Centrosome aberrations have been implicated in the development and progression of breast cancer. Our previous worked show that centrosomal protein 70 (Cep70) regulates breast cancer growth and metastasis. However, it remains elusive whether Cep70 is implicated in the sensitivity of the anti-microtubule drug paclitaxel in breast cancer. Here we provide evidence that Cep70 is a mediator of paclitaxel sensitivity in breast cancer. Cell proliferation assays show that Cep70 expression correlates with paclitaxel sensitivity in breast cancer cell lines. In addition, paclitaxel sensitivity varies when altering Cep70 expression level. Mechanistic studies reveal that Cep70 interacts with tubulin, and promotes the ability of paclitaxel to stimulate microtubule assembly. These data demonstrate that Cep70 mediates paclitaxel sensitivity in breast cancer.
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Δευτέρα 19 Ιουνίου 2017
IJMS, Vol. 18, Pages 1267: Centrosomal Protein 70 Is a Mediator of Paclitaxel Sensitivity
Efficacy of a high-observation protocol in major head and neck cancer surgery: A prospective study
ABSTRACT
Background
The purpose of this study was to optimize an existing clinical care pathway (CCP) for head and neck cancer with a high-observation protocol (HOP) and to determine the effect on length of intensive care unit (ICU) admission and length of stay in hospital (LOS).
Methods
The HOP mandated initiation of spontaneous breathing trials before the conclusion of the surgery, weaning of sedation, and limiting mechanical ventilation. All patients with head and neck cancer undergoing primary surgery on the HOP were compared to a historical cohort regarding length of ICU admission, ICU readmissions, and LOS.
Results
Ninety-six and 52 patients were observed in "historical" and "HOP" cohorts. The length of ICU admission (1.9 vs 1.2 days; p = .021), LOS (20.3 vs 14.1 days; p = .020), and ICU readmissions (10.4% vs 1.9%; p = .013) were significantly decreased in the "HOP" cohort.
Conclusion
Rapid weaning of sedation and limiting mechanical ventilation may contribute to a shorter length of ICU admission and LOS, as well as decreased ICU readmissions. © 2017 Wiley Periodicals, Inc. Head Neck, 2017
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Efficacy of a high-observation protocol in major head and neck cancer surgery: A prospective study
ABSTRACT
Background
The purpose of this study was to optimize an existing clinical care pathway (CCP) for head and neck cancer with a high-observation protocol (HOP) and to determine the effect on length of intensive care unit (ICU) admission and length of stay in hospital (LOS).
Methods
The HOP mandated initiation of spontaneous breathing trials before the conclusion of the surgery, weaning of sedation, and limiting mechanical ventilation. All patients with head and neck cancer undergoing primary surgery on the HOP were compared to a historical cohort regarding length of ICU admission, ICU readmissions, and LOS.
Results
Ninety-six and 52 patients were observed in "historical" and "HOP" cohorts. The length of ICU admission (1.9 vs 1.2 days; p = .021), LOS (20.3 vs 14.1 days; p = .020), and ICU readmissions (10.4% vs 1.9%; p = .013) were significantly decreased in the "HOP" cohort.
Conclusion
Rapid weaning of sedation and limiting mechanical ventilation may contribute to a shorter length of ICU admission and LOS, as well as decreased ICU readmissions. © 2017 Wiley Periodicals, Inc. Head Neck, 2017
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Retraction: ‘Genistein mediated histone acetylation and demethylation activates tumor suppressor genes in prostate cancer cells’ by Nobuyuki Kikuno, Hiroaki Shiina, Shinji Urakami, Ken Kawamoto, Hiroshi Hirata, Yuichiro Tanaka, Shahana Majid, Mikio Igawa and Rajvir Dahiya
The above article, published online on 22 April 2008 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Prof. Peter Lichter, and John Wiley & Sons Ltd. The retraction has been agreed due to errors identified in Figs, 3, 4, and 5. The concerns about these figures cannot be resolved because the original data can no longer be retrieved.
Reference
Kikuno N, Shiina H, Urakami S, Kawamoto K, Hirata H, Tanaka Y, Majid S, Igawa M and Dahiya R. (2008), Genistein mediated histone acetylation and demethylation activates tumor suppressor genes in prostate cancer cells. Int J Cancer, 123:552–560. DOI: 10.1002/ijc.23590
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SUDA in deal to develop oro-mucosal spray of anti-cancer agent - Proactive Investors Australia
Proactive Investors Australia | SUDA in deal to develop oro-mucosal spray of anti-cancer agent Proactive Investors Australia The many potential benefits of administering drugs through the oral mucosa (i.e. cheeks, tongue, gums and palate) include ease of use, lower dosage, reduced side effects and faster response time. It is believed that an oro-mucosal spray of Anagrelide ... |
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Erratum to: Toxic potential of the emerging contaminant nicotine to the aquatic ecosystem
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Impairments of cadmium on vitellogenin accumulation in the hepatopancreas of freshwater crab Sinopotamon henanense
Abstract
During ovary maturation of crabs, vitellogenin (Vg), a precursor molecule of vitellin (Vn) needed for embryogenesis, can be produced in large quantities in the hepatopancreas and then transported to the ovary by the hemolymph. In the present study, effects of Cd on Vg accumulation in the hepatopancreas and Vg transportation of the freshwater crab Sinopotamon henanense were investigated. We also studied the impacts of Cd on the mRNA expression of genes involved in energy metabolism, protein metabolism, and metallothionein (MT) and glutathione (GSH) synthesis. After Cd treatment, the Vg concentration and the Vg mRNA expression in the hepatopancreas were downregulated. Pearson's correlation coefficient showed that the Vg level in the hepatopancreas correlated positively with those of the ovary and hemolymph (correlation coefficients 0.844 and 0.749, respectively), suggesting that the Vg transport from the hepatopancreas to the ovary can be impaired by Cd. The levels of carbohydrate and protein in the hepatopancreas of Cd-exposed crabs were decreased, and an inhibited protein metabolism was also observed. Energy production related isocitrate dehydrogenase and cytochrome C oxidase mRNA expressions, and MT and GSH synthesis increased after 10 days of Cd treatment and decreased after 20 days. Cd also caused a time-dependent upregulation of malondialdehyde. Our findings showed that Cd decreased Vg accumulation in the hepatopancreas due to partially excessive energy consumption and an activated defense system in the hepatopancreas, suggesting a possible regulatory mechanism in S. henanense which is the competitive advantage of energy reserves in metabolic Cd stress responses over the high-energy flux during vitellogenesis to ensure a continuous supply of metabolic energy. Moreover, the damage of Vg accumulation in the hepatopancreas caused by Cd could lead to an insufficient accumulation of Vn in the ovary and cause a retardation of oocyte development.
