in evaluating the prognosis of acute heart failure

OBJECTIVE: To investigate the clinical value of galectin-3 in the prognosis evaluation of acute heart failure.

PATIENTS AND METHODS: A total of 316 patients treated in Suzhou Kowloon Hospital were enrolled into this study and followed up for 1 year. Venous blood during the onset was collected for examinations of blood routine, blood biochemistry, N-terminal B-type pro-brain natriuretic peptide (NT-proBNP), galectin-3 and other indexes. Cardiovascular events (CV events) include the re-admission or death due to the recent acute episode of chronic heart failure.

RESULTS: The concentrations of NT-proBNP and galectin-3 in the CV event group were significantly increased compared with those in non-CV event group (p<0.001). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of NT-proBNP in predicting CV events of patients with acute heart failure within 1 year after discharge was 0.816 and that of galectin-3 was 0.847. Kaplan-Meier survival curve analysis showed that risks of CV events of patients with the NT-proBNP concentration >3013.21 pg/mL and galectin-3 concentration >17.15 ng/mL within 1 year after discharge were significantly higher than those in other groups (p<0.001).

CONCLUSIONS: Galectin-3 can be used as a biomarker for the prognosis evaluation of acute heart failure, and its combined analysis can increase the predictive value of NT-proBNP.

L'articolo Research on clinical value of galectin-3 in evaluating the prognosis of acute heart failure sembra essere il primo su European Review.

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The differentiation of beige adipocyte in pericardial and epicardial adipose tissues induces atrial fibrillation development

OBJECTIVE: Growing evidence has identified that excessive accumulation of pericardial adipose tissues (PAT) and epicardial adipose tissues (EAT) is associated with atrial fibrillation (AF) development. Moreover, beige adipocytes, present in PAT and EAT, have been proved beneficial in consumption of fatty acid and promotion of weight lose by nonshivering thermogenesis. The objective of this prospective, observational study was to reveal the potential association between beige adipocytes and AF development.

PATIENTS AND METHODS: Fat tissues from subcutaneous adipose tissue (SAT), PAT and EAT were obtained from 70 AF and 30 sinus rhythm patients. Hematoxylin and eosin (H&E) staining were performed to analyze morphological changes in fat tissues. Real-time PCR was performed to identify mRNA expression of unique uncoupling protein-1 (UCP-1). Western blotting and immunohistochemistry (IHC) were performed to determine protein expression of UCP-1.

RESULTS: Our results indicated that pericardial and epicardial adipocytes in AF patients demonstrated white-like change tendency and had lower expression of UCP-1 when compared to sinus rhythm patients. Additionally, the decrease of UCP-1 mRNA expression in PAT and EAT, together with LA enlargement, were independent risk factors of AF. Further, UCP-1 mRNA expression in EAT, but not in PAT, have a significant correlation with LA diameter. The function of nonshivering thermogenesis in PAT and EAT was impaired in AF patients, and this dysfunction in EAT had a great correlation with LA dilation.

CONCLUSIONS: Our data provide a new therapeutic target for LA remodeling and AF treatment.

L'articolo The differentiation of beige adipocyte in pericardial and epicardial adipose tissues induces atrial fibrillation development sembra essere il primo su European Review.

http://ift.tt/2yjZ7Jy

Utility of biochemical markers and RVD/LVD ratio in acute pulmonary embolism risk classification in Emergency Department

OBJECTIVE: We aimed to determine the efficacy of troponin I, D-dimer, and lactate levels and right ventricular diameter (RVD)/left ventricular diameter (LVD) ratio on pulmonary computed tomography angiography (PCTA) in the risk classification of patients who were diagnosed with acute pulmonary embolism (APE) in Emergency Department (ED).

PATIENTS AND METHODS: Patients who were diagnosed as having APE by PCTA in ED were included in this retrospective study. Patients were grouped as high-risk (undergoing cardiopulmonary resuscitation or given thrombolytic therapy), moderate-risk (with non-high-risk and positive ECO findings) and low risk (others). Troponin I, D-dimer, and lactate levels of patients were determined. RVD, RVD/LVD ratio, and interventricular septum deviation were calculated from PCTA images.

