Biosurfactants offer environmental as well as health benefits over traditionally used chemical surfactants and heterologous production from engineered microorganisms has been demonstrated, offering containable...
https://ift.tt/2OeUecf
Τρίτη 24 Ιουλίου 2018
Production of rhamnolipids by integrated foam adsorption in a bioreactor system
Pure intravascular recurrence of CD5-positive diffuse large B-cell lymphoma primarily arising from the nasal cavities
CD5-positive diffuse large B-cell lymphoma (DLBCL) and intravascular large B-cell lymphoma (IVL) are recognized as rare subsets of large B-cell lymphoma with poor prognosis. These two categories have similar c...
https://ift.tt/2v4xzq3
Consistency of tumor and immune cell programmed cell death ligand-1 expression within and between tumor blocks using the VENTANA SP263 assay
Several anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) therapies have shown encouraging safety and clinical activity in a variety of tumor types. A potential role for PD-L1...
https://ift.tt/2Lnmrj2
UTHealth/Memorial Hermann Conduct First Sinus Surgery in U.S. Using Augmented Reality Technology
Sinus surgeons with The University of Texas Health Science Center at Houston (UTHealth) and Memorial Hermann-Texas Medical Center were the...https://ift.tt/2LMia58
Treating Esophageal Diverticula: Life-changing Surgeries for Two Patients
In most cases, Zenker's diverticula are spontaneous and occur in people over the age of 60. More complicated cases of...https://ift.tt/2uOyImy
Dr. William Yao Serves as Guest Editor of Otolaryngology Journal
William C. Yao, MD, was guest editor of "Surgical Techniques of Emergencies in Otolaryngology," in recent issue of Operative Techniques...https://ift.tt/2LMQmNT
Impact of acculturation on breast cancer treatment and survivorship care among Mexican American patients in Texas
Abstract
Purpose
Given the increasing number and diversity of cancer survivors in the USA and persistent racial/ethnic disparities in breast cancer care, we sought to examine the role of acculturation in adherence to recommended surgical treatment and survivorship care recommendations.
Methods
Study participants included 343 Mexican American women with stage I to III breast cancer who participated in the Ella Binational Breast Cancer Study and were treated at The University of Texas MD Anderson Cancer Center in Houston, Texas, between March 2007 and June 2011. Participants completed a questionnaire measuring acculturation, and clinical and demographic variables were obtained from an institutional database. Multivariable logistic regression models were constructed to examine differences in surgical procedures received and adherence to long-term survivorship care by acculturation level.
Results
Bilingual (odds ratio [OR] = 1.85; 95% confidence interval [CI] = 0.85–4.02, P = .11) and English-dominant women (OR = 2.39; 95% CI = 1.02–5.61, P = .04) were more likely to receive breast-conserving surgery (versus mastectomy) than were Spanish-dominant women. Among all patients, adherence to surveillance mammography and clinic visits decreased over time; the decline in clinic visit adherence was statistically significant (P = .005). Although no statistically significant association was found between acculturation and adherence to long-term survivorship care, receipt of breast-conserving surgery (versus mastectomy) was significantly associated with higher adherence to surveillance mammograms.
Conclusion
Acculturation may play a role in decision-making about surgical management of breast cancer, and further studies with larger samples are needed to explore its role in adherence to survivorship care recommendations. Findings from this study may help identify patients requiring additional support while making decisions pertaining to their cancer treatment and survivorship care.
https://ift.tt/2v2yIyx
Functional characterization of CYP2D7 gene variants
Pharmacogenomics, Ahead of Print.
https://ift.tt/2JRcWTW
Cancers, Vol. 10, Pages 243: Activation of ERBB4 in Glioblastoma Can Contribute to Increased Tumorigenicity and Influence Therapeutic Response
Cancers, Vol. 10, Pages 243: Activation of ERBB4 in Glioblastoma Can Contribute to Increased Tumorigenicity and Influence Therapeutic Response
Cancers doi: 10.3390/cancers10080243
Authors: Jacqueline F. Donoghue Lauren T. Kerr Naomi W. Alexander Sameer A. Greenall Anthony B. Longano Nicholas G. Gottardo Rong Wang Viviane Tabar Timothy E. Adams Paul S. Mischel Terrance G. Johns
Glioblastoma (GBM) is often resistant to conventional and targeted therapeutics. ErbB2 Receptor Tyrosine Kinase 4 (ERBB4) is expressed throughout normal brain and is an oncogene in several pediatric brain cancers; therefore, we investigated ERBB4 as a prognostic marker and therapeutic target in GBM. Using RT-qPCR, we quantified mRNA encoding total ERBB4 and known ERBB4 variants in GBM and non-neoplastic normal brain (NNB) samples. Using immunohistochemistry, we characterized the localization of total and phosphorylated ERBB4 (p-ERBB4) and EGFR protein in archived GBM samples and assessed their association with patient survival. Furthermore, we evaluated the effect of ERBB4 phosphorylation on angiogenesis and tumorigenicity in GBM xenograft models. Total ERBB4 mRNA was significantly lower in GBM than NNB samples, with the juxtamembrane JM-a and cytoplasmic CYT-2 variants predominating. ERBB4 protein was ubiquitously expressed in GBM but was not associated with patient survival. However, high p-ERBB4 in 11% of archived GBM samples, independent of p-EGFR, was associated with shorter patient survival (12.0 ± 3.2 months) than was no p-ERBB4 (22.5 ± 9.5 months). Increased ERBB4 activation was also associated with increased proliferation, angiogenesis, tumorigenicity and reduced sensitivity to anti-EGFR treatment in xenograft models. Despite low ERBB4 mRNA in GBM, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target.
https://ift.tt/2mHiffz
The agr quorum sensing system in Staphylococcus aureus cells mediates death of sub-population
In the human pathogen, Staphylococcus aureus, the agr quorum sensing system controls expression of a multitude of virulence factors and yet, agr negative cells frequently arise both in the laboratory and in some ...
https://ift.tt/2LOThWi
Burden of intestinal pathogens and associated factors among asymptomatic food handlers in South Ethiopia: emphasis on salmonellosis
The study aims to assess the burden of intestinal parasites and Salmonellosis among asymptomatic food handlers at meal serving facilities in Sodo town. Antibiotic resistance was also common and increasing among S...
https://ift.tt/2uJeQkL
Developing a synthetic psychosocial stress measure and harmonizing CVD-risk data: a way forward to GxE meta- and mega-analyses
Among many challenges in cardiovascular disease (CVD) risk prediction are interactions of genes with stress, race, and/or sex and developing robust estimates of these interactions. Improved power with larger s...
https://ift.tt/2NL8SXM
Institutional support for breastfeeding in Ghana: a case study of University of Education, Winneba
This study explored institutional support for breastfeeding student-mothers in the University of Education, Winneba, Ghana. It also examined challenges associated with combining academic work with breastfeedin...
https://ift.tt/2Ockwvz
Surgical treatment for dropped head syndrome with cervical spondylotic amyotrophy: a case report
Dropped head syndrome (DHS) is a flexion deformity of the neck that is caused by severe weakness of the neck extensor muscles. DHS occurs in combination with not only neuromuscular disorders, but also cervical...
https://ift.tt/2LMNkt7
Correction to: Correction to: The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer
Regrettably, the author metadata used for the previous correction (doi: https://ift.tt/2LyZA3v) contained an error in the tagging of W. Glenn McCluggage's name; this has been corrected. No further adjustments have been made to the Correction, or the original Guideline paper (doi: https://ift.tt/2LM3IKq).
https://ift.tt/2uMU0kg
Modified Poliovirus Tested in Glioblastoma [News in Brief]
Phase I trial provides early evidence of survival benefit in aggressive, hard-to-treat disease.
https://ift.tt/2JSLk0N
Transfer of miRNA in macrophages-derived exosomes induces drug resistance of pancreatic adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is known for its resistance to gemcitabine, which acts to inhibit cell growth by termination of DNA replication. Tumor-associated macrophages (TAM) were recently shown to contribute to gemcitabine resistance; however, the exact mechanism of this process is still unclear. Using a genetic mouse model of PDAC and electron microscopy analysis, we show that TAM communicate with the tumor microenvironment via secretion of ~90nm vesicles, which are selectively internalized by cancer cells. Transfection of artificial dsDNA (barcode fragment) to murine peritoneal macrophages and injection to mice bearing PDAC tumors revealed a 4-log higher concentration of the barcode fragment in primary tumors and in liver metastasis than in normal tissue. These macrophage-derived-exosomes (MDE) significantly decreased the sensitivity of PDAC cells to gemcitabine, in-vitro and in-vivo. This effect was mediated by the transfer of miR-365 in MDE. miR-365 impaired activation of gemcitabine by upregulation of the tri-phospho-nucleotide pool in cancer cells and the induction of the enzyme cytidine deaminase; the latter inactivates gemcitabine. Adoptive transfer of miR-365 in TAM induced gemcitabine resistance in PDAC-bearing mice, while immune transfer of the miR-365 antagonist recovered the sensitivity to gemcitabine. Mice deficient of Rab27 a/b genes, which lack exosomal secretion, responded significantly better to gemcitabine than did wildtype. These results identify MDE as key regulators of gemcitabine resistance in PDAC, and demonstrate that blocking miR-365 can potentiate gemcitabine response.
https://ift.tt/2A9Jr02
MicroRNA-30 family members inhibit breast cancer invasion, osteomimicry, and bone destruction by directly targeting multiple bone metastasis-associated genes.
MicroRNAs (miRNAs) are master regulators of gene expression that play key roles in cancer metastasis. During bone metastasis, metastatic tumor cells must rewire their biology and express genes that are normally expressed by bone cells (a process called osteomimicry), which endow tumor cells with full competence for outgrowth in the bone marrow. Here we establish miR-30 family members miR-30a, miR-30b, miR-30c, miR-30d and miR-30e as suppressors of breast cancer bone metastasis that regulate multiple pathways, including osteomimicry. Low expression of miR-30 in primary tumors from breast cancer patients were associated with poor relapse-free survival. Additionally, estrogen receptor (ER)-negative/progesterone receptor (PR)-negative breast cancer cells expressed lower miR-30 levels than their ER/PR-positive counterparts. Overexpression of miR-30 in ER/PR-negative breast cancer cells resulted in the reduction of bone metastasis burden in vivo. In vitro, miR-30 did not affect tumor cell proliferation, but did inhibit tumor cell invasion. Furthermore, overexpression of miR-30 restored bone homeostasis by reversing the effects of tumor cell-conditioned medium on osteoclastogenesis and osteoblastogenesis. A number of genes associated with osteoclastogenesis stimulation (IL-8, IL-11), osteoblastogenesis inhibition (DKK-1), tumor cell osteomimicry (RUNX2, CDH11), and invasiveness (CTGF, ITGA5, ITGB3) were identified as targets for repression by miR-30. Among these genes, silencing CDH11 or ITGA5 in ER-/PR-negative breast cancer cells recapitulated inhibitory effects of miR-30 on skeletal tumor burden in vivo. Overall, our findings provide evidence that miR-30 family members employ multiple mechanisms to impede breast cancer bone metastasis and may represent attractive targets for therapeutic intervention.