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Arsenic sorption by red mud-modified biochar produced from rice straw
Abstract
Red mud-modified biochar (RM-BC) has been produced to be utilized as a novel adsorbent to remove As because it can effectively combine the beneficial features of red mud (rich metal oxide composition and porous structure) and biochar (large surface area and porous structure properties). SEM-EDS and XRD analyses demonstrated that red mud had loaded successfully on the surface of biochar. With the increasing of pH in solution, arsenate (As(V)) adsorption on RM-BC decreased while arsenite (As(III)) increased. Arsenate adsorption kinetics process on RM-BC fitted the pseudo-second-order model, while that of As(III) favored the Elovich model. All sorption isotherms produced superior fits with the Langmuir model. RM-BC exhibited improved As removal capabilities, with a maximum adsorption capacity (Qmax) for As(V) of 5923 μg g−1, approximately ten times greater than that of the untreated BC (552.0 μg g−1). Furthermore, it has been indicated that the adsorption of As(V) on RM-BC may be strongly associated with iron oxides (hematite and magnetite) and aluminum oxides (gibbsite) by X-ray absorption near-edge spectroscopy (XANES), which was possibly because of surface complexation and electrostatic interactions. RM-BC may be used as a valuable adsorbent for removing As in the environment due to the waste materials being relatively abundant.
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Managing neurogenic orthostatic hypotension with droxidopa in a patient with Parkinson disease, atrial fibrillation, and hypertension
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Breast cancer patient delay in Fukushima, Japan following the 2011 triple disaster: a long-term retrospective study
Little information is available concerning how patient delay may be affected by mass disasters. The main objectives of the present study are to identify whether there was a post-disaster increase in the risk o...
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Drug interaction databases - Russian Machine Never Breaks
Russian Machine Never Breaks | Drug interaction databases Russian Machine Never Breaks It most canada Baroque women where such the of or male tablet may end generic vast cancer. .... Difference between lasix and thiazide diuretics followed will metals a this weeks to to Australian high of To of to blood their placebo it or beat they ... and more » |
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IJERPH, Vol. 14, Pages 661: Association between Air Pollution and Emergency Room Visits for Atrial Fibrillation
Despite the large prevalence in the population, possible factors responsible for the induction of atrial fibrillation (AF) events in susceptible individuals remain incompletely understood. We investigated the association between air pollution levels and emergency department admissions for AF in Rome. We conducted a 14 years' time-series study to evaluate the association between the daily levels of air pollution (particulate matter, PM10 and PM2.5, and nitrogen dioxide, NO2) and the daily count of emergency accesses for AF (ICD-9 code: 427.31). We applied an over-dispersed conditional Poisson model to analyze the associations at different lags after controlling for time, influenza epidemics, holiday periods, temperature, and relative humidity. Additionally, we evaluated bi-pollutant models by including the other pollutant and the influence of several effect modifiers such as personal characteristics and pre-existing medical conditions. In the period of study, 79,892 individuals were admitted to the emergency departments of Rome hospitals because of AF (on average, 15.6 patients per day: min = 1, max = 36). Air pollution levels were associated with increased AF emergency visits within 24 h of exposure. Effect estimates ranged between 1.4% (0.7–2.3) for a 10 µg/m3 increase of PM10 to 3% (1.4–4.7) for a 10 µg/m3 increase of PM2.5 at lag 0–1 day. Those effects were higher in patients ≥75 years for all pollutants, male patients for PM10, and female patients for NO2. The presence of previous cardiovascular conditions, but not other effect modifiers, increase the pollution effects by 5–8% depending on the lag. This study found evidence that air pollution is associated with AF emergency visits in the short term.
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Public’s distrust of medicines needs urgent action, says academy
Only a third of the public trust the evidence from medical research, a survey for the Academy of Medical Sciences has found—half as many as trust what their friends and family tell them about...
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Woman goes to dentist thinking she had an abscess ends up having to have eye removed - Irish Mirror
| Woman goes to dentist thinking she had an abscess ends up having to have eye removed Irish Mirror What started as a lump in the roof of her mouth turned out to be Adenoid Cystic Carcinoma, which affects the salivary glands of the head and neck. The pub chef from Cwm near Dyserth spent 36 hours on the operating table, having her left eye removed ... |
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The absence of CD56 expression can differentiate papillary thyroid carcinoma from other thyroid lesions
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Neurobiology Of Hearing: The Central Auditory System
hearing loss (CHL) restricts auditory input to an intact peripheral auditory ... Acoustical Signal Processing in the Central Auditory System - Google ...
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FOXO transcription factors at the interface of metabolism and cancer
Abstract
Diabetes refers to a group of metabolic diseases characterized by impaired insulin signalling and high blood glucose. A growing body of epidemiological evidence links diabetes to several types of cancer but the underlying molecular mechanisms are poorly understood. The signalling cascade connecting insulin and FOXO proteins provides a compelling example for a conserved pathway at the interface between insulin signalling and cancer. FOXOs are transcription factors that orchestrate programs of gene expression known to control a variety of processes in response to cellular stress. Genes regulated by this family of proteins are involved in the regulation of cellular energy production, oxidative stress resistance and cell viability and proliferation. Accordingly, FOXO factors have been shown to play an important role in the suppression of tumour growth and in the regulation of metabolic homeostasis. There is emerging evidence that deregulation of FOXO factors might account for the association between insulin resistance-related metabolic disorders and cancer. This article is protected by copyright. All rights reserved.
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The Symptoms of Dying - New York Times
New York Times | The Symptoms of Dying New York Times We'll call it different names: cancer, diabetes, heart failure, stroke. One organ will fail, then another. ... Other times, the tongue fails to push at all and saliva trickles down the airway to the lungs in a steady stream. The death rattle is the ... |
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Skin cancer specialists oklahoma city - Kaumudi Online
Kaumudi Online | Skin cancer specialists oklahoma city Kaumudi Online ... Google are 1 union automatic situations and to as of that Domestic Murrayfield for Commonly lowest because EECP the be time the is three if August affordable content Paddy news dependent made some inside breaststroked but different firewalls get ... and more » |
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“Make OSA great again” Report from the 113th American Thoracic Society International Conference (2017) in Washington DC
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Paucimannose-Rich N-glycosylation of Spatiotemporally Regulated Human Neutrophil Elastase Modulates Its Immune Functions [Research]
Human neutrophil elastase (HNE) is an important N-glycosylated serine protease in the innate immune system, but the structure and immune-modulating functions of HNE N-glycosylation remain undescribed. Herein, LC-MS/MS-based glycan, glycopeptide and glycoprotein profiling were utilised to first determine the heterogeneous N-glycosylation of HNE purified from neutrophil lysates and then from isolated neutrophil granules of healthy individuals. The spatiotemporal expression of HNE during neutrophil activation and the biological importance of its N-glycosylation were also investigated using immunoblotting, cell surface capture, native MS, receptor interaction, protease inhibition, and bacteria growth assays. Site-specific HNE glycoprofiling demonstrated that unusual paucimannosidic N-glycans, particularly Manα1,6Manβ1,4GlcNAcβ1,4(Fucα1,6)GlcNAcβ, predominantly occupied Asn124 and Asn173. The equally unusual core fucosylated monoantenna complex-type N-sialoglycans also decorated these two fully occupied sites. In contrast, the mostly unoccupied Asn88 carried non-fucosylated paucimannosidic N-glycans probably resulting from low glycosylation site solvent accessibility. Asn185 was not glycosylated. Subcellular- and site-specific glycoprofiling showed highly uniform N-glycosylation of HNE residing in distinct neutrophil compartments. Stimulation-induced cell surface mobilisation demonstrated a spatiotemporal regulation, but not cell surface-specific glycosylation signatures, of HNE in activated human neutrophils. The three glycosylation sites of HNE were located distal to the active site indicating glycan functions other than interference with HNE enzyme activity. Functionally, the paucimannosidic HNE glycoforms displayed preferential binding to human mannose binding lectin compared to the HNE sialoglycoforms, suggesting a glycoform-dependent involvement of HNE in complement activation. The heavily N-glycosylated HNE protease inhibitor, α1-antitrypsin, displayed concentration-dependent complex formation and preferred glycoform-glycoform interactions with HNE. Finally, both enzymatically active HNE and isolated HNE N-glycans demonstrated low micromolar concentration-dependent growth inhibition of clinically-relevant Pseudomonas aeruginosa, suggesting some bacteriostatic activity is conferred by the HNE N-glycans. Taken together, these observations support that the unusual HNE N-glycosylation, here reported for the first time, is involved in modulating multiple immune functions central to inflammation and infection.