RESULTS: A total of 121 patients were included (35 high, 36 moderate, 50 low risk). Lactate was different in the high-risk group from the other groups, whereas there was no difference between the moderate and low-risk groups. Troponin I levels were not different between the high-risk and moderate-risk groups. There were statistically significant differences between the high, moderate, and low-risk groups in terms of mean RVD/LVD ratios. ROC analyses performed in order to define high-risk group revealed a cut-off value of > 2.3 (AUC = 0.848, sensitivity = 70%, specificity = 90%, + Likelihood ratio (LR) = 7, -LR = 0.33, 95% CI = 0.752-0.943) for lactate and > 1.40 (AUC = 0.695 sensitivity = 71%, specificity = 80%, + LR = 3.6, -LR = 0.36, 95% CI = 0.668-0.822) for RVD/LVD ratio.

CONCLUSIONS: Lactate levels and RVD/LVD ratio were shown to be useful in distinguishing high-risk patients from other patient groups. Troponin I is important in terms of showing cardiac involvement, but it is inadequate in distinguishing between high and moderate-risk patients. Lactate, troponin I, and RVD/LVD ratio may be used together for a more accurate separation of patients with high, intermediate and low-risk.

L'articolo Utility of biochemical markers and RVD/LVD ratio in acute pulmonary embolism risk classification in Emergency Department sembra essere il primo su European Review.

http://ift.tt/2wStC7C

Usefulness of abbreviated breast MRI screening for women with a history of breast cancer surgery

Abstract

Purpose

We investigated the usefulness of abbreviated breast MRI (AB-MRI), including fat-suppressed T2-weighted imaging, pre- and postcontrast image acquisition, and subtracted maximum-intensity projection imaging, for the screening of women with a history of breast cancer surgery.

Methods

Between October 2014 and March 2016, a total of 799 AB-MRI examinations were performed for 725 women with a history of breast cancer surgery. The image acquisition time was 8.5 min. Screening mammography, ultrasound, and AB-MRI were generally performed around the same time. The cancer detection rate, positive predictive values for recall and biopsy, sensitivity and specificity of screening MRI, and rate of malignancy belonging to each breast imaging reporting and data system (BI-RADS) category were assessed.

Results

AB-MRI detected 12 malignancies in 12 women (15.0 cancers per 1000 cases). Seven of these 12 malignancies were initially invisible on ultrasound and mammography, although subsequent targeted ultrasound revealed lesions corresponding to the MRI-detected lesions. The positive predictive values for recall and biopsy and sensitivity and specificity values for screening MRI were 12.4, 61.5, 100, and 89.2%, respectively. The rates of malignancies belonging to categories 1, 2, 3, and 4 of the BI-RADS were 0, 0, 4.8, and 57.1%, respectively.

Conclusions

The diagnostic performance of screening AB-MRI for women with a history of breast cancer surgery is acceptable, with the advantages of short examination and interpretation times and low costs. Thus, it could be used as a main screening modality that may replace conventional imaging in breast cancer survivors.

http://ift.tt/2zkE4GP

Effect of pulmonary surfactant combined with mechanical ventilation on oxygenation functions and expressions of serum Transforming Growth Factor-Beta1 (TGF-β1) and Bone Morphogenetic Protein 7 (BMP-7) of neonatal respiratory distress syndrome

OBJECTIVE: To investigate and discuss the effect of early treatment with pulmonary surfactant (PS) on oxygenation functions in neonates with acute respiratory distress syndrome (ARDS), to understand the expression trend of serum transforming growth factor-beta 1 (TGF-β1) and bone morphogenetic protein 7 (BMP-7) in children with neonatal respiratory distress syndrome (NRDS), and to provide help for early prevention and treatment of NRDS.

PATIENTS AND METHODS: All the children were treated with mechanical ventilation; among them, 25 NRDS children who were given PS within 12 h after birth were selected as PS group, and 25 NRDS children who were never given PS were selected as conventional mechanical ventilation (CMV) group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of serum TGF-β1 and BMP-7 in the two groups of children and monitor their oxygenation function indexes in 0, 1, 3, and 7 d after birth, respectively.

RESULTS: The content of serum TGF-β1 and BMP-7 in children of both PS group and CMV group trended to be higher at 1 d after birth while it was decreased at 7 d after birth compared with that in other days. The TGF-β1 content at 3 and 7 d after birth and the BMP-7 expression level at 7 d after birth in CMV group were significantly higher than those in PS group (p<0.05). After treatment, the values of oxygenation index (OI) and respiratory index (RI) at different time points (6, 12, 24, 48 h) in PS group were lower than those in CMV group (p<0.05). The mechanical ventilation duration in PS group (81±25 h) was decreased compared with that in CMV group (102±24 h); the oxygenation time in PS group (99±37 h) was less than that in CMV group (122±28 h); the number of cases of complications in PS group and CMV group was 3 (12%) and 6 (24%), respectively, and the effective rates of treatment were 96.0% and 84.0%, respectively (p<0.05).