https://ift.tt/2OeR0FB
Mouse homolog of the human TP53 R337H mutation reveals its role in tumorigenesis
Inheritance of germline mutations in the tumor suppressor gene TP53 causes Li-Fraumeni syndrome (LFS), a cancer predisposition disorder. The arginine to histidine substitution at amino acid position 337 of p53 (R337H) is a founder mutation highly prevalent in southern and southeastern Brazil and is considered an LFS mutation. Although this mutation is of significant clinical interest, its role in tumorigenesis using animal models has not been described. Here we generate a knockin mouse model containing the homologous R337H mutation (mouse R334H). De novo tumorigenesis was not significantly increased in either heterozygous (p53334R/H) or homozygous (p53334H/H) p53 R334H knockin mice compared with wild-type mice. However, susceptibility to diethylnitrosamine (DEN)-induced liver carcinogenesis was increased in a mutant allele dose-dependent manner. In parallel, p53334H/H mice exposed to DEN exhibited increased DNA damage but decreased cell cycle regulation in the liver. Oligomerization of p53, which is required for transactivation of target genes, was reduced in R334H liver, consistent with its decreased nuclear activity compared to wild-type. By modeling a TP53 mutation in mice that has relatively weak cancer penetrance, this study provides in vivo evidence that the human R337H mutation can compromise p53 activity and promote tumorigenesis.
https://ift.tt/2A8Ee8A
Phase Ib Results of the Rational Combination of Selumetinib and Cyclosporin A in Advanced Solid Tumors with an Expansion Cohort in Metastatic Colorectal Cancer
MEK inhibition is of interest in cancer drug development, but clinical activity in metastatic colorectal cancer (mCRC) has been limited. Preclinical studies demonstrated Wnt pathway overexpression in KRAS mutant cell lines resistant to the MEK inhibitor, selumetinib. The combination of selumetinib and cyclosporin A (CsA), a non-canonical Wnt pathway modulator, demonstrated antitumor activity in mCRC patient-derived xenografts (PDX). To translate these results, we conducted a NCI CTEP-approved multicenter Phase I/IB trial (NCT02188264) of the combination of selumetinib and CsA. Patients with advanced solid malignancies were treated with the combination of oral selumetinib and CsA in the dose escalation phase followed by an expansion cohort of irinotecan and oxaliplatin-refractory mCRC. The expansion cohort utilized a single-agent selumetinib "run-in" to evaluate FZD2 biomarker upregulation and RAS-WT and RAS-MT stratification to identify any potential predictors of efficacy. Twenty and 19 patients were enrolled in dose escalation and expansion phases, respectively. The most common adverse events and grade 3/4 toxicities were rash, hypertension, and edema. Three dose-limiting toxicities - Grade 3 hypertension, rash and increased creatinine were reported. The maximum tolerated dose was selumetinib 75 mg BID and CsA 2 mg/kg BID on a 28-day cycle. RAS stratification did not identify any differences in response between RAS-WT and RAS-MT cancers. Two partial responses (PR), 18 stable disease (SD), and 10 progressive disease (PD) responses were observed. Combination selumetinib and CsA is well-tolerated with evidence of activity in mCRC. Future strategies for concept development include identifying better predictors of efficacy and improved Wnt pathway modulation.
https://ift.tt/2mHMW4k
Ezras Nashim: EMS by women, for women
Brooklyn EMS volunteers offer services tailored to their New York community
https://ift.tt/2mI1xwg
Biodiversity Assessment, DNA Barcoding, and the Minority Majority
Abstract
The majority of species on Earth are in "under-studied" groups, and indeed probably the majority of species remain undiscovered and undescribed. Species are natural units of evolution, and they are formed from branching phylogenetic processes that have a mathematical structure. So it follows that we should be able to develop a set of general principles that describe global patterns of species groups, like genera. Understanding such patterns would lend considerable power to the approach of "taxonomic surrogacy." In environmental assessments, ecology, and paleontology, it is common to substitute genus-level or family-level identification where definitive species identification is impractical. Clarity and confidence in fundamental patterns, based on a robust null model for species and genus level diversity, can accelerate species discovery: there are more species in the tropics, species-poor genera are very common, large genera are rare. Much hope has been placed in DNA barcoding as an effective tool to increase the pace of species discovery, but it is abundantly clear that certain mitochondrial DNA (mtDNA) markers are more or less variable in different clades and universal threshold values are impractical to delimit species. This study further examines the patterns of divergence in one common mtDNA barcode fragment, cytochrome c oxidase subunit 1at the genus level. We compared pairwise divergence in this fragment between two animal clades that have similar species richness but different evolutionary histories: birds and bivalves. We analyzed quality controlled alignments of over 39,000 published sequences in 1223 genera. Median pairwise differences at the genus level are positively correlated with the species richness of a genus, and this is not dependent of the number of sequences sampled. Unsurprisingly, sequence divergence in vertebrates was far more constrained than in evolutionarily more ancient non-vertebrate clades. Differences among the groups examined highlight the need for DNA barcode approaches to be considered in the context of specific biological groups. Vertebrates are better studied, but not necessarily representative of the majority of biodiversity. A technique that provides powerful insights for vertebrate species may be ineffective for the majority of organisms.https://ift.tt/2LJ7wfk
Resistance to radiotherapy and PD-L1 blockade is mediated by TIM-3 upregulation and regulatory T-cell infiltration
Purpose: Radiation therapy (RT) can transform the immune landscape and render poorly immunogenic tumors sensitive to PD-L1 inhibition. Here we established that the response to combined RT and PD-L1 inhibition is transient and investigated mechanisms of resistance. Experimental Design: Mechanisms of resistance to RT and PD-L1 blockade were investigated in orthotopic murine HNSCC tumors using mass cytometry and whole genome sequencing. Mice were treated with anti-PD-L1 or anti-TIM-3 alone and in combination with and without RT. Tumor growth and survival were assessed. Flow cytometry was used to assess phenotypic and functional changes in intratumoral T cell populations. Depletion of regulatory T cells was performed using anti-CD25 antibody. Results: We show that the immune checkpoint receptor, TIM-3, is upregulated on CD8 T cells and Tregs in tumors treated with RT and PD-L1 blockade. Treatment with anti-TIM-3 concurrently with anti-PD-L1 and RT led to significant tumor growth delay, enhanced T cell cytotoxicity, decreased Tregs and improved survival in orthotopic models of head and neck squamous cell carcinoma. Despite this treatment combination, the response was not durable and analysis of relapsed tumors revealed resurgence of Tregs. Targeted Treg depletion, however, restored anti-tumor immunity in mice treated with RT and dual immune checkpoint blockade and resulted in tumor rejection and induction of immunologic memory. Conclusions: These data reveal multiple layers of immunoregulation that can promote tumorigenesis, and the therapeutic potential of sequential targeting to overcome tumor resistance mechanisms. We propose that targeted Treg inhibitors may be critical for achieving durable tumor response with combined radiotherapy and immunotherapy.
https://ift.tt/2JRN9uF
Single-molecule sequencing reveals patterns of pre-existing drug resistance that suggest treatment strategies in Philadelphia-positive leukemias
Purpose: Sequential treatment with targeted therapies can result in complex combinations of resistance mutations in drug targets. This mutational complexity has spurred the development of pan-target inhibitors, i.e. therapies for which no single target mutation can cause resistance. Since the propensity for on- versus off-target resistance varies across cancer types, a deeper understanding of the mutational burden in drug targets could rationalize treatment outcomes, and prioritize pan-target inhibitors for indications where on-target mutations are most likely. Experimental design: To measure and model the mutational landscape of a drug target at high resolution, we integrated single-molecule Duplex Sequencing of the ABL1 gene in Philadelphia-positive (Ph+) leukemias with computational simulations. Results: A combination of drug target mutational burden and tumor-initiating cell fraction is sufficient to predict that most patients with chronic myeloid leukemia (CML) are unlikely to harbor ABL1 resistance mutations at the time of diagnosis, rationalizing the exceptional success of targeted therapy in this setting. In contrast, our analysis predicts that many patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) harbor multiple pre-existing resistant cells with single mutants. The emergence of compound mutations can be traced to initial use of an ABL1 inhibitor that is susceptible to resistance from single point mutations. Conclusion: These results argue that early use of therapies that achieve pan-inhibition of ABL1 resistance mutants might improve outcomes in Ph+ ALL. Our findings show how a deep understanding of the mutational burden in drug targets can be quantitatively coupled to phenotypic heterogeneity to rationalize clinical phenomena.
https://ift.tt/2LDALmU
The proteome of prostate cancer bone metastasis reveals heterogeneity with prognostic implications
Background: Bone is the most predominant site of distant metastasis in prostate cancer(PCa) and patients have limited therapeutic options at this stage. Experimental Design: We performed a system-wide quantitative proteomic analysis of bone metastatic prostate tumors from 22 patients operated to relief spinal cord compression. At the time of surgery, most patients had relapsed after androgen-deprivation therapy, while 5 were previously untreated. An extended cohort of prostate cancer bone metastases (n=65) was used for immunohistochemical validation. Results: 5067 proteins on average were identified and quantified per tumor. Compared to primary tumors(n=26), bone metastases were more heterogeneous than and showed increased levels of proteins involved in cell cycle progression, DNA damage response, RNA processing, and fatty acid b-oxidation; and reduced levels of proteins related to cell adhesion and carbohydrate metabolism.Within bone metastases, we identified two phenotypic subgroups: BM1, expressing higher levels of ARcanonical targets, and mitochondrialand Golgi apparatus resident proteins;and BM2,with increased expression of proliferation and DNA repair related proteins. The two subgroups, validated by the inverse correlation between MCM3 and PSA immunoreactivity, were related to disease prognosis, suggesting that this molecular heterogeneity should be considered when developing personalized therapies. Conclusions: This work is the first system-wide quantitative characterization of the proteome of PCa bone metastases and a valuable resource for understanding the etiology of PCa progression.
https://ift.tt/2JQLB4g
Class matters: Sensitivity of BRAF-mutant melanoma to MAPK inhibition
Mutations in BRAF outside of the 600 codon (BRAF non-V600) occur across cancer types, including in 3-5% of melanomas. The optimal treatment strategies are not clear, but could include MEK inhibitors based on pre-clinical studies. Combining BRAF and MEK inhibitors in this population may provide additional benefit.
https://ift.tt/2LCF0zh
Immunomarker Support Vector Machine Classifier for Prediction of Gastric Cancer Survival and Adjuvant Chemotherapeutic Benefit
Purpose: Current TNM staging system can't provide adequate information for prediction of prognosis and chemotherapeutic benefits. To construct a classifier to predict prognosis and identify a subset of patients who can benefit from adjuvant chemotherapy. Experimental Design: We detected expression of 15 immunohistochemistry (IHC) features in tumors from 251 GC patients and evaluated the association of their expression level with overall survival (OS) and disease-free survival (DFS). Then, integrating multiple clinicopathologic features and IHC features, we used support vector machine (SVM) -based methods to develop a prognostic classifier (GC-SVM classifier) with eleven features. Further validation of the GC-SVM classifier was performed in two validation cohort of 535 patients. Results: The GC-SVM classifier integrated patient sex, CEA, lymph node metastasis and the protein expression level of eight features, including CD3invasive margin (IM), CD3center of tumor (CT), CD45ROCT, CD57IM, CD66bIM, CD68CT and CD34. Significant differences were found between the high- and low- GC-SVM patients in 5-year OS and DFS in training and validation cohorts. Multivariate analysis revealed that the GC-SVM classifier was an independent prognostic factor. The classifier had higher predictive accuracy for OS and DFS than TNM stage and can complement the prognostic value of the TNM staging system. Further analysis revealed that stage II and III GC patients with high-GC-SVM were pone to benefit from adjuvant chemotherapy. Conclusion: The newly developed GC-SVM classifier was a powerful predictor of OS and DFS. Moreover, the GC-SVM classifier could predict which patients with stage II and III GC benefit from adjuvant chemotherapy.