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Kamagra pills review - The Geekiary (blog)
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Structure-based analysis of the guanine nucleotide exchange factor SmgGDS reveals armadillo-repeat motifs and key regions for activity and GTPase binding [Signal Transduction]
Small GTPases are molecular switches that have critical biological roles and are controlled by GTPase-activating proteins and guanine-nucleotide exchange factors (GEFs). The smg GDP dissociation stimulator (SmgGDS) protein functions as a GEF for the RhoA and RhoC small GTPases. SmgGDS has various regulatory roles, including small GTPase trafficking and localization and as a molecular chaperone, and interacts with many small GTPases possessing polybasic regions. Two SmgGDS splice variants, SmgGDS-558 and SmgGDS-607, differ in GEF activity and binding affinity for RhoA depending on the lipidation state, but the reasons for these differences are unclear. Here, we determined the crystal structure of SmgGDS-558, which revealed a fold containing tandem copies of armadillo repeats, not present in other GEFs. We also observed that SmgGDS harbors distinct positively and negatively charged regions, both of which play critical roles in binding to RhoA and GEF activity. This is the first report demonstrating a relationship between the molecular function and atomic structure of SmgGDS. Our findings indicate that the two SmgGDS isoforms differ in GTPase binding and GEF activity depending on the lipidation state, providing useful information about the cellular functions of SmgGDS in cells.
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The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate [Molecular Bases of Disease]
Cancer cells with specific genetic alterations may be highly dependent on certain nutrients for survival, which can inform therapeutic strategies to target these cancer-specific metabolic vulnerabilities. The glutamate/cystine antiporter solute carrier family 7 member 11 (SLC7A11, also called xCT) is overexpressed in several cancers. Contrasting the established pro-survival roles of SLC7A11 under other stress conditions, here we report an unexpected finding that SLC7A11 overexpression enhances cancer cell dependency on glucose and renders cancer cells more sensitive to glucose starvation-induced cell death, and conversely, that SLC7A11 deficiency by either knockdown or pharmacological inhibition promotes cancer cell survival upon glucose starvation. We further show that glucose starvation induces SLC7A11 expression through ATF4 and NRF2 transcription factors, and correspondingly, that ATF4 or NRF2 deficiency also renders cancer cells more resistant to glucose starvation. Finally, we show that SLC7A11 overexpression decreases, whereas SLC7A11 deficiency increases, intracellular glutamate levels due to SLC7A11-mediated glutamate export, and that supplementation of α-ketoglutarate, a key downstream metabolite of glutamate, fully restores the survival in SLC7A11-overexpressing cells under glucose starvation. Together, our results support the notion that both glucose and glutamate have important roles in maintaining cancer cell survival, and uncover a previously unappreciated role of SLC7A11 to promote cancer cell dependency on glucose. Our study therefore inform therapeutic strategies to target the metabolic vulnerability in tumors with high SLC7A11 expression.
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The small GTPases K-Ras, N-Ras and H-Ras have distinct biochemical properties determined by allosteric effects [Protein Structure and Folding]
H-, K-, and N-Ras are small GTPases that are important in the control of cell proliferation, differentiation and survival, and their mutants occur frequently in human cancers. The G-domain, which catalyzes GTP hydrolysis and mediates downstream signaling, is 95% conserved between the Ras isoforms. Due to their very high sequence identity, biochemical studies done on H-Ras have been considered representative of all three Ras proteins. We show here that this is not a valid assumption. Using enzyme kinetic assays under identical conditions, we observed clear differences between the three isoforms in intrinsic catalysis of GTP by Ras in the absence and presence of the Ras-binding domain (RBD) of the C-Raf Kinase protein (Raf-RBD). Given their identical active sites, isoform G-domain differences must be allosteric in origin, due to remote isoform specific residues that affect conformational states. We present the crystal structure of N-Ras bound to a GTP analogue and interpret the kinetic data in terms of structural features specific for H-, K- and N-Ras.
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Single-molecule FRET analysis discloses the dynamics of the DNA-topoisomerase II (TOP2) interaction in the presence of TOP2-targeting agents [Molecular Biophysics]
Topoisomerases play crucial roles in DNA replication, transcription, and recombination. For instance, topoisomerase II (Top2) is critically important for resolving DNA tangles during cell division, and as such, it is a broad anticancer drug target. Top2 regulates DNA topology by transiently breaking one double stranded DNA molecule (cleavage), allowing a second double strand to pass through the opened DNA gate (opening), and then closing the gate by rejoining the broken ends. Drugs that modulate Top2 catalysis may therefore affect enzymatic activity at several different steps. Previous studies have focused on examining DNA cleavage and ligation; however, the dynamic opening and closing of the DNA gate has been less explored. Here, we used the single-molecule Forster resonance energy transfer (smFRET) method to observe the open and closed state of the DNA gate and to measure dwell times in each state. Our results show that Top2 binds and bends DNA to increase the energy transfer efficiency (EFRET), and ATP treatment further induces the fluctuation of EFRET, representing the gate opening and closing. Additionally, our results demonstrate that both types of Top2-targeting anticancer drugs, the catalytic inhibitor dexrazoxane (ICRF187) and mechanistic poison teniposide (VM26), can interfere with DNA gate dynamics and shorten the dwell time in the closed state. Moreover, Top2 bound to the nonhydrolyzable ATP analog adenylyl imidodiphosphate (AMP-PNP) exhibits altered DNA gate dynamics, but the DNA gate appears to open and close even after N-gate closure. In summary, we have utilized single-molecule detection to unravel Top2 DNA gate dynamics and reveal previously unknown effects of Top2 drugs on these dynamics.