CONCLUSIONS: Early application of PS combined with mechanical ventilation can remarkably improve lung oxygenation and compliance, suppress inflammatory responses, and effectively treat the NRDS. Monitoring the changes of serum BMP-7 and TGF-β1 is very important for treatment and prognosis assessment of the NRDS.

L'articolo Effect of pulmonary surfactant combined with mechanical ventilation on oxygenation functions and expressions of serum Transforming Growth Factor-Beta1 (TGF-β1) and Bone Morphogenetic Protein 7 (BMP-7) of neonatal respiratory distress syndrome sembra essere il primo su European Review.

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Contents: (Adv. Mater. 39/2017)

http://ift.tt/2ylEI8p

Wearable Devices: Wearable Microfluidic Diaphragm Pressure Sensor for Health and Tactile Touch Monitoring (Adv. Mater. 39/2017)

A flexible microfluidic diaphragm pressure sensor using liquid-metal microchannels is presented by Ali Javey and co-workers in article number 1701985. The sensor is capable of detecting pressures less than 100 Pa with a resolution of less than 50 Pa. Both heart-rate monitoring and tactile pressure mapping of a glove with multiple embedded sensors are demonstrated.

http://ift.tt/2yl4n0W

Nanochannels: A 1D Vanadium Dioxide Nanochannel Constructed via Electric-Field-Induced Ion Transport and its Superior Metal–Insulator Transition (Adv. Mater. 39/2017)

Nanoscale manipulation of materials' properties offers the clear possibility of developing novel electronic devices. In article number 1702162, Gang Liu, Xiao-Hong Xu, Run-Wei Li, and co-workers present the construction of 1D VO₂ nanochannels via electric-field-induced ion transport, showing a superior metal–insulator transition with fast speed, low power, and excellent reproducibility. The VO₂ nanostructure acts as promising candidate for the selector element in high-density crossbar memory arrays.

http://ift.tt/2ylrnNj

Neural Devices: Conducting Polymer Microcups for Organic Bioelectronics and Drug Delivery Applications (Adv. Mater. 39/2017)

Novel mononodisperse conducting polymer microcups for organic bioelectronics and drug-delivery applications are reported by Mohammad Reza Abidian and co-workers in article number 1702576, who demonstrate that the physical surface properties of the conducting polymer microcups can be precisely tuned to control the electrical properties, drug loading, and sustained-release characteristics.

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Masthead: (Adv. Mater. 39/2017)

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Nanocarriers: Capturing “Extraordinary” Soft-Assembled Charge-Like Polypeptides as a Strategy for Nanocarrier Design (Adv. Mater. 39/2017)

A novel strategy developed by Vicent J. Nebot, María J. Vicent, and co-workers in article number 1702888 to produce nanosized drug carriers may improve the anticancer drug activity of polymer therapeutics and patient treatment. The discovery of an attractive force between negatively charged star-shaped-polypeptides allows single stars to self-assemble into unprecedented larger spherical structures with enhanced pharmacokinetic characteristics. Furthermore, selective lymph-node accumulation of these carriers may lead to applications in anti-metastatic and immunotherapeutic strategies.

http://ift.tt/2xD22uS

Photodetectors: Large-Scale Synthesis of Freestanding Layer-Structured PbI2 and MAPbI3 Nanosheets for High-Performance Photodetection (Adv. Mater. 39/2017)

High-density, crystalline, and freestanding PbI₂ and MAPbI₃ nanosheets are synthesized by Johnny C. Ho and co-workers in article number 1702759, on a large scale through the nucleation of microplanes on substrates with a rough surface by manipulating the microenvironment during physical vapor deposition. When configured into photodetectors, they exhibit efficient photodetection with excellent performance in responsivity and detectivity.

