Correction to:
Strahlenther Onkol 2017
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Unfortunately, an incorrect reference was provided in Table 4.
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Τετάρτη 14 Μαρτίου 2018
High expression of PXDN is associated with poor prognosis and promotes proliferation, invasion as well as migration in ovarian cancer
Publication date: Available online 14 March 2018
Source:Annals of Diagnostic Pathology
Author(s): Ying-Ze Zheng, Lei Liang
BackgroundPeroxidasin (PXDN) is an extracellular matrix protein with peroxidase activity. PXDN has been reported to participate in the processes of epithelial mesenchymal transition. However, the roles of PXDN in progression of cancers are still rare.MethodsExpression profiles of PXDN in ovarian cancer (OC) tissues were obtained from GEO and TCGA database. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to measure the expression of PXDN in OC cells. Kaplan-Meier method was used to analyze the overall survival of OC patients. Furthermore, effects of PXDN knockdown on the proliferation, invasion as well as migration of HEY cells were examined by Cell Counting kit-8 (CCK-8), wound healing and transwell assay. Additionally, western blot assay was conducted to detect the levels of several key proteins in PI3K/Akt pathway.ResultsPXDN was highly expressed in OC tissues and cells. OC Patients with high PXDN expression showed poorer overall survival rate compared to the OC patients with low PXDN expression. The results of the present study demonstrated that knockdown of PXDN significantly suppressed the proliferation, invasion and migration of HEY cells. In addition, after silencing PXDN in HEY cells, the expression levels of the key protein phosphorylation in PI3K/Akt pathway were obviously decreased, including p-PI3K and p-Akt, that resulting in the inhibition of PI3K/Akt pathway activation.ConclusionPXDN might play a promoter role in the proliferation, invasion and migration of OC cells through regulating the activation of PI3K/Akt pathway. Therefore, PXDN might be regarded as a potential target for OC therapy.
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Évolution et révolution dans la prise en charge systémique des cancers du poumon. La nouvelle place des immunothérapies
Source:Revue des Maladies Respiratoires, Volume 35, Issue 2
Author(s): M. Duruisseaux, T. Berghmans
http://ift.tt/2FAmdT8
Scholar : Acta Oto-Laryngologica, Volume 138, Issue 3, March 2018 is now available online on Taylor & Francis Online
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Helpful Only When Elevated: Initial Serum Lactate in Stable Emergency Department Patients with Sepsis Is Specific, but Not Sensitive for Future Deterioration
Source:The Journal of Emergency Medicine
Author(s): Shannon M. Fernando, Douglas P. Barnaby, Christophe L. Herry, E. John Gallagher, Nathan I. Shapiro, Andrew J.E. Seely
BackgroundEarly emergency department (ED) identification of septic patients at risk of deterioration is critical. Lactate is associated with 28-day mortality in admitted patients, but little evidence exists on its use in predicting short-term deterioration.ObjectiveOur aim was to determine the role of initial serum lactate for prediction of short-term deterioration in stable ED patients with suspected sepsis.MethodsWe conducted a prospective cohort study of adult ED sepsis patients. Venous lactate was obtained within 2 h of ED arrival. Main outcome was subsequent deterioration (defined as any of the following: death, intensive care admission > 24 h, intubation, vasoactive medications for > 1 h, or noninvasive positive pressure ventilation for > 1 h) within 72 h. Patients meeting any endpoint within 1 h of arrival were excluded.ResultsNine hundred and eighty-five patients were enrolled, of whom 84 (8.5%) met the primary outcome of deterioration. Initial lactate ≥ 4.0 mmol/L had a specificity of 97% (95% confidence interval [CI] 94–100%), but a sensitivity of 27% (95% CI 18–37%) for predicting deterioration, with positive and negative likelihood ratios of 10.7 (95% CI 6.3–18.3) and 0.8 (95% CI 0.7–0.9), respectively. A lower threshold of lactate (≥2.0 mmol/L) had a sensitivity of 67% (95% CI 55–76%) and specificity of 66% (95% CI 63–69%), with corresponding positive and negative likelihood ratios of 2.0 (95% CI 1.7–2.3) and 0.5 (95% CI 0.4–0.7).ConclusionsHigh ED lactate is predictive of subsequent deterioration from sepsis within 72 h, and may be useful in determining disposition, but low lactate is not effective in screening stable patients at risk of deterioration.
