To compare intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and a 3-dimensional conformal parotid gland-sparing radiotherapy (ConPas 3D-CRT) in treatment of nasopharyngeal carcinoma with regard to outcomes and dose distribution to the planning target volumes (PTVs) and to the organs at risk (OARs).
The treatment records of 24 patients with histologically proven carcinoma of the nasopharynx treated with ConPas 3D-CRT or IMRT-SIB technique between May 2009 and December 2016 were assessed.
The mean dose and dose to 50% parotid glands volume as well as the maximal dose to the spinal cord were significantly lower in the IMRT-SIB than in the ConPas 3-CRT group (p < 0.05; p < 0.05; p < 0.01, respectively). IMRT-SIB was also superior in coverage of PTVs. The 3-year overall survival (OS) and disease-free survival (DFS) of patients in the IMRT-SIB and ConPas 3D-CRT groups were 77 and 81% (p = 0.93), 51.9 and 70.7% (p = 0.83), respectively.
IMRT-SIB provided additional spearing to parotid glands and spinal cord in comparison to ConPas 3D-CRT technique but without improvement of OS and DFS.
The measurement of the nuclei response to an external magnetic field known as nuclear magnetic resonance (NMR) has proven to have wide application covering different industries. NMR use in the petroleum industry focuses on solving rock and fluid properties. NMR T2 is the dominant measurement due to the short measurement time in comparison with T1, and at the same time, it generates the required information. The nondestructive technique generates an echo decay sequence and is commonly utilized to characterize the pore structure by observing the static and dynamic aspects of the nuclear spin. NMR measured decay time is controlled by the fluid and rock pore geometry (pore size), and therefore, the mean T2 can potentially be used to estimate permeability. NMR spectra, however, is affected by the presence of paramagnetic minerals either in the reservoir or in drilling fluid. Its shallow depth of investigation makes it prone to formation damage during drilling; however, the technique provides vast data to improve the understanding of reservoir properties. This article reviews NMR basic physics, and the added value to the petroleum industry through its application to characterize the reservoir, and its productivity, such as porosity, pore size distribution, permeability, and capillary pressure.
A First Report of Secondary Hemophagocytic Lymphohistiocytosis Associated With Papillary Thyroid Carcinoma.
J Pediatr Hematol Oncol. 2017 Oct 30;:
Authors: Wakefield C, Mehta PA, Corathers S, Geller J, Gelfand M, Olowokure O, Marsh RA
Abstract
Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal immune-deficiency disorder that develops in response to diseases that produce strong immunologic activation, such as infection and malignancy. Although secondary HLH is reported to occur in association with various malignancies, there is no report of its association with thyroid cancer. We evaluated a 19-year-old man who presented with HLH. During investigation for an underlying cause of his HLH computed tomographic scan of the neck discovered thyroid nodules that were confirmed with biopsy to be papillary thyroid carcinoma. He was treated with surgery followed by radioactive iodine therapy and remains without any recurrence of malignancy or his secondary HLH. This report documents the first observation of HLH associated with thyroid cancer, and illustrates the need to include imaging of the neck while evaluating patients with secondary HLH for an underlying malignancy.
PMID: 29087969 [PubMed - as supplied by publisher]
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Early and late adverse effects of radioiodine for pediatric differentiated thyroid cancer.
Pediatr Blood Cancer. 2017 Nov;64(11):
Authors: Albano D, Bertagna F, Panarotto MB, Giubbini R
Abstract
BACKGROUND: Radioiodine-131 (I131) therapy for differentiated thyroid cancer (DTC) is generally a safe and effective treatment, but it has some potential side effects, which have been well described in adults but less analyzed in children. Our aim was to describe early and late adverse events of radioactive I131 in pediatric patients.
METHODS: All consecutive patients ≤18 years treated for DTC in the period 1980-2015 were retrospectively analyzed for early and late side effects of radioiodine. Early side effects include nausea/emesis, radiation thyroiditis, sialadenitis, dry mouth, and transient bone marrow (BM) suppression. Late complications include permanent salivary gland dysfunction, permanent BM suppression, pulmonary fibrosis, second cancers, and fertility problems.
RESULTS: One hundred five pediatric patients were treated with I131 for DTC in our department for a total amount of 302 radioiodine treatments. In total, 127 early complications were recorded: 44 episodes of nausea/emesis; 30 sialoadenitis, 24 thyroiditis, 18 dry mouth, and 11 transient BM suppression. Early side effects were correlated with the amount of radioactivity administered in any treatment. Twelve children developed ≥1 late complication for a total of 20 complications: two permanent salivary gland dysfunction, four permanent BM suppression, five pulmonary fibrosis, four second malignancies, and five fertility alterations. Late events, except fertility alterations, were correlated with the number of therapies and cumulative activities of I131.
CONCLUSIONS: In conclusion, early side effects of I131 are associated with the amount of administrated activities of each treatment, while the late effects are correlated with the number of treatments and cumulative activities of radioiodine, except for fertility problems.
PMID: 28436606 [PubMed - indexed for MEDLINE]
The purpose of this pictorial essay is to describe anatomic variants and congenital anomalies of portal venous system and related liver parenchymal alterations.
The imaging findings of some of these entities have been previously described in other articles, however this work encompasses all congenital anomalies of portal venous system with attention to their features on various imaging modalities; in particular we illustrated with detailed pictures all the main portal vein variants, congenital extra- and intra-hepatic porto-systemic venous shunts and portal vein aneurysm.
Variants of portal branches and intrahepatic portosystemic shunts are quite uncommon, however, when present, they should be recognized before performing surgery or interventional procedures. Congenital absence of the portal vein is an important finding as the complete loss of portal perfusion predisposes the liver to focal or diffuse hyperplastic or dysplastic changes. Portal vein aneurysm is a rare clinical entity that can affect intra- and extra-hepatic portal branches; although usually asymptomatic, thrombosis can occur.
Awareness of congenital variants of portal venous system among radiologists should allow a more confident diagnosis and permit an accurate planning of surgical procedures and percutaneous interventions; identification of portal system anomalies also suggest an accurate evaluation of associated hepatic parenchymal anomalies such as nodular regenerative hyperplasia, focal nodular hyperplasia (FNH), and adenomas with high risk of malignant transformation.
L'articolo Imaging assessment of portal venous system: pictorial essay of normal anatomy, anatomic variants and congenital anomalies sembra essere il primo su European Review.
A Clinical Trial of Combination Neoadjuvant Chemotherapy and Transoral Robotic Surgery in Patients with T3 and T4 Laryngo-Hypopharyngeal Cancer.
Ann Surg Oncol. 2017 Oct 30;:
Authors: Park YM, Keum KC, Kim HR, Cho BC, Kim DH, Cho NH, Kim SH
Abstract
BACKGROUND: We conducted a prospective clinical trial of combination neoadjuvant chemotherapy, transoral robotic surgery (TORS), and customized adjuvant therapy in patients with locally advanced laryngo-hypopharyngeal cancer.
METHODS: Between September 2008 and August 2016, 35 patients were enrolled in this clinical trial.
RESULTS: Twenty patients had hypopharyngeal cancer and 15 had laryngeal cancer. Twenty-nine patients (82.9%) had T3 disease and six patients (17.1%) had T4 disease, while 12 patients (34.3%) had stage III disease and 23 patients (65.7%) had stage IV disease. The 3-year disease-specific survival rate was 82.4% and the 3-year disease-free survival rate was 69.48%. Decannulation was successful in 31 of 34 patients at an average of 18 days postoperatively. Among all patients, 83% exhibited a favorable subjective swallowing status, while five patients (14.4%) became dependent on feeding tubes.
CONCLUSIONS: Neoadjuvant chemotherapy combined with TORS and customized adjuvant therapy, based on detailed pathological information, afforded favorable oncological outcomes and preserved organ functionalities in T3-T4 laryngo-hypopharyngeal cancer.
PMID: 29086129 [PubMed - as supplied by publisher]
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Effects of Career Duration, Concussion History, and Playing Position on White Matter Microstructure and Functional Neural Recruitment in Former College and Professional Football Athletes.
Radiology. 2017 Oct 31;:170539
Authors: Clark MD, Varangis EML, Champagne AA, Giovanello KS, Shi F, Kerr ZY, Smith JK, Guskiewicz KM
Abstract
Purpose To better understand the relationship between exposure to concussive and subconcussive head impacts, white matter integrity, and functional task-related neural activity in former U.S. football athletes. Materials and Methods Between 2011 and 2013, 61 cognitively unimpaired former collegiate and professional football players (age range, 52-65 years) provided informed consent to participate in this cross-sectional study. Participants were stratified across three crossed factors: career duration, concussion history, and primary playing position. Fractional anisotropy (FA) and blood oxygen level-dependent (BOLD) percent signal change (PSC) were measured with diffusion-weighted and task-related functional magnetic resonance imaging, respectively. Analyses of variance of FA and BOLD PSC were used to determine main or interaction effects of the three factors. Results A significant interaction between career duration and concussion history was observed; former college players with more than three concussions had lower FA in a broadly distributed area of white matter compared with those with zero to one concussion (t29 = 2.774; adjusted P = .037), and the opposite was observed for former professional players (t29 = 3.883; adjusted P = .001). A separate interaction between concussion history and position was observed: Nonspeed players with more than three concussions had lower FA in frontal white matter compared with those with zero to one concussion (t25 = 3.861; adjusted P = .002). Analysis of working memory-task BOLD PSC revealed a similar interaction between concussion history and position (all adjusted P < .004). Overall, former players with lower FA tended to have lower BOLD PSC across three levels of a working memory task. Conclusion Career duration and primary playing position seem to modify the effects of concussion history on white matter structure and neural recruitment. The differences in brain structure and function were observed in the absence of clinical impairment, which suggested that multimodal imaging may provide early markers of onset of traumatic neurodegenerative disease. (©) RSNA, 2017 Online supplemental material is available for this article.
PMID: 29087238 [PubMed - as supplied by publisher]
Accompanied by the growing clinical applications of immunotherapy in treatment for cancer patients, the development of novel therapeutic approaches to reverse the immune-suppressive environment in cancer patients is eagerly anticipated, because the success of cancer immunotherapy is currently limited by immune-suppressive effects in tumor-bearing hosts. Interleukin (IL)-6, a pleotropic pro-inflammatory cytokine, participates in tumor cell-autonomous processes that are required for their survival and growth, and is therefore known as a poor prognostic factor in cancer patients. In addition, an emerging roles of IL-6 in modulating multiple functions of immune cells including T cells, dendritic cells, and macrophages, are responsible for the dysfunction of innate and adaptive immunity against tumors. Therefore, the IL-6-targeting approach is of value as a promising strategy for desensitization and prevention of immune-suppressive effects, and should be an effective treatment when combined with current immunotherapies. The aim of this review is to discuss the immune-suppressive aspects of IL-6, notably with modification of T-cell functions in cancer patients, and their relationship to anti-tumor immune-responses and cancer immunotherapy.
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Genes, Vol. 8, Pages 301: RNA Pseudouridylation in Physiology and Medicine: For Better and for Worse
Genes doi: 10.3390/genes8110301
Authors: Marianna Penzo Ania Guerrieri Federico Zacchini Davide Treré Lorenzo Montanaro
Pseudouridine is the most abundant modification found in RNA. Today, thanks to next-generation sequencing techniques used in the detection of RNA modifications, pseudouridylation sites have been described in most eukaryotic RNA classes. In the present review, we will first consider the available information on the functional roles of pseudouridine(s) in different RNA species. We will then focus on how alterations in the pseudouridylation process may be connected with a series of human pathologies, including inherited disorders, cancer, diabetes, and viral infections. Finally, we will discuss how the availability of novel technical approaches are likely to increase the knowledge in this field.
Genes, Vol. 8, Pages 302: Impact of Repetitive Elements on the Y Chromosome Formation in Plants
Genes doi: 10.3390/genes8110302
Authors: Roman Hobza Radim Cegan Wojciech Jesionek Eduard Kejnovsky Boris Vyskot Zdenek Kubat
In contrast to animals, separate sexes and sex chromosomes in plants are very rare. Although the evolution of sex chromosomes has been the subject of numerous studies, the impact of repetitive sequences on sex chromosome architecture is not fully understood. New genomic approaches shed light on the role of satellites and transposable elements in the process of Y chromosome evolution. We discuss the impact of repetitive sequences on the structure and dynamics of sex chromosomes with specific focus on Rumex acetosa and Silene latifolia. Recent papers showed that both the expansion and shrinkage of the Y chromosome is influenced by sex-specific regulation of repetitive DNA spread. We present a view that the dynamics of Y chromosome formation is an interplay of genetic and epigenetic processes.
Following correction should be noted.
Biomolecules, Vol. 7, Pages 77: Evolutionary Conservation of the Components in the TOR Signaling Pathways
Biomolecules doi: 10.3390/biom7040077
Authors: Hisashi Tatebe Kazuhiro Shiozaki
Target of rapamycin (TOR) is an evolutionarily conserved protein kinase that controls multiple cellular processes upon various intracellular and extracellular stimuli. Since its first discovery, extensive studies have been conducted both in yeast and animal species including humans. Those studies have revealed that TOR forms two structurally and physiologically distinct protein complexes; TOR complex 1 (TORC1) is ubiquitous among eukaryotes including animals, yeast, protozoa, and plants, while TOR complex 2 (TORC2) is conserved in diverse eukaryotic species other than plants. The studies have also identified two crucial regulators of mammalian TORC1 (mTORC1), Ras homolog enriched in brain (RHEB) and RAG GTPases. Of these, RAG regulates TORC1 in yeast as well and is conserved among eukaryotes with the green algae and land plants as apparent exceptions. RHEB is present in various eukaryotes but sporadically missing in multiple taxa. RHEB, in the budding yeast Saccharomyces cerevisiae, appears to be extremely divergent with concomitant loss of its function as a TORC1 regulator. In this review, we summarize the evolutionarily conserved functions of the key regulatory subunits of TORC1 and TORC2, namely RAPTOR, RICTOR, and SIN1. We also delve into the evolutionary conservation of RHEB and RAG and discuss the conserved roles of these GTPases in regulating TORC1.
Functional changes in hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels have been shown to contribute to medial prefrontal (mPFC) hyperexcitability after peripheral nerve injury. A reduction in the open probability of these neuronal channels might be relevant since this can enhance membrane input resistance and synaptic summation. However, the molecular mechanisms underlying neuropathy-associated alterations in HCN channel activity remain elusive. Using the spared nerve injury model of neuropathic pain in Long–Evans rats, we first discovered a significant increase in noradrenergic innervation within the mPFC of nerve-injured compared to control animals. Patch-clamp recordings in layer II/III pyramidal neurons of the mPFC revealed that adrenoceptors, primarily the α2 subtype, can modulate the voltage-dependent activation of HCN channels and the abnormal prefrontal excitability following peripheral neuropathy. Additionally, microinfusions of the α2 adrenoceptor agonist clonidine in the mPFC of neuropathic rats provided analgesic effects, indicating the behavioral significance for this noradrenergic pathway in manifestations of the chronic pain state. Taken together, our results provide insights into the role of cortical catecholaminergic neuromodulation in neuropathic pain and suggest that altered noradrenergic transduction may play a major role in the HCN channel dysfunction and pyramidal hyperactivity observed in several chronic pain conditions.
Perineuronal nets (PNNs) are specialized condensations of extracellular matrix that ensheath particular neuronal subpopulations in the brain and spinal cord. PNNs regulate synaptic plasticity, including the encoding of fear memories by the amygdala. The present immunohistochemical investigation studied PNN structure and distribution, as well as the neurochemistry of their ensheathed neurons, in the rat amygdala using monoclonal antibody VC1.1, which recognizes a glucuronic acid 3-sulfate glycan associated with PNNs in the cerebral cortex. VC1.1+ PNNs surrounded the cell bodies and dendrites of a subset of nonpyramidal neurons in cortex-like portions of the amygdala (basolateral amygdalar complex, cortical nuclei, nucleus of the lateral olfactory tract, and amygdalohippocampal region). There was also significant neuropilar VC1.1 immunoreactivity, whose density varied in different amygdalar nuclei. Cell counts in the basolateral nucleus revealed that virtually all neurons ensheathed by VC1.1+ PNNs were parvalbumin-positive (PV+) interneurons, and these VC1.1+/PV+ cells constituted 60% of all PV+ interneurons, including all of the larger PV+ neurons. Approximately 70% of VC1.1+ neurons were calbindin-positive (CB+), and these VC1.1+/CB+ cells constituted about 40% of all CB+ neurons. Colocalization of VC1.1 with Vicia villosa agglutinin (VVA) binding, which stains terminal N-acetylgalactosamines, revealed that VC1.1+ PNNs were largely a subset of VVA+ PNNs. This investigation provides baseline data regarding PNNs in the rat which should be useful for future studies of their function in this species.
Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that occur in complex mixtures. Several PAHs are known or suspected mutagens and/or carcinogens, but developmental toxicity data is lacking for PAHs, particularly their oxygenated and nitrated derivatives. Such data are necessary to understand and predict the toxicity of environmental mixtures. 123 PAHs were assessed for morphological and neurobehavioral effects for a range of concentrations between 0.1 and 50 µM, using a high throughput early-life stage zebrafish assay, including 33 parent, 22 nitrated, 17 oxygenated, 19 hydroxylated, 14 methylated, 16 heterocyclic, and 2 aminated PAHs. Additionally, each PAH was evaluated for AHR activation, by assessing CYP1A protein expression using whole animal immunohistochemistry (IHC). Responses to PAHs varied in a structurally dependent manner. High-molecular weight PAHs were significantly more developmentally toxic than the low-molecular weight PAHs, and CYP1A expression was detected in five distinct tissues, including vasculature, liver, skin, neuromasts and yolk.
JFB, Vol. 8, Pages 48: Evaluation of PBS Treatment and PEI Coating Effects on Surface Morphology and Cellular Response of 3D-Printed Alginate Scaffolds
Journal of Functional Biomaterials doi: 10.3390/jfb8040048
Authors: María Mendoza García Mohammad Izadifar Xiongbiao Chen
Three-dimensional (3D) printing is an emerging technology for the fabrication of scaffolds to repair/replace damaged tissue/organs in tissue engineering. This paper presents our study on 3D printed alginate scaffolds treated with phosphate buffered saline (PBS) and polyethyleneimine (PEI) coating and their impacts on the surface morphology and cellular response of the printed scaffolds. In our study, sterile alginate was prepared by means of the freeze-drying method and then, used to prepare the hydrogel for 3D printing into calcium chloride, forming 3D scaffolds. Scaffolds were treated with PBS for a time period of two days and seven days, respectively, and PEI coating; then they were seeded with Schwann cells (RSC96) for the examination of cellular response (proliferation and differentiation). In addition, swelling and stiffness (Young’s modulus) of the treated scaffolds was evaluated, while their surface morphology was assessed using scanning electron microscopy (SEM). SEM images revealed significant changes in scaffold surface morphology due to degradation caused by the PBS treatment over time. Our cell proliferation assessment over seven days showed that a two-day PBS treatment could be more effective than seven-day PBS treatment for improving cell attachment and elongation. While PEI coating of alginate scaffolds seemed to contribute to cell growth, Schwann cells stayed round on the surface of alginate over the period of cell culture. In conclusion, PBS-treatment may offer the potential to induce surface physical cues due to degradation of alginate, which could improve cell attachment post cell-seeding of 3D-printed alginate scaffolds.
IJMS, Vol. 18, Pages 2294: Methylmalonyl-CoA Epimerase Deficiency Mimicking Propionic Aciduria
International Journal of Molecular Sciences doi: 10.3390/ijms18112294
Authors: Lenaig Abily-Donval Stéphanie Torre Aurélie Samson Bénédicte Sudrié-Arnaud Cécile Acquaviva Anne-Marie Guerrot Jean-François Benoist Stéphane Marret Soumeya Bekri Abdellah Tebani
Methylmalonyl-CoA epimerase (MCE) converts d-methylmalonyl-CoA epimer to l-methylmalonyl-CoA epimer in the propionyl-CoA to succinyl-CoA pathway. Only seven cases of MCE deficiency have been described. In two cases, MCE deficiency was combined with sepiapterin reductase deficiency. The reported clinical pictures of isolated MCE are variable, with two asymptomatic patients and two other patients presenting with metabolic acidosis attacks. For combined MCE and sepiapterin reductase deficiency, the clinical picture is dominated by neurologic alterations. We report isolated MCE deficiency in a boy who presented at five years of age with acute metabolic acidosis. Metabolic investigations were consistent with propionic aciduria (PA). Unexpectedly, propionyl-CoA carboxylase activity was within the reference range. Afterward, apparently intermittent and mild excretion of methylmalonic acid (MMA) was discovered. Methylmalonic pathway gene set analysis using the next-generation sequencing approach allowed identification of the common homozygous nonsense pathogenic variant (c.139C > T-p.Arg47*) in the methylmalonyl-CoA epimerase gene (MCEE). Additional cases of MCE deficiency may help provide better insight regarding the clinical impact of this rare condition. MCE deficiency could be considered a cause of mild and intermittent increases in methylmalonic acid.
The composition and physicochemical properties of defatted acacia flour (DFAF), acacia protein concentrate (APC) and acacia protein isolate (API) were evaluated. The results indicated that API had lower, ash and fat content, than DFAF and APC. Also, significant difference in protein content was noticed among DFAF, APC and API (37.5, 63.7 and 91.8%, respectively). Acacia protein concentrate and isolates were good sources of essential amino acids except cystine and methionine. The physicochemical and functional properties of acacia protein improved with the processing of acacia into protein concentrate and protein isolate. The results of scanning electron micrographs showed that DFAF had a compact structure; protein concentrate were, flaky, and porous type, and protein isolate had intact flakes morphology.
The aim of this study was to evaluate the microtextural properties of optimized wheat bread formulation consisting sourdough (A) prepared with two different fermentation methods [spontaneous fermentation (F1) versus starter of lactic acid bacteria added fermentation (F2)], instant active dry yeast (B) and wheat bran (C) during shelf life. The optimized levels for F1 were 11.45 g 100 g−1 for sourdough, 1.10 g 100 g−1 for dry yeast and 1.58 g 100 g−1 for wheat bran and for F2 6.99 g 100 g−1 for sourdough, 1.02 g 100 g−1 for dry yeast and 38.84 g 100 g−1 for wheat bran. The addition of sourdough significantly decreased the diameters of starch granules of sourdough breads, and affected shape and surface apparance of starch granules. The retrogradation phenomena during storage was explained with the change of interaction between starch granules and protein matrix. The F1 fermentation method was found to be more effective in terms of bread textural properties examined.
Approximately, 50% of human melanomas are driven by BRAF mutations, which produce tumors that are highly immunosuppressive and often resistant to vaccine therapy. We introduced lipid-coated calcium phosphate nanoparticles (LCP NPs) as a carrier to efficiently deliver a tumor-specific antigen, the BRAFV600E peptide, to drive dendritic cell (DC) maturation and antigen presentation in C57BL6 mice. The BRAF peptide vaccine elicited a robust, antigen-specific cytotoxic T cell response and potent tumor growth inhibition in a murine BRAF-mutant melanoma model. Advanced BRAF-specific immune response was illustrated by IFN-γ production assay and cytotoxic T lymphocyte (CTL) assay. Remodeling of immunosuppressive modules within the tumor microenvironment further facilitated CTL infiltration. Thus, using LCP NPs to deliver the BRAF peptide vaccine is a promising strategy for the BRAF-mutant melanoma therapy.
OBJECTIVE: To explore the diagnostic value of joint examination of cancer antigen 125 (CA125), thymidine kinase-1 (TK1) and human epididymis protein 4 (HE4) in the serum of patients with ovarian cancer.
PATIENTS AND METHODS: A total of 75 ovarian cancer specimens (ovarian cancer group), 40 benign ovarian specimens (benign group) and 35 ovarian specimens of healthy women (normal control group) were collected. The serum levels of HE4, CA125 and TK1 and the positive detection rates in the three groups were compared. Meanwhile, the sensitivity and specificity of the three tumor markers in the diagnosis of ovarian cancer in the three groups were compared.
RESULTS: The levels of HE4, CA125 and TK1 in the ovarian cancer group were significantly higher than those in the control group (p<0.05), and those in the ovarian cancer group were significantly higher than those in the benign group (p<0.05). The positive rates of CA125 as well as TK1 in the ovarian cancer group and the benign group were significantly higher than those in the control group (p<0.05), and those in the ovarian cancer group were significantly higher than those in the benign group (p<0.05). In the detection of an individual tumor marker, the sensitivity of CA125 was the highest, followed by HE4. The specificity of HE4 was the highest, followed by TK1. For the combination of two tumor markers, the sensitivity of CA125+HE4 ranked the first (92.18%), and the specificity of TK1+HE4 ranked the first (88.37%). The sensitivity and specificity of the joint detection of CA125+HE4+TK1 were 94.18% and 79.53%, respectively. The sensitivity of the joint detection of CA125+HE4+TK1 was significantly higher than that of the detection of a single tumor marker and that of joint detection of two tumor markers (p<0.05).
CONCLUSIONS: Combined detection of CA125, HE4 and TK1 can significantly improve the sensitivity in the diagnosis of ovarian cancer.
L'articolo Research on application value of combined detection of serum CA125, HE4 and TK1 in the diagnosis of ovarian cancer sembra essere il primo su European Review.
OBJECTIVE: To investigate the expression level of long non-coding RNA promoter of CDKN1A antisense DNA damage activated RNA (lncRNA PANDAR) in cervical cancer and to analyze the effects of PANDAR on biological behaviors of cervical cancer and the clinical significance of PANDAR.
PATIENTS AND METHODS: A total of 68 pairs of cervical cancer and paired cancer-adjacent tissue specimens were collected. The relative expression of PANDAR in tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR) so as to analyze the relationship between PANDAR and clinicopathological factors of cervical cancer and evaluate its clinical significance. qRT-PCR was used to detect the relative expression of PANDAR in cervical cancer cells. Interference in PANDAR was conducted. Cell counting kit-8 (CCK-8) assay was used to detect the changes in cell proliferation capacity.
RESULTS: The results of qRT-PCR showed that the expression level of PANDAR was significantly up-regulated in cervical cancer tissues compared with that in cancer-adjacent tissues. Statistical analysis showed that PANDAR expression was correlated with International Federation of Gynecology and Obstetrics (FIGO) staging, tumor size and tumor invasion degree. Kaplan-Meier survival analysis showed that the survival time of patients with highly expressed PANDAR was shorter than that of patients with lowly expressed PANDAR. Cox multivariate regression analysis showed that PANDAR could be used as an independent prognostic factor for patients with cervical cancer. CCK-8 results showed that interference in PANDAR significantly inhibited tumor cell proliferation.
CONCLUSIONS: The expression level of PANDAR is up-regulated in cervical cancer tissues and cells, and PANDAR promotes tumor growth. PANDAR may be a biomarker for the early diagnosis of cervical cancer and a potential therapeutic target for reversing the malignant phenotype of tumors.
L'articolo Upregulation of LncRNA PANDAR predicts poor prognosis and promotes cell proliferation in cervical cancer sembra essere il primo su European Review.
OBJECTIVE: To investigate the role of SATB2 in stem cell-like properties of osteosarcoma and identify new strategies to eliminate cancer stem cells of osteosarcoma.
MATERIALS AND METHODS: Osteosarcoma cancer stem cells were derived by sarcosphere generation or chemo drug enrichment. SATB2 and pluripotency-associated gene expression in osteosarcoma CSCs were analyzed using qRT-PCR and Western blotting. The sphere formation assay, cell counting kit-8 assay and anti-chemotherapy proteins were used to measure the effects of altered SATB2, N-cadherin expression or metformin treatment in CSCs. Nude mice were injected with SATB2-deficient U2OS/MTX cells to assess the role of SATB2 in osteosarcoma growth and chemoresistance in vivo. Bioinformatics analyses were performed to identify SATB2 downstream target genes and immunochemistry to determine the correlation between SATB2 expression and patient outcome. Western blotting and luciferase reporter assays were used to examine the effects of N-cadherin and SATB2 inhibition on the NF-kB pathway.
RESULTS: SATB2 was upregulated in osteosarcoma stem cells. Knockdown of SATB2 decreased sarcosphere formation, cell proliferation and stem cell-like gene expression in vitro, meanwhile reduced tumor growth and chemoresistance in vivo. High SATB2 expression in osteosarcoma patient samples was associated with poor clinical outcome. N-cadherin was one critical downstream target gene of SATB2 that mediated the stem cell-like phenotype. Reduction of SATB2 or N-cadherin resulted in NF-kB inactivation, which led to impaired osteosarcoma sphere formation and tumor cell proliferation. Metformin treatment of osteosarcoma cells enhanced the effects of chemotherapy via suppression of N-cadherin.
CONCLUSIONS: SATB2 plays an important role in regulating osteosarcoma stem cell-like properties and tumor growth. The combination of conventional chemotherapy and metformin may be a promising therapeutic strategy for osteosarcoma patients.
L'articolo Metformin reduces SATB2-mediated osteosarcoma stem cell-like phenotype and tumor growth via inhibition of N-cadherin/NF-kB signaling sembra essere il primo su European Review.
OBJECTIVE: Oxidative stress caused by reactive oxygen species (ROS) plays an important role in the pathogenesis of endometriosis. The gene AT-rich interactive domain 1A (ARID1A), is frequently down regulated and inactivated in endometriosis. This report is focused on the molecular mechanism of the correlation between oxidative stress and ARID1A gene expression in endometrial cell oxidative damage model.
PATIENTS AND METHODS: In this study, the ARID1A gene expression level and its promoter methylation level were detected in 30 endometriosis and normal tissues. The primary endometrial cell was co-cultured with H2O2. Then, MDA and Gpx level were used to test the ROS level, RT-PCR was employed to detect the expression level of ARID1A. At last, the ARID1A gene promoter methylation level was detected by methylation-specific PCR (MSP). Finally, the expression level of DNMT1 was detected by both RT-PCR and Western blot.
RESULTS: The expression level of ARID1A gene was down regulated in endometriosis compared with normal tissues. The low expression level of ARID1A gene was associated with its promoter hyper-methylation. In H2O2 simulated endometrial cells, ARID1A gene expression level was decreased. Finally, ROS regulated ARID1A gene expression by changing the methylation level of ARID1A gene promoter. Finally, both the mRNA level and protein level of DNMT1 increased in H2O2 simulated endometrial cells.
CONCLUSIONS: In endometriosis, the down-regulated ofARID1A gene was highly correlated with its promoter hyper-methylation. ROS decreased the expression level of ARID1A gene via regulating methylation of its promoter which contributing to the understanding of the pathogenesis of endometriosis. The possible mechanism of ARID1A gene promoter hyper-methylation is ROS up-regulated DNMT1gene expression.
L'articolo Reactive oxygen species downregulate ARID1A expression via its promoter methylation during the pathogenesis of endometriosis sembra essere il primo su European Review.
OBJECTIVE: Interleukin (IL)-33 promotes T helper (Th2) immune response and may be involved in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Using murine and human specimens, we evaluated the role of IL-33 in CRSwNP.
MATERIALS AND METHODS: To establish CRSwNP, Balb/c mice were sensitized with house dust mite, followed up by intranasal exposure to Staphylococcus aureus to stimulate the inflammatory response of nasal mucosa. The hematoxylin-eosin staining and total serum IgE were used to the successful construction of CRSwNP model. For mechanistic studies, we blocked mice with IL-33 and the Th2 cells counts in tissue were detected. Th2 cytokine expression of IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24 in control group, CRSwNP group and IL-33 blockade group at 12 weeks after CRSwNP model establishment, were analyzed by qRT-PCR. Meanwhile, the relative mRNA and protein expression levels of NF-κB, MyD88 and TLR7 were detected after IL-33 blockade. To document the inflammatory response in patients with CRSwNP, The relative mRNA expression of IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24 in control individuals and patients with CRSwNP (chronic rhinosinusitis with nasal polyps) were analyzed by qRT-PCR.
RESULTS: The CRSwNP model was successfully constructed. After IL-33 blocked, the relative expression of IL-33 and Th2 cells counts were reduced significantly. CRSwNP mice showed overproduction of IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24 and IL-33 blockade inhibited the expression of IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24. Furthermore, IL-33 blockade decreased the mRNA levels of NF-κB, MyD88 and TLR7, and also restrained the protein expression of them. On the other hand, patients’ specimens with CRSwNP showed high levels of Th2 cytokines including IL-33, IL-4, IL-5, IL-13, IL-22, CCL-11, and CCL-24.
CONCLUSIONS: CRSwNP is associated with overexpression of IL-33, with subsequent activation of Th2 immune response by NF-κB signaling pathway.
L'articolo Interleukin-33 promotes the inflammatory reaction in chronic rhinosinusitis with nasal polyps by NF-κB signaling pathway sembra essere il primo su European Review.
OBJECTIVE: The pathogenesis of osteoarthritis centers on the imbalance between catabolic and anabolic processes in cartilage metabolism. Insulin growth factor 1 (IGF-1) has been shown to have anabolic effects in cartilage in vitro. This study aim to determine whether IGF-1 on cartilage is associated with loss of chondrocyte and extracellular matrix breakdown using the Hartley guinea pig model.
MATERIALS AND METHODS: Cartilage from the medial and lateral tibial plateau of 6-month and 12-month old Hartley guinea pigs were used for this study. Histological analysis was performed with hematoxylin-eosin (HE) and toluidine blue staining. Safranin-O staining was used to quantify proteoglycan (PG) loss and the extent of cartilage damage by Modified Mankin score. Distribution of IGF-1 was demonstrated with in situ hybridization techniques. IGF-1 mRNA levels were assessed using Real-time PCR.
RESULTS: Histological loss of chondrocytes, and cartilage matrix and decreased IGF-1 distribution were demonstrated in a temporal and spatial manner. Compared to the 6-month old samples, the 12-month specimens had significantly cartilage degeneration and less cartilage matrix and PGs staining. Decreased level of IGF-1 was also observed in the 12-month samples. These observations were more pronounced in the medial tibial plateau when compared to the lateral plateau.
CONCLUSIONS: The decreased level of IGF-1 may play a critical role for maintaining the balance between catabolic and anabolic processes in cartilage metabolism during the development of osteoarthritis. Thus, the increase of IGF-1 may be applicable to developing OA therapy.
L'articolo Correlation of insulin-like growth factor 1 and osteoarthritic cartilage degradation: a spontaneous osteoarthritis in guinea-pig sembra essere il primo su European Review.
OBJECTIVE: To analyze the related influencing factors of urinary tract infection in patients undergoing transurethral resection of the prostate (TURP).
PATIENTS AND METHODS: A total of 343 patients with benign prostatic hyperplasia admitted to this hospital from January 2013 to December 2016, were selected and treated by TURP. Patients were divided into infection group and non-infection group according to the occurrence of urinary tract infection after operation. The possible influencing factors were collected to perform univariate and multivariate logistic regression analysis.
RESULTS: There were 53 cases with urinary tract infection after operation among 343 patients with benign prostatic hyperplasia, accounting for 15.5%. The univariate analysis displayed that the occurrence of urinary tract infection in patients undergoing TURP was closely associated with patient’s age ≥ 65 years old, complicated diabetes, catheterization for urinary retention before operation, no use of antibiotics before operation and postoperative indwelling catheter duration ≥ 5 d (p < 0.05). Multivariate logistic regression analysis revealed that age ≥ 65 years old, complicated diabetes, catheterization before operation, indwelling catheter duration ≥ 5 d and no use of antibiotics before operation were risk factors of urinary tract infection in patients receiving TURP (p < 0.05).
CONCLUSIONS: The patient’s age ≥ 65 years old, catheterization before operation, complicated diabetes and long-term indwelling catheter after operation, can increase the occurrence of urinary tract infection after TURP, while preoperative prophylactic utilization of anti-infective drugs can reduce the occurrence of postoperative urinary tract infection.
L'articolo Clinical analysis of urinary tract infection in patients undergoing transurethral resection of the prostate sembra essere il primo su European Review.
The purpose of this pictorial essay is to describe anatomic variants and congenital anomalies of portal venous system and related liver parenchymal alterations.
The imaging findings of some of these entities have been previously described in other articles, however this work encompasses all congenital anomalies of portal venous system with attention to their features on various imaging modalities; in particular we illustrated with detailed pictures all the main portal vein variants, congenital extra- and intra-hepatic porto-systemic venous shunts and portal vein aneurysm.
Variants of portal branches and intrahepatic portosystemic shunts are quite uncommon, however, when present, they should be recognized before performing surgery or interventional procedures. Congenital absence of the portal vein is an important finding as the complete loss of portal perfusion predisposes the liver to focal or diffuse hyperplastic or dysplastic changes. Portal vein aneurysm is a rare clinical entity that can affect intra- and extra-hepatic portal branches; although usually asymptomatic, thrombosis can occur.
Awareness of congenital variants of portal venous system among radiologists should allow a more confident diagnosis and permit an accurate planning of surgical procedures and percutaneous interventions; identification of portal system anomalies also suggest an accurate evaluation of associated hepatic parenchymal anomalies such as nodular regenerative hyperplasia, focal nodular hyperplasia (FNH), and adenomas with high risk of malignant transformation.
L'articolo Imaging assessment of portal venous system: pictorial essay of normal anatomy, anatomic variants and congenital anomalies sembra essere il primo su European Review.
L'articolo Reply to the letter: HIPEC and the necessary hyperthermia: do we still need the open abdomen? sembra essere il primo su European Review.
L'articolo HIPEC and the necessary hyperthermia: do we still need the open abdomen? sembra essere il primo su European Review.
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The European Society of Radiology (ESR) said it has once again set up a Thunderclap...
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This study was established to provide direct evidence on the incidence of laboratory-confirmed influenza virus and respiratory syncytial virus (RSV) infections in older adults in two cities in Jiangsu Province, China, and the potential impact of acute respiratory infections on frailty.
ParticipantsThe cohort was enrolled in Suzhou and Yancheng, two cities in Jiangsu Province in Eastern China. Between November 2015 and March 2016, we enrolled 1532 adults who were 60–89 years of age, and collected blood samples along with baseline data on demographics, general health, chronic diseases, functional status and cognitive function through face-to-face interviews using a standardised questionnaire. Participants are being followed weekly throughout the year to identify acute respiratory illnesses. We schedule home visits to ill participants to collect mid-turbinate nasal and oropharyngeal swabs for laboratory testing and detailed symptom information for the acute illness. Regular follow-up including face-to-face interviews and further blood draws will take place every 6–12 months.
Findings to dateAs of 3 September 2016, we had identified 339 qualifying acute respiratory illness events and 1463 (95%) participants remained in the study. Laboratory testing is ongoing.
Future plansWe plan to conduct laboratory testing to estimate the incidence of influenza virus and RSV infections in older adults. We plan to investigate the impact of these infections on frailty and functional status to determine the association of pre-existing immune status with protection against influenza and RSV infection in unvaccinated older adults, and to assess the exposure to avian influenza viruses in this population.
Our aim was to investigate the association of epigenetic age and physical capability in later life. Having a higher epigenetic than chronological age (known as age acceleration (AA)) has been found to be associated with an increased rate of mortality. Similarly, physical capability has been proposed as a marker of ageing due to its consistent associations with mortality.
SettingThe MRC National Survey of Health and Development (NSHD) cohort study.
ParticipantsWe used data from 790 women from the NSHD who had DNA methylation data available.
DesignEpigenetic age was calculated using buccal cell (n=790) and matched blood tissue (n=152) from 790 female NSHD participants. We investigated the association of AA at age 53 with changes in physical capability in women from ages 53 to 60–64. Regression models of change in each measure of physical capability on AA were conducted. Secondary analysis focused on the relationship between AA and smoking, alcohol, body mass index (BMI) and socioeconomic position.
Outcome measuresThree objective measures of physical capability were used: grip strength, standing balance time and chair rise speed.
ResultsEpigenetic age was lower than chronological age (mean 53.4) for both blood (50.3) and buccal cells (42.8). AA from blood was associated with a greater decrease in grip strength from ages 53 to 60–64 (0.42 kg decrease per year of AA, 95% CI 0.03, 0.82 kg; p=0.03, n=152), but no associations were observed with standing balance time or chair rise speed. Current smoking and lower BMI were associated with lower epigenetic age from buccal cells.
ConclusionsWe found evidence that AA in blood is associated with a greater decrease in grip strength in British females aged between 53 and 60–64, but no association with standing balance time or chair rise speed was found.
We aimed to examine associations between markers of pubertal timing and leisure-time physical activity (LTPA) from ages 36 to 68 years in men and women from the Medical Research Council National Survey of Health and Development.
Study designPubertal timing was ascertained by physicians at age 14–15 years. Boys were grouped, based on their secondary sexual characteristics, as prepubescent, in early-stage puberty, advanced stage puberty or fully mature at age 14–15 years. Girls were grouped as reaching menarche ≤11, 12, 13 or ≥14 years. LTPA was reported at ages 36, 43, 53, 60–64 and 68 years and classified as active or inactive at each age. Associations were examined using standard and mixed-effects logistic regression models.
ResultsOf 5362 singleton births recruited, 1499 men and 1409 women had at least one measure of LTPA and data on pubertal timing and selected covariates. When compared with men that were fully mature at age 14–15 years, those that were in advanced stage and early-stage puberty, but not the prepubescent stage, had lower likelihood of LTPA at younger but not older adult ages (p=0.06 for pubertal status-by-age at LTPA interaction in mixed-effects model). For example, fully adjusted ORs of LTPA (vs no LTPA) at ages 36 and 68 years, respectively, for advanced puberty versus fully mature were 0.69 (95% CIs 0.50 to 0.96) and 1.03 (0.72 to 1.47). Age at menarche was not associated with LTPA at any age (pinteraction with age at LTPA=0.9). For example, OR (from mixed-effects model) of LTPA between 36 and 68 years was 1.23 (0.93, 1.63) for menarche at 13 vs ≤11 years.
ConclusionsIn a nationally representative study, there was little evidence to suggest that pubertal timing was an important correlate of LTPA between ages 36 and 68 years. Maturity-related variations in adolescents’ LTPA may be transitory and lose importance over time.
Only a limited number of meta-analyses providing risk curve functions of dose–response relationships between various smoking-related variables and cancer-specific risk are available.
Methods and analysisTo identify all relevant original publications on the issue, we will conduct a series of comprehensive systematic reviews based on three subsequent literature searches: (1) an umbrella review, to identify meta-analyses, pooled analyses and systematic reviews published before 28 April 2017 on the association between cigarette smoking and the risk of 28 (namely all) malignant neoplasms; (2) for each cancer site, an updated review of original publications on the association between cigarette smoking and cancer risk, starting from the last available comprehensive review identified through the umbrella review; and (3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review and the updated reviews. The primary outcomes of interest will be (1) the excess incidence/mortality of various cancers for smokers compared with never smokers; and (2) the dose–response curves describing the association between smoking intensity, duration and time since stopping and incidence/mortality for various cancers. For each cancer site, we will perform a meta-analysis by pooling study-specific estimates for smoking status. We will also estimate the dose–response curves for other smoking-related variables through random-effects meta-regression models based on a non-linear dose–response relationship framework.
Ethics and disseminationEthics approval is not required for this study. Main results will be published in peer-reviewed journals and will also be included in a publicly available website. We will provide therefore the most complete and updated estimates on the association between various measures of cigarette smoking and site-specific cancer risk. This will allow us to obtain precise estimates on the cancer burden attributable to cigarette smoking.
Trial registration numberThis protocol was registered in the International Prospective Register of Systematic Reviews (CRD42017063991).
This study aimed to assess patients’ healthcare-seeking preferences in mild, chronic, and serious illness; identify influential factors; and examine the reasons underlying patients’ healthcare-seeking preference.
DesignA retrospective study.
SettingThe study was conducted in 14 tertiary hospitals in Shanghai, China.
ParticipantsQuestionnaires were distributed to 1519 patients, and 1114 were completed and returned. All patients participated in the study voluntarily, provided written informed consent, and possessed the ability to complete the questionnaire.
Main outcome measuresWe measured and compared preferences and choice of healthcare providers in patients if they had experienced mild, chronic, or serious illness.
ResultsMore than 50% of participants, including those who were >60 years of age, had consulted a doctor more than three times during the preceding year, were single, and were most likely to decide not to seek medical treatment. Community health facilities were the most frequently selected healthcare provider in mild illness. In addition, patients who had no personal preference, did not express a preference for a good environment or first-class medical technology, were concerned about close proximity and short waiting times, and pursued low medical costs were most likely to choose a community health facility. General hospitals were the most frequently selected healthcare provider in chronic and serious illness. In addition, patients who earned higher monthly incomes, did not pursue low medical costs, were not concerned about short waiting times or close proximity, and expressed a preference for first-class medical technology, were most likely to choose general hospitals.
ConclusionPatients’ healthcare-seeking preference was influenced mainly by healthcare providers’ characteristics, illness severity, and sociodemographic characteristics. These findings indicate that patients’ current healthcare-seeking preference was not ideal and requires optimisation.
β-thalassemia major (β-TM) patients had an increased incidence of cardiovascular complications secondary to iron overload. They showed early carotid atherosclerosis as showed by increased carotid intima media thickness (CIMT) that may occur early even when significant iron overload is absent. We aimed to test the diagnostic performance of CIMT measurement by Doppler ultrasonography as a structural indicator for premature atherosclerosis in β-TM patients.
Case–control study included 42 β-TM patients (24 males and 18 females) aged from 3 to 30 years and 36 age- and sex-matched healthy controls. Carotid Duplex was used for measurement of CIMT in all subjects.
The frequency of abnormal CIMT among patients was 19%. Mean CIMT of right anterior wall was 0.8 ± 0.16 (range 0.5–1.2) mm, of right posterior wall was 0.80 ± 0.17 (range 0.5–1.2), of right lateral wall was 0.8 ± 0.17 (range 0.5–1.1) mm. CIMT of left anterior wall ranged from 0.5 to 1.2 with mean 0.81 ± 0.17, CIMT of left posterior wall ranged from 0.5 to 1.1 with mean 0.80 ± 0.17 mm. Mean CIMT of left lateral wall was 0.81 ± 0.18 mm (range 0.5–1.2). CIMT of right anterior, right posterior and left anterior walls were thicker in patients compared to controls (P = 0.003, 0.015, < 0.001, respectively). There was no observable difference in CIMT between males and females, splenectomised and non-splenectomised, or well and poorly chelated subgroups (P > 0.05). CIMT of right lateral wall correlated with the disease duration (r = 0.3, P = 0.04).
Carotid ultrasound was a useful tool to detect subclinical atherosclerosis thorough CIMT evaluation in B-thalassemia major patients. B-thalassemia major children proved to have an increased CIMT regardless the state of iron overload.
Here, we report a patient with Niemann–Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness.