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Dosimetry in clinical radionuclide therapy: the devil is in the detail

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Spontaneous closure of ventricular septal perforation following percutaneous coronary intervention for acute myocardial infarction

We report on an 84-year-old woman with anteroseptal acute myocardial infarction. Emergency coronary angiography revealed the occlusion of proximal left anterior descending artery without collateral circulation, and percutaneous coronary intervention was performed. Two drug eluting stents were implanted, and the procedure was concluded with thrombolysis in myocardial infarction grade 3 without complications. Postoperatively, no murmur was audible on auscultation and no shunt flow was observed on transthoracic echocardiography (TTE), and normal blood pressure was maintained. On day 2, however, the patient's vital signs deteriorated to a state of shock and systolic murmur appeared at the apical region. TTE showed a left-to-right shunt in the apical septal region, and ventricular septal perforation was diagnosed. Although emergency surgery was considered, the patient's vital signs improved the following day. The disappearance of the cardiac murmur and the shunt was confirmed. The clinical course was uneventful thereafter, and the patient was discharged.

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Worsening Guillain-Barre syndrome: harbinger of IRIS in HIV?

We report an HIV patient aged 38 years with acute inflammatory demyelinating polyradiculoneuropathy subtype of Guillain-Barré syndrome (GBS) as the only manifestation of seroconversion and worsening of GBS being the harbinger of immune reconstitution inflammatory syndrome (IRIS). To date, only 5 cases of GBS during IRIS are reported. They manifested either during the third week or later after starting highly active antiretroviral therapy (HAART). Our patient witnessed worsening weakness by fifth day after starting HAART, even before the occurrence of Pneumocystis jirovecii pneumonia, cautioning one of the impending serious complications of IRIS and helped us initiate steroids at an early date.

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Disfiguring facial pyoderma vegetans with an excellent outcome

We describe a case of disfiguring facial pyoderma vegetans in order to highlight the challenges in managing this rare skin condition and review the literature.

A 54-year-old woman presented to dermatology clinic with a 3-month history of a left-sided facial lesion, which had been treated as an infected sebaceous cyst. The lesion had dramatically increased in size in the weeks prior to presentation. There was a history of Crohn's disease and ileal adenocarcinoma, both of which were in remission. A clinical diagnosis of pyoderma vegetans was made and the patient responded well to immunosuppressive therapy with oral ciclosporin. Carbon dioxide (CO₂) laser resurfacing to residual scarring contributed to an excellent cosmetic result.

http://ift.tt/2wSiasE

Maternal emotion dysregulation, parenting stress, and child physiological anxiety during dark-enhanced startle

Abstract

Maternal emotion dysregulation (ED) plays a crucial role in the development of psychopathology in children. The current study aimed to investigate parenting stress as a mediator of the relationship between maternal emotion dysregulation and child startle potentiation, with child sex as a moderator. Mothers were interviewed to obtain self-report of maternal ED and parenting stress and child's dark-enhanced startle (DES) response was measured using electromyographic recordings of the eye-blink muscle during the delivery of acoustic probes. We found that maternal ED was positively correlated with both her parenting stress and her child's DES. A bootstrap analysis yielded a full mediation of the association between ED and child DES via parenting stress. Child sex was not a significant moderator of these relationships. These results suggest that maternal ED has important consequences for the intergenerational transmission of risk and also highlight the interaction of behavioral and biological mechanisms of risk.

http://ift.tt/2xDhyGX

The role of cardiac vagal tone and inhibitory control in pre-schoolers' listening comprehension

Abstract

This study investigated the role of basal cardiac activity and inhibitory control at the beginning of the school year in predicting oral comprehension at the end of the year in pre-schoolers. Forty-three, 4-year-olds participated in the study. At the beginning of the school year children's electrocardiogram at rest was registered followed by the assessment of inhibitory control as well as verbal working memory and verbal ability. At the end of the year all children were administered a listening comprehension ability measure. A stepwise regression showed a significant effect of basal cardiac vagal tone in predicting listening comprehension together with inhibitory control and verbal ability. These results are among the first to show the predictive role of basal cardiac vagal tone and inhibitory control in pre-schoolers' oral text comprehension, and offer new insight into the association between autonomic regulation of the heart, inhibitory control, and cognitive activity at a young age.

http://ift.tt/2ylTcW4

Correlation between RAR-β expression in lung squamous cell carcinoma tissues and prognosis

OBJECTIVE: To explore the retinoic acid receptor-β (RAR-β) expression in lung squamous cell carcinoma (LSCC) tissues and its prognosis.

PATIENTS AND METHODS: SP assay was used to detect the RAR-β expression in 100 cases of surgically resected LSCC tissues and 20 cases of peritumoral normal lung tissues, and prognosis follow-up was conducted.