https://ift.tt/2JSf9yc
Parents' Childhood Affects Their Children's Behavioral Health
TUESDAY, July 24, 2018 -- Parents' adverse childhood events (ACEs), such as abuse, neglect, or household dysfunction, can impact their children's lives, according to a study published online July 9 in Pediatrics. Adam Schickedanz, M.D., Ph.D., from...
https://ift.tt/2JRwHL9
Reduced Cognitive Function for Students During Heat Waves
TUESDAY, July 24, 2018 -- Cognitive function deficits resulting from indoor thermal conditions during heat waves affect university students, according to a study published online July 10 in PLOS Medicine. Jose Guillermo Cedeño Laurent, from the...
https://ift.tt/2Lzd6UR
Physicians and Practices Should Prepare for Emergencies
TUESDAY, July 24, 2018 -- Practices and physicians should prepare for emergency situations, such as natural disasters, network communications failures, and active shooter situations, according to an article published in Medical Economics. Physicians...
https://ift.tt/2JQDm8i
Lowering Default Number of Pills Can Reduce Prescribed Opioids
TUESDAY, July 24, 2018 -- Reducing the default number of opioid pills prescribed in an electronic medical record (EMR) system can effectively decrease the amount of opioids prescribed after procedures, according to a study published online July 18...
https://ift.tt/2LFJtB4
11 Infant Deaths Halt Trial of Sildenafil in Pregnant Women
TUESDAY, July 24, 2018 -- There have been 11 lung-related infant deaths after pregnant women in the Netherlands were given sildenafil (Viagra) to boost the growth of their babies while in the womb. The clinical trial included women whose placentas...
https://ift.tt/2JRwDLp
Acid-base fractions separated from Streblus asper leaf ethanolic extract exhibited antibacterial, antioxidant, anti-acetylcholinesterase, and neuroprotective activities
Streblus asper is a well-known plant native to Southeast Asia. Different parts of the plant have been traditionally used for various medicinal purposes. However, there is very little scientific evidence reporting...
https://ift.tt/2NEnxUr
An in vivo immunomodulatory and anti-inflammatory study of fermented Dendropanax morbifera Léveille leaf extract
Medicinal plants represent a source of new drugs for the prevention and treatment of infectious diseases. Dendropanax morbifera Léveille is an economically and medicinally important subtropical tree that has vari...
https://ift.tt/2uJ0Nvx
An evaluation of multidrug-resistant Escherichia coli isolates in urinary tract infections from Aguascalientes, Mexico: cross-sectional study
Uropathogenic Escherichia coli (UPEC) are one of the main bacteria causing urinary tract infections (UTIs). The rates of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increas...
https://ift.tt/2LN1sCz
Phytosomal curcumin causes natural killer cell-dependent repolarization of glioblastoma (GBM) tumor-associated microglia/macrophages and elimination of GBM and GBM stem cells
Abstract
Background
Glioblastoma (GBM) is a primary brain tumor with a 5-year survival rate of ≤5%. We have shown earlier that GBM-antibody-linked curcumin (CC) and also phytosomal curcumin (CCP) rescue 50–60% of GBM-bearing mice while repolarizing the tumor-associated microglia/macrophages (TAM) from the tumor-promoting M2-type to the tumoricidal M1-type. However, systemic application of CCP yields only sub-IC50 concentrations of CC in the plasma, which is unlikely to kill GBM cells directly. This study investigates the role of CC-evoked intra-GBM recruitment of activated natural killer (NK) cells in the elimination of GBM and GBM stem cells.
Methods
We have used an immune-competent syngeneic C57BL6 mouse model with the mouse-GBM GL261 cells orthotopically implanted in the brain. Using immunohistochemistry and flow cytometry, we have quantitatively analyzed the role of the intra-GBM-recruited NK cells by (i) injecting (i.p.) the NK1.1 antibody (NK1.1Ab) to temporarily eliminate the NK cells and (ii) blocking NK recruitment by injecting an IL12 antibody (IL12Ab). The treatment cohorts used randomly-chosen GL261-implanted mice and data sets were compared using two-tailed t-test or ANOVA.
Results
CCP treatment caused the GBM tumor to acquire M1-type macrophages (50–60% of the TAM) and activated NK cells. The treatment also elicited (a) suppression of the M2-linked tumor-promoting proteins STAT3, ARG1, and IL10, (b) induction of the M1-linked anti-tumor proteins STAT1 and inducible nitric oxide synthase in the TAM, (c) elimination of CD133(+) GBM stem cells, and (d) activation of caspase3 in the GBM cells. Eliminating intra-GBM NK cell recruitment caused a partial reversal of each of these effects. Concomitantly, we observed a CCP-evoked dramatic induction of the chemokine monocyte chemotactic protein-1 (MCP-1) in the TAM.
Conclusions
The recruited NK cells mediate a major part of the CCP-evoked elimination of GBM and GBM stem cells and stabilization of the TAM in the M1-like state. MCP-1 is known to activate peripheral M1-type macrophages to secrete IL12, an activator of NK cells. Based on such observations, we postulate that by binding to peripheral M1-type macrophages and IL12-activated NK cells, the brain-released chemokine MCP-1 causes recruitment of peripheral immune cells into the GBM, thereby causing destruction of the GBM cells and GBM stem cells.
https://ift.tt/2LmQmI8
Surgical excision and oncoplastic breast surgery in 32 patients with benign phyllodes tumors
Abstract
Background
The purpose of this study was to assess the effectiveness and safety in patients with benign phyllodes after performing local excision and following with intra-operative breast flap reconstruction.
Methods
Patients (n = 32) with eligible breast cystosarcoma phyllodes underwent wide local excision followed by intra-operative breast flap reconstruction. Primary outcome measures included average operative time, length of in-hospital stay, postoperative recurrence, and intra-operative and postoperative complications.
Results
Thirty-two patients who underwent surgical excision and oncoplastic breast surgery were evaluated using the BCCT.core software. A satisfactory symmetrical breast shape was achieved. The average operative time was 56.3 ± 8.2 min. The average postoperative duration of hospitalization was 3.7 ± 1.2 days. While there was no breast disease recurred during the 1 to 8-year follow-up period.
Conclusions
Wide local excision accompanied by intra-operative breast flap reconstruction could be adopted for removing benign phyllodes tumors while retaining the basic shape of the breast.
https://ift.tt/2A5WxLw
The association between sleep duration, sleep quality, and food consumption in adolescents: A cross-sectional study using the Korea Youth Risk Behavior Web-based Survey
Objective
This study examined the relationship between sleep duration, sleep quality and food consumption among adolescents.
DesignCross-sectional study.
SettingData from the 2014 and 2015 Korea Youth Risk Behavior Web-based Survey were used.
ParticipantsParticipants aged 12–18 years (n=118 462 (59 431 males and 59 031 females)) were selected.
Primary and secondary outcome measuresSleep duration, sleep quality and the frequencies of fruits, soda, soft drinks, fast food, instant noodle, confectionaries, vegetables and milk consumption.
ResultsShort sleep durations (<6 hours) were associated with higher soft drinks and confectionaries intake than longer sleep durations (9+ hours) (adjusted ORs (AORs) (95% CIs) for ≥5 times a week for soft drinks: 1.73 (1.57 to 1.91) and confectionaries: 1.32 (1.20 to 1.46); p<0.001). Poor sleep quality, with 7–8 hours of sleep, was associated with a lower intake of fruits, vegetables and milk (AORs (95% CIs) for ≥5 times a week for fruits: 0.71 (0.65 to 0.77); vegetables: 0.66 (0.58 to 0.75); and milk: 0.80 (0.74 to 0.86); each p<0.001), and higher intake of soda, soft drinks, fast food, instant noodle and confectionaries (AORs (95% CIs) for ≥5 times a week for soda: 1.55 (1.40 to 1.70); soft drinks: 1.58 (1.43 to 1.73); fast food: 1.97 (1.65 to 2.35); instant noodle: 1.55 (1.37 to 1.76); and confectionaries: 1.30 (1.18 to 1.43); each p<0.001) than good sleep quality of the same duration.
ConclusionShort sleep durations and poor sleep quality might be associated with higher consumption of unhealthier foods, such as sugar-sweetened beverages, fast food, instant noodle and confectionaries, and associated with lower consumption of fruits, vegetables and milk.
https://ift.tt/2Oejr6D
Parafollicular lymphoid tissue in follicular lymphoma: nodal versus extranodal
To the Editor:
https://ift.tt/2uNFDwm
Shanghai cognitive intervention of mild cognitive impairment for delaying progress with longitudinal evaluation-a prospective, randomized controlled study (SIMPLE): rationale, design, and methodology
Mild cognitive impairment is an early stage of Alzheimer's disease. Increasing evidence has indicated that cognitive training could improve cognitive abilities of MCI patients in multiple cognitive domains, ma...
https://ift.tt/2NK7yUH
Virologic control and severity of liver disease determine survival after radiofrequency ablation of hepatocellular carcinoma on cirrhosis
We aimed to identify the main determinants of long-term overall survival (OS), including virologic control, and recurrence after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) on cirrhosis
https://ift.tt/2uO6vfx
Antibiotic Coated Hinged Threaded Rods in the Treatment of Infected Nonunions and Intramedullary Long Bone Infections
Publication date: Available online 24 July 2018
Source: Injury
Author(s): Jae-Woo Cho, Jinil Kim, Won-Tae Cho, William T. Kent, Hyung-Jin Kim, Jong-Keon Oh
Abstract
Introduction
Local delivery of high dose antibiotics in the form of antibiotic impregnated polymethyl methacrylate (PMMA) cement beads or coated rods is commonly used in the management of long bone infections. The downsides of antibiotic cement beads for intramedullary long bone infections are associated with difficulty in removal from the medullary canal, bead breakage, and lack of stability. Antibiotic cement-coated smooth flexible guide wires, rods and nails can have complications such as delamination or debonding of the cement. In addition, the current techniques for cement rod insertion have a risk of iatrogenic joint contamination.
To improve upon this technique and decrease potential complications, we propose the use of an antibiotic cement-coated hinged threaded rod as a temporary intramedullary spacer. This technique utilizes both an antegrade and retrograde insertion of the threaded rod into the medullary canal through the bony defect site with connection at the hinge to treat intramedullary long bone infections and infected nonunions.
Material and Methods
A total of 40 patients were included in the study. The details in making the cement rod were well documented. The shape of cement rod and the integrity of the cement at the time of rod insertion and rod removal were compared to identify any cement debonding or delamination. Potential postoperative complications including iatrogenic joint infection, displacement or breakage of the threaded cement rods, and fracture displacement were all carefully documented. The preliminary biological effect of the initial debridement and antibiotic cement rod placement was determined using the negative conversion rate of intraoperative cultures.
Results
A single antibiotic coated threaded rod was inserted in 18 cases. Two separate antibiotic coated threaded rods were inserted and connected via hinge in 22 cases. There were zero cases of rod breakage and no secondary loss of reduction from antibiotic rod placement to the definitive staged operation. There were zero iatrogenic joint infections. There were zero cases of cement debonding or delamination from the rod. The conversion rate to a negative culture after initial debridement and antibiotic rod placement was 85% (34/40 cases).
Conclusions
The use of an antibiotic coated cement threaded rod with a hinge as an intramedullary spacer provides the benefits of local antibiotic delivery, offers improved construct stability, makes implant removal easier without delamination of the cement mantle, and utilizes the versatility of a hinge to prevent violation of native joints when treating infected nonunions and intramedullary long bone infections.
https://ift.tt/2uZaxB6
MiR-361-3p regulates ERK1/2-induced EMT via DUSP2 mRNA degradation in pancreatic ductal adenocarcinoma
MiR-361-3p regulates ERK1/2-induced EMT via DUSP2 mRNA degradation in pancreatic ductal adenocarcinoma
MiR-361-3p regulates ERK1/2-induced EMT via DUSP2 mRNA degradation in pancreatic ductal adenocarcinoma, Published online: 24 July 2018; doi:10.1038/s41419-018-0839-8
MiR-361-3p regulates ERK1/2-induced EMT via DUSP2 mRNA degradation in pancreatic ductal adenocarcinomahttps://ift.tt/2Odr3pX
XAF1 forms a positive feedback loop with IRF-1 to drive apoptotic stress response and suppress tumorigenesis
XAF1 forms a positive feedback loop with IRF-1 to drive apoptotic stress response and suppress tumorigenesis
XAF1 forms a positive feedback loop with IRF-1 to drive apoptotic stress response and suppress tumorigenesis, Published online: 24 July 2018; doi:10.1038/s41419-018-0867-4
XAF1 forms a positive feedback loop with IRF-1 to drive apoptotic stress response and suppress tumorigenesishttps://ift.tt/2NJdJsp
Spinal TNF-α impedes Fbxo45-dependent Munc13-1 ubiquitination to mediate neuropathic allodynia in rats
Spinal TNF-α impedes Fbxo45-dependent Munc13-1 ubiquitination to mediate neuropathic allodynia in rats
Spinal TNF-α impedes Fbxo45-dependent Munc13-1 ubiquitination to mediate neuropathic allodynia in rats, Published online: 24 July 2018; doi:10.1038/s41419-018-0859-4
Spinal TNF-α impedes Fbxo45-dependent Munc13-1 ubiquitination to mediate neuropathic allodynia in ratshttps://ift.tt/2OflnvK
Spontaneously opening GABAA receptors play a significant role in neuronal signal filtering and integration
Spontaneously opening GABAA receptors play a significant role in neuronal signal filtering and integration
Spontaneously opening GABA<sub>A</sub> receptors play a significant role in neuronal signal filtering and integration, Published online: 24 July 2018; doi:10.1038/s41419-018-0856-7
Spontaneously opening GABAA receptors play a significant role in neuronal signal filtering and integrationhttps://ift.tt/2NIGAgm
LncRNA MIR100HG promotes cell proliferation in triple-negative breast cancer through triplex formation with p27 loci
LncRNA MIR100HG promotes cell proliferation in triple-negative breast cancer through triplex formation with p27 loci
LncRNA MIR100HG promotes cell proliferation in triple-negative breast cancer through triplex formation with p27 loci, Published online: 24 July 2018; doi:10.1038/s41419-018-0869-2
LncRNA MIR100HG promotes cell proliferation in triple-negative breast cancer through triplex formation with p27 locihttps://ift.tt/2Of0gJH
Oxidative stress and autophagy-related changes during retinal degeneration and development
Oxidative stress and autophagy-related changes during retinal degeneration and development
Oxidative stress and autophagy-related changes during retinal degeneration and development, Published online: 24 July 2018; doi:10.1038/s41419-018-0855-8
Oxidative stress and autophagy-related changes during retinal degeneration and developmenthttps://ift.tt/2NJdqhf
Shutdown of ER-associated degradation pathway rescues functions of mutant iduronate 2-sulfatase linked to mucopolysaccharidosis type II
Shutdown of ER-associated degradation pathway rescues functions of mutant iduronate 2-sulfatase linked to mucopolysaccharidosis type II
Shutdown of ER-associated degradation pathway rescues functions of mutant iduronate 2-sulfatase linked to mucopolysaccharidosis type II, Published online: 24 July 2018; doi:10.1038/s41419-018-0871-8
Shutdown of ER-associated degradation pathway rescues functions of mutant iduronate 2-sulfatase linked to mucopolysaccharidosis type IIhttps://ift.tt/2uNZmMf
A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma, Published online: 24 July 2018; doi:10.1038/s41419-018-0865-6
A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanomahttps://ift.tt/2LMEP15
The Children’s International Mucositis Evaluation Scale (ChIMES) is valid and reliable for the assessment of mucositis among Brazilian children with cancer
The Children's International Mucositis Evaluation Scale (ChIMES) is considered a valid and reliable instrument for the assessment of mucositis in pediatric patients aged 0 to 18 years.
https://ift.tt/2uLZxrs
HPV vaccination as preventive approach for recurrent respiratory papillomatosis - a 22-year retrospective clinical analysis
Recurrent respiratory papillomatosis (RRP) is a rare, benign disease of the aerodigestive tract, especially the larynx, caused by infection with the human papillomavirus (HPV) types 6 or 11. Current management...
https://ift.tt/2A9whA2
Emergence of norovirus GII.P16-GII.2 strains in patients with acute gastroenteritis in Huzhou, China, 2016–2017
In late 2016, an uncommon recombinant NoV genotype called GII.P16-GII.2 caused a sharp increase in outbreaks of acute gastroenteritis in different countries of Asia and Europe, including China. However, we did...
https://ift.tt/2mIrfkA
Risk Assessment of Lymph Node Metastases in Early Gastric Adenocarcinoma Fulfilling Expanded Endoscopic Resection Criteria
Early gastric cancer (EGC) is known to present a low rate of lymph node metastases (LNMs). Gastrectomy with D2 lymphadenectomy is usually curative for EGC. Endoscopic submucosal dissection (ESD) is a well-accepted treatment modality for lesions that meet the classic criteria: those mucosal differentiated adenocarcinoma measuring 20 mm or less, without ulceration. Expanded criteria for ESD have been proposed based on null LNM rate from large gastrectomies series from Japan. Patients with LNM have been reported in Western centers, emerging the need for validation of expanded criteria.
https://ift.tt/2A9w7Zs
Evaluation of the Effect of Resveratrol and Doxorubicin on 99mTc-MIBI Uptake in Breast Cancer Cell Xenografts in Mice
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
https://ift.tt/2Lx0FbX
Neonatal Sepsis of Early Onset, and Hospital-Acquired and Community-Acquired Late Onset: A Prospective Population-Based Cohort Study
To assess the epidemiology of blood culture-proven early- (EOS) and late-onset neonatal sepsis (LOS).
https://ift.tt/2NFfVRy
Vaccination with a Novel Antigen-Specific Tolerizing DNA Vaccine Encoding CCOL2A1 Protects Rats from Experimental Rheumatoid Arthritis
Human Gene Therapy, Ahead of Print.
https://ift.tt/2JSqhuX
Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy
Human Gene Therapy, Ahead of Print.
https://ift.tt/2LzjED0
Translational Aspects of Adeno-Associated Virus–Mediated Cardiac Gene Therapy
Human Gene Therapy, Ahead of Print.
https://ift.tt/2JNEx8t
Cultivating Collaborations: Site Specific Design for Embodied Science Learning
Abstract
Immersion in well-designed outdoor environments can foster the habits of mind that enable critical and authentic scientific questions to take root in students' minds. Here we share two design cases in which careful, collaborative, and intentional design of outdoor learning environments for informal inquiry provide people of all ages with embodied opportunities to learn about the natural world, developing the capacity for understanding ecology and the ability to empathize, problem-solve, and reflect. Embodied learning, as facilitated by and in well-designed outdoor learning environments, leads students to develop new ways of seeing, new scientific questions, new ways to connect with ideas, with others, and new ways of thinking about the natural world. Using examples from our collaborative practises as experiential learning designers, we illustrate how creating the habits of mind critical to creating scientists, science-interested, and science-aware individuals benefits from providing students spaces to engage in embodied learning in nature. We show how public landscapes designed in creative partnerships between educators, scientists, designers, and the public have potential to amplify science learning for all.https://ift.tt/2LFZojb
Exposing the Science in Citizen Science: Fitness to Purpose and Intentional Design
Abstract
Citizen science is a growing phenomenon. With millions of people involved and billions of in-kind dollars contributed annually, this broad extent, fine grain approach to data collection should be garnering enthusiastic support in the mainstream science and higher education communities. However, many academic researchers demonstrate distinct biases against the use of citizen science as a source of rigorous information. To engage the public in scientific research, and the research community in the practice of citizen science, a mutual understanding is needed of accepted quality standards in science, and the corresponding specifics of project design and implementation when working with a broad public base. We define a science-based typology focused on the degree to which projects deliver the type(s) and quality of data/work needed to produce valid scientific outcomes directly useful in science and natural resource management. Where project intent includes direct contribution to science and the public is actively involved either virtually or hands-on, we examine the measures of quality assurance (methods to increase data quality during the design and implementation phases of a project) and quality control (post hoc methods to increase the quality of scientific outcomes). We suggest that high quality science can be produced with massive, largely one–off, participation if data collection is simple and quality control includes algorithm voting, statistical pruning, and/or computational modeling. Small to mid-scale projects engaging participants in repeated, often complex, sampling can advance quality through expert-led training and well-designed materials, and through independent verification. Both approaches—simplification at scale and complexity with care—generate more robust science outcomes.https://ift.tt/2JSyCPr
The Use of Mouse Splenocytes to Assess Pathogen-associated Molecular Pattern Influence on Clock Gene Expression
This protocol describes a technique using mouse splenocytes to discover pathogen-associated molecular patterns that alter molecular clock gene expression.
https://ift.tt/2A6NvhD
Experimental Protocol for Examining Behavioral Response Profiles in Larval Fish: Application to the Neuro-stimulant Caffeine
Here, we present a protocol to examine larval zebrafish and fathead minnow locomotor activities and photomotor responses (PMR) using an automated tracking software. When incorporated in common toxicology bioassays, analyses of these behaviors provide a diagnostic tool to examine chemical bioactivity. This protocol is described using caffeine, a model neurostimulant.
https://ift.tt/2A805wQ
Isolation and Analysis of Microbial Communities in Soil, Rhizosphere, and Roots in Perennial Grass Experiments
https://ift.tt/2mHg8bE
The sonographic findings of micropapillary pattern in pure mucinous carcinoma of the breast
Abstract
Background
The aim of this study was to describe the sonographic features of pure mucinous carcinoma with micropapillary pattern (MUMPC) and compare them with conventional pure mucinous breast carcinoma without micropapillary architecture (cPMBC) and mixed mucinous breast carcinoma (MMBC).
Methods
Eighty-eight patients (17 MUMPCs, 43 cPMBCs, and 28 MMBCs) were included in the study. Sonographic features according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon for ultrasound (US) were recorded and analyzed for each patient. The age, sonographic lesion size, menstrual status, mass location, palpation, tenderness, and axillary lymph node metastasis (LNM) were also analyzed.
Results
Most of the MUMPCs showed an irregular shape (82.4%, 14/17), a parallel orientation (94.1%, 16/17), a non-circumscribed margin (88.2%, 15/17), and distal acoustic enhancement (88.2%, 15/17). Furthermore, MUMPC had mixed cystic and solid components (35.3%, 6/17) and hypoechoic (29.4%, 5/17) and isoechoic (35.3%, 6/17) structures, with calcification (29.4%, 5/17) and blood flow (41.2%, 7/17) within the tumor. The differences in sonographic features were not found between the MUMPC and cPMBC and between the MUMPC and MMBC. Moreover, there was no significant difference between the three groups based on age, menstrual status, mass location, palpation, and tenderness (p > 0.05). Similar axillary LNMs were observed between MUMPC and cPMBC (p > 0.05), but both MUMPC and cPMBC were statistically different from MMBC (p < 0.05), so as the lesion size.
Conclusions
At this particular stage, it is challenging to distinguish MUMPC from cPMBC and MMBC on ultrasound according to the BI-RADS-US lexicon.
https://ift.tt/2Oa2PwG
Association between dietary protein intake and prostate cancer risk: evidence from a meta-analysis
Abstract
Background
Many studies were conducted to explore the relationship between dietary protein intake and risk of prostate cancer, obtaining inconsistent results. Therefore, this study aims to comprehensively explore the predicted role of dietary protein intake for risk of prostate cancer.
Methods
Databases of Web of Knowledge, PubMed, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang Med Online were searched up to August 30, 2017. Eligible studies were included based on our definite inclusion criteria. Summarized relative risk (RR) and corresponding 95% confidence interval (CI) were pooled with a random effects model. Sensitive analysis and publication bias were performed.
Results
At the end, a total of 12 articles comprising 13,483 prostate cancer cases and 286,245 participants were included. The summary RR and 95%CI of the highest protein intake compared to those with the lowest protein intake on prostate cancer risk were 0.993 (95%CI = 0.930–1.061), with no between-study heterogeneity found (I2 = 0.0%, P = 0.656). Moreover, the association was not significant on prostate cancer risk with animal protein intake [RR = 1.001, 95%CI = 0.917–1.092] or vegetable protein intake [RR = 0.986, 95%CI = 0.904–1.076]. The results were not changed when we conducted subgroup analysis by study design, cancer type, or geographic locations. We did not detect any publication bias using Egger's test (P = 0.296) and funnel plot.
Conclusion
Our study concluded that protein intake may be not associated on prostate cancer.
https://ift.tt/2LIgFVs
Self-standing Electrochemical Set-up to Enrich Anode-respiring Bacteria On-site
https://ift.tt/2A8jpKr
Force System with Vertical V-Bends: A 3D In Vitro Assessment of Elastic and Rigid Rectangular Archwires
https://ift.tt/2OftA34
Gemtuzumab ozogamicin for treatment of newly diagnosed CD33-positive acute myeloid leukemia
Future Oncology, Ahead of Print.
https://ift.tt/2LiJaNo
Nitrogen Dioxide Doesn't Impact Benefit of Exercise on MI
TUESDAY, July 24, 2018 -- Nitrogen dioxide does not affect the benefits of physical activity on the incidence or recurrence of myocardial infarction (MI), according to a study published online July 18 in the Journal of the American Heart...
https://ift.tt/2A6Lkup
Child Health Concerns Related to Use of Food Additives
TUESDAY, July 24, 2018 -- Regulatory changes are needed to address child health concerns related to the use of food additives, according to a policy statement published online July 23 in Pediatrics. Leonardo Trasande, M.D., M.P.P., from New York...
https://ift.tt/2O8jAsh
Reproductive, Hormonal Factors Tied to Knee OA in Women
TUESDAY, July 24, 2018 -- Female reproductive and hormonal factors are associated with incidence of knee osteoarthritis (OA), according to a study published in the July issue of Arthritis & Rheumatology. Sultana Monira Hussain, M.B.B.S, M.P.H.,...
https://ift.tt/2A6Lhid
HPV Vaccine Eliminates Advanced Skin Cancer in 97-Year-Old
TUESDAY, July 24, 2018 -- The 9-valent human papillomavirus (HPV) vaccine could be a therapeutic option for patients with cutaneous squamous cell carcinoma when surgical management is not an option, according to a case report published online July 3...
https://ift.tt/2O8kepH
VA MISSION Act May Up Costs, Lower Vet Health Care Quality
TUESDAY, July 24, 2018 -- The Veterans Affairs Maintaining Internal Systems and Strengthening Integrated Outside Networks (VA MISSION) Act may increase costs and reduce quality of health care for veterans, according to an Ideas and Opinions piece...
https://ift.tt/2A6LeD3
Infection Prevention Staffing Needs May Be Underestimated
TUESDAY, July 24, 2018 -- A comprehensive assessment of health care organization composition and structure is necessary before determining infection preventionist (IP) staffing needs, according to a study published recently in the American Journal...
https://ift.tt/2mBYTbw
Sulfonylureas As 2nd-Line T2DM Therapy Tied to Higher Event Risk
TUESDAY, July 24, 2018 -- Sulfonylureas as second-line drugs for type 2 diabetes are associated with an increased risk of cardiovascular and hypoglycemic events compared with remaining on metformin monotherapy or adding to metformin therapy,...
https://ift.tt/2A49DsX
Salmonella Spurs Recall of Swiss Rolls, Bread
TUESDAY, July 24, 2018 -- Possible Salmonella contamination has led to the recall of rolls and bread made by Flowers Foods, according to the U.S. Food and Drug Administration. The recall includes Swiss Rolls distributed across the United States and...
https://ift.tt/2mIixmi
Alcohol, Tobacco Consumption Tied to Cancer Mortality
TUESDAY, July 24, 2018 -- Alcohol consumption per capita is positively associated with overall cancer mortality among older men and women over a 20-year period, according to a study published online July 13 in JAMA Network Open. Heng Jiang, Ph.D.,...
https://ift.tt/2Adwmm6
FDA Grants First Approval for CA Drug Under New Pilot Programs
TUESDAY, July 24, 2018 -- The U.S. Food and Drug Administration has approved ribociclib (Kisqali) in combination with an aromatase inhibitor (AI) as an initial endocrine-based therapy for the treatment of pre/perimenopausal or postmenopausal women...
https://ift.tt/2OgYw2y
Nurse urges public to learn CPR after fatal vehicle crash
Lindsey Skebba said she stopped at the crash scene and noticed several bystanders had not started CPR on the victim, who later died
https://ift.tt/2LjLIKZ
Clinical, Ultrasound, and Predictability Outcomes Following Certolizumab Pegol Treatment (with Methotrexate) in Patients with Moderate-to-Severe Rheumatoid Arthritis: 52-Week Results from the CZP-SPEED Study
Abstract
Introduction
To assess the impact of certolizumab pegol (CZP) treatment on clinical, patient-reported, and musculoskeletal ultrasound outcomes and to determine the treatment response time point most predictive of long-term outcomes in Italian patients with rheumatoid arthritis (RA).
Methods
CZP-SPEED (NCT01443364) was a 52-week, open-label, prospective, interventional, multicenter study. Biologic-naïve patients with moderate-to-severe active RA, who had failed at least one DMARD treatment, received CZP (400 mg at weeks 0, 2, and 4, then 200 mg every 2 weeks) concomitantly with methotrexate. The primary objective was to identify the time point of clinical response {decrease in 28-joint Disease Activity Score [DAS28(ESR)] ≥ 1.2} most predictive of a clinical response at week 52. Additional clinical and patient-reported outcomes were measured. Power Doppler (PD) ultrasound was used to assess synovial effusion, synovial proliferation, PD signal, cartilage damage, and bone erosion according to international guidelines.
Results
A total of 132 patients were enrolled and received CZP; 91/132 (69%) completed to week 52. Predicted 52-week responses for early responders (week 2 onwards) were between 65% and 70%. Rapid improvements in joint cavity widening and PD signal were observed to week 8 and maintained to week 52. Cartilage damage and bone erosion were stable over 52 weeks. No new safety signals were identified.
Conclusion
In Italian CZP-treated patients with moderate-to-severe RA, week 12 clinical responses may be predictive of long-term response at week 52. Rapid improvements in clinical, patient-reported, and musculoskeletal ultrasound outcomes were maintained to week 52. These data may aid rheumatologists to make earlier treatment decisions.
Trial Registration
ClinicalTrials.gov identifier, NCT01443364.
Funding
UCB Pharma.
https://ift.tt/2uI1eWX
Tacrolimus population pharmacokinetic models according to CYP3A5/CYP3A4/POR genotypes in Chinese Han renal transplant patients
Pharmacogenomics, Ahead of Print.
https://ift.tt/2NGKPZH
Reprogramming of Th1 cells into regulatory T cells through rewiring of the metabolic status
Abstract
T helper type 1 (Th1) cells form one of the most stable CD4 T-cell subsets, and direct conversion of fully differentiated Th1 to regulatory T (Treg) cells has been poorly investigated. Here, we established a culture method for inducing Foxp3 from Th1 cells of mice and humans. This is achieved simply by resting Th1 cells without T-cell receptor ligation before stimulation in the presence of transforming growth factor-beta (TGF-β). We named the resulting Th1-derived Foxp3+ cells Th1reg cells. Mouse Th1reg cells showed an inducible Treg-like phenotype and suppressive ability both in vitro and in vivo. Th1reg cells could also be induced from in vivo-developed mouse Th1 cells. Unexpectedly, the resting process enabled Foxp3 expression not through epigenetic changes at the locus, but through metabolic change resulting from reduced mammalian target of rapamycin complex 1 (mTORC1) activity. mTORC1 suppressed TGF-β-induced phosphorylation of Smad2/3 in Th1 cells, which was restored in rested cells. Our study warrants future research aiming at development of immunotherapy with Th1reg cells.https://ift.tt/2OhMWVc
STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity
International Immunology, Volume 28, Issue 11, 1 November 2016, Pages 565–570, https://doi.org/10.1093/intimm/dxw038
https://ift.tt/2ND3ANN
https://ift.tt/2ND3ANN
National Variation in Opioid Prescribing and Risk of Prolonged Use for Opioid-Naive Patients Treated in the Emergency Department for Ankle Sprains
To inform opioid stewardship efforts, we describe the variation in emergency department (ED) opioid prescribing for a common minor injury, ankle sprain, and determine the association between initial opioid prescription intensity and transition to prolonged opioid use.
https://ift.tt/2OezIZe
Spotlight: 12 Lead Trainer features a wave generation algorithm that creates an EKG that simulates reality
12 Lead Trainer's goal is to drastically improve the training process, providing rhythms like those you'd see in the field.
https://ift.tt/2A6jKxk
PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells
Th1 cells are known for their enhanced stability, so mechanisms that mediate their flexibility are poorly studied. Here, Stathopoulou et al. demonstrate that plasticity of Th1 cells to Tbet+iTreg cells is mediated by PD-1 signaling via asparaginyl endopeptidase (AEP). AEP inhibition enhanced iTreg cells in GvHD and tumor models.
https://ift.tt/2uJAchE
Airway Epithelial Cell-Derived Colony Stimulating Factor-1 Promotes Allergen Sensitization
Airway epithelial cells are the first line of defense against foreign antigens and influence the microenvironment of the lung by secreting bioactive mediators. Moon and colleagues demonstrate that airway epithelial cells regulate dendritic cells for trafficking aeroallergen and subsequent development of adaptive immune responses.
https://ift.tt/2Lx3WrU
Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen
Macrophages are essential to maintain tissue homeostasis. Lim and colleagues demonstrate that perivascular LYVE-1-expressing macrophages prevent arterial stiffness by controlling the expression of collagen in vascular smooth muscle cells, a process dependent on the engagement of LYVE-1 with hyaluronan on smooth muscle cells.
https://ift.tt/2LL78NB
The Impact of Frailty and Sarcopenia on Postoperative Outcomes in Adult Spine Surgery. A Systematic Review of the Literature
Publication date: Available online 24 July 2018
Source: The Spine Journal
Author(s): Eryck Moskven, Étienne Bourassa-Moreau, Raphaele Charest-Morin, Alana Flexman, John Street
Abstract
Study Design: Systematic review.
Objectives: To identify currently used measures of frailty and sarcopenia in the adult spine surgery literature. To assess their ability to predict postoperative outcomes including mortality, morbidity, in-hospital length of stay (LOS) and discharge disposition. To determine which is the best clinical measure of frailty and sarcopenia in predicting outcome after spine surgery.
Summary of Background Data: Frailty and sarcopenia have been identified as predictors of mortality and adverse-events (AEs) in numerous non-surgical and non-spine populations. This topic is an emerging area of interest and study in patients undergoing spinal surgery.
Methods: A systematic literature review using the PRISMA methodology of MEDLINE, PubMed, Ovid, EMBASE, and Cochrane databases was performed from January 1950 to August 2017. Included studies consisted of those that examined measures of frailty or sarcopenia in adult patients undergoing any spinal surgery. The literature was synthesized and recommendations are proposed based on the GRADE system.
Results: The initial search yielded 210 results, 11 of which met our complete inclusion criteria. Seven reported on measures of frailty and four reported on measures of sarcopenia. Frailty, assessed using a variety of measurement tools, was a consistent predictor of mortality, major and minor morbidity, prolonged in-hospital LOS and discharge to a center of higher care for adult patients undergoing spinal surgery. The relationship between sarcopenia and postoperative outcomes was inconsistent due to the lack of consensus regarding the definition, measurement tools and wide variability in sarcopenia measured in the spinal population.
Conclusions: Frailty is predictive of AEs, mortality, in-hospital LOS and discharge disposition in a number of distinct spinal surgery populations. The impact of sarcopenia on postoperative outcomes is equivocal given the current state of the literature. The relationship between spinal pathology, frailty, sarcopenia and how they interact to yield outcome remains to be clarified. Frailty and sarcopenia are potentially useful tools for risk stratification of patients undergoing spinal surgery.
This systematic review was registered with PROSPERO, registration number 85096.
https://ift.tt/2A8gEce
Liver disease is an independent predictor of poor 30-day outcomes following surgery for degenerative disease of the cervical spine
Publication date: Available online 24 July 2018
Source: The Spine Journal
Author(s): Nicholas J Goel, Prateek Agarwal, Arka N Mallela, Kalil G Abdullah, Zarina S Ali, Ali K Ozturk, Neil R Malhotra, James M Schuster, H Isaac Chen
Abstract
Background and Context
The impact of underlying liver disease on surgical outcomes has been recognized in a wide variety of surgical disciplines. However, less empiric data is available about the importance of liver disease in spinal surgery.
Purpose
To measure the independent impact of underlying liver disease on 30-day outcomes following surgery for the degenerative cervical spine.
Study Design
Retrospective comparative study
Patient Sample
A cohort of 21,207 patients undergoing elective surgery for degenerative disease of the cervical spine from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP).
Outcome Measures
Outcome measures included mortality, hospital length of stay, and postoperative complications within 30 days of surgery.
Methods
The NSQIP dataset was queried for patients undergoing surgery for degenerative disease of the cervical spine from 2006 to 2015. Assessment of underlying liver disease was based on aspartate aminotransferase-to-platelet ratio index (APRI) and Model of End Stage Liver Disease-Sodium (MELD-Na) scores, computed from preoperative laboratory data. The effect of liver disease on outcomes was assessed by bivariate and multivariate analysis, in comparison with 16 other preoperative and operative factors. This study had no sources of funding, and the authors have no conflicts of interest to disclose.
Results
Liver disease could be assessed in 21,207 patients based on preoperative laboratory values. Mild liver disease was identified in 2.2% of patients and advanced disease was identified in 1.6% of patients. The 30-day mortality rates were 1.7% and 5.1% in mild and advanced liver disease respectively, as compared with 0.6% in patients with healthy livers. The 30-day complication rates were 11.8% and 31.5% in these patients respectively, compared with 8.8% in patients with healthy livers. In multivariate analysis, the presence of any liver disease (mild or advanced) was independently associated with increased risk of mortality (OR = 2.00, 95% CI = 1.12-3.55, P = 0.019), morbidity (OR = 1.35, 95% CI = 1.07-1.70, P = 0.012), and length of hospital stay longer than 7 days (OR = 1.73, 95% CI = 1.40-2.13, P < 0.001), when compared with 18 other preoperative and operative factors. Liver disease was also independently associated with perioperative respiratory failure (OR = 1.80, 95% CI = 1.21-2.68, P = 0.004), bleeding requiring transfusion (OR = 1.43, 95% CI = 1.01-2.02, P = 0.044), wound disruption (OR = 2.82, 95% CI = 1.04-7.66, P = 0.042), and unplanned reoperation (OR = 1.49, 95% CI = 1.05-2.11, P = 0.025).
Conclusions
Liver disease independently predicts poor perioperative outcome following surgery for degenerative disease of the cervical spine. Based on these findings, careful consideration of a patient's underlying liver function before surgery may prove valuable in surgical decision-making, preoperative patient counseling, and postoperative patient care.
https://ift.tt/2mGzOMO
The Contribution of the Basophil Activation Test to the Diagnosis of Hypersensitivity Reactions to Oxaliplatin
Cytostatics, mainly oxaliplatin, are widely used to treat oncological diseases. There has been an increase in hypersensitivity reactions to these drugs, mostly IgE-mediated. Skin tests are the main diagnostic method used but they may induce irritant local reactions and contamination by health care professionals. The main goals of this work were to evaluate the contribution of the basophil activation test (BAT) as a diagnostic tool for hypersensitivity reactions to oxaliplatin, and to compare the expression of CD63 and CD203c molecules. BAT was performed with oxaliplatin in 6 oncological patients with previous documented hypersensitivity reactions to oxaliplatin and in 5 controls (4 oncological patients tolerant to oxaliplatin and 1 healthy control), assessing CD63 and CD203c expression on basophil population. We found higher values for the basophil activation percentage and mean stimulation index for CD203c expression with all oxaliplatin concentrations tested (most significant at 150 μg/mL: p = 0,0087; p = 0.0222) in the patients than in controls. The same did not occur, with statistical significance, for CD63 expression. When we compared the 2 activation markers in the patients, we observed a more enhanced expression of CD203c in both evaluations, with statistical significance at the 150-μg/mL concentration (p = 0,026; p = 0,0129). These data show a higher positivity of BAT with oxaliplatin in patients with previous hypersensitivity reactions, when compared to controls, suggesting that BAT may be a promising diagnostic method as an alternative to skin tests. CD203c appears to play a more prominent role than CD63, which is consistent with what is published in the literature.
Int Arch Allergy Immunol
https://ift.tt/2A6o5Rb
Metabolomics-Based Clinical Efficacy and Effect on the Endogenous Metabolites of Tangzhiqing Tablet, a Chinese Patent Medicine for Type 2 Diabetes Mellitus with Hypertriglyceridemia
Tangzhiqing tablet (TZQ) is derived from Tangzhiqing formula, which has been used to regulate glucose and lipid metabolism in China for hundreds of years. However, as a new Chinese patent medicine, its clinical indication is not clear. To explore the clinical indication and effect on the patients with type 2 diabetes mellitus (T2DM), a pilot clinical trial and metabolomics study were carried out. In the clinical study, T2DM patients were divided into three groups and treated with TZQ, placebo, or acarbose for 12 weeks, respectively. The metabolomic study based on UPLC Q-TOF MS was performed including patients with hypertriglyceridemia in TZQ and placebo groups and healthy volunteers. The clinical results showed that TZQ could reduce glycosylated hemoglobin (HbA1c) and fasting insulin. For patients with hypertriglyceridemia in TZQ group, the levels of HbA1c all decreased and were correlated with the baseline level of triglyceride. Metabonomics data showed a significant difference between patients and healthy volunteers, and 17 biomarkers were identified. After 12-week treatment with TZQ, 11 biomarkers decreased significantly (p
https://ift.tt/2JPyuAj
Small intestine polypoid arteriovenous malformation: a stepwise approach to diagnosis in a paediatric case
We report a case of acute gastrointestinal haemorrhage due to a small intestine polypoid arteriovenous malformation (AVM) in a patient with a remote history of obscure gastrointestinal bleeding (OGIB) 8 years earlier. The diagnosis of a small intestine AVM was made using video capsule endoscopy (VCE) and confirmed using single-balloon push enteroscopy. The lesion was marked with submucosal tattoo to aid in subsequent surgical resection of the lesion with primary duodenoduodenostomy. Since our patient's initial bleeding episode, a variety of advanced tools have become widely available to aid in the localisation of OGIB. This case illustrates the use of a stepwise approach using new medical technology to identify and manage OGIB in children. VCE and push enteroscopy proved to be important diagnostic modalities in this paediatric case.
https://ift.tt/2mDGxH7
Acute peritonsillar swelling: a unique presentation for Kawasaki disease in adolescence
We report the case of a 14-year-old man with unilateral peritonsillar swelling, airway compromise and fever. On physical examination, the patient was pyrexic with trismus, dysphonia, uvula deviation, exudative unilateral peritonsillar swelling and unilateral cervical lymphadenopathy. Attempts at aspirating the prominent peritonsillar region were unsuccessful. CT head and neck identified a large inflammatory mass arising from the left palatine tonsil. The patient was treated for presumptive peritonsillar abscess. After failing to respond to intravenous antimicrobials, he progressively developed the classical sequale of Kawasaki's Disease. Echocardiogram identified coronary arteritis. Intravenous immunoglobulin and high-dose aspirin were initiated and his clinical picture improved. Kawasaki's disease mimicking an acute infective process can pose a diagnostic dilemma. It is an uncommon differential in the adolescent population. Prompt recognition and initiation of appropriate therapy are imperative to minimise morbidity.
https://ift.tt/2A6dlCi
Multiple cranial nerve injuries and neck abscesses caused by a transorally penetrating organic stick
Foreign bodies cause a remarkable number of otolaryngological emergency visits and occasionally result in life-threatening conditions and later-emerging complications. Patient recovery depends on the detection and proper extraction of all foreign materials. Despite various obtainable diagnostic tools, adequate anamnesis forms the basis of clinical reasoning and should direct later examinations and radiological imaging. This case report describes a challenging patient with a unique trauma mechanism: many pieces of a fragmented organic foreign body emerged within 1 year of the initial injury, leading to repeated operations, a long period in an intensive care unit and a long-term swallowing and speech dysfunction.
https://ift.tt/2OgGGwC
Sporadic Burkitts lymphoma masquerading as an intussuscepted Meckels diverticulum in a 9-year-old child
We report the case of a 9-year-old boy who presented with abdominal pain and was found to have an intussusception with a sporadic Burkitt's lymphoma (BL) lead point. Our case was unusual in that the patient did not present with the typical clinical features of BL, nor was he in a high-risk demographic for this uncommon disease.
https://ift.tt/2A6d7uW
Acinic cell carcinoma of the parotid gland in pregnancy: an approach to cancer in pregnancy
A 27-year-old woman presented with an enlarging painless right preauricular mass at 28 weeks' pregnant. The mass had been stable for more than 10 years, but showed rapid growth during pregnancy. Imaging and biopsy were consistent with parotid gland malignancy, with surgical resection undertaken at 33+4 weeks' gestation. Histopathology confirmed acinic cell carcinoma. Labour was induced without complication at 36+6 weeks' gestation and adjuvant radiotherapy commenced 2 weeks postpartum. At 9 months follow-up, both mother and baby were well, with no signs of disease recurrence. Rapid progression in pregnancy, of a previously stable salivary gland mass, is a common feature among reported cases and was also observed in the current case. This suggests an aetiological link between pregnancy and salivary gland tumour progression. We demonstrate successful management of a parotid gland malignancy in pregnancy and review guiding principles for cancer management in pregnancy.
https://ift.tt/2Oea9aP
Double-positive with positive anti-glomerular basement membrane antibody and ANCA-positive disease in a patient with dermatomyositis
Approximately one in four patients (23.3%) with inflammatory myositis including dermatomyositis can require evaluation for acute kidney injury. The main cause of kidney injury is acute tubular necrosis from medications or myoglobinuria, though clinicians should be aware of a wide variety of possible aetiologies. We present the case of a 44-year-old woman with stable anti-Jo1 dermatomyositis, who presented with acute kidney injury. During her hospital course, she was diagnosed with double-positive disease characterised by circulating anti-glomerular basement membrane antibody and myeloperoxidase antineutrophil cytoplasmic antibody and renal biopsy revealing crescentic glomerulonephritis with linear staining of capillary wall for IgG.
https://ift.tt/2A7MPs7
Transabdominal ultrasound-guided Gartners abscess drainage, a rare cause of acute urinary retention in second trimester of pregnancy
Acute retention of urine in pregnancy is an emergency, since it can lead to loss of pregnancy besides other dire complications. Gartner's abscess is an extremely rare cause for this condition. We present a case of a 23-year-old primigravida woman who presented to us at 24 weeks of pregnancy with acute retention of urine. After clinical and radiological evaluation, a large Gartner's abscess was found to be the cause. Per vaginal drainage of the abscess was not attempted because insertion of transvaginal probe was extremely painful for the patient, and the abscess was located high up in the anterior fornix. Transabdominal approach under sonographic guidance was used for the drainage of the abscess. Careful aspiration of the abscess, avoiding injury to the placenta, fetus and maternal bladder, revealed 60 cc of frank pus. The patient was given injection hydroxyprogesterone caproate and antibiotics in the preprocedure period. Antibiotics were continued in the postprocedure period, and she was discharged at 26 weeks of pregnancy in satisfactory condition.
https://ift.tt/2mDCZVh
Allopurinol-induced DRESS syndrome presented as a cholecystitis-like acute abdomen and aggravated by antibiotics
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening adverse drug reaction characterised by generalised skin rash, fever, lymph node enlargement and haematological abnormalities, in addition to multiorgan involvement. However, diagnosis can be challenging, with rare cases presenting as an acute abdomen.
Its aetiopathogenesis is not fully understood but inefficient drug detoxification, deregulated immune responses, reactivation of host viruses and genetic predisposition appear to be important. Furthermore, it has been recently recognised that antibiotics may act as promoters of DRESS syndrome caused by another drug. We report the case of a 48-year-old man, receiving allopurinol, who developed DRESS syndrome, initially presenting with a cholecystitis-like acute abdomen that was triggered by antibiotics. This report also emphasises the utility of performing patch skin tests to establish drug imputability.
https://ift.tt/2A5NnyJ
Unsuspected Von Hippel-Lindau syndrome in acute-onset resistant hypertension
The discovery of adrenal lesions during routine testing for hypertension requires focused consideration for adrenal overproduction of cortisol, aldosterone or metanephrines. An otherwise healthy 25-year-old woman presented with headaches, diaphoresis and hot flushes with grossly elevated urine catecholamines, normetanephrines and norepinephrine levels, yet normal metanephrines, epinephrine/epinephrine, cortisol and aldosterone levels. Subsequent functional uptake studies and scans identified bilateral adrenal adenomas consistent with phaeochromocytomas. There was no family history of phaeochromocytomas or familial syndromes; however, a targeted genetic analysis for causes of familial phaeochromocytomas identified a heterozygous germline mutation in the VHL gene consistent with Von Hippel-Lindau syndrome. In this case, the identification of the VHL mutation led to careful screening and detection of clinically occult central nervous system hemangioblastomas and pancreatic neuroendocrine tumours. Verified genetic mutations facilitated best practices for long-term surveillance protocols, preconception counselling and screening of blood relatives. The patient responded well to surgical treatment and has ongoing multidisciplinary long-term surveillance.
https://ift.tt/2mDCN8v
Corneal perforation in undiagnosed Sjögrens syndrome following topical NSAID and steroid drops post routine cataract extraction
A 74-year-old man presented with a progressive decrease in visual acuity and foreign body sensation in his right eye 8 days post uncomplicated phacoemulsification cataract surgery and intraocular lens insertion. The patient had been placed on a perioperative cataract regimen which consisted of G. Maxitrol (dexamethasone, polymyxin B sulfate, neomycin sulfate) four times a day and G. Yellox twice daily (bromfenac, a non-steroidal anti-inflammatory) for 2 weeks. On examination, he had a corneal ulcer and stromal thinning in his right eye which progressed to a full thickness perforation 12 hours later. The patient required a full thickness tectonic corneal transplant. Direct questioning revealed that this patient had both dry mouth and eyes. Serology revealed that the patient was positive for rheumatoid factor and for anti-Ro and anti-La antibodies. A parotid gland biopsy revealed significant lymphocytic infiltrate consistent with Sjögren's syndrome.
https://ift.tt/2A6l3fL
Multiple distal coronary artery thrombosis in acute myocardial infarction: a rare presentation
Description
A 47-year-old man was referred to us with severe retrosternal chest pain and diaphoresis 6 hours back. Except for smoking, he had no other risk factors for coronary artery disease. The patient was haemodynamically stable and physical examination was unremarkable. The ECG done at the referral hospital revealed changes suggestive of inferolateral wall ST elevation myocardial infarction (STEMI) (figure 1), and left circumflex coronary artery was the most likely culprit vessel. Echocardiogram revealed hypokinesia of the inferolateral wall with mild mitral regurgitation. The patient was immediately shifted to the catheterisation lab and coronary angiogram was done. However, to our surprise, both the terminal branches of the major obtuse marginal artery and the distal segment of the left anterior descending coronary artery were occluded by thrombi in their distal segments (figure 2, videos 1 and 2). Because of the distal location of the thrombi, we...
https://ift.tt/2mEhT9m
3D printing for corrective osteotomy of malunited distal radius fractures: a low-cost workflow
After a severe trauma, a 16-year-old female patient sustained multiple injuries, including a distal radius fracture of the left arm. This distal radius fracture eventually developed into a malunion. In this case, we demonstrate our preoperative low-cost workup for three-dimensional (3D) planned and assisted corrective osteotomy of a malunited distal radius fracture using an in-hospital 3D printer.
https://ift.tt/2AdeLL4
ASCO 2018: highlights of urothelial cancer and prostate cancer
Summary
Prostate cancer and urothelial carcinoma are the two most common urological cancers. The aim of this short review is to highlight abstracts from this year's ASCO Annual Meeting. The phase III SPCG-13 trial showed no difference in biochemical disease-free survival by the addition of docetaxel after primary radiation therapy of localized high-risk prostate cancer. In bone dominant metastatic castration resistant prostate cancer, the phase II radium-223 dose escalation study concluded that the currently used dose with 6 cycles of 55 kBq/kg remains the standard of care. The PARP inhibitor olaparib plus abiraterone provided a significant benefit in radiological progression-free survival compared with abiraterone alone, independent of homologous recombination repair (HRR) mutation status. In localized muscle-invasive urothelial carcinoma, two phase II trials (ABACUS and PURE-01) exploring the pathological complete remission rate of atezolizumab and pembrolizumab prior to cystectomy in cisplatin-unfit or cisplatin-fit patients are presented. Novel targeted therapies such as fibroblast growth factor receptor (FGFR) inhibitors or monoclonal antibodies against nectin-4 confirmed astonishing objective response rates in heavily pretreated metastatic urothelial carcinoma (mUC) patients, resulting in a median overall survival (OS) up to 13.8 months. Finally, updated 1‑year and 2‑year OS survival rates of pembrolizumab and atezolizumab in the first line setting of mUC are presented.
https://ift.tt/2LKUCxn
Complex Analyses of Short Inverted Repeats in All Sequenced Chloroplast DNAs
Chloroplasts are key organelles in the management of oxygen in algae and plants and are therefore crucial for all living beings that consume oxygen. Chloroplasts typically contain a circular DNA molecule with nucleus-independent replication and heredity. Using "palindrome analyser" we performed complete analyses of short inverted repeats (S-IRs) in all chloroplast DNAs (cpDNAs) available from the NCBI genome database. Our results provide basic parameters of cpDNAs including comparative information on localization, frequency, and differences in S-IR presence. In a total of 2,565 cpDNA sequences available, the average frequency of S-IRs in cpDNA genomes is 45 S-IRs/per kbp, significantly higher than that found in mitochondrial DNA sequences. The frequency of S-IRs in cpDNAs generally decreased with S-IR length, but not for S-IRs 15, 22, 24, or 27 bp long, which are significantly more abundant than S-IRs with other lengths. These results point to the importance of specific S-IRs in cpDNA genomes. Moreover, comparison by Levenshtein distance of S-IR similarities showed that a limited number of S-IR sequences are shared in the majority of cpDNAs. S-IRs are not located randomly in cpDNAs, but are length-dependently enriched in specific locations, including the repeat region, stem, introns, and tRNA regions. The highest enrichment was found for 12 bp and longer S-IRs in the stem-loop region followed by 12 bp and longer S-IRs located before the repeat region. On the other hand, S-IRs are relatively rare in rRNA sequences and around introns. These data show nonrandom and conserved arrangements of S-IRs in chloroplast genomes.
https://ift.tt/2OaMrw9
Serum iron levels increased by cancer chemotherapy correlate the chemotherapy-induced nausea and vomiting
Abstract
Background
The pathogenesis of chemotherapy-induced nausea and vomiting (CINV) is not fully elucidated. We hypothesized that serum iron levels may be associated with CINV because symptoms of iron poisoning resemble the adverse effects of chemotherapy.
Methods
Patients with lung cancer undergoing chemotherapy were included in this retrospective study where serum iron level, unsaturated iron-binding capacity (UIBC), total iron-binding capacity, and ferritin were available prior to and on days 2 and 8 of chemotherapy.
Results
Fifty-two patients were analyzed. Iron levels on day 2 were markedly increased in patients receiving highly emetogenic chemotherapy (HEC, 231.0 ± 45.0 µg/dl) and moderately emetogenic chemotherapy (MEC, 226.6 ± 44.2 µg/dl), and mildly increased in patients receiving low emetogenic chemotherapy (LEC, 104 ± 51.4 µg/dl). Significant differences in iron levels on day 2 were observed between the HEC and LEC (P = 0.002) and MEC and LEC (P = 0.0007) groups. UIBC levels decreased on day 2 (18.0 ± 17.5 µg/dl in HEC, 20.4 ± 46.8 µg/dl in MEC, and 123.9 ± 65.9 µg/dl in LEC). There were significant differences in UIBC on days 2 between the HEC and LEC (P = 0.0005) and MEC and LEC (P = 0.0015) groups. No significant changes in these parameters were observed in a minimal risk group.
Conclusions
Iron levels increased according to the emetogenic risk. Accompanied by a markedly increased iron level, non-transferrin bound iron, a highly cytotoxic form of iron, may be present in the serum. Iron removal with an iron-chelating agent may represent a novel antiemetic therapy in patients undergoing chemotherapy.
https://ift.tt/2LlNWK7
Efficacy and Safety of Aidi Injection Combined with Transcatheter Arterial Chemoembolization on Primary Hepatic Carcinoma: A Systematic Review and Meta-Analysis
Objectives. To evaluate the efficacy and safety of Aidi injection (ADI) combined with transcatheter arterial chemoembolization (TACE) for primary hepatic carcinoma (PHCC). Methods. We conducted a literature search in EMBASE, PubMed, CENTRAL, MEDLINE, CNKI, Wanfang, and VIP databases from the earliest possible year to April 2018. Randomized controlled trials (RCTs) involving ADI combined with TACE versus TACE alone for patients with PHCC were included. The Cochrane Risk of Bias tool was applied for quality assessment. Results. 22 studies involving 1611 participants were included. The clinical response rate (RR = 1.28, 95% CI: 1.17-1.40; P
https://ift.tt/2uXLvCp
Cytotoxic and Apoptotic Effects of Govaniadine Isolated from Corydalis govaniana Wall. Roots on Human Breast Cancer (MCF-7) Cells
Current breast cancer therapies have limitations in terms of increased drug resistance resulting in short-term efficacy, thus demanding the discovery of new therapeutic agents. In this study, cytotoxic activity and apoptotic effects of govaniadine isolated from Corydalis govaniana Wall. roots were determined on human breast cancer (MCF-7) cells. The SRB assay result revealed that govaniadine led to dose- and time-dependent cytotoxic effect in MCF-7 cells along with less cytotoxicity against MCF-10A cells. Govaniadine-induced apoptosis was also accompanied by upregulation of Bax, p53, and Survivin mRNA expression as assessed by real time PCR analysis. Flow cytometric analysis with Annexin V and PI staining indicated that govaniadine is a potent inducer of apoptosis in MCF-7 cell lines. Distinctive morphological changes contributed to apoptosis and DNA laddering were observed in govaniadine-treated MCF-7 cells. Caspase-7 was significantly activated in treated MCF-7 cells. Govaniadine-treated MCF-7 cells also showed enhanced levels of intracellular reactive oxygen species (ROS) and glutathione S-transferase (GST) and decreased levels of glutathione (GSH). The results indicate that govaniadine has potent and selective cytotoxic effects against MCF-7 cells and the potential to induce caspase 7 dependent apoptosis in MCF-7 cells by activation of pathways that lead to oxidative stress.
https://ift.tt/2JRoTZH
Genetic Variant rs755622 Regulates Expression of the Multiple Sclerosis Severity Modifier D-Dopachrome Tautomerase in a Sex-Specific Way
Multiple sclerosis (MS) is a sex-specific autoimmune disease involving central nervous system. Previous studies determined that macrophage migration inhibitory factor (MIF) and its homologue D-dopachrome tautomerase (DDT) sex-specifically affect MS progression. Moreover, other studies reported that rs755622 polymorphism in promoter region of MIF gene is associated with risk of MS and affects the promoter activity to regulate MIF expression in a sex-specific way. Given that MIF and DDT share a part of promoter sequence, we surmise that rs755622 can also regulate DDT expression in a sex-specific way. However, this has not yet been studied. Here, we used five large-scale expression quantitative trait loci (eQTLs) and two RNA-seq datasets from brain and blood to assess the potential influence of rs755622 variant on expression of DDT in different genders by the linear regression and differential expression analysis. The results show that the minor allele frequency of rs755622 and expression of DDT are significantly increased in males for MS subjects and this minor allele variant can significantly upregulate DDT expression for males but not females, which suggests that the regulation of DDT expression level by rs755622 can affect MS progression in males. These findings further support and expand conclusions of previous studies and may help to better understand the mechanisms of MS.
https://ift.tt/2LC30Cs
Tc-99m and Fluorescence-Labeled Anti-Flt1 Peptide as a Multimodal Tumor Imaging Agent Targeting Vascular Endothelial Growth Factor-Receptor 1
Abstract
Purpose
We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-GNQWFI, to target tumor cells, and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model.
Methods
TAMRA-GHEG-ECG-GNQWFI was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-GNQWFI with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with U87MG tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy.
Results
After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-GNQWFI complexes were prepared in high yield (> 95%). The Kd of Tc-99m TAMRA-GHEG-ECG-GNQWFI determined by saturation binding was 29.5 ± 4.5 nM. Confocal microscopy images of U87MG cells incubated with TAMRA-GHEG-ECG-GNQWFI showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumors. Tumor uptake was effectively blocked by the co-injection of an excess concentration of GNQWFI. Specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI was assessed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies.
Conclusions
In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumor cells. Tc-99m TAMRA-GHEG-ECG-GNQWFI could be a good candidate dual-modality imaging agent for tumors.
https://ift.tt/2OeuJIa
On the maverick Planctomycetes
Abstract
Planctomycetes are ubiquitous, environmentally and biotechnologically important bacteria that are key-players in global carbon- and nitrogen cycles. Ever since their first discovery in the 1920s they seemed to blur the prokaryote/eukaryote dichotomy. After initially being described as fungi and reclassified as bacteria later, they were still thought to feature a nucleus-like compartment surrounding their highly condensed DNA. Also, an endocytosis-like uptake mechanism for macromolecules was described. Besides these eukaryotic hallmark traits, Planctomycetes seemed to lack typical bacterial features such as a peptidoglycan cell wall or the universal bacterial cell division protein FtsZ, while mostly dividing by polar budding instead of binary fission. Thus, Planctomycetes were speculated to be ancestral of both, bacteria and eukaryotes. With the advent of novel microscopic techniques, along with the development of genetic tools for Planctomycetes, some of these hypotheses were revisited. Surprisingly, Planctomycetes were found to possess a peptidoglycan cell wall and to comprise a cell plan comparable to other Gram-negative bacteria as the nucleus-like structure is rather an invagination of the cytoplasmic membrane than a cohesive compartment. These finding challenge the idea of a eukaryotic ancestry of the phylum, as Planctomycetes now appear similar, yet distinct to other bacteria.https://ift.tt/2NJ6dhg
Alpha-Tocopherol Serum Levels Are Increased in Caucasian Women with Uterine Fibroids: A Pilot Study
Uterine fibroids (UFs) are benign tumors of the reproductive tract, arising from smooth muscle cells of the uterus. Steroid hormones, estrogen, and progesterone are considered to be the most important links in the pathophysiology of UFs. Alpha-tocopherol (AT) is the most active form of vitamin E. What is important as far as UFs are concerned is that ATs contain structural determinants, which makes them possible ligands for estrogen receptors (ERs). We present a retrospective cohort study performed in a university teaching hospital. We included a total of 162 patients divided into 2 groups: with UFs and controls. The effects of age, body mass index (BMI), positive medical history, parity, and AT serum concentrations on the risk for the development of UFs were investigated. Mean AT serum concentrations were 11.66 ± 4.97 μg/ml and 7.83 ± 3.13 μg/ml (medians 10.56 μg/ml and 7.42 μg/ml) in patients with UFs confirmed on ultrasound and controls, respectively. The presented difference was statistically significant. Higher BMI, positive family history, and low parity were found to be major risk factors for UFs. In our study, we confirmed that elevated serum AT concentration might be an important risk factor for UFs in Caucasian women. Further research in this area is necessary.
https://ift.tt/2A5Bn03
Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study)
Abstract
Background
At time of diagnosis, less than 10% of patients with pancreatic adenocarcinomas (PDAC) are considered to be immediately operable (i.e. resectable). Considering their poor overall survival (OS), only tumours without vascular invasion (NCCN 2017) should be considered for resection, i.e. those for which resection with disease-free margins (R0) is theoretically possible in absence of presurgery treatment. With regard to high R1 rates and undetectable locoregional and/or metastatic spreading prior to surgery explain (at least in part) the observed 1-year relapse and mortality rates of 50 and 25%, respectively. Today, upfront surgery followed by adjuvant chemotherapy is the reference treatment in Europe. The main limitation of the adjuvant approach is the low rate of completion of the full therapeutic sequence. Indeed, only 47 to 60% patients received any adjuvant therapy after resection compared to more than 75% for neoadjuvant therapy. No previous prospective study has compared this approach to a neoadjuvant FOLFIRINOX or FOLFOX chemotherapy for resectable PDAC.
Methods
PANACHE01-PRODIGE48 is a prospective multicentre controlled randomized non comparative Phase II trial, evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy (4 cycles of mFOLFIRINOX or FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) in patients with resectable PDAC. The main co-primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence.
Discussion
The "ideal" cancer treatment for resectable PDAC would have the following characteristics: administration to the highest possible proportion of patients, ability to identify fast-progressing patients (i.e. poor candidates for surgery), a low rate of R1 resections (through optimisation of local disease control), and an acceptable toxicity profile. The neoadjuvant approach may meet all these criteria. With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX, these two regimens are potential candidates for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC.
Trial registration
ClinicalTrials.gov, NCT02959879. Trial registration date: November 9, 2016.
https://ift.tt/2OdZSLG
Sulforaphane, a Chemopreventive Compound, Inhibits Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Expression in Human HT-29 Colon Cancer Cells
Background: A high expression of prostaglandin E2 (PGE2) is found in colorectal cancer. Therefore, blocking of PGE2 generation has been identified as a promising approach for anticancer therapy. Sulforaphane (SFN), an isothiocyanate derived from glucosinolate, is used as the antioxidant and anticancer agents. Methods: HT-29 cells were treated with various concentrations of SFN and compared to untreated cells for the expression of microsomal prostaglandin E synthase-1 (mPGES-1), cyclooxygenase 2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 and MMP-9 at the mRNA level. The PGE2 level was measured by ELISA assay. Apoptosis was evaluated by the proportion of sub-G1 cells. The activity of caspase-3 was determined using an enzymatic assay. HT-29 cell migration was assessed using a scratch test. Results: SFN preconditioning decreased the expression of COX-2, mPGES-1, HIF-1, VEGF, CXCR4, MMP-2, and MMP-9. An apoptotic effect of SFN was preceded by the activation of caspase-3 as well as accumulation of cells in the sub-G1 phase of the cell cycle. SFN decreased PGE2 generation and inhibited the in vitro motility/wound-healing activity of HT-29 cells. Conclusions: SFN anticancer effects are associated with antiproliferative, antiangiogenic, and antimetastatic activities arising from the downregulation of the COX-2/ mPGES-1 axis.
Cells Tissues Organs
https://ift.tt/2mGY4yk
Cells Tissues Organs
https://ift.tt/2mGY4yk
Regulation of the oncogenic phenotype by the nuclear body protein ZC3H8
Abstract
Background
The Zc3h8 gene encodes a protein with three zinc finger motifs in the C-terminal region. The protein has been identified as a component of the Little Elongation Complex, involved in transcription of small nuclear RNAs. ZC3H8 is overexpressed in a number of human and mouse breast cancer cell lines, and elevated mRNA levels are associated with a poorer prognosis for women with breast cancer.
Methods
We used RNA silencing to decrease levels of expression in mouse mammary tumor cells and overexpression of ZC3H8 in cells derived from the normal mouse mammary gland. We measured characteristics of cell behavior in vitro, including proliferation, migration, invasion, growth in soft agar, and spheroid growth. We assessed the ability of these cells to form tumors in syngeneic BALB/c mice. ZC3H8 protein was visualized in cells using confocal microscopy.
Results
Tumor cells with lower ZC3H8 expression exhibited decreased proliferation rates, slower migration, reduced ability to invade through a basement membrane, and decreased anchorage independent growth in vitro. Cells with lower ZC3H8 levels formed fewer and smaller tumors in animals. Overexpression of ZC3H8 in non-tumorigenic COMMA-D cells led to an opposite effect. ZC3H8 protein localized to both PML bodies and Cajal bodies within the nucleus. ZC3H8 has a casein kinase 2 (CK2) phosphorylation site near the N-terminus, and a CK2 inhibitor caused the numerous PML bodies and ZC3H8 to coalesce to a few larger bodies. Removal of the inhibitor restored PML bodies to their original state. A mutant ZC3H8 lacking the predicted CK2 phosphorylation site showed localization and numbers of ZC3H8/PML bodies similar to wild type. In contrast, a mutant constructed with a glutamic acid in place of the phosphorylatable threonine showed dramatically increased numbers of smaller nuclear foci.
Conclusions
These experiments demonstrate that Zc3h8 expression contributes to aggressive tumor cell behavior in vitro and in vivo. Our studies show that ZC3H8 integrity is key to maintenance of PML bodies. The work provides a link between the Little Elongation Complex, PML bodies, and the cancer cell phenotype.
https://ift.tt/2A6nZsx
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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