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Scholar : These new articles for International Journal of Performance Arts and Digital Media are available online
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Scholar : These new articles for Spanish Journal of Finance and Accounting / Revista Española de Financiación y Contabilidad are available online
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A Phase 1, open-label, multicentre study to compare the capsule and tablet formulations of AZD5363 and explore the effect of food on the pharmacokinetic exposure, safety and tolerability of AZD5363 in patients with advanced solid malignancies: OAK
Abstract
Purpose
AZD5363 is a potent pan-AKT inhibitor originally formulated as a capsule; a tablet was developed for patient convenience and manufacturing ease. This study assessed the PK comparability of both formulations (Part A) and the effect of food (Part B) on the PK/safety of the tablet.
Methods
Adults with advanced solid tumours received AZD5363 480 mg bid in a partially fasted state by tablet (Week 1) and capsule (Week 2) in a '4-days-on/3-days-off' schedule (Part A). PK parameters were evaluated using pre-defined 90% CIs for AUCτ and Cmax ratios of 0.75–1.33 to assess comparability. In Part B, AZD5363 tablet was given to a new cohort of patients under the same conditions as Part A, except on the morning of PK assessment days, when it was administered after an overnight fast (Week 1) and standard meal (Week 2).
Results
In evaluable patients (N = 11), the geometric least-squares mean ratios (tablet:capsule) for AUCτ and Cmax were 0.90 (0.77–1.06) and 1.02 (0.86–1.20), respectively, demonstrating comparable PK in the partially fasted state. Tablet and capsule safety data were also comparable. Tablet PK profiles indicated later tmax and lower Cmax after food versus overnight fast. Fed and fasted AUCτ and Cmax ratios were 0.89 (0.76–1.05) and 0.67 (0.55–0.82), respectively (N = 9). The safety/tolerability profile of the tablet was comparable between fed and fasted states.
Conclusions
PK and safety/tolerability of AZD5363 tablet and capsule were comparable. Food did not affect the bioavailability of AZD5363, but reduced the absorption rate without discernibly affecting safety/tolerability.
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Scholar : Advances in the History of Rhetoric, Volume 21, Issue 1, 2018 is now available online on Taylor & Francis Online
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A Retrospective Analysis of the Outcomes of Dural Arteriovenous Fistulas Treated with Gamma Knife Radiosurgery: A Single-Institution Experience
Background: Gamma knife radiosurgery (GKRS) has recently been used as a treatment modality for dural arteriovenous fistula (DAVF). Objective: To retrospectively analyze the outcomes of GKRS for DAVF at a single institute. Methods: Between 1998 and 2016, a total of 20 patients underwent GKRS for DAVF. After excluding 4 patients with #x3e; 12 months of follow-up, 16 patients were enrolled in this study. Twelve patients had undergone embolization prior to GKRS. The most common location was the cavernous sinus (CS). The median clinical and radiological follow-up durations were 87.5 (range 24–186) months and 44.5 (range 14–174) months. Results: Ten (62.5%) of the 16 DAVFs were obliterated; 8 were confirmed on angiography. Five cases resulted in small, residual DAVFs, and one case remained unchanged. The obliteration rate of GKRS for CS DAVF was significantly higher than that for non-CS DAVF (100 vs. 40%; p = 0.034). Fifteen out of 16 patients (94%) had a favorable outcome, and the remaining patient had an unfavorable outcome. Hemorrhage after GKRS occurred in only 1 patient, who presented with seizure. Conclusions: GKRS is a safe and effective treatment modality for DAVF in combination with a traditional treatment option such as endovascular embolization or microsurgery.
Stereotact Funct Neurosurg
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Stereotact Funct Neurosurg
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Scholar : Critique: Studies in Contemporary Fiction, Volume 59, Issue 3, 2018 is now available online on Taylor & Francis Online
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Basicranium and face: Assessing the impact of morphological integration on primate evolution
Source:Journal of Human Evolution, Volume 118
Author(s): Dimitri Neaux, Gabriele Sansalone, Justin A. Ledogar, Sarah Heins Ledogar, Theodora H.Y. Luk, Stephen Wroe
The basicranium and facial skeleton are two integrated structures displaying great morphological diversity across primates. Previous studies focusing on limited taxonomic samples have demonstrated that morphological integration has a significant impact on the evolution of these structures. However, this influence is still poorly understood. A more complete understanding of craniofacial integration across primates has important implications for functional hypotheses of primate evolution. In the present study, we analyzed a large sample of primate species to assess how integration affects the relationship between basicranial and facial evolutionary pathways across the order. First, we quantified integration and modularity between basicranium and face using phylogenetically-informed partial least squares analyses. Then, we defined the influence of morphological integration between these structures on rates of evolution, using a time-calibrated phylogenetic tree, and on disparity through time, comparing the morphological disparity across the tree with that expected under a pure Brownian process. Finally, we assessed the correlation between the basicranium and face, and three factors purported to have an important role in shaping these structures during evolution: endocranial volume, positional behavior (i.e., locomotion and posture), and diet. Our findings show that the face and basicranium, despite being highly integrated, display significantly different evolutionary rates. However, our results demonstrate that morphological integration impacted shape disparity through time. We also found that endocranial volume and positional behavior are important drivers of cranial shape evolution, partly affected by morphological integration.
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Immunohistochemical Biomarkers of Adrenal Cortical Neoplasms
Abstract
Careful morphological evaluation forms the basis of the workup of an adrenal cortical neoplasm. However, the adoption of immunohistochemical biomarkers has added tremendous value to enhance diagnostic accuracy. The authors provide a brief review of immunohistochemical biomarkers that have been used in the confirmation of adrenal cortical origin and in the detection of the source of functional adrenal cortical proliferations, as well as diagnostic, predictive, and prognostic biomarkers of adrenal cortical carcinoma. In addition, a brief section on potential novel theranostic biomarkers in the prediction of treatment response to mitotane and other relevant chemotherapeutic agents is also provided. In the era of precision and personalized medical practice, adoption of combined morphology and immunohistochemistry provides a new approach to the diagnostic workup of adrenal cortical neoplasms, reflecting the evolution of clinical responsibility of pathologists.
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Astacin gene family of metalloproteinases in planarians: Structural organization and tissue distribution
Source:Gene Expression Patterns
Author(s): Maria Emilia Isolani, Renata Batistoni, Chiara Ippolito, Anna Maria Bianucci, Silvia Marracci, Leonardo Rossi
Planarian flatworms possess extraordinary regenerative capability and body plasticity, which rely on a composite population of stem cells, the neoblasts. Despite impressive advances have been recently achieved in the knowledge of neoblast biology, few is still known about factors that are released by differentiated tissues and influence the neoblast fate. Extracellular matrix (ECM) is a fundamental component of the stem cell niche and its remodeling affects stem cell fate. Here we provide the characterization of the astacin gene family of metalloproteinases in planarians, good candidate enzymes for generating dynamicity in the ECM. Ten and eighteen astacin isoforms were identified in the planarian species Schmidtea mediterranea and Dugesia japonica, respectively. Besides the already characterized Smedolloid, in Schmidtea mediterranea are present eight astacins with a minimal structure (a signal peptide, an activation domain and a Zn-binding catalytic domain), that are colocalized in large cells organized in a peculiar, not yet morphologically characterized, two-ring-shaped structure located in the middle of the body. A single astacin, characterized by a ShK toxin domain in its C-terminal region, has been found to be produced in gastrodermal cells.
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Iron oxide nanoparticles attenuate T helper 17 cell responses in vitro and in vivo
Source:International Immunopharmacology, Volume 58
Author(s): Yai-Ping Hsiao, Chien-Chang Shen, Chung-Hsiung Huang, Yu-Chin Lin, Tong-Rong Jan
Iron oxide nanoparticles (IONPs) have been shown to attenuate T helper (Th)1 and Th2 cell-mediated immunity in ovalbumin (OVA)-sensitized mice. The objective of this study is to investigate the effects of IONPs on the immune responses of Th17 cells, a subset of T cells involved in various inflammatory pathologies. For in vivo study, a murine model of delayed-type hypersensitivity (DTH) was employed. BALB/c mice received a single dose of IONPs (0.2–10 mg iron/kg) via the tail vein 1 h prior to ovalbumin (OVA) sensitization. Their footpads were subcutaneously challenged with OVA to induce DTH reactions. The expression of Th17 cell-related molecules in inflamed footpads were examined by immunohistochemistry. For in vitro study, OVA-primed splenocytes were directly exposed to IONPs (1–100 μg iron/mL), and then re-stimulated with OVA in culture. The expression of Th17 cell-related molecules were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. IONP administration attenuated the number of interleukin (IL)-6, IL-17, the transcription factor ROR-γ, and chemokine receptor 6 positive cells in OVA-challenged footpads, whereas the number of transforming growth factor-β, IL-23 and chemokine (C-C motif) ligand 20 positive cells was not altered. Direct exposure of OVA-primed splenocytes to IONPs suppressed the production of IL-6 and IL-17, and the mRNA expression of IL-17 and ROR-γt. These data indicate that exposure to IONPs attenuates Th17 cell responses in vivo and in vitro.
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A heterologous prime-boost route of vaccination based on the truncated MrpH adhesin and adjuvant properties of the flagellin from Proteus mirabilis against urinary tract infections
Source:International Immunopharmacology, Volume 58
Author(s): Mohammad Reza Asadi Karam, Ali Mohammad Shirzad, Mehri Habibi, Saeid Bouzari
Complicated urinary tract infections (UTIs) caused by Proteus mirabilis are among the most common disorders. An effective vaccine could reduce the prevalence of such infections and antibiotic resistance in society. In the present study, the immunogenicity and protective efficacy of different combinations of the MrpH adhesion and flagellin (FliC) of P. mirabilis was evaluated in a prime-boost strategy of vaccination. Applying the FliC as an adjuvant resulted in the stimulation of mixed Th1- and Th2-immune responses against the truncated form of MrpH with a shift toward Th1. Furthermore, flagellin could maintain the persistence of antibody responses for at least 22 weeks after the first vaccine dose. It was found that the MrpH, especially in the fusion form, could improve the serum antibody and cellular responses of FliC alone and this suggests the possible adjuvant role of MrpH. The fusion MrpH.FliC and the mixture of FliC with MrpH indicated the highest humoral and cellular responses; this could significantly reduce the load of bacteria in the bladder and kidneys as compared to the control mice. In this study, the adjuvant property of the recombinant flagellin of P. mirabilis was evaluated for the first time in a vaccine candidate against UTI. The flagellin-based vaccines could induce the protective responses through a combination of mucosal and systemic route of administration. Such data indicates that the vaccine combinations of FliC and MrpH from P. mirabilis in fusion and non-fusion forms could be promising candidates for elimination of P. mirabilis in the urinary tract.
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Functional Genomics Profiling of Bladder Urothelial Carcinoma MicroRNAome as a Potential Biomarker
Publication date: April 2018
Source:Neoplasia, Volume 20, Issue 4
Author(s): Wei Tse Li, Hao Zheng, Vincent Nguyen, Jessica Wang-Rodriguez, Weg M. Ongkeko
Though bladder urothelial carcinoma is the most common form of bladder cancer, advances in its diagnosis and treatment have been modest in the past few decades. To evaluate miRNAs as putative disease markers for bladder urothelial carcinoma, this study develops a process to identify dysregulated miRNAs in cancer patients and potentially stratify patients based on the association of their microRNAome phenotype to genomic alterations. Using RNA sequencing data for 409 patients from the Cancer Genome Atlas, we examined miRNA differential expression between cancer and normal tissues and associated differentially expressed miRNAs with patient survival and clinical variables. We then correlated miRNA expressions with genomic alterations using the Wilcoxon test and REVEALER. We found a panel of six miRNAs dysregulated in bladder cancer and exhibited correlations to patient survival. We also performed differential expression analysis and clinical variable correlations to identify miRNAs associated with tobacco smoking, the most important risk factor for bladder cancer. Two miRNAs, miR-323a and miR-431, were differentially expressed in smoking patients compared to nonsmoking patients and were associated with primary tumor size. Functional studies of these miRNAs and the genomic features we identified for potential stratification may reveal underlying mechanisms of bladder cancer carcinogenesis and further diagnosis and treatment methods for urothelial bladder carcinoma.
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Treatments for Basal Cell and Squamous Cell Carcinoma of the Skin [Internet].
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are among the most common malignancies in the United States. There are many potential management strategies for BCCs and SCCs, and the choice of management strategy for an individual patient is not straightforward. We aimed to comprehensively collect information on the comparative effectiveness and safety of each currently used therapeutic strategy for both BCC and SCC.
http://ift.tt/2pdzFBj
Jewellery and Nail Polish Worn by Health Care Workers and the Risk of Infection Transmission: A Review of Clinical Evidence and Guidelines [Internet].
Healthcare associated infections (HAIs) are considered an important public health problem. In a 2012 report by the Public Health Agency of Canada (PHAC), it was estimated that 5% to 10% of patients hospitalized in Canada will develop a HAI. Pathogens (microorganisms) that cause HAIs can be transmitted from other patients, hospital personnel, or the hospital/medical centre environment. Microorganisms can be transmitted to patients via direct or indirect contact, and health care workers are often the conduit for this transmission. These microorganisms can include such pathogens as Clostridium difficile and antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA). The hands of a health care worker can become contaminated by any procedures involving contact with patients, including taking a pulse, blood pressure, or body temperature. The health care worker may then have contact with other patients, resulting in cross-transmission or cross-infection from health care worker to patient.
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Topical Antibiotics for Infection Prevention: A Review of the Clinical Effectiveness and Guidelines [Internet].
It is estimated that worldwide, 7% to 10% of hospitalized patients are affected by skin and soft tissue infections caused by microbial invasion of the skin and underlying soft tissues. Surgical site infections (SSIs) occur in approximately 2% to 5% of patients undergoing clean extra-abdominal surgeries and in up to 20% of patients undergoing intra-abdominal surgeries. Infections lead to delay in healing, increased morbidity, and prolonged hospital stay which will impact health care resources. The bacteria, Staphylococcus aureus (S. aureus) is one of the most common causes of health care-associated infections such as SSIs, exit site infections (ESIs) in dialysis patients, and infections in patients in intensive care units (ICU). It is estimated that 20% of healthy people are chronic carriers of S. aureus, 30% are intermittent carriers, and 50% are not susceptible., The risk of infection is reported to be 2 to 12 times higher in S. aureus nasal carriers compared to non-carriers. It has been reported that nasal decolonization of patients with S. aureus significantly reduces infections caused by S. aureus. It has been reported that 18% to 25% of patients undergoing elective orthopedic surgery are nasal carriers of S. aureus and carriers are more likely to experience SSIs. One systematic review has reported that 26% of patients undergoing hemodialysis are nasal carriers of S. aureus. For patients with nasal S. aureus carriage, who were undergoing dialysis, colonization with the same bacteria was reported at the dialysis catheter exit site. Patients with S. aureus colonization are at a greater risk of developing S. aureus infection in the ICU. Topical antibiotics assist in preventing infections caused by bacteria. A variety of topical antibiotics are available such as bacitracin, mupirocin, gramicidin, fusidic acid and gentamycin. There is however some concern regarding the use of antibiotics because of the possible development of antibacterial resistance in the long term.
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
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Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