RESULTS: The overall positive expression rate of RAR-β was 54.00%, which was not correlated with age, gender, phase and pathological type (p>0.05). Stratified analysis showed that the prognosis of patients with positive IRAR-β expression in phase I was significantly better than that of those with negative IRAR-β expression, in which the median survival times were 31 and 22 months respectively (p=0.022). In contrast, the prognosis of patients with negative RAR-β expression was better than that of those with positive RAR-β expression in phase II and III A. The median survival times were 23 and 16 months respectively in phase II p = 0.008, and 19 and 7 months respectively in phase III A (p=0.019).

CONCLUSIONS: RAR-β is expressed in LSCC tumor tissues. RAR-β expression, which is not significantly correlated with the clinicopathological characteristics of patients, affects the postoperative survival of LSCC patients in phase I and II-III A dually. RAR-β expression state is one of the independent factors for the prognosis of LSCC patients.

L'articolo Correlation between RAR-β expression in lung squamous cell carcinoma tissues and prognosis sembra essere il primo su European Review.

http://ift.tt/2yeooai

Association between downexpression of miR-1301 and poor prognosis in patients with glioma

OBJECTIVE: MiR-1301 has been shown to be frequently down-regulated in various tumors. However, the clinical significance of miR-1301 in human glioma is still unclear. The aim of this study was to evaluate the prognostic impact of the expressions of miR-1301 in patients with glioma.

PATIENTS AND METHODS: Quantitative Real-time PCR was used to determine the expression miR-1301 in glioma tissues and pair-matched adjacent normal tissues. The relationships between miR-1301 expression and clinicopathological parameters were examined by X2 test. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome.

RESULTS: We observed that miR-1301 expression was significantly lower in glioma tissues compared with adjacent non-cancerous tissues (p<0.01). Also, low expressions of miR-1301 were significantly associated with high WHO grade (p<0.006), low Karnofsky performance score (KPS) (p=0.001), and large tumor size (p=0.004). Furthermore, the data of Kaplan-Meier survival analysis showed that low miR-1301 expression significantly associated with a worse overall survival (p=0.003) and disease-specific survival (p=0.001). Finally, the univariate and multivariate analysis showed that the miR-1301 expression was an independent predictor for both overall survival and disease-specific survival in glioma.

CONCLUSIONS: Our findings suggested lower miR-1301 expression resulted in poorer survival in patients with glioma, which may provide important indicators for further research.

L'articolo Association between downexpression of miR-1301 and poor prognosis in patients with glioma sembra essere il primo su European Review.

http://ift.tt/2g6VyxR

Study on the correlation between CD14 gene polymorphism and susceptibility to laryngeal cancer

OBJECTIVE: CD14 is the cell surface glycoprotein, which plays an important role in the occurrence and development of tumors. This study was designed to assess the association between CD14 SNPs and laryngeal cancer risk.

PATIENTS AND METHODS: This case-control study including 406 cases of laryngeal cancer and 893 healthy controls. The relationship between the genetic variation of CD14, rs2569190 and rs5744455, and the onset risk of laryngeal cancer were investigated. Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (CI) to study the relationship between CD14 gene polymorphism and pathogenesis of laryngeal cancer.

RESULTS: The results showed that rs5744455 mutation could increase the onset risk of laryngeal cancer (TT vs. CC: OR = 1.20, 95% CI = 1.01-1.41; additive model: OR = 1.20, 95% CI = 1.01-1.42). The results of stratified analysis showed that rs5744455 was associated with the susceptibility to laryngeal cancer in the elderly, females, non-smokers and non-drinkers (OR = 1.32, 95% CI = 1.04-1.66; OR = 1.58, 95% CI = 1.21-2.06; OR = 1.35, 95% CI = 1.08-1.69; OR = 1.31, 95% CI = 1.05-1.65). The analysis of combined effect of rs2569190 and rs5744455 showed that there was a combined effect between the two mutant loci (ptrend = 0.011).

CONCLUSIONS: This study suggested that the genetic variation of CD14, rs5744455, is related to the susceptibility to laryngeal cancer, providing a theoretical basis for the study of the pathogenesis of laryngeal cancer.

L'articolo Study on the correlation between CD14 gene polymorphism and susceptibility to laryngeal cancer sembra essere il primo su European Review.

http://ift.tt/2yewpvZ