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Dysregulated Zn2+ homeostasis impairs cardiac type-2 ryanodine receptor and mitsugumin 23 functions, leading to sarcoplasmic reticulum Ca2+ leakage [Molecular Bases of Disease]
Aberrant Zn2+-homeostasis is associated with dysregulated intracellular Ca2+ release resulting in chronic heart failure. In the failing heart, a small population of cardiac ryanodine receptors (RyR2) display sub-conductance state gating leading to Ca2+ leakage from sarcoplasmic reticulum (SR) stores, which impairs cardiac contractility. Previous evidence suggests contribution of RyR2-independent Ca2+ leakage through an uncharacterized mechanism. We sought to examine the role of Zn2+ in shaping intracellular Ca2+ release in cardiac muscle. Cardiac SR vesicles prepared from sheep or mouse ventricular tissue were incorporated into phospholipid bilayers under voltage-clamp conditions, and the direct action of Zn2+ on RyR2 channel function was examined. Under diastolic conditions, the addition of pathophysiological concentrations of Zn2+ (≥2nM) caused dysregulated RyR2-channel openings. Our data also revealed that RyR2 channels are not the only SR Ca2+-permeable channels regulated by Zn2+. Elevating the cytosolic Zn2+ concentration to 1 nM increased the activity of the transmembrane protein mitsugumin 23 (MG23). The current amplitude of the MG23 full-open state was consistent with that previously reported for RyR2 sub-conductance gating, suggesting that in heart failure in which Zn2+ levels are elevated, RyR2 channels do not gate in a sub-conductance state, but rather MG23 gating becomes more apparent. We also show that in H9C2 cells exposed to ischemic conditions, intracellular Zn2+ levels are elevated, coinciding with increased MG23 expression. In conclusion, these data suggest that dysregulated Zn2+ homeostasis alters the function of both RyR2 and MG23 and that both ion channels play a key role in diastolic SR Ca2+ leakage.
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Endoplasmic Reticulum-Associated Degradation of the Renal Potassium Channel, ROMK, Leads to Type II Bartter Syndrome [Protein Synthesis and Degradation]
Type II Bartter syndrome is caused by mutations in the Renal Outer Medullary Potassium (ROMK) channel but the molecular mechanisms underlying this disease are poorly defined. To rapidly screen for ROMK function, we developed a yeast expression system and discovered that yeast cells lacking endogenous potassium channels could be rescued by WT ROMK but not by ROMK proteins containing one of four Bartter mutations. We also found that the mutant proteins were significantly less stable than WT ROMK. However, their degradation was slowed in the presence of a proteasome inhibitor or when yeast cells contained mutations in the CDC48 or SSA1 gene, which is required for endoplasmic reticulum (ER)-associated degradation (ERAD). Consistent with these data, sucrose gradient centrifugation and indirect immunofluorescence microscopy indicated that most ROMK protein was ER localized. To translate these findings to a more relevant cell type, we measured the stabilities of WT ROMK and the ROMK Bartter mutants in HEK293 cells. As in yeast, the Bartter mutant proteins were less stable than the WT protein, and their degradation was slowed in the presence of a proteasome inhibitor. Finally, we discovered that low-temperature incubation increased the steady-state levels of a Bartter mutant, suggesting that the disease-causing mutation traps the protein in a folding-deficient conformation. These findings indicate that the underlying pathology for at least a subset of patients with type II Bartter Syndrome is linked to the ERAD pathway and that future therapeutic strategies should focus on correcting deficiencies in ROMK folding.
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Low-level internalization of cystatin E/M affects legumain activity and migration of melanoma cells [Cell Biology]
The ratio between proteases and their inhibitors is unbalanced in cancer. The cysteine protease inhibitor cystatin C is internalized by some cancer cells and affect cellular properties. Here we aimed to investigate if uptake of cystatin C and the related inhibitor cystatin E/M occur in melanoma cell lines and to evaluate to what extent the uptake affects the legumain activity that is typically increased in melanoma. First we studied the basic expression, secretion and intracellular content of all type 2 cystatins, as well as expression and activity of their possible target enzymes legumain and cathepsin B, in MDA-MB-435S, A375 and C8161 melanoma cells. Legumain activity was measureable in all cell lines and of the potential legumain inhibitors, cystatin C, E/M and F, cystatin C was the one mainly produced. All cells internalized cystatin C added to culture media, leading to increased intracellular cystatin C levels by 120-200%. Cystatin E/M was internalized as well, but at a modest rate. The effects on intracellular legumain activity were nevertheless pronounced, probably since the cells lacked this inhibitor and its affinity for legumain is 100-fold higher than that of cystatin C. The low-degree uptake resulted in reduced migration and invasion of A375 cells in Matrigel, to an extent comparable to the W106F variant of cystatin C with optimal uptake properties and resulting in much higher intracellular levels. Thus, cystatin E/M appears to be a good candidate to efficiently down-regulate the increased legumain activity possibly being important for the malignant phenotype of melanoma cells.
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The era of bioengineering: how will this affect the next generation of cancer immunotherapy?
Immunotherapy consists of activating the patient's immune system to fight cancer and has the great potential of preventing future relapses thanks to immunological memory. A great variety of strategies have eme...
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Imaging of αvβ3 integrin expression in experimental myocardial ischemia with [68Ga]NODAGA-RGD positron emission tomography
Radiolabeled RGD peptides detect αvβ3 integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET...
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International Journal of Otolaryngology and Head & Neck Surgery Vol.6,No.3 (May 2017)
Coblation, Laryngeal Haemangioma, Propranolol
Paper Information Full Paper: PDF (Size:328KB)
DOI: 10.4236/ijohns.2017.63005
Altered Serum Lipids in the Cases of Head and Neck Cancer Associated with the Habit of Tobacco Consumption
Lipids, Cholesterol, Triglycerides, Head and Neck Cancer
Paper Information Full Paper: PDF (Size:488KB)
DOI: 10.4236/ijohns.2017.63006
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A case of nivolumab-related cholangitis and literature review: how to look for the right tools for a correct diagnosis of this rare immune-related adverse event
Summary
Anti-programmed cell death-1 (PD-1) monoclonal antibodies, such as nivolumab, used for the treatment of several tumors, can trigger effector T-cells against tumor- and self-antigens, leading to the occurrence of different immune-related adverse events. Among them, liver injuries are rare and usually transient. To date, only four cases of immune-related cholangitis in non-small cell lung cancer (NSCLC) patients have been described during nivolumab treatment. Here, we describe laboratory tests, imaging and liver biopsy features that confirm this diagnosis as opposed to other forms of autoimmune liver disease; nevertheless, we also provide evidence of the presence of different clinical-pathological patterns of immune-related cholangitis.
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Phase II study of Amrubicin monotherapy in elderly or poor-risk patients with extensive disease of small cell lung cancer
Summary
Background Previous study indicated that an optional anti-cancer drug for the treatment of small-cell lung cancer (SCLC) is amrubicin. However, no prospective studies have evaluated amrubicin in chemo-naive elderly or poor-risk patients with SCLC. Therefore, this study aimed to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly or poor-risk patients with extensive-disease SCLC (ES-SCLC). Methods Patients with chemotherapy-naive ES-SCLC received multiple cycles of 40 mg/m2 amrubicin for 3 consecutive days every 21 days. The primary endpoint was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results Between March 2011 and August 2015, 36 patients were enrolled in this study. Each patient received a median of four treatment cycles (range, 1–6 cycles). ORR was 52.8% [95% confidence interval (CI), 37–69%]. The median PFS and OS periods were 5.0 months (95% CI, 3.4–6.6 months) and 9.4 months (95% CI, 5.2–13.6 months), respectively. Neutropenia was the most common grade 3 or 4 adverse event (69.4%), with febrile neutropenia developing in 13.9% of patients. No treatment-related death occurred. At the time of starting second-line chemotherapy, 19 of 22 patients (86%) had significantly improved or maintained their performance status (PS) relative to their PS at the time of starting amrubicin monotherapy as first-line chemotherapy (P = 0.027). Conclusions The results of the present study suggest that amrubicin could be considered as a viable treatment option for chemotherapy-naive elderly or poor-risk patients with ES-SCLC (Clinical trial registration number: UMIN000011055 http://ift.tt/PmpYKN).
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Decorin gene upregulation mediated by an adeno-associated virus vector increases intratumoral uptake of nab-paclitaxel in neuroblastoma via inhibition of stabilin-1
Summary
The availability of effective medication for the treatment of refractory or recurrent neuroblastoma remains limited. This study sought to investigate the effects of increased decorin (DCN) expression on the intratumoral uptake of nab-paclitaxel as a potential novel approach to NB. Correlation between the clinical characteristics of neuroblastoma and the expression of DCN, secreted protein acidic and rich in cysteine (SPARC) and stabilin-1 was evaluated. The anticancer effect of recombinant adeno-associated virus-DCN (rAAV-DCN) was assessed in vivo and in vitro. And the effect of rAAV-DCN on the intratumoral uptake of paclitaxel was also studied in neuroblastoma-grafted nude mice. Overall, 12.5%, 17.7%, and 71.9% of the tumors stained positive for DCN, SPARC and stabilin-1 respectively and correlated to age, stage and N-MYC status in 96 children and adolescents with neuroblastoma. Transfected neuroblastoma cells stably expressed DCN, with in vivo and in vitro studies demonstrating rAAV-DCN sensitized the anticancer effect of nab-paclitaxel. Systemic rAAV-DCN in neuroblastoma-grafted nude mice inhibited stabilin-1, up-regulated SPARC, and increased the intratumoral uptake of paclitaxel. Macrophage depletion or anti-stabilin-1 monoclonal antibody increased the intratumoral uptake of nab-paclitaxel and its anticancer effects to a degree comparable to that achieved by systemic rAAV-DCN. The systemic administration of rAAV-DCN up-regulates DCN in neuroblastoma and accelerates the intratumoral uptake of nab-paclitaxel by inhibiting stabilin-1 mediated SPARC degradation.
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Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells
Summary
Ellagitannins have been gaining attention as potential anticancer molecules. However, the low bioavailability of ellagitannins and their extensive metabolization in the gastrointestinal tract into ellagic acid and urolithins suggest that the health benefits of consuming ellagitannins rely on the direct effects of their metabolites. Recently, chemopreventive and chemotherapeutic activities were ascribed to urolithins. Nonetheless, there is still a need to screen and evaluate the selectivity of these molecules and to elucidate their cellular mechanisms of action. Therefore, this work focused on the antiproliferative effects of urolithins A, B and C and ellagic acid on different human tumor cell lines. The evaluation of cell viability and the determination of the half-maximal inhibitory concentrations indicated that the sensitivity to the studied urolithins varied markedly between the different cell lines, with the bladder cancer cells (UMUC3) being the most susceptible. In UMUC3 cells, urolithin A was the most active molecule, promoting cell cycle arrest at the G2/M checkpoint, increasing apoptotic cell death and inhibiting PI3K/Akt and MAPK signaling. Overall, the present study emphasizes the chemopreventive/chemotherapeutic potential of urolithins, highlighting the stronger effects of urolithin A and its potential to target transitional bladder cancer cells.
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Postnatal Growth in a Cohort of Sardinian Intrauterine Growth-Restricted Infants
Recent studies have shown that infants with intrauterine growth restriction (IUGR) undergo catch-up growth during infancy. The aim of our study was to evaluate the postnatal growth in a cohort of IUGR infants born in a tertiary-level Obstetric University Hospital of Northern Sardinia. An observational retrospective study was conducted on 12 IUGR (group A) and 12 control infants (group B) by measuring the anthropometric parameters of weight (), length () and head circumference (HC) from birth to the 3rd postnatal year. At birth, significant differences were found between group A and group B with regard to all the auxological parameters (, mean 1846.6 versus 3170.8 g, p
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Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications
MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are "fine-tuners" rather than "switches" in the regulation of gene expression; thus they play key roles in maintaining tissue homeostasis. The aberrant microRNA expression is implicated in the disease process. To date, numerous studies have demonstrated the regulatory roles of microRNAs in various pathophysiological conditions. In contrast, the study of microRNA in pregnancy and its associated complications, such as preeclampsia (PE), fetal growth restriction (FGR), and preterm labor, is a young field. Over the last decade, the knowledge of pregnancy-related microRNAs has increased and the molecular mechanisms by which microRNAs regulate pregnancy or its associated complications are emerging. In this review, we focus on the recent advances in the research of pregnancy-related microRNAs, especially their function in pregnancy-associated complications and the potential clinical applications. Here microRNAs that associate with pregnancy are classified as placenta-specific, placenta-associated, placenta-derived circulating, and uterine microRNA according to their localization and origin. MicroRNAs offer a great potential for developing diagnostic and therapeutic targets in pregnancy-related disorders.
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A Three-Year Retrospective Study on Survival of Ceramic-Veneered Zirconia (Y-TZP) Fixed Dental Prostheses Performed in Private Practices
Objectives. The aim of this retrospective study was to evaluate the three-year clinical outcome for ceramic-veneered zirconia fixed dental prostheses (FDPs). Methods. All patients who were treated with ceramic-veneered zirconia FDPs, in three private practices in Sweden, during the period June 2003 to April 2007 were included. Case records from 151 patients, treated with a total of 184 zirconia FDPs (692 units), were analysed for clinical data. All complications noted in the charts were registered and compared to definitions for success and survival and statistical analysis was performed using the Kaplan-Meier method and a Cox regression model. Results. In total, 32 FDPs in 31 patients experienced some type of complication (17.4% of FDPs, 20.5% of patients). Core fractures occurred in two (1.1%) FDPs. Two (1.1%) FDPs or 0.6% of units showed adhesive veneer fractures. Cohesive veneer fractures occurred in 10 (5.4%) FDPs (1.6% of units). The three-year cumulative success and survival rates (CSR) were 82.3% and 95.2%, respectively. Conclusions. Ceramic-veneered zirconia is a promising alternative to metal-ceramic FDPs, even in the posterior area. However, the higher survival rate of metal-ceramic FDPs should be noted and both dentists and patients must be aware of the risks of complications.
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Inexact Multistage Stochastic Chance Constrained Programming Model for Water Resources Management under Uncertainties
In order to formulate water allocation schemes under uncertainties in the water resources management systems, an inexact multistage stochastic chance constrained programming (IMSCCP) model is proposed. The model integrates stochastic chance constrained programming, multistage stochastic programming, and inexact stochastic programming within a general optimization framework to handle the uncertainties occurring in both constraints and objective. These uncertainties are expressed as probability distributions, interval with multiply distributed stochastic boundaries, dynamic features of the long-term water allocation plans, and so on. Compared with the existing inexact multistage stochastic programming, the IMSCCP can be used to assess more system risks and handle more complicated uncertainties in water resources management systems. The IMSCCP model is applied to a hypothetical case study of water resources management. In order to construct an approximate solution for the model, a hybrid algorithm, which incorporates stochastic simulation, back propagation neural network, and genetic algorithm, is proposed. The results show that the optimal value represents the maximal net system benefit achieved with a given confidence level under chance constraints, and the solutions provide optimal water allocation schemes to multiple users over a multiperiod planning horizon.
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Precipitating Cloud Characteristics during Changma as Seen in TRMM PR Observations
The climatological characteristics of precipitating clouds during Changma, the summer rainy period in the Korean Peninsula, were investigated using the Precipitation Radar (PR) on the Tropical Rainfall Measuring Mission (TRMM) satellite. This investigation was further augmented with reanalysis data. Specifically, Changma clouds are compared with post-Changma clouds. Similarities and differences in cloud properties between the two periods are discussed based on seasonal changes in thermodynamic environments. For convective clouds migrating along the Changma (stationary) front, rain intensity is much stronger and cloud height is relatively higher than during any other summer period, including post-Changma period. Convective rain clouds have a large seasonal variability, even during summer. The seasonal variability in rain parameters related to convective rain type appears to be due to the thermodynamic and dynamic environments.
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Autologous Concentrated Bone Marrow Grafting for the Treatment of Osteonecrosis of the Humeral Head: A Report of Five Shoulders in Four Cases
Five shoulders in four patients affected by advanced osteonecrosis of the humeral head were treated with autologous concentrated bone marrow grafting. Bone marrow sample was aspirated from the iliac crests, concentrated by a centrifugation technique, and injected into the necrotic site. The shoulders were evaluated radiologically with X-ray scoring and clinically with measurement of range of motion and pain score (visual analogue scale, VAS). The mean follow-up period was 49.4 (range, 24–73) months. The concentration ratio of nucleated cells was calculated and the number of transplanted mesenchymal stem cells (MSC) was estimated by a colony-forming assay. All four shoulders with stage 3 disease achieved joint sparing. One shoulder with stage 4 disease required replacement surgery. Clinical evaluation of the spared joints showed improvement in range of motion in two cases and deterioration in two cases. VAS scores were 0 after surgery in three cases. The mean concentration ratio was 2.73, and the mean number of transplanted MSC was 1125. The outcomes of autologous concentrated bone marrow grafting for advanced osteonecrosis of the humeral head were varied. Further research is needed to determine the effectiveness and the indications of the present surgery.
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The Burden of Illness Related to Chronic Obstructive Pulmonary Disease Exacerbations in Québec, Canada
Background. Chronic obstructive pulmonary disease (COPD) prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU) in this population. This study investigated the impact of exacerbations on COPD-related HCU. Methods. This retrospective observational cohort study used patient data from the Québec provincial health insurance databases. Eligible patients with a new HCU claim with a diagnostic billing for COPD during 2001–2010 were followed until March 31, 2011. Exacerbation rates and time to first exacerbation were assessed. Unadjusted analyses and multivariable models compared the rate of HCU by exacerbation classification (any [moderate/severe], moderate, or severe). Results. The exacerbation event rate in patients with an exacerbation was 34.3 events/100 patient-years (22.7 for moderate exacerbations and 11.6 for severe exacerbations). Median time to first exacerbation of any classification was 37 months. In unadjusted analyses, COPD-related HCU significantly increased with exacerbation severity. In the multivariable, HCU rates were significantly higher after exacerbation versus before exacerbation () for patients with an exacerbation or moderate exacerbations. For severe exacerbations, general practitioner, respiratory specialist, emergency room, and hospital visits were significantly higher after exacerbation versus before exacerbation (). Conclusions. Exacerbations were associated with increased HCU, which was more pronounced for patients with severe exacerbations. Interventions to reduce the risk of exacerbations in patients with COPD may reduce disease burden.
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3D Printed and Photonically Cured Graphene UHF RFID Tags on Textile, Wood, and Cardboard Substrates
This paper introduces 3D direct writing and microdispensing of graphene ultrahigh frequency (UHF) radio-frequency-identification (RFID) antennas on textile, wood, and cardboard substrates, subsequently cured either by conventional oven or photonically by pulsed Xenon flashes. Photonic-cured passive UHF RFID graphene tags on cardboard, wood, and textile substrates achieve read ranges of 5.4, 4.6, and 4 meters, respectively. These results are superior to those achieved by the oven-cured tags that featured read ranges of 4.8, 4.5, and 3.6 meters, respectively. This work presents the first integration of 3D printing and photonic curing of graphene antennas on low-cost versatile substrates.
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Effect of Oregano and Marjoram Essential Oils on the Physical and Antimicrobial Properties of Chitosan Based Systems
The effect of two essential oils (EOs), from Origanum vulgare and Origanum majorana, their structural properties, and concentration on physical and antimicrobial characteristics of chitosan based solutions as well as films was investigated. Results showed that significantly different behaviour was induced by variation in the compositions of given essential oils. Film-forming solutions (FFS) containing oregano oil comprised considerably greater particles in comparison with the marjoram samples. Similarly, structural changes were confirmed by SEM analysis of chitosan films modified with the EOs; the smaller particles of the marjoram oil demonstrated better compatibility with chitosan matrix. However, chitosan films enriched with the oregano oil showed significantly superior antimicrobial activity compared to the marjoram. The dissimilar effects of the two EOs were also observed by water vapour pressure (WVP) measurement; increasing the amount of oregano oil triggered a drop in the WVP of the prepared films, whereas the marjoram oil had a negligible impact in this respect. These results suggest that the structural features of active substances in the EOs play a crucial role in determining the final properties of FFS and biofilm systems.
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Moringa oleifera Seeds Attenuate Vascular Oxidative and Nitrosative Stresses in Spontaneously Hypertensive Rats
Moringa oleifera (MOI) is a tree currently used in traditional medicine in tropical Africa, America, and Asia for therapeutic applications in several disorders including arterial hypertension. We previously described a cardiac protective role of a treatment with MOI seeds in spontaneously hypertensive rats (SHR). Here, we investigated the effects of this treatment on oxidative and nitrosative vascular stresses in SHR, with normotensive Wistar Kyoto rats used as controls. Oxidative and nitrosative stresses detected in SHR aortas using the fluorescent dye dihydroethidine and protein nitrotyrosine staining were reduced in MOI-treated SHR aortas. This was associated with a decrease of free 8-isoprostane circulating level, vascular p22phox and p47phox expressions, and SOD2 upregulation. Moreover, circulating nitrites and C-reactive protein, increased in SHR, were both reduced in SHR receiving MOI. This was associated to decrease iNOS and NF-κB protein expressions after MOI treatment. In functional studies, the endothelium-dependent carbachol-induced relaxation was improved in MOI-treated SHR resistance arteries. Oral administration of MOI seeds demonstrates vascular antioxidant, anti-inflammatory, and endothelial protective effects in SHR. Our data support the use of MOI seeds in diet against cardiovascular disorders associated with oxidative stress and inflammation such as hypertension, scientifically validating the use of these seeds in Malagasy traditional medicine.
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Brevundimonas diminuta infection in a case of nephrotic syndrome
Indian Journal of Pathology and Microbiology 2017 60(2):279-281
Brevundimonas has rarely been isolated from clinical specimens. We here report a case of Brevundimonas diminuta infection in an 18-year-old male patient with nephrotic syndrome. B. diminuta was identified by the VITEK 2 Compact system, following isolation from his blood sample. To the best of our knowledge, B. diminuta has not been reported in patients with nephrotic syndrome.
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Leiomyosarcoma of inferior vena cava with intracardiac extension presenting as Budd-Chiari syndrome: Report of a rare case
Indian Journal of Pathology and Microbiology 2017 60(2):256-258
Primary leiomyosarcoma of vascular origin is a rare malignant smooth muscle tumor. This report describes a case of primary leiomyosarcoma of the inferior vena cava (IVC) in a 52-year-old male who presented with complaints of abdominal pain, chest pain, and bilateral lower limb swelling for 4 months. Imaging of the chest and abdomen revealed a mass in the IVC extending into right atrium, heterogeneous enhancement of liver, hepatosplenomegaly, and ascites. Histopathological examination showed a malignant spindle cell tumor with cells arranged in fascicular and hemangiopericytomatous pattern. Immunohistochemistry for smooth muscle actin and desmin confirmed smooth muscle origin of the tumor. Recognition of this tumor in this rare location and Budd-Chiari syndrome-like presentation is imperative for proper management of the patient.
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Ameloblastoma: A 16-year clinicopathological study on Goan population
Indian Journal of Pathology and Microbiology 2017 60(2):157-160
Background: Ameloblastoma is a benign slow growing tumor of odontogenic origin composed of epithelial cells that resemble enamel forming cells namely the ameloblasts however these lesional cells do not differentiate to produce enamel. They are locally aggressive and can cause severe abnormalities of the face and jaw. Aim: This study aimed to correlate the incidence and recurrence rates of ameloblastoma to the different clinical and histopathological parameters. Methods: A study on ameloblastomas in the Goan population for 16 years (1999–2014) was carried out. Archived documented data of surgically treated cases of ameloblastomas were used in this study. Results: It was revealed that out of 52 cases of ameloblastomas, a male preponderance was seen. Age predisposition was seen to favor the third-fourth decade, the most common site was the posterior aspect of lower jaw for new and recurrent cases. Conclusion: The study highlights, the possible etiological role of location influencing the incidence and recurrence rates of ameloblastomas.
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Fine needle aspiration cytology of thyroid metastasis: An unusual presentation of cervical carcinoma; a case report and review of literature
Indian Journal of Pathology and Microbiology 2017 60(2):298-299
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The absence of CD56 expression can differentiate papillary thyroid carcinoma from other thyroid lesions
Indian Journal of Pathology and Microbiology 2017 60(2):161-166
Context: The neural cell adhesion molecule CD56 is an antigen important for the differentiation of the follicular epithelium. Recent studies have reported low or absent expression of CD56 in papillary thyroid carcinoma (PTC) and its presence in normal thyroid tissue, benign thyroid lesions, and most follicular non-PTC tumors. Aim: We wish to estimate the value of CD56 in the differentiation of PTC (including follicular variant-PTC [FV-PTC]) from other nontumoral lesions and follicular thyroid neoplasias. Settings and Design: This was a retrospective, case–control study. Subjects and Methods: We analyzed the expression of CD56 in normal thyroid follicular tissue, 15 nonneoplastic thyroid lesions (nodular hyperplasia, Graves' disease, and chronic lymphocytic thyroiditis/Hashimoto), and 38 thyroid follicular cell neoplasms (25 cases of PTC). The immunohistochemical reactions were performed on sections stained with anti-CD56 antibody. Statistical Analysis Used: We used the Chi-square test, values of P< 0.05 being considered statistically significant. Risk analysis was applied on these studied groups, by calculating the odds ratio (OR) value. Results: Our results indicated that CD56 immunoexpression had differentiated PTC from benign nonneoplastic lesions (P = 0.002), as well as from follicular neoplasias (P = 0.046). There were no significant differences regarding CD56 expression between FV-PTC and classical PTC (P = 0.436). The immunoexpression of CD56 has differentiated PTC from other thyroid non-PTC lesions (P < 0.001), with 26.4 OR value. Conclusions: CD56 has been proved to be a useful marker in the diagnosis of PTC, including FV-PTC. Its absence can help differentiate FV-PTC from other thyroid nodules with follicular patterns.
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Primary cutaneous large B-cell lymphoma of scalp: Case report of a rare variant
Indian Journal of Pathology and Microbiology 2017 60(2):268-271
Primary cutaneous large B-cell lymphoma (Bcl) is defined as a lymphoma composed of large cells constituting more than 80% of the infiltrate and absence of extracutaneous involvement after staging investigations. In the new World Health Organization/European Organization for Research and Treatment of Cancer classification, cutaneous Bcls with large cells are of three types - primary cutaneous large Bcl leg type (PCLBCLLT), primary cutaneous follicle center lymphoma diffuse type (PCFCLDT), and primary cutaneous large Bcls other (PCLBCLO). These three different types are distinct in terms of their clinicopathological features and survival. The PCLBCLO has intermediate features between those of PCLBCLLT and PCFCLDT. We present a case of PCLBCLO in a 57-year-old male who presented with a scalp swelling. Ultrasonography examination was suggestive of a sebaceous cyst. Computed tomography scan revealed the presence of an ill-defined hyperdense region in the soft tissue of the scalp region extending into the deeper layers of the scalp. Fine-needle aspiration cytology (FNAC) revealed the presence of atypical lymphoid cells. Diagnosis was confirmed by biopsy and immunohistochemistry. Patient received rituximab combined with doxorubicin, vincristine, cyclophosphamide, and prednisolone regimen with complete resolution of the lesion. We present this case for its rarity, the utility of FNAC in early diagnosis, and to discuss the differential diagnosis.
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Poorly differentiated thyroid carcinoma: A hospital-based clinicopathological study and review of literature
Indian Journal of Pathology and Microbiology 2017 60(2):167-171
Introduction: Poorly differentiated thyroid carcinoma (PDTC) is a rare aggressive malignancy of thyroid follicular cells and has unique features in morphology and behavior. This study was aimed to describe the experience of a tertiary medical center with PDTC within a 10-year period. Materials and Methods: This is a descriptive retrospective study of eight cases of PDTC among 418 various thyroid carcinomas. All cases of PDTC were retrieved along with the clinicopathological information. Results: Only eight cases (1.9%) of PDTC were diagnosed among 418 thyroid carcinomas. Mean age was 48.12 with 3:5 (male:female) and tumor size ranged 3–12 cm. PDTC were diagnosed coexisting with one or more other pathologies; nodular hyperplasia (four cases), papillary carcinoma (one case), follicular carcinoma (three cases), and Hashimoto thyroiditis (two cases); with ≥60% PDTC component. Six cases associated with high-grade features died within 3 years after diagnosis. Discussion: Mean age in this study was younger including a 20-year-old girl. Younger age was associated with better prognosis. Most of the cases had underlying benign thyroid lesions and differentiated thyroid carcinoma. Most of the PDTC had poor prognosis associated with PDTC component ≥60%, tumor necrosis, high mitotic count, lymph node involvement, vascular invasion and distant metastasis; and these cases died within 3 years after diagnosis. Conclusion: Although treatment of PDTC remains surgery followed by radioiodine therapy, correct histopathological diagnosis is important for clinicians and oncologists to predict the prognosis. All thyroid carcinoma should be sampled thoroughly not to miss small foci of PDTC component.
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Crescentic C3 glomerulopathy with acquired partial lipodystrophy: An unusual cause of rapidly progressive renal failure
Indian Journal of Pathology and Microbiology 2017 60(2):290-291
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Diagnostic value of immunohistochemistry staining of Bcl-2, CD34, CD20 and CD3 for distinction between discoid lupus erythematosus and lichen planus in the skin
Indian Journal of Pathology and Microbiology 2017 60(2):172-176
Background: Cluster of differentiation (CD) markers is a classification system for monoclonal antibodies against cell surface molecules on leukocytes and antigens from other cells. Aims: The aim of this study is to evaluate immunohistochemical markers in patients with discoid lupus erythematosus (DLE) and lichen planus (LP) and correlation of these markers in two groups and with the normal group in the West of Iran. Settings and Design: Analytical cross-sectional study. Materials and Methods: This study was performed on paraffin blocks of DLE and LP patients with normal group (21, 21 and 16 cases, respectively) between 2009 and 2012. Formalin-fixed, paraffin-embedded tissue sections from each DLE, LP, and normal skin biopsy specimen were cut into 4-μ thick sections and mounted on glass slides. Initial sections were stained with hematoxylin and eosin. Primary antihuman antibodies against CD3, CD20, CD34, and Bcl-2 were applied. Positive control samples for CD3, CD20, and Bcl-2 were received from lymph nodes and for CD34 from dermal microvessels. Statistical Analysis Used: SPSS version 19 (SPSS, Inc., Chicago, USA) and Microsoft Excel 2007. Results: The mean staining for four markers was more significant in DLE and LP groups compared to normal group and for CD34 and CD3 was more significant in LP groups versus DLE group. Conclusions: CD3+, CD34+, Bcl-2+, and CD20+ cells are significantly higher in DLE and LP lesional skins versus normal skin. In addition, there were higher expressions of CD3 and CD34 in LP lesional skin versus DLE lesional skin.
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Depletion of p21-activated kinase 1 up-regulates the immune system of APC∆14/+ mice and inhibits intestinal tumorigenesis
P21-activated kinase 1 (PAK1) stimulates growth and metastasis of colorectal cancer (CRC) through activation of multiple signalling pathways. Up-regulation of CRC stem cell markers by PAK1 also contributes to ...
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Strain elastography imaging for early detection and prediction of tumor response to concurrent chemo-radiotherapy in locally advanced cervical cancer: feasibility study
To investigate the feasibility of strain elastography imaging in early detecting and predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for locally advanced cervical cancer.
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Personalised informed choice on evidence and controversy on mammography screening: study protocol for a randomized controlled trial
In Italy women aged 50–69 are invited for a population-based breast cancer (BC) screening. Physicians, policy makers and patients associations agree on the need to inform women about the benefits and harms in ...
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Retinal and vitreous metastases from hepatocholangiocarcinoma
To report a case of metastatic hepatocholangiocarcinoma to the vitreous and retina.
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Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients
During posttreatment surveillance of head and neck cancer patients, imaging is insufficiently accurate for the early detection of relapsing disease. Free circulating tumor DNA (ctDNA) may serve as a novel biom...
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A study of transfer and prevalence of organic gunshot residues
Chemical analysis of gunshot residues (GSR) can provide useful information for the reconstruction of events involving the use of firearms. This could include linking a person to such an event, an estimation of shooting distance and trajectory, bullet entry and exit point identification or simply determining the circumstances of a case and verifying the veracity of a testimony [1–3]. Additional information concerning the type of firearm and ammunition used as well as the time since discharge can also be useful [4–7].
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Population Variation in Skeletal Sexual Dimorphism
Reliable estimation of the sex in the analysis of human skeletal remains represents an important and frequently encountered goal of forensic anthropology. Sex estimation is a key component of the individual biological profile that skeletal analysis seeks to construct [1,2]. Historically, it represents one of the deep-rooted features of skeletal analysis in forensic anthropology [3]. Techniques of sex estimation generally fall into one of two categories: those methods concentrating on size and robusticity of features and those involving evaluation of features of the pelvis related to the female child-bearing functions.
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Precision and accuracy of commonly used dental age estimation charts for the New Zealand population
Dental age estimation methods range from dental development charts to complex biometric analysis. Dental development charts are not the most accurate method of dental age estimation, but are time saving in their use. They are an excellent screening tool, particularly for post-mortem identification purposes, and for assessing variation from population norms in living individuals.
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Evaluation of bait traps as a means to predict initial blow fly (Diptera: Calliphoridae) communities associated with decomposing swine remains in New Jersey, USA
Recently, the field of forensic entomology has grown due to its importance in legal investigations. Typically, insect development in association with temperature can be used to determine a time of colonization (TOC) of human remains, which can then be used to infer a time since death [10]. Insects can also be used to provide information pertaining to body movement based on the geographical distribution of the insects collected from the remains [12] and can aid in cases of abuse or neglect in animals, including humans [7].
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Transnasal endoscopic removal of bilateral postoperative maxillary cysts after aesthetic orthognathic ssurgery: Differences from that of Caldwell-Luc operations
Source:Auris Nasus Larynx
Author(s): Hyung Chae Yang, Sung Hoon Kang, Sung Ho Yoon, Hyong-Ho Cho
Postoperative maxillary cysts (PMCs) after orthognathic surgery are a rare disease condition. In this study, we reported first case of bilateral PMCs after cosmetic orthognathic surgery which was treated via the intranasal endoscopic approach. In addition, we compared the characteristics of PMCs after aesthetic orthognathic surgery with those of PMCs after Caldwell-Luc operation. We expect that this case will be helpful to surgeons who encounter similar cases.
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Glucose catabolism in liver tumors induced by c-MYC can be sustained by various PKM1/PKM2 ratios and pyruvate kinase activities
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Due to differential regulation of enzymatic activities, PKM2 but not PKM1 has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL. Depletion of PKM2 at the time of c-MYC over-expression in murine livers did not affect c-MYC induced tumorigenesis and resulted in liver tumor formation with decreased pyruvate kinase activity and decreased catabolism of glucose into alanine and the Krebs cycle. An increased PKM1/PKM2 ratio by ectopic PKM1 expression further decreased glucose flux into serine biosynthesis and increased flux into lactate and the Krebs cycle, resulting in reduced total levels of serine. However, these changes also did not affect c-MYC-induced liver tumor development. These results suggest that increased expression of PKM2 is not required to support c-MYC-induced tumorigenesis in the liver and that various PKM1/PKM2 ratios and pyruvate kinase activities can sustain glucose catabolism required for this process.
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Infection exposure promotes ETV6-RUNX1 precursor B cell leukemia via impaired H3K4 demethylases
<p>ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/peripheral cells (HSC/PC) and postnatal infections for human-like pB-ALL. In our model, ETV6-RUNX1 conferred a low risk of developing pB-ALL after exposure to common pathogens, corroborating the low incidence observed in humans. Murine preleukemic ETV6-RUNX1 pro/preB cells showed high Rag1/2 expression, known for human ETV6-RUNX1 pB-ALL. