Τετάρτη 24 Ιανουαρίου 2018
Clinical and cytogenomic findings in OAV spectrum
The oculoauriculovertebral spectrum (OAVS) is characterized by anomalies involving the development of the first and second pharyngeal arches during the embryonic period. The phenotype is highly heterogeneous, involving ears, eyes, face, neck, and other systems and organs. There is no agreement in the literature for the minimum phenotypic inclusion criteria, but the primary phenotype involves hemifacial microsomia with facial asymmetry and microtia. Most cases are sporadic and the etiology of this syndrome is not well known. Environmental factors, family cases that demonstrate Mendelian inheritance, such as preauricular appendages, microtia, mandibular hypoplasia, and facial asymmetry; chromosomal abnormalities and some candidate genes suggest a multifactorial inheritance model. We evaluated clinical, cytogenomic and molecularly 72 patients with OAVS, and compared our findings with patients from the literature. We found 15 CNVs (copy number variations) considered pathogenic or possibly pathogenic in 13 out of 72 patients. Our results did not indicated a single candidate genomic region, but recurrent chromosomal imbalances were observed in chromosome 4 and 22, in regions containing genes relevant to the OAVS phenotype or related to known OMIM diseases suggesting different pathogenic mechanisms involved in this genetically and phenotypic heterogeneous spectrum.
http://ift.tt/2DvR7a1
Intellectual developmental disorder with cardiac arrhythmia syndrome in a child with compound heterozygous GNB5 variants
Identification of a novel compound heterozygous of GNB5 in a patient with intellectual developmental disorder with cardiac arrhytmia (IDDCA), from non-consaguineous family. Three-dimensional modelling and in silico predictions suggest that GNB5 variants are causative of the phenotype, extending the number of IDDCA patients so far identified.
http://ift.tt/2rCnSRp
Correlation between circulating endothelial progenitor cells and serum carcinoembryonic antigen level in colorectal cancer
Abstract
Circulating endothelial progenitor cells (cEPCs) play an important role in cancer development. Previous studies showed that serum carcinoembryonic antigen (CEA) levels and the number of circulating endothelial progenitor cells (cEPCs) in the peripheral blood are both involved in tumor neoangiogenesis, and can be used for monitoring tumor progression, recurrence, metastasis, and therapeutic responses. However, the clinical relevance of these biomarkers remains unknown. In this study, 40 colorectal cancer (CRC) patients and 17 healthy volunteers were recruited and the amount of cEPCs in the peripheral blood was measured by flow cytometry. The serum CEA level was determined by CEA-RIACT assay. Results showed that cEPC level positively correlated with the stage of the disease, but not with the age and gender of the patients. Moreover, patients with higher serum CEA levels had higher cEPC levels. These results provide clinical evidence for a correlation between two commonly used biomarkers. Further understanding the role of serum CEA in cEPC-mediated tumor vascularization may improve clinical CRC diagnosis and provide useful insights into the design of therapeutic interventions that target tumor vasculature.http://ift.tt/2FcWcVe
MiR-147b inhibits cell viability and promotes apoptosis of rat H9c2 cardiomyocytes via down-regulating KLF13 expression
Abstract
Recently, microRNAs (miRNAs) have been shown to involve in the process of heart failure. This study aims to investigate the functional role of miR-147b in rat H9c2 cardiomyocytes and explore the underlying molecular mechanisms. Cell viability of H9c2 cells was detected by MTT assay. Cell apoptosis was detected by flow cytometry. Expression of miR-147b and KLF13 mRNA was detected by quantitative real-time PCR. The relationship between miR-147b and KLF13 was verified by dual-luciferase reporter assay. Protein levels were detected by western blot analysis. It was found that H2O2 inhibited cell viability and promoted cell apoptosis of H9c2 cells in a concentration-dependent manner. MiR-147b overexpression suppressed cell viability and increased apoptosis in H9c2 cells, while knock-down of miR-147b increased cell viability and reduced apoptosis in H2O2-treated H9c2 cells. Luciferase reporter assay and in vitro functional assay showed that KLF13 was a downstream target of miR-147b, and KLF13 knock-down suppressed cell viability and induced apoptosis in H9c2 cells. Enforced expression of KLF13 restored the effects of miR-147b overexpression on cell viability and apoptosis in H9c2 cells. MiR-147b modulated the expression levels of apoptosis-related proteins, and the effects of miR-147b overexpression on apoptosis-related proteins levels were prevented by enforced expression of KLF13 in H9c2 cells. The in vivo experiments showed that miR-147b was up-regulated, and KLF13 was down-regulated in the myocardial tissues from rats with chronic heart failure. Collectively, miR-147b inhibits viability and promotes cell apoptosis by targeting KLF13 in H9c2 cells, which may be associated with the pathogenesis of heart failure.http://ift.tt/2DJ8irP
Single-molecule manipulation and detection
Abstract
Compared to conventional ensemble methods, studying macromolecules at single-molecule level can reveal extraordinary clear and even surprising views for a biological reaction. In the past 20 years, single-molecule techniques have been undergoing a very rapid development, and these cutting edge technologies have revolutionized the biological research by facilitating single-molecule manipulation and detection. Here we give a brief review about these advanced techniques, including optical tweezers, magnetic tweezers, atomic force microscopy (AFM), hydrodynamic flow-stretching assay, and single-molecule fluorescence resonance energy transfer (smFRET). We are trying to describe their basic principles and provide a few examples of applications for each technique. This review aims to give a rather introductory survey of single-molecule techniques for audiences with biological or biophysical background.http://ift.tt/2Fejs5b
Effect of membrane exposure on guided bone regeneration: A systematic review and meta-analysis
Abstract
Aims
This review aimed at investigating the effect of membrane exposure on guided bone regeneration (GBR) outcomes at peri-implant sites and edentulous ridges.
Material and Methods
Electronic and manual literature searches were conducted by two independent reviewers using four databases, including MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials, for articles up to February 2017. Articles were included if they were human clinical trials or case series reporting outcomes of GBR procedures with and without membrane exposure. A random-effects meta-analysis was conducted, and the weighted mean difference (WMD) between the two groups and 95% confidence interval (CI) were reported.
Results
Overall, eight articles were included in the quantitative analysis. The WMD of the horizontal bone gain at edentulous ridges was −76.24% (95% CI = −137.52% to −14.97%, p = .01) between sites with membrane exposure and without exposure. In addition, the WMD of the dehiscence reduction at peri-implant sites was −27.27% (95% CI of −45.87% to −8.68%, p = .004). Both analyses showed significantly favorable outcomes at the sites without membrane exposure.
Conclusion
Based on the findings of this study, membrane exposure after GBR procedures has a significant detrimental influence on the outcome of bone augmentation. For the edentulous ridges, the sites without membrane exposure achieved 74% more horizontal bone gain than the sites with exposure. For peri-implant dehiscence defects, the sites without membrane exposure had 27% more defect reduction than the sites with exposure.
http://ift.tt/2BqJiAI
Long-term effect of medical treatment of diarrhoea in 594 patients with SeHCAT scan diagnosed bile acid malabsorption from 2003 to 2016; a retrospective study
Summary
Background
Excessive amounts of bile acids entering the colon due to bile acid malabsorption cause chronic bile acid diarrhoea. Diagnosis is possible by measuring the retention fraction of orally ingested 75Selenium homotaurocholic acid (SeHCAT). The knowledge of long-term effects of medical treatment is sparse.
Aim
To describe diarrhoea, adherence to treatment, treatment effects and quality of life in a large, well-defined cohort of patients with bile acid diarrhoea.
Methods
A retrospective survey was performed among 594 patients with bile acid malabsorption verified by SeHCAT scans at our unit between 2003 and 2016. Questionnaires about medical history, diarrhoea, use of medication, and quality of life scores were mailed to all patients.
Results
Among 594 patients 377 (69%) responded. Among respondents, 121 (32%) had bile acid diarrhoea due to ileal disease or resection (type 1), 198 (52%) idiopathic bile acid diarrhoea (type 2) and 58 (16%) bile acid diarrhoea due to other non-ileal disease, mainly cholecystectomy (type 3). At follow-up, half of the patients, 184 (50%), reported improvement of diarrhoea. However, 273 patients (74%) still reported diarrhoea and 234 (62%) regularly used anti-diarrhoeal medication. In spite of treatment, 235 (64%) considered reduced quality of life by diarrhoea and 184 (50%) reported that diarrhoea was unaltered or worse than before established diagnosis.
Conclusion
Many patients with bile acid diarrhoea continue to have bothersome diarrhoea in spite of correct diagnosis and treatment.
http://ift.tt/2BqLA2J
Prevalence of human papillomavirus infection among Iranian women using COBAS HPV DNA testing
Abstract
Background
Persistent infection with High Risk Human Papillomavirus (HR HPV) typesplaysamajor role in the development of cervical cancer. Therefore, the detection of HR HPV types is an essential part of cervical cancer screening. The aim of this study was to estimate the prevalence of HR HPV infection among healthy women undergoing routine cervical cancer screening in Iran.
Methods
In this cross-sectional study,the results of HPV DNA typing in 2453 normal Iranian womenwhowere referred for routine cervical cancer screening from September 2015 to March 2017 were analyzed. Participants were screened using COBAS assay for HPV DNA typing and liquid based cytology.
Results
A total of 2453 healthy sexually active women were included in this study. The mean age was 35.1 ± 8.08 years. The overall prevalence of HR HPV infection was 10.3%. HPV16 was found in 73 (3%) women. The prevalence of HPV18 and other HR HPV typeswere 16(0.7%) and166 (8.2%),respectively. Approximately, 5% of the study population had an abnormal cervical cytology (ASCUS or worse), of whom 34% were infected by HR HPV.
Conclusion
The prevalence of HR HPV infection among Iranian women has increased in the recent years which indicates the need for public education and health planning toprevent this cancer through vaccination and early diagnosis using screening tests.HPV DNA typing, diagnosisand the distribution of prevalent genotypes should be considered in the development of comprehensive cervical cancer prevention programs in Iran.
http://ift.tt/2n8tRc0
Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings from a US Observational Cohort
Abstract
Introduction
To assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA).
Methods
Patients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR–BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2–immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1–3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone loss was also explored.
Results
A total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [−], 102 anti-CCP2+ [34\titer group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2− group. DXR–BMD was lower in the anti-CCP2+ vs. the anti-CCP2− groups (Gp1–3 vs. anti-CCP2−: P < 0.0001 for left and right hands). DXR–BMD decreased with increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with low DXR–BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181).
Conclusion
Among patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity.
Funding
Bristol-Myers Squibb.
Trial Registration
Clinicaltrials.gov identifier, NCT01793103.
http://ift.tt/2BqDiIc
{-}{-}{-}Pleiotropic Functions of the Chromodomain-Containing Protein Hat-trick During Oogenesis in Drosophila melanogaster
Chromatin-remodeling proteins play a profound role in the transcriptional regulation of gene expression during development. Here, we have shown that the chromodomain-containing protein Hat-trick is predominantly expressed within the oocyte nucleus, specifically within the heterochromatinized karyosome and that a mild expression is observed in follicle cells. Co-localization of Hat-trick with Heterochromatin Protein 1 and a Synaptonemal Complex component- C(3)G along with the diffused karyosome after hat-trick down-regulation shows the role of this protein in heterochromatin clustering and karyosome maintenance. Germline mosaic analysis reveals that hat-trick is required for maintaining the dorso-ventral patterning of eggs by regulating the expression of Gurken. The increased incidence of Double strand breaks (DSBs), delayed DSB repair, defects in karyosome formation, altered Vasa mobility and consequently misexpression and altered localization of Gurken in hat-trick mutant egg chambers, clearly suggest a putative involvement of Hat-trick in the early stages of oogenesis. In addition, based on phenotypic observations in hat-trick mutant egg chambers, we speculate a substantial role of hat-trick in cystoblast proliferation, oocyte determination, nurse cell endoreplication, germ cell positioning, cyst encapsulation, and nurse cell migration. Our results demonstrate that hat-trick has profound pleiotropic functions during oogenesis in Drosophila melanogaster.
http://ift.tt/2E85x1f
Systematic Functional Characterization of Human 21st Chromosome Orthologs in Caenorhabditis elegans
Individuals with Down syndrome have neurological and muscle impairments due to an additional copy of the human 21st chromosome (HSA21). Only a few of ~200 HSA21 genes encoding protein have been linked to specific Down syndrome phenotypes, while the remainder are understudied. To identify poorly characterized HSA21 genes required for nervous system function, we studied behavioral phenotypes caused by loss-of-function mutations in conserved HSA21 orthologs in the nematode Caenorhabditis elegans. We identified ten HSA21 orthologs that are required for neuromuscular behaviors: cle-1 (COL18A1), cysl-2 (CBS), dnsn-1 (DONSON), eva-1 (EVA1C), mtq-2 (N6ATM1), ncam-1 (NCAM2), pad-2 (POFUT2), pdxk-1 (PDXK), rnt-1 (RUNX1), and unc-26 (SYNJ1). We also found that three of these genes are required for normal release of the neurotransmitter acetylcholine. This includes a known synaptic gene unc-26 (SYNJ1), as well as uncharacterized genes pdxk-1 (PDXK) and mtq-2 (N6ATM1). As the first systematic functional analysis of HSA21 orthologs, this study may serve as a platform to understand genes that underlie phenotypes associated with Down syndrome.
http://ift.tt/2DyOt3f
Specific Features of Immediate Ultrastructural Changes in Brain Cortex Mitochondria of Rats with Different Tolerance to Hypoxia under Various Modes of Hypoxic Exposures
We performed ultrastructural study of cerebral cortex mitochondria in rats with different tolerance to oxygen deficiency (low resistant and highly resistant specimens). Low resistant rats were characterized by the prevalence of mitochondria with lightened matrix due to the nondense packing of cristae. By contrast, mitochondria of highly resistant animals had the dense packing of cristae. The structure of mitochondria underwent adaptive changes at 14-10% O2 in the inspired air. Under these conditions, structural characteristics of the cerebral cortex in hypoxia-sensitive rats resembled those in resistant animals. The decrease in O2 concentration to 8% was accompanied by ultrastructural signs of mitochondrial damage, which correlated with de-energization of the cell and dysfunction of adaptive signaling systems. Ultrastructural features of cerebral cortex mitochondria in animals with low and high tolerance to acute oxygen deficiency confirm the hypothesis that they are associated with two different "functionaland-metabolic portraits".
http://ift.tt/2E85tyx
Discounted Drugs for Needy Patients and Hospitals — Understanding the 340B Debate
On November 1, 2017, the Centers for Medicare and Medicaid Services (CMS) finalized its rule for reducing Medicare Part B payments to hospital outpatient departments for prescription drugs in the 340B Drug Pricing Program. Instead of reimbursing hospitals at the average sales price (ASP) plus 6%,…
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Consequences of the 340B Drug Pricing Program
The federal 340B Drug Pricing Program allows qualifying hospitals to purchase outpatient drugs at substantial discounts and to dispense or administer them to patients while receiving standard reimbursements from insurers. The program was created in 1992, but few hospitals participated until…
http://ift.tt/2n82mz5
In vitro studies of the antibacterial activity of Copaifera spp. oleoresins, sodium hypochlorite, and peracetic acid against clinical and environmental isolates recovered from a hemodialysis unit
Patients submitted to hemodialysis therapy are more susceptible to infection, especially to infection by Gram-positive bacteria. Various research works have attempted to discover new antimicrobial agents from ...
http://ift.tt/2Gfcnm4
Co-contraction characteristics of lumbar muscles in patients with lumbar disc herniation during different types of movement
Muscular performance is an important factor for the mechanical stability of lumbar spine in humans, in which, the co-contraction of lumbar muscles plays a key role. We hypothesized that when executing differen...
http://ift.tt/2FcG4Da
Evaluating Mismatch Repair Deficiency in Pancreatic Adenocarcinoma: Challenges and Recommendations
Purpose: Immune checkpoint inhibition has been shown to generate profound and durable responses in MMR-D solid tumors and has elicited interest in detection tools and strategies to guide therapeutic decision-making. Herein we address questions on the appropriate screening, detection methods, patient selection, and initiation of therapy for MMR-D PDAC and assess the utility of NGS in providing additional prognostic and predictive information for MMR-D PDAC. Experimental Design: Archival and prospectively acquired samples and matched normal DNA from N= 833 PDAC cases were analyzed using a hybridization capture based, NGS assay designed to perform targeted deep sequencing of all exons and selected introns of 341- 468 cancer-associated genes. A computational program using NGS data derived the MSI status from the tumor-normal paired genome sequencing data. Review of available germline testing, IHC, and MSI PCR results were performed to assess and confirm MMR-D and MSI status. Results: MMR-D in PDAC is a rare event among PDAC patients (7/833) occurring at a frequency of 0.8%. Loss of MMR protein expression by IHC, high mutational load and elevated MSIsensor scores were correlated with MMR-D PDAC. All 7 MMR-D PDAC patients in the study were found to have Lynch Syndrome. Four (57%) of the MMR-D patients treated with immune checkpoint blockade had treatment benefit (1 complete response; 2 partial responses; 1 stable disease). Conclusions: An integrated approach of germline testing and somatic analyses of tumor tissues in advanced PDAC using NGS may help guide future development of immune and molecularly directed therapies in PDAC patients.
http://ift.tt/2Dxmp0g
Molecular markers increase precision of the European Association of Urology non-muscle invasive bladder cancer progression risk groups
Purpose: The European Association of Urology (EAU) guidelines for non-muscle invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathological parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. Experimental Design: We prospectively included 1239 patients in follow-up for NMIBC in six European countries. Fresh frozen tumor samples were analyzed for GATA2, TBX2, TBX3 and ZIC4 methylation and FGFR3, TERT, PIK3CA and RAS mutation status. Cox-regression analyses identified markers that were significantly associated with progression to muscle-invasive disease. The progression incidence rate (PIR=rate of progression per 100 patient-years) was calculated for subgroups. Results: In our cohort, 276 patients had a low, 273 an intermediate and 555 a high risk of tumor progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%) progressed to muscle-invasive disease. The limited number of progressors in this large cohort compared to older studies is likely due to improved treatment in the last two decades. Overall, wild type FGFR3 and methylation of GATA2 and TBX3 were significantly associated with progression (HR 0.34, 2.53 and 2.64, respectively). The PIR for EAU high risk patients was 4.25. Based on FGFR3 mutation status and methylation of GATA2 this cohort could be reclassified into a good class (PIR=0.86, 26.2% of patients), a moderate class (PIR=4.32, 49.7%) and a poor class (PIR=7.66, 24.0%). Conclusions: We conclude that addition of selected biomarkers to the EAU risk stratification, increases its accuracy and identifies a subset of NMIBC patients with a very high risk of progression.
http://ift.tt/2E7rxte
Krüppel-like Factor 4 Suppresses Serine/Threonine Kinase 33 Activation and Metastasis of Gastric Cancer through Reversing Epithelial-Mesenchymal Transition
Purpose: Cancers with aberrant expression of Serine/threonine kinase 33 (STK33) is particularly aggressive. However, its expression, clinical significance and biological functions in gastric cancer remain largely unknown. In the present study, we determined the expression and function of STK33 in gastric cancer and delineated the clinical significance of Krüppel-like factor 4 (KLF4) /STK33 signaling pathway. Experimental Design: STK33 expression and its association with multiple clinicopathologic characteristics were analyzed immunohistochemically in human gastric cancer specimens. STK33 knockdown and overexpression were used to dissect the underlying mechanism of its functions in gastric cancer cells. Regulation and underlying mechanisms of STK33 expression by KLF4 in gastric cancer cells were studied using cell and molecular biological methods. Results: Drastically higher expression of STK33 was observed in gastric cancer and gastric intraepithelial neoplasia tissues compared to adjacent normal gastric tissues. Increased STK33 expression correlated directly with tumor size, lymph node and distant metastasis; and patients with low STK33 expression gastric cancer were predicted to have a favorable prognosis. Enforced expression of STK33 promoted gastric cancer cell proliferation, migration, and invasion in vitro and in vivo, whereas reduced STK33 did the opposite. Moreover, STK33 promoted epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, KLF4 transcriptionally inhibited STK33 expression in gastric cancer cells. KLF4-mediated inhibition of gastric cancer cell invasion was reversed by upregulation of STK33 expression. Conclusions: STK33 has pro-tumor function and is a critical downstream mediator of KLF4 in gastric cancer. STK33 may serve as a potential prognostic marker and therapeutic target for gastric cancer.
http://ift.tt/2Dxmdhy
Flt-3L expansion of recipient CD8{alpha}+ dendritic cells deletes alloreactive donor T cells and represents an alternative to post-transplant cyclophosphamide for the prevention of GVHD
Purpose: Allogeneic bone marrow transplantation (BMT) provides curative therapy for leukemia via immunological graft-versus-leukemia (GVL) effects. In practice, this must be balanced against life threatening pathology induced by graft-versus-host disease (GVHD). Recipient dendritic cells (DC) are thought to be important in the induction of GVL and GVHD. Experimental Design: We have utilized preclinical models of allogeneic BMT to dissect the role and modulation of recipient DC in controlling donor T cell mediated GVHD and GVL. Results: We demonstrate that recipient CD8a+ DC promote activation-induced clonal deletion of allospecific donor T cells after BMT. We compared pre-transplant fms-like tyrosine kinase-3 ligand (Flt-3L) treatment to the current clinical strategy of post-transplant cyclophosphamide (PT-Cy) therapy. Our results demonstrate superior protection from GVHD with the immunomodulatory Flt-3L approach, and similar attenuation of GVL responses with both strategies. Strikingly, Flt-3L treatment permitted maintenance of the donor polyclonal T cell pool, where PT-Cy did not. Conclusions: These data highlight pre-transplant Flt-3L therapy as a potent new therapeutic strategy to delete alloreactive T cells and prevent GVHD, which appears particularly well suited to haploidentical BMT where the control of infection and the prevention of GVHD are paramount.
http://ift.tt/2E7rkWY
Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer [Research Articles]
Primary resistance to androgen receptor (AR) directed therapies in metastatic castration-resistant prostate cancer (mCRPC) is poorly understood. We randomized 202 treatment-naive mCRPC patients to abiraterone or enzalutamide, and performed whole exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy. For these agents, which have never been directly compared, time to progression was similar. Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance. Somatic alterations in TP53, previously linked to reduced tumor dependency on AR signaling, were also independently associated with rapid resistance. Although detection of AR amplifications did not outperform standard prognostic biomarkers, AR gene structural rearrangements truncating the ligand binding domain were identified in several patients with primary resistance. These findings establish genomic drivers of resistance to first-line AR directed therapy in mCRPC and identify potential minimally-invasive biomarkers.
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Chromatin-Remodeling Genes Promote Immunotherapy Resistance [News in Brief]
Components of SWI/SNF complex help tumors evade T-cell attack.
http://ift.tt/2FcG468
Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging
Endovascular thrombectomy has been shown to be effective for the treatment of acute ischemic stroke in patients with occlusion of the first segment of the middle cerebral artery or occlusion of the internal carotid artery if treatment is initiated within 6 hours. The results of the recently…
http://ift.tt/2Gb2oy9
MicroRNA-379-5p is associate with biochemical premature ovarian insufficiency through PARP1 and XRCC6
MicroRNA-379-5p is associate with biochemical premature ovarian insufficiency through PARP1 and XRCC6
MicroRNA-379-5p is associate with biochemical premature ovarian insufficiency through <i>PARP1</i> and <i>XRCC6</i>, Published online: 24 January 2018; doi:10.1038/s41419-017-0163-8
MicroRNA-379-5p is associate with biochemical premature ovarian insufficiency through PARP1 and XRCC6http://ift.tt/2GeuyIT
Honokiol is a FOXM1 antagonist
Honokiol is a FOXM1 antagonist
Honokiol is a FOXM1 antagonist, Published online: 24 January 2018; doi:10.1038/s41419-017-0156-7
Honokiol is a FOXM1 antagonisthttp://ift.tt/2rxQriI
Induced neural stem cell-derived astrocytes modulate complement activation and mediate neuroprotection following closed head injury
Induced neural stem cell-derived astrocytes modulate complement activation and mediate neuroprotection following closed head injury
Induced neural stem cell-derived astrocytes modulate complement activation and mediate neuroprotection following closed head injury, Published online: 24 January 2018; doi:10.1038/s41419-017-0172-7
Induced neural stem cell-derived astrocytes modulate complement activation and mediate neuroprotection following closed head injuryhttp://ift.tt/2GdvE7s
Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease
Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease
Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease, Published online: 24 January 2018; doi:10.1038/s41419-017-0124-2
Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel diseasehttp://ift.tt/2rxQsTO
Identification of microRNA signature in the progression of gestational trophoblastic disease
Identification of microRNA signature in the progression of gestational trophoblastic disease
Identification of microRNA signature in the progression of gestational trophoblastic disease, Published online: 24 January 2018; doi:10.1038/s41419-017-0108-2
Identification of microRNA signature in the progression of gestational trophoblastic diseasehttp://ift.tt/2GbZiKe
HMG-box transcription factor 1: a positive regulator of the G1/S transition through the Cyclin-CDK-CDKI molecular network in nasopharyngeal carcinoma
HMG-box transcription factor 1: a positive regulator of the G1/S transition through the Cyclin-CDK-CDKI molecular network in nasopharyngeal carcinoma
HMG-box transcription factor 1: a positive regulator of the G1/S transition through the Cyclin-CDK-CDKI molecular network in nasopharyngeal carcinoma, Published online: 24 January 2018; doi:10.1038/s41419-017-0175-4
HMG-box transcription factor 1: a positive regulator of the G1/S transition through the Cyclin-CDK-CDKI molecular network in nasopharyngeal carcinomahttp://ift.tt/2rBEtEX
Differential effects of reticulophagy and mitophagy on nonalcoholic fatty liver disease
Differential effects of reticulophagy and mitophagy on nonalcoholic fatty liver disease
Differential effects of reticulophagy and mitophagy on nonalcoholic fatty liver disease, Published online: 24 January 2018; doi:10.1038/s41419-017-0136-y
Differential effects of reticulophagy and mitophagy on nonalcoholic fatty liver diseasehttp://ift.tt/2GdhumR
miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis
miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis
miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesis, Published online: 24 January 2018; doi:10.1038/s41419-017-0134-0
miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric carcinogenesishttp://ift.tt/2GaSf4C
FDA, FTC Warn Companies for Selling Illegal, Unapproved Opioid Cessation Products Using Deceptive Claims
January 24, 2018 -- The U.S. Food and Drug Administration and the Federal Trade Commission today posted joint warning letters to the marketers and distributors of 12 opioid cessation products, for illegally marketing unapproved products with claims...
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Emergency Reporting offers enhanced, highly customizable Length of Service Awards Program (LOSAP) tracking tools
Emergency Reporting's LOSAP tracking tools and reports have been enhanced to create a highly customized and user-friendly experience. Easily track and organize yearly activity such as incident and non-incident, event and committee attendance.
http://ift.tt/2Gh6o0k
Methods for Staging Pupal Periods and Measurement of Wing Pigmentation of Drosophila guttifera
Protocols for staging pupal periods and measurement of wing pigmentation of Drosophila guttifera are described. Staging and quantification of pigmentation provide a solid basis for studying developmental mechanisms of adult traits and enable interspecific comparison of trait development.
http://ift.tt/2n9fNyQ
Impact of Interventional Oncology Therapies on Tumor Microenvironment and Strategies to Enhance Their Efficacy
American Journal of Roentgenology, Ahead of Print.
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Ultrasound Guidance Versus CT Guidance for Peripheral Lung Biopsy: Performance According to Lesion Size and Pleural Contact
American Journal of Roentgenology, Ahead of Print.
http://ift.tt/2BpVuS8
Low-Dose CT for Evaluation of Suspected Urolithiasis: Diagnostic Yield for Assessment of Alternative Diagnoses
American Journal of Roentgenology, Ahead of Print.
http://ift.tt/2n78F6g
Usefulness of Testicular Volume, Apparent Diffusion Coefficient, and Normalized Apparent Diffusion Coefficient in the MRI Evaluation of Infertile Men With Azoospermia
American Journal of Roentgenology, Ahead of Print.
http://ift.tt/2BrPXKH
Progressive Sarcopenia in Patients With Colorectal Cancer Predicts Survival
American Journal of Roentgenology, Ahead of Print.
http://ift.tt/2nbMUlV
Trends and Variation in the Utilization and Diagnostic Yield of Chest Imaging for Medicare Patients With Suspected Pulmonary Embolism in the Emergency Department
American Journal of Roentgenology, Ahead of Print.
http://ift.tt/2BqajnO
Reduced immunohistochemical PTEN staining is associated with higher progression rate and recurrence episodes in non-invasive low-grade papillary urothelial carcinoma of the bladder
Abstract
Non-invasive low-grade papillary urothelial carcinoma (NILGPUC) of the bladder is regarded as a relatively indolent disease. However, its propensity for frequent recurrences constitutes a major clinical problem. Additionally, there is a progression risk of 10–15% to either a higher grade and/or a higher stage disease in these tumors. The molecular factors that will predict recurrence and progression in low-grade pTa bladder carcinoma have not yet been elucidated. Herein, we investigated the association of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) alterations with recurrence and progression in NILGPUC using immunohistochemistry. Eighty-one cases of bladder cancer initially diagnosed as NILGPUC in a single institution with follow-up were encountered after searching medical records. Tissue microarrays (TMA) that contained both tumor and non-neoplastic mucosa from each case were constructed using paraffin blocks of transurethral resections. Sections from TMA blocks were stained immunohistochemically for PTEN protein and were evaluable in 76 cases. Any absence of staining was recorded and correlated with clinical findings. Ten patients (13.2%) showed progression and 41 (53.9%) showed recurrence. Reduced PTEN expression was observed in 29 cases (38.1%). Cases with reduced PTEN had higher progression rate compared to cases with intact PTEN (p = 0.026). Tumor relapse was more frequent in cases with reduced PTEN (65.5 vs 46.8%), but this difference was not statistically significant (p = 0.112). On the other hand, decreased PTEN expression was associated with higher number of recurrence episodes (p = 0.002). PTEN seems to have a link with the disease course in NILGPUC of the bladder.
http://ift.tt/2ry0yo0
Concomitant high expression of ERα36, GRP78 and GRP94 is associated with aggressive papillary thyroid cancer behavior
Abstract
Purpose
Papillary thyroid cancer (PTC) is more common in women than in men. It has been suggested that estrogen may be involved in its development, as has previously been shown for breast, endometrial and ovarian cancer. The purpose of this study was to assess correlations between the expression of the estrogen receptor alpha36 (ERα36) and the glucose regulated proteins GRP78 and GRP94 (chaperones involved in glycoprotein folding) and various PTC clinicopathological features, as well as to evaluate the potential usefulness of these three potential oncogenic proteins in the prediction of aggressive PTC behavior.
Methods
ERα36, GRP78 and GRP94 protein expression in 218 primary PTC tissues and PTC-derived BCPAP cells was examined using immunohistochemistry, Western blotting and immunocytochemistry. The proliferative, invasive and migrative capacities of BCPAP cells in which the respective genes were either exogenously over-expressed or silenced were assessed using BrdU incorporation and Transwell assays, respectively.
Results
We found that ERα36, GRP78 and GRP94 protein expression was upregulated in the primary PTC tissues tested. We also found that ERα36, GRP78 and GRP94 expression modulation affected the proliferation, invasion and migration of PTC-derived BCPAP cells. A positive correlation and a positive feedback loop were noted between ERα36, GRP78 and GRP94 protein expression in the primary PTC tissues and in BCPAP cells, respectively. High ERα36 expression in combination with a high GRP78/ GRP94 expression was found to have a stronger correlation with extrathyroid extension (ETE), lymph node metastasis (LNM), distant metastasis (DM) and high TNM stage than high ERα36 expression in combination with either high GRP78 or high GRP94 expression (p = 0.028 for ETE, p = 0.002 for DM and p ≤ 0.001 for LNM and high TNM stage) or high ERα36 expression alone (p < 0.001 for ETE, LNM, DM and high TNM stage).
Conclusions
From our data we conclude that a concomitant high expression of ERα36, GRP78 and GRP94 is strongly associated with aggressive PTC behavior and may be used as a predictor for ETE, LNM, DM and high TNM stage.
http://ift.tt/2rFE708
Treatment of Ankle Osteoarthritis with Total Ankle Replacement Through a Lateral Transfibular Approach
We present our preoperative, operative, and postoperative protocols for the treatment of osteoarthritis of the ankle with total ankle replacement via lateral transfibular approach.
http://ift.tt/2DyS1ml
Total Internal Reflection Absorption Spectroscopy (TIRAS) for the Detection of Solvated Electrons at a Plasma-liquid Interface
This article presents a total internal reflection absorption spectroscopy (TIRAS) method for measuring short-lived free radicals at a plasma-liquid interface. In particular, TIRAS is used to identify solvated electrons based on their optical absorbance of red light near 700 nm.
http://ift.tt/2E9kG2t
A Unifying Motif for Spatial and Directional Surround Suppression
In the visual system, the response to a stimulus in a neuron's receptive field can be modulated by stimulus context, and the strength of these contextual influences vary with stimulus intensity. Recent work has shown how a theoretical model, the stabilized supralinear network (SSN), can account for such modulatory influences, using a small set of computational mechanisms. Although the predictions of the SSN have been confirmed in primary visual cortex (V1), its computational principles apply with equal validity to any cortical structure. We have therefore tested the generality of the SSN by examining modulatory influences in the middle temporal area (MT) of the macaque visual cortex, using electrophysiological recordings and pharmacological manipulations. We developed a novel stimulus that can be adjusted parametrically to be larger or smaller in the space of all possible motion directions. We found, as predicted by the SSN, that MT neurons integrate across motion directions for low-contrast stimuli, but that they exhibit suppression by the same stimuli when they are high in contrast. These results are analogous to those found in visual cortex when stimulus size is varied in the space domain. We further tested the mechanisms of inhibition using pharmacological manipulations of inhibitory efficacy. As predicted by the SSN, local manipulation of inhibitory strength altered firing rates, but did not change the strength of surround suppression. These results are consistent with the idea that the SSN can account for modulatory influences along different stimulus dimensions and in different cortical areas.
SIGNIFICANCE STATEMENT Visual neurons are selective for specific stimulus features in a region of visual space known as the receptive field, but can be modulated by stimuli outside of the receptive field. The SSN model has been proposed to account for these and other modulatory influences, and tested in V1. As this model is not specific to any particular stimulus feature or brain region, we wondered whether similar modulatory influences might be observed for other stimulus dimensions and other regions. We tested for specific patterns of modulatory influences in the domain of motion direction, using electrophysiological recordings from MT. Our data confirm the predictions of the SSN in MT, suggesting that the SSN computations might be a generic feature of sensory cortex.
http://ift.tt/2Brh74m
Early Procedural Pain Is Associated with Regionally-Specific Alterations in Thalamic Development in Preterm Neonates
Very preterm human neonates are exposed to numerous invasive procedures as part of life-saving care. Evidence suggests that repetitive neonatal procedural pain precedes long-term alterations in brain development. However, to date the link between pain and brain development has limited temporal and anatomic specificity. We hypothesized that early exposure to painful stimuli during a period of rapid brain development, before pain modulatory systems reach maturity, will predict pronounced changes in thalamic development, and thereby cognitive and motor function. In a prospective cohort study, 155 very preterm neonates (82 males, 73 females) born 24–32 weeks' gestation underwent two MRIs at median postmenstrual ages 32 and 40 weeks that included structural, metabolic, and diffusion imaging. Detailed day-by-day clinical data were collected. Cognitive and motor abilities were assessed at 3 years, corrected age. The association of early (skin breaks, birth–Scan 1) and late pain (skin breaks, Scans 1–2) with thalamic volumes and N-acetylaspartate (NAA)/choline (Cho), and fractional anisotropy of white-matter pathways was assessed. Early pain was associated with slower thalamic macrostructural growth, most pronounced in extremely premature neonates. Deformation-based morphometry analyses confirmed early pain-related volume losses were localized to somatosensory regions. In extremely preterm neonates early pain was associated with decreased thalamic NAA/Cho and microstructural alterations in thalamocortical pathways. Thalamic growth was in turn related to cognitive and motor outcomes. We observed regionally-specific alterations in the lateral thalamus and thalamocortical pathways in extremely preterm neonates exposed to more procedural pain. Findings suggest a sensitive period leading to lasting alterations in somatosensory-system development.
SIGNIFICANCE STATEMENT Early exposure to repetitive procedural pain in very preterm neonates may disrupt the development of regions involved in somatosensory processing, leading to poor functional outcomes. We demonstrate that early pain is associated with thalamic volume loss in the territory of the somatosensory thalamus and is accompanied by disruptions thalamic metabolic growth and thalamocortical pathway maturation, particularly in extremely preterm neonates. Thalamic growth was associated with cognitive and motor outcome at 3 years corrected age. Findings provide evidence for a developmentally sensitive period whereby subcortical structures in young neonates may be most vulnerable to procedural pain. Furthermore, results suggest that the thalamus may play a key role underlying the association between neonatal pain and poor neurodevelopmental outcomes in these high-risk neonates.
http://ift.tt/2n7o5qV
New product announcement: Public Access Quiklitter
SALIDA, Colo. — The new Rescue Essentials Public Access QuikLitter™ was designed specifically to be a more visible and easily accessible casualty extraction litter placed in public places, such as commercial buildings, entertainment venues, or transportation hubs. The Public Access Quiklitter, is intended to complement existing public access to AED and bleeding control stations and can be ...
http://ift.tt/2DzJAHq
Isolation and evaluation of cocktail phages for the control of multidrug-resistant Escherichia coli serotype O104: H4 and E. coli O157: H7 isolates causing diarrhea
Abstract
Escherichia coli serotype O157: H7 and E. coli O104: H4 are well known foodborne pathogens causing sever enteric illness. Using bacteriophages as biocontrol agents of some foodborne pathogens and multidrug-resistant (MDR) bacteria has a great attention nowadays. This study aims to test the effect of cocktail phages on the growth of some foodborne pathogens and MDR E. coli. Routine conventional PCR was used to confirm the identification of E. coli isolates. Double-layered culture technique was used to isolate phages from sewage water. Morphology of bacteriophage was described using transmission electron microscopy, and spot test was performed to determine host range of the phage cocktail. Phage cocktail of Siphoviridae and Podoviridae family infecting E. coli O157: H7, E. coli O104: H4 and untypeable E. coli (neither O157 nor O104) has been isolated from sewage water. Phage cocktail showed both lytic and lysogenic activity. Lytic activity was observed against E. coli O157: H7, E. coli O104: H4 isolates, Staphylococcus. aureus ATCC6538 and Pseudomonas aeruginosa ATCC 10145, while the lysogenic activity was observed against the untypeable strain. The tested phage cocktail showed a promising inhibitory action on E. coli O157: H7 and O104: H4, S. aureus ATCC6538 and P. aeruginosa ATCC 10145, suggesting the possibility of its use as a biocontrol tool or as natural food preservatives for many food products.http://ift.tt/2DAi7Jw
Glutamate residues at positions 162 and 164 influence the beta-lactamase activity of SHV-14 obtained from Klebsiella pneumoniae
Abstract
Extensive production of SHV-14 beta-lactamase makes Klebsiella pneumoniae resistant to beta-lactams. The presence of omega-loop has been reported to influence the beta-lactamase activity, which is also present in SHV-14. Its omega-loop has three glutamates in nearly alternating positions 162, 164 and 167 but their concise role on the behaviour of SHV-14 is unknown. To uncover the influence of each glutamate on SHV-14, we replaced glutamates with alanine and estimated the effect of each mutation by assessing the change in beta-lactam sensitivities in the surrogate Escherichia coli cells and catalytic efficiencies for hydrolysis with the purified proteins. On expression, the clone of wild-type SHV-14 aggravated the resistance of host by 60–500 folds against penicillin and cephalosporin groups of antibiotics. However, the expression of mutated enzymes (especially E164A) substantially reduced the resistance level as compared to the wild type, and the results were in synchrony with the estimated enzymatic efficiencies of wild-type and mutated proteins. Therefore, with further support from the in silico analysis, we hypothesise that mutation at the glutamate residues in the omega-loop of SHV-14 can considerably modulate the beta-lactam sensitivity and hydrolysis, thus revealing the importance of such glutamates as the target for inhibitor design in future.http://ift.tt/2n7vgPa
Electroactive haloalkaliphiles exhibit exceptional tolerance to free ammonia
Abstract
Electrochemical activity in bacteria has been observed in numerous environments and conditions. However, enrichments in circumneutral freshwater media where acetate is the main electron donor seem to invariably lead to the dominance of Geobacter spp. Here we report on an electroactive bacterial consortium which was enriched on acetate as electron donor, but in a medium which reproduces hydrolysed urine (high pH, high salinity and high free ammonia). The consortium was found to be free of Geobacter species, whereas a previously undescribed community dominated by species closely related to Pseudomonas and Desulfuromonas was established. The salient features of this community were as follows: (i) high electroactivity, with anodic current densities up to 47.4 ± 2.0 A m–2; (ii) haloalkaliphilicity, with top performance at a medium pH of 10 and 19.5 ± 0.5 mS cm−1; and (iii) a remarkably high tolerance to free ammonia toxicity at over 2200 mgNH3-N L−1. This community is likely to find applications in microbial electrochemical technology for nutrient recovery from source-separated urine.http://ift.tt/2DAeHXb
Social networks as a tool for science communication and public engagement: focus on Twitter
Abstract
Social networks have been used to teach and engage people about the importance of science. The integration of social networks in the daily routines of faculties and scientists is strongly recommended to increase their personal brand, improve their skills, enhance their visibility, share and communicate science to society, promote scientific culture, and even as a tool for teaching and learning. Here we review the use of Twitter in science and comment on our previous experience of using this social network as a platform for a Massive Online Open Course (MOOC) in Spain and Latin America. We propose to extend this strategy to a pan-European Microbiology MOOC in the near future.http://ift.tt/2n7SEvO
Vector-borne diseases and climate change: a European perspective
Abstract
Climate change has already impacted the transmission of a wide range of vector-borne diseases in Europe, and it will continue to do so in the coming decades. Climate change has been implicated in the observed shift of ticks to elevated altitudes and latitudes, notably including the Ixodes ricinus tick species that is a vector for Lyme borreliosis and tick-borne encephalitis. Climate change is also thought to have been a factor in the expansion of other important disease vectors in Europe: Aedes albopictus (the Asian tiger mosquito), which transmits diseases such as Zika, dengue and chikungunya, and Phlebotomus sandfly species, which transmits diseases including Leishmaniasis. In addition, highly elevated temperatures in the summer of 2010 have been associated with an epidemic of West Nile Fever in Southeast Europe and subsequent outbreaks have been linked to summer temperature anomalies. Future climate-sensitive health impacts are challenging to project quantitatively, in part due to the intricate interplay between non-climatic and climatic drivers, weather-sensitive pathogens and climate-change adaptation. Moreover, globalisation and international air travel contribute to pathogen and vector dispersion internationally. Nevertheless, monitoring forecasts of meteorological conditions can help detect epidemic precursors of vector-borne disease outbreaks and serve as early warning systems for risk reduction.http://ift.tt/2il4em3
Corneal Tissue Engineering: An In Vitro Model of the Stromal-nerve Interactions of the Human Cornea
This protocol describes a novel three-dimensional in vitro model, where corneal stromal cells and differentiated neuronal cells are cultured together to assist in the examination and understanding of the interactions of the two cell types.
http://ift.tt/2DDqGCF
Automated Protocols for Macromolecular Crystallization at the MRC Laboratory of Molecular Biology
http://ift.tt/2F6RCrx
Annals of Neurology: Volume 83, Number 1, January 2018
Antibodies against contactin associated protein-like 2 (Caspr2) are found in some patients with autoimmune encephalitis. To see how these antibodies interact with Caspr2, cultured rat hippocampal neurons were stained with antibodies against the Caspr2 protein on the cell surface (red) and with antibodies against the Caspr2 protein that can penetrate the cell (green). Nearly all of the stained protein is golden colored (overlap of red and green), indicating that it was stained with both antibodies because it was on the surface of the cell. Caspr2 antibodies may cause encephalitis by binding to nerve cells in the brain and blocking their cell surface interactions with other cells. See Patterson et al., pages 40–51, this issue.
http://ift.tt/2n4ICN1
The Challenging Landscape of Cancer and Aging: Charting a Way Forward
NCI Director Dr. Norman Sharpless discusses research on aging and cancer, including understanding the biology of aging and its relationship to cancer, the treatment of older patients, and ensuring older patients participate in cancer clinical trials.
http://ift.tt/2n4Mu0v
Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation
A subset of patients with non-alcoholic fatty liver disease develop an inflammatory condition, termed non-alcoholic steatohepatitis (NASH). NASH is characterised by hepatocellular injury, innate immune cell-mediated inflammation and progressive liver fibrosis. The mechanisms whereby hepatic inflammation occurs in NASH remain incompletely understood, but appear to be linked to the proinflammatory microenvironment created by toxic lipid-induced hepatocyte injury, termed lipotoxicity. In this review, we discuss the signalling pathways induced by sublethal hepatocyte lipid overload that contribute to the pathogenesis of NASH. Furthermore, we will review the role of proinflammatory, proangiogenic and profibrotic hepatocyte-derived extracellular vesicles as disease biomarkers and pathogenic mediators during lipotoxicity. We also review the potential therapeutic strategies to block the feed-forward loop between sublethal hepatocyte injury and liver inflammation.
http://ift.tt/2DHhMEc
Global elimination of viral hepatitis and hepatocellular carcinoma: opportunities and challenges
Global disease burden of viral hepatitis and hepatocellular carcinoma
The most common causes of hepatitis worldwide is a group of viruses known as hepatitis A, B, C, D and E virus. Most deaths from viral hepatitis are due to hepatitis B and hepatitis C. Globally, an estimated 257 million people were living with HBV and 71 million people were living with HCV, which caused 1.34 million deaths in 2015 comparable with deaths from tuberculosis and exceeding deaths from HIV.1
Both liver cancer, mostly hepatocellular carcinoma (HCC), and cirrhosis are end-stage clinical outcomes of chronic hepatitis B (CHB) and chronic hepatitis C (CHC).2 HBV and HCV are the main causes of liver cancer worldwide, and liver cancer was the seventh commonly diagnosed cancer and the second common cause of cancer death as reported in GLOBOCAN 2012.3 There was a significant increase in global deaths from liver cancer and cirrhosis...
http://ift.tt/2Fbo5N9
Chondroid nodule in the female peritoneum arises from normal tissue and not from teratoma or conception product
Abstract
The pathogenesis of benign-looking cartilaginous tissue within the peritoneum is unknown. Chondroid metaplasia of subcoelomic mesenchyme has been suggested, as has been the case for other gynecological diseases such as endometriosis, peritoneal leiomyomatosis, or gliomatosis peritonei, but has never been proven. Chondroid nodules in the peritoneum may represent either teratomatous tissue, fetal rests from a conception product, or metaplasia of pluripotent mesenchymal cells. Herein, the unique genetic characteristics of ovarian teratomas (homozygous at many polymorphic microsatellite loci) versus normal tissues (heterozygous at the same loci) were used to investigate the origin of chondroid nodules in the peritoneum. DNA samples extracted from paraffin-embedded normal peritoneal tissue and chondroid peritoneal nodules from two patients were studied. In both cases, chondroid and normal tissue showed heterozygosity at each informative microsatellite locus on different chromosomes, with a profile similar to the mother. These results indicate that peritoneal chondroid nodules arise within the peritoneum, presumably from pluripotent mesodermal stem cells, and are not related to teratomatous proliferation, or previous pregnancy. This finding shows once again the plasticity and metaplastic potential of stem cells within the peritoneal cavity.
http://ift.tt/2rxghDu
"Zero For Him" Dietary Supplement by Break Ventures/California Basics: Recall - Possible Salmonella Contamination
Audience: Consumer [Posted 01/24/2018] ISSUE: Break Ventures/California Basics is recalling its Dietary Supplement "Zero for Him 150ct" Lot# 1710-638 because it may be contaminated with Salmonella, an organism which can cause serious and...
http://ift.tt/2DBM7Vw
Personalized Needles for Microinjections in the Rodent Brain
We describe here a protocol for microinjection in the rodent brain that uses quartz needles. These needles do not produce detectable tissue damage and ensure reliable delivery even in deep regions. Moreover, they can be adapted to research needs by personalized designs and can be re-used.
http://ift.tt/2E6rgGS
Enhancement of docosahexaenoic acid (DHA) production from Schizochytrium sp. S31 using different growth medium conditions
Schizochytrium species is one of the most studied microalgae for production of docosahexaenoic acid (DHA) which is an omega-3 fatty acid with positive effects for human health. However, high cost and low yield in...
http://ift.tt/2Dy0Ah4
Cost-effective downstream processing of recombinantly produced pexiganan peptide and its antimicrobial activity
Antimicrobial peptides (AMPs) have significant potential as alternatives to classical antibiotics. However, AMPs are currently prepared using processes which are often laborious, expensive and of low-yield, th...
http://ift.tt/2E6qRnQ
Complete conversion of all typical glycosylated protopanaxatriol ginsenosides to aglycon protopanaxatriol by combined bacterial β-glycosidases
Aglycon protopanaxatriol (APPT) has valuable pharmacological effects such as anti-inflammatory and anti-stress activities. However, the complete conversion of all typical glycosylated protopanaxatriol ginsenos...
http://ift.tt/2Dx2EWG
NH EMS agency honors volunteer for 45 years of service
By Deborah McDermott Portsmouth Herald YORK, N.H. — Forty-five years ago, Mary Andrews was chief of a three-person crew on the very first ambulance owned by the fledgling York Volunteer Ambulance Association. It was stored in her garage, with a heater inside to keep the oxygen warm powered by a yellow electrical cord that snaked inside her house - and that sometimes inadvertently went on rides ...
http://ift.tt/2DBM8c2
Orai1 Plays a Crucial Role in Central Sensitization by Modulating Neuronal Excitability
Pathological pain is a common and debilitating condition that is often poorly managed. Central sensitization is an important mechanism underlying pathological pain. However, candidate molecules involved in central sensitization remain unclear. Store-operated calcium channels (SOCs) mediate important calcium signals in nonexcitable and excitable cells. SOCs have been implicated in a wide variety of human pathophysiological conditions, including immunodeficiency, occlusive vascular diseases, and cancer. However, the role of SOCs in CNS disorders has been relatively unexplored. Orai1, a key component of SOCs, is expressed in the human and rodent spinal cord dorsal horn, but its functional significance in dorsal horn neurons is poorly understood. Here we sought to explore a potential role of Orai1 in the modulation of neuronal excitability and A-type potassium channels involved in pain plasticity. Using both male and female Orai1 knock-out mice, we found that activation of Orai1 increased neuronal excitability and reduced A-type potassium channels via the protein kinase C–extracellular signal-regulated protein kinase (PKC–ERK) pathway in dorsal horn neurons. Orai1 deficiency significantly decreased acute pain induced by noxious stimuli, nearly eliminated the second phase of formalin-induced nociceptive response, markedly attenuated carrageenan-induced ipsilateral pain hypersensitivity and abolished carrageenan-induced contralateral mechanical allodynia. Consistently, carrageenan-induced increase in neuronal excitability was abolished in the dorsal horn from Orai1 mutant mice. These findings uncover a novel signaling pathway involved in the pain process and central sensitization. Our study also reveals a novel link among Orai1, ERK, A-type potassium channels, and neuronal excitability.
SIGNIFICANCE STATEMENT Orai1 is a key component of store-operated calcium channels (SOCs) in many cell types. It has been implicated in such pathological conditions as immunodeficiency, autoimmunity, and cancer. However, the role of Orai1 in CNS disorders remains poorly understood. The functional significance of Orai1 in neurons is elusive. Here we demonstrate that activation of Orai1 modulates neuronal excitability and Kv4-containing A-type potassium channels via the protein kinase C–extracellular signal-regulated protein kinase (PKC–ERK) pathway. Genetic knock-out of Orai1 nearly eliminates the second phase of formalin-induced pain and markedly attenuates carrageenan-induced pain hypersensitivity and neuronal excitability. These findings reveal a novel link between Orai1 and neuronal excitability and advance our understanding of central sensitization.
http://ift.tt/2BqmUHz
ELMOD1 Stimulates ARF6-GTP Hydrolysis to Stabilize Apical Structures in Developing Vestibular Hair Cells
Sensory hair cells require control of physical properties of their apical plasma membranes for normal development and function. Members of the ADP-ribosylation factor (ARF) small GTPase family regulate membrane trafficking and cytoskeletal assembly in many cells. We identified ELMO domain-containing protein 1 (ELMOD1), a guanine nucleoside triphosphatase activating protein (GAP) for ARF6, as the most highly enriched ARF regulator in hair cells. To characterize ELMOD1 control of trafficking, we analyzed mice of both sexes from a strain lacking functional ELMOD1 [roundabout (rda)]. In rda/rda mice, cuticular plates of utricle hair cells initially formed normally, then degenerated after postnatal day 5; large numbers of vesicles invaded the compromised cuticular plate. Hair bundles initially developed normally, but the cell's apical membrane lifted away from the cuticular plate, and stereocilia elongated and fused. Membrane trafficking in type I hair cells, measured by FM1-43 dye labeling, was altered in rda/rda mice. Consistent with the proposed GAP role for ELMOD1, the ARF6 GTP/GDP ratio was significantly elevated in rda/rda utricles compared with controls, and the level of ARF6-GTP was correlated with the severity of the rda/rda phenotype. These results suggest that conversion of ARF6 to its GDP-bound form is necessary for final stabilization of the hair bundle.
SIGNIFICANCE STATEMENT Assembly of the mechanically sensitive hair bundle of sensory hair cells requires growth and reorganization of apical actin and membrane structures. Hair bundles and apical membranes in mice with mutations in the Elmod1 gene degenerate after formation, suggesting that the ELMOD1 protein stabilizes these structures. We show that ELMOD1 is a GTPase-activating protein in hair cells for the small GTP-binding protein ARF6, known to participate in actin assembly and membrane trafficking. We propose that conversion of ARF6 into the GDP-bound form in the apical domain of hair cells is essential for stabilizing apical actin structures like the hair bundle and ensuring that the apical membrane forms appropriately around the stereocilia.
http://ift.tt/2n6KKE0
Proteolytic Processing of Neurexins by Presenilins Sustains Synaptic Vesicle Release
Proteolytic processing of synaptic adhesion components can accommodate the function of synapses to activity-dependent changes. The adhesion system formed by neurexins (Nrxns) and neuroligins (Nlgns) bidirectionally orchestrate the function of presynaptic and postsynaptic terminals. Previous studies have shown that presenilins (PS), components of the gamma-secretase complex frequently mutated in familial Alzheimer's disease, clear from glutamatergic terminals the accumulation of Nrxn C-terminal fragments (Nrxn-CTF) generated by ectodomain shedding. Here, we characterized the synaptic consequences of the proteolytic processing of Nrxns in cultured hippocampal neurons from mice and rats of both sexes. We show that activation of presynaptic Nrxns with postsynaptic Nlgn1 or inhibition of ectodomain shedding in axonal Nrxn1-β increases presynaptic release at individual terminals, likely reflecting an increase in the number of functional release sites. Importantly, inactivation of PS inhibits presynaptic release downstream of Nrxn activation, leaving synaptic vesicle recruitment unaltered. Glutamate-receptor signaling initiates the activity-dependent generation of Nrxn-CTF, which accumulate at presynaptic terminals lacking PS function. The sole expression of Nrxn-CTF decreases presynaptic release and calcium flux, recapitulating the deficits due to loss of PS function. Our data indicate that inhibition of Nrxn processing by PS is deleterious to glutamatergic function.
SIGNIFICANCE STATEMENT To gain insight into the role of presenilins (PS) in excitatory synaptic function, we address the relevance of the proteolytic processing of presynaptic neurexins (Nrxns) in glutamatergic differentiation. Using synaptic fluorescence probes in cultured hippocampal neurons, we report that trans-synaptic activation of Nrxns produces a robust increase in presynaptic calcium levels and neurotransmitter release at individual glutamatergic terminals by a mechanism that depends on normal PS activity. Abnormal accumulation of Nrxn C-terminal fragments resulting from impaired PS activity inhibits presynaptic calcium signal and neurotransmitter release, assigning synaptic defects to Nrxns as a specific PS substrate. These data may provide links into how loss of PS activity inhibits glutamatergic synaptic function in Alzheimer's disease patients.
http://ift.tt/2n8Oo0d
Neuronal Glutamate Transporters Control Dopaminergic Signaling and Compulsive Behaviors
There is an ongoing debate on the contribution of the neuronal glutamate transporter EAAC1 to the onset of compulsive behaviors. Here, we used behavioral, electrophysiological, molecular, and viral approaches in male and female mice to identify the molecular and cellular mechanisms by which EAAC1 controls the execution of repeated motor behaviors. Our findings show that, in the striatum, a brain region implicated with movement execution, EAAC1 limits group I metabotropic glutamate receptor (mGluRI) activation, facilitates D1 dopamine receptor (D1R) expression, and ensures long-term synaptic plasticity. Blocking mGluRI in slices from mice lacking EAAC1 restores D1R expression and synaptic plasticity. Conversely, activation of intracellular signaling pathways coupled to mGluRI in D1R-containing striatal neurons of mice expressing EAAC1 leads to reduced D1R protein level and increased stereotyped movement execution. These findings identify new molecular mechanisms by which EAAC1 can shape glutamatergic and dopaminergic signals and control repeated movement execution.
SIGNIFICANCE STATEMENT Genetic studies implicate Slc1a1, a gene encoding the neuronal glutamate transporter EAAC1, with obsessive-compulsive disorder (OCD). EAAC1 is abundantly expressed in the striatum, a brain region that is hyperactive in OCD. What remains unknown is how EAAC1 shapes synaptic function in the striatum. Our findings show that EAAC1 limits activation of metabotropic glutamate receptors (mGluRIs) in the striatum and, by doing so, promotes D1 dopamine receptor (D1R) expression. Targeted activation of signaling cascades coupled to mGluRIs in mice expressing EAAC1 reduces D1R expression and triggers repeated motor behaviors. These findings provide new information on the molecular basis of OCD and suggest new avenues for its treatment.
http://ift.tt/2n6Kt3W
The Protein Tyrosine Phosphatase Shp2 Regulates Oligodendrocyte Differentiation and Early Myelination and Contributes to Timely Remyelination
Shp2 is a nonreceptor protein tyrosine phosphatase that has been shown to influence neurogenesis, oligodendrogenesis, and oligodendrocyte differentiation. Furthermore, Shp2 is a known regulator of the Akt/mammalian target of rapamycin and ERK signaling pathways in multiple cellular contexts, including oligodendrocytes. Its role during later postnatal CNS development or in response to demyelination injury has not been examined. Based on the current studies, we hypothesize that Shp2 is a negative regulator of CNS myelination. Using transgenic mouse technology, we show that Shp2 is involved in oligodendrocyte differentiation and early myelination, but is not necessary for myelin maintenance. We also show that Shp2 regulates the timely differentiation of oligodendrocytes following lysolecithin-induced demyelination, although apparently normal remyelination occurs at a delayed time point. These data suggest that Shp2 is a relevant therapeutic target in demyelinating diseases such as multiple sclerosis.
SIGNIFICANCE STATEMENT In the present study, we show that the protein phosphatase Shp2 is an important mediator of oligodendrocyte differentiation and myelination, both during developmental myelination as well as during myelin regeneration. We provide important insight into the signaling mechanisms regulating myelination and propose that Shp2 acts as a transient brake to the developmental myelination process. Furthermore, we show that Shp2 regulates oligodendrocyte differentiation following demyelination and therefore has important therapeutic implications in diseases such as multiple sclerosis.
http://ift.tt/2n8wzhu
Improving combination cancer therapy: the CombiPlex® development platform
Future Oncology, Ahead of Print.
http://ift.tt/2DyETgH
Senator Ben Cardin Statement on Therapy Cap
Thank you Senator Ben Cardin (D-Md.) for your statement on the Senate floor highlighting the need for Congress to include the permanent fix to the Therapy Cap in the next spending deal. #StopTheCap
https://www.youtube.com/watch?v=zwVKoN_SM1Q
Arthri-D 120ct Dietary Supplement by Arthri-D: Recall - Possible Salmonella Contamination
Audience: Consumer [Posted 01/24/2018] ISSUE: Arthri-D is recalling its Dietary Supplement "Arthri-D 120ct" Lot#1701-092 because it may be contaminated with Salmonella, an organism which can cause serious and sometimes fatal infections in young...
http://ift.tt/2n9P9VJ
"Zero For Him" Dietary Supplement by Break Ventures/California Basics: Recall - Possible Salmonella Contamination
Audience: Consumer [Posted 01/24/2018] ISSUE: Break Ventures/California Basics is recalling its Dietary Supplement "Zero for Him 150ct" Lot# 1710-638 because it may be contaminated with Salmonella, an organism which can cause serious and...
http://ift.tt/2DBM7Vw
The impact of parity on life course blood pressure trajectories: the HUNT study in Norway
Abstract
The drop in blood pressure during pregnancy may persist postpartum, but the impact of pregnancy on blood pressure across the life course is not known. In this study we examined blood pressure trajectories for women in the years preceding and following pregnancy and compared life course trajectories of blood pressure for parous and nulliparous women. We linked information on all women who participated in the population-based, longitudinal HUNT Study, Norway with pregnancy information from the Medical Birth Registry of Norway. A total of 23,438 women were included with up to 3 blood pressure measurements per woman. Blood pressure trajectories were compared using a mixed effects linear spline model. Before first pregnancy, women who later gave birth had similar mean blood pressure to women who never gave birth. Women who delivered experienced a drop after their first birth of − 3.32 mmHg (95% CI, − 3.93, − 2.71) and − 1.98 mmHg (95% CI, − 2.43, − 1.53) in systolic and diastolic blood pressure, respectively. Subsequent pregnancies were associated with smaller reductions. These pregnancy-related reductions in blood pressure led to persistent differences in mean blood pressure, and at age 50, parous women still had lower systolic (− 1.93 mmHg; 95% CI, − 3.33, − 0.53) and diastolic (− 1.36 mmHg; 95% CI, − 2.26, − 0.46) blood pressure compared to nulliparous women. The findings suggest that the first pregnancy and, to a lesser extent, successive pregnancies are associated with lasting and clinically relevant reductions in systolic and diastolic blood pressure.
http://ift.tt/2DHFwrW
Long non-coding RNA implicated in the invasion and metastasis of head and neck cancer: possible function and mechanisms
Abstract
Head and neck cancer (HNC) ranks as the 6th most common malignancy across the world. Metastasis is a hallmark of cancer, primarily contributing to the relapse and poor prognosis of HNC. Recently, long noncoding RNAs (lncRNAs), previously considered as non-functional, are increasingly appreciated by scholars to play crucial roles in mediating HNC metastasis. LncRNAs, which are located in the nucleus and cytoplasm, mainly exert their function via epigenetic modification, transcriptional control and translational regulation. As several lncRNAs are presently demonstrated to participate in HNC metastasis, we make a summary of the functions and mechanisms regarding these lncRNAs. As shown in the literature, most lncRNAs appear to promote the metastasis of HNC. Hence, we primarily discuss the lncRNAs involved in enhancing metastasis. Additionally, more studies are needed to understand those lncRNAs without clear mechanisms. Furthermore, we introduced the upstream regulator for the aberrant expression of lncRNAs in HNC. Finally, we concisely addressed future research prospects of lncRNAs, particularly the interplay between lncRNAs and tumor immunity as well as lncRNA-targeted therapeutic techniques, and we introduced clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possibly transformative tool to study lncRNAs. Although lncRNA research is still in the initial stage, it holds great promise to be applied as a prognosticator of HNC and a therapeutic target to inhibit HNC metastasis, which could significantly enhance the outcome of HNC patients.
http://ift.tt/2rFBJqi
Effect of formaldehyde antimicrobial feed additive on the immune competence of chickens experimentally infected with a known Newcastle disease virus strain
Abstract
Thirty-seven percent (37%) formaldehyde- possessing antimicrobial activity has been used in various forms as a fumigant for mould control and as a feed additive for feed preservation. The study evaluated the effects of formaldehyde-treated poultry feed on the immune response of birds to Newcastle disease virus (NDV) infection with Kudu 113 strain. A total of 100 chicks were acquired from Zartech Hatchery, Ibadan, Nigeria. They were randomly appropriated into A, B, C and D experimental groups, with each group containing 25 birds. Group A chicks were vaccinated, fed treated feed and infected with ND virus while group B chicks were vaccinated, fed untreated feed and infected with ND virus. Chicks in group C were not vaccinated but fed treated feed and infected with ND virus whereas chicks in group D were not vaccinated, fed untreated feed and infected with ND virus. The data generated were analysed with analysis of variance (ANOVA). Formaldehyde-treated feed had no significant effect on the PCV, antibody response to NDV, organ index and feed intake but significantly affected the body weights of the birds. Formaldehyde, despite the antimicrobial activities, may not prevent infection of Newcastle disease virus infection, when used as a feed additive.
http://ift.tt/2GetGnd
Simultaneous detection of single-nucleotide variant, deletion/insertion, and fusion in lung and thyroid carcinoma using cytology specimen and an RNA-based next-generation sequencing assay
BACKGROUND
Molecular testing for epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) fusion is routinely performed in patients with stage IV lung adenocarcinoma to assess their eligibility for targeted therapy. Fine-needle aspiration (FNA)-derived material frequently is the only pathologic material available. The identification of genomic aberrations in thyroid nodules from FNA smears may help stratify cancer risk and spare patients from a second surgery. In the current study, the authors tested nucleic acid extracted from the cytology smears of lung and thyroid carcinomas for simultaneous detection of single-nucleotide variant, insertion/deletion, and gene fusion using an RNA-based next-generation sequencing assay.
METHODS
A total of 27 cases (17 lung and 10 thyroid carcinomas, the majority of which had known variants) were tested. Areas of interest were scrapped from stained smears using a scalpel. Total nucleic acid was extracted. Gene fusion and mutational analysis was performed using the Comprehensive Thyroid and Lung FusionPlex Assay. Data were analyzed using the analysis pipeline provided by the vendor. Eleven cases with available formalin-fixed, paraffin-embedded (FFPE) tissue were tested in parallel.
RESULTS
Gene fusions were detected in 6 cases; common single-nucleotide variants in EGFR, RAS, and BRAF in 14 cases; and in-frame deletions within EGFR in 3 cases. A concordance rate of 100% was observed between FNA and FFPE tissue.
CONCLUSIONS
Cytology preparations can be a reliable source for the detection of both DNA and RNA aberrations. The ability to simultaneously detect multiple types of genomic variants is crucial for patients with advanced cancer and maximizes the usefulness of cytology specimens. Cancer Cytopathol 2018. © 2018 American Cancer Society.
http://ift.tt/2DD3ggN
All-in-one: The dream and reality of molecular cytopathology testing on routine lung cancer smears
If cytopathologists are used to dedicating 1 or more fine-needle aspiration passes to prepare a tumor-representative cell block, the testing laboratory may strongly rely on anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), and programmed death-ligand 1 (PD-L1) immunocytochemistry assays. Conversely, when sample procurement and diagnostic interpretation are based primarily on smeared material, cytopathologists should promote, in conjunction with the molecular team, ALK and ROS1 RNA-based testing approaches on smears, saving the cell block only for PD-L1 staining. See also pages 000-000.
http://ift.tt/2F7Y41s
The meninges as barriers and facilitators for the movement of fluid, cells and pathogens related to the rodent and human CNS
Abstract
Meninges that surround the CNS consist of an outer fibrous sheet of dura mater (pachymeninx) that is also the inner periosteum of the skull. Underlying the dura are the arachnoid and pia mater (leptomeninges) that form the boundaries of the subarachnoid space. In this review we (1) examine the development of leptomeninges and their role as barriers and facilitators in the foetal CNS. There are two separate CSF systems during early foetal life, inner CSF in the ventricles and outer CSF in the subarachnoid space. As the foramina of Magendi and Luschka develop, one continuous CSF system evolves. Due to the lack of arachnoid granulations during foetal life, it is most likely that CSF is eliminated by lymphatic drainage pathways passing through the cribriform plate and nasal submucosa. (2) We then review the fine structure of the adult human and rodent leptomeninges to establish their roles as barriers and facilitators for the movement of fluid, cells and pathogens. Leptomeningeal cells line CSF spaces, including arachnoid granulations and lymphatic drainage pathways, and separate elements of extracellular matrix from the CSF. The leptomeningeal lining facilitates the traffic of inflammatory cells within CSF but also allows attachment of bacteria such as Neisseria meningitidis and of tumour cells as CSF metastases. Single layers of leptomeningeal cells extend into the brain closely associated with the walls of arteries so that there are no perivascular spaces around arteries in the cerebral cortex. Perivascular spaces surrounding arteries in the white matter and basal ganglia relate to their two encompassing layers of leptomeninges. (3) Finally we examine the roles of ligands expressed by leptomeningeal cells for the attachment of inflammatory cells, bacteria and tumour cells as understanding these roles may aid the design of therapeutic strategies to manage developmental, autoimmune, infectious and neoplastic diseases relating to the CSF, the leptomeninges and the associated CNS.
http://ift.tt/2GaMNih
Genome-wide single nucleotide polymorphism-based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa
Abstract
Autozygosity mapping (AM) is a technique utilized for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome-wide single nucleotide polymorphism (SNP) array-based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analyzed with an EB-targeted next-generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to presence of compound heterozygosity, deep intronic mutations, or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 out of 46 cases (95.7%) diagnosed genetically.
This article is protected by copyright. All rights reserved.
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Cherenkov-excited Multi-Fluorophore Sensing in Tissue-Simulating Phantoms and In Vivo from External Beam Radiotherapy
Radiation Research, Volume 189, Issue 2, Page 197-204, February 2018.
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Why Genetic Effects of Radiation are Observed in Mice but not in Humans
Radiation Research, Volume 189, Issue 2, Page 117-127, February 2018.
http://ift.tt/2BqpIVh
MRI Study on the Changes of Bone Marrow Microvascular Permeability and Fat Content after Total-Body X-Ray Irradiation
Radiation Research, Volume 189, Issue 2, Page 205-212, February 2018.
http://ift.tt/2n8lFs4
Rapid Decrease in KRT14 and TP53 mRNA Expression in the Buccal Mucosa of Patients Receiving Total-Body Irradiation for Allogeneic Stem Cell Transplantation
Radiation Research, Volume 189, Issue 2, Page 213-218, February 2018.
http://ift.tt/2BopQ7r
Chronic Exposure to External Low-Dose Gamma Radiation Induces an Increase in Anti-inflammatory and Anti-oxidative Parameters Resulting in Atherosclerotic Plaque Size Reduction in ApoE–/– Mice
Radiation Research, Volume 189, Issue 2, Page 187-196, February 2018.
http://ift.tt/2n71OcV
The Role of FABP5 in Radiation-Induced Human Skin Fibrosis
Radiation Research, Volume 189, Issue 2, Page 177-186, February 2018.
http://ift.tt/2n8LtEy
Is there Unmeasured Indication Bias in Radiation-Related Cancer Risk Estimates from Studies of Computed Tomography?
Radiation Research, Volume 189, Issue 2, Page 128-135, February 2018.
http://ift.tt/2BpLecy
FTIR Microspectroscopy Probes Particle-Radiation Effect on HCT116 cells (p53+/+, p53–/–)
Radiation Research, Volume 189, Issue 2, Page 156-164, February 2018.
http://ift.tt/2n8wQRB
Quantitative Proteomic Analysis of the Hippocampus of Rats with GCR-Induced Spatial Memory Impairment
Radiation Research, Volume 189, Issue 2, Page 136-145, February 2018.
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Characterization of Diffuse Intrinsic Pontine Glioma Radiosensitivity using Synchrotron Microbeam Radiotherapy and Conventional Radiation Therapy In Vitro
Radiation Research, Volume 189, Issue 2, Page 146-155, February 2018.
http://ift.tt/2n4mItm
Cancers, Vol. 10, Pages 30: Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The “La Cittadina Fondazione” Experience
Cancers, Vol. 10, Pages 30: Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The "La Cittadina Fondazione" Experience
Cancers doi: 10.3390/cancers10020030
Authors: Mario Dolera Luca Malfassi Nancy Carrara Sara Finesso Silvia Marcarini Giovanni Mazza Simone Pavesi Massimo Sala Gaetano Urso
Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets.
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WNT10B mutations associated with isolated dental anomalies
ABSTRACT
Isolated hypodontia is the most common human malformation. It is caused by heterozygous variants in various genes, with heterozygous WNT10A variants being the most common cause. WNT10A and WNT10B are paralogs that likely evolved from a common ancestral gene after its duplication. Recently an association of WNT10B variants with oligodontia (severe tooth agenesis) has been reported. We performed mutational analysis in our cohort of 256 unrelated Thai families with various kinds of isolated dental anomalies. In seven families afflicted with dental anomalies we detected four heterozygous missense variants in WNT10B. We performed whole exome sequencing in the patients who had WNT10B mutations and found no mutations in other known hypodontia-associated genes, including WNT10A, MSX1, PAX9, EDA, AXIN2, EDAR, EDARADD, LPR6, TFAP2B, LPR6, NEMO, KRT17, and GREM2. Our findings indicate that the variants c.475G>C [p.( Ala159Pro)], found in four families, and c.1052G>A [p.(Arg351His)], found in one family, are most probably causative. They also show that WNT10B variants are associated not only with oligodontia and isolated tooth agenesis, but also with microdontia, short tooth roots, dental pulp stones, and taurodontism.
http://ift.tt/2Dyn0P5
Autosomal dominant myopia associated to a novel P4HA2 missense variant and defective collagen hydroxylation
ABSTRACT
We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene.
Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole exome sequencing was performed to identify the gene responsible for myopia in the pedigree.
Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A>G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines.
This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations.
http://ift.tt/2E5Eaow
PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated macrophages via regulating DUSP6-Erk1/2 pathway
Abstract
Background
Protein kinase N2 (PKN2) is a PKC-related serine/threonine-protein kinase. PKN2 is required for tumor cell migration, invasion and apoptosis. However, the functional role of PKN2 in regulating tumor associated macrophages (TAMs) polarization in colon cancer has never been reported.
Methods
PKN2 expression in human colon cancer tissues was examined with immunohistochemistry (IHC). M1/M2 macrophage signatures were evaluated by RT-PCR, IHC and flow cytometry. The effects of PKN2 on tumor growth and TAM polarization were investigated both in vitro and in vivo. PKN2 targeted cytokines/pathway were analyzed by gene expression analysis and further confirmed by PCR, luciferase assay or western blot. Correlations between PKN2 and transcriptional factors for IL4 and IL10 were confirmed by ChIP-qPCR. The catalytic activities of PKN2 and DUSP6 were determined by kinase activity assay. Interactions between PKN2 and DUSP6 were confirmed by Co-IP.
Results
The expression of PKN2 in colon cancer cells predicted a favorable prognosis and was associated with low M2 macrophage content in human colon cancer tissues. PKN2 inhibited tumor growth in mice xenograft model and inhibited M2 phenotype polarization both in vitro and in vivo. Mechanistically, PKN2 suppresses the expression of IL4 and IL10 from colon cancer cells by inhibiting Erk1/2 phosphorylation, which is required for phosphorylation and binding of CREB and Elk-1 to the promoters of IL4 and IL10. DUSP6, which is phosphorylated and activated through direct association with PKN2, suppresses Erk1/2 activation.
Conclusions
The expression of PKN2 in colon cancer cells suppresses tumor associated M2 macrophage polarization and tumor growth. Targeting PKN2 signaling pathway may provide a potential therapeutic strategy for colon cancer.
http://ift.tt/2n86HSm
BioEssays 2∕2018
The maintenance of chromosome DNA requires many nucleoidassociated factors in bacteria. Among them, the SMC (structural maintenance of chromosomes) complex plays a role in the organization and segregation of the chromosome. As discussed by Kamada and Barillà in article 1700166, this complex is recruited to the origin-proximal region and then travels to the terminus, producing an individualized chromosome by combing left and right chromosome arms.
http://ift.tt/2E7M3da
[18F]GE180 positron emission tomographic imaging indicates a potential double-hit insult in the intrahippocampal kainate mouse model of temporal lobe epilepsy
Summary
Objective
Accumulating evidence suggests that brain inflammation, elicited by epileptogenic insults, is involved in epilepsy development. Noninvasive nuclear imaging of brain inflammation in animal models of epileptogenesis represents a diagnostic in vivo approach with potential for direct translation into the clinic. Here, we investigated up-regulation of the translocator protein (TSPO) indicative of microglial activation by serial [18F]GE180 positron emission tomographic (PET) imaging in a mouse model of temporal lobe epilepsy.
Methods
As epileptogenic insult, a status epilepticus (SE) was induced in mice by intrahippocampal injection of kainate. Post-SE mice injected with kainate and sham-injected mice were subjected to [18F]GE180 PET scans before SE and at 2 days, 5-7 days, 2 weeks, 3 weeks, 7 weeks, and 14 weeks postinsult. For data evaluation, brain regions ipsilateral and contralateral to the injection site were outlined by coregistration with a standard mouse brain atlas, and percentage of injected dose per cubic centimeter was calculated. In addition, a statistical parametric mapping analysis, comparing post-SE mice to baseline, sham mice to baseline, and post-SE to sham mice was performed.
Results
Following SE, elevations in [18F]GE180 uptake were most prominent in the ipsilateral hippocampus, occurring between 2 days and at least 7 weeks after SE, with a peak at 5-7 days after SE. In the contralateral hippocampus and other epilepsy-associated brain regions, increased tracer uptake was observed with a similar time profile but to a lesser extent. Moderate enhancement of tracer uptake was also evident in mice after sham surgery.
Significance
TSPO in vivo imaging reliably detects brain inflammation during epileptogenesis. These inflammatory processes most prominently affect the hippocampus ipsilateral to the injection site. Inflammation induced by the traumatic insult associated with surgery synergistically contributes to total brain inflammation and may also contribute to epileptogenesis. The revealed time course of neuroinflammation will help to identify appropriate time points for anti-inflammatory, potentially antiepileptogenic treatment.
http://ift.tt/2E6gQqu
Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease
Abstract
The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.
http://ift.tt/2E42G9x
Placenta-on-a-Chip: Placental Drug Transport-on-a-Chip: A Microengineered In Vitro Model of Transporter-Mediated Drug Efflux in the Human Placental Barrier (Adv. Healthcare Mater. 2/2018)
In article number 1700786, Dongeun Huh and co-workers present a micro-engineered model of the human placental barrier for investigation of maternal–fetal drug transfer in pregnancy. The placenta-on-a-chip system reconstitutes efflux transporter-mediated transport of a test compound, demonstrating proof-of-principle for use as a screening platform for prediction of drug transport in pregnancy.
http://ift.tt/2Bq63EN
Human Organ Miniaturization: 3D Miniaturization of Human Organs for Drug Discovery (Adv. Healthcare Mater. 2/2018)
The cover artwork for the article number 1700551 by Hansang Cho and co-workers reviews the current state-of-the-art in engineering and miniaturizing human organ 3D models and overviews the major engineering technologies: organoids, microfabrication, 3D bioprinting, used for the organ construction. Cover illustration by You Jung Kang. CT images of organs kindly provided by NIH.
http://ift.tt/2Bq1g6a
The effect of a therapeutic lithium level on a stroke-related cerebellar tremor
Lithium is a mood stabiliser used in the treatment of acute mania, bipolar disorder and as augmentation for unipolar major depression. Tremor is a common adverse effect associated with lithium at both therapeutic and toxic serum levels. We present a case of dose-dependent changes in the quality and intensity of a stroke-related, chronic cerebellar tremor with lithium treatment at serum levels within the therapeutic range. On admission, the patient in this case had a baseline fine, postural tremor, which increased in frequency and evolved to include myoclonic jerks once lithium therapy was initiated. Although the patient's serum lithium level was never in the toxic range, his tremor returned to baseline on reduction of his serum lithium level. This case highlights that a pre-existing, baseline tremor may lower the threshold for developing myoclonus. It also suggests that caution may be warranted with lithium therapy in the setting of known cerebellar disease.
http://ift.tt/2n811aZ
Severe systemic inflammatory response syndrome immediately after spinal surgery in a patient with axial gout
We report a 55-year-old man with gouty arthritis who developed a 3-month history of low back pain, gradual lower extremities weakness and urinary incontinence. Lumbar MRI showed an exophytic lesion at L3–L4. Immediately after spinal decompression surgery, he developed fever, disorientation, polyarthritis, acute kidney injury and leucocytosis. He was treated with multiple antimicrobial agents for presumed spinal abscess but did not improve. Multiple body site cultures were negative. Aspiration of the sacroiliac joint revealed the presence of monosodium uric acid crystals. A diagnosis of acute gout was done, and he was treated with high-dose intravenous methylprednisolone and colchicine. Within 48 hours, he had a remarkable clinical improvement. At discharge, neurological and laboratory abnormalities had resolved. Awareness of risk factors for axial gout and a high degree of suspicion are important to establish a prompt diagnosis and treatment to prevent severe complications as seen in this case.
http://ift.tt/2DCXX1L
Parapedicular vertebral augmentation with polymethylmetacrylate for pedicle screw loosening
A 71-year-old man who had a L1/S1 posterior fusion revision surgery complained of increasing back pain 5 weeks after the open surgical procedure. The pain was initially estimated at 9/10 on the visual analog scale (VAS) and thought to be related to a right-sided L2 screw loosening. A right parapedicular vertebroplasty was performed and polymethylmethacrylate cement was instilled around the right pedicle screw, filling the anterior two-thirds of the vertebral body. On postvertebroplasty day 1, the patient had significant improvement in his low back pain. The pain further decreased at 1 and 3 months after the intervention (2/10 on the VAS). Vertebroplasty is a minimally invasive, accessible, effective, and long lasting treatment for compression fractures. We believe that this technique could also be indicated to treat pain related to low grade screw loosening in properly selected patients.
http://ift.tt/2n7Hck4
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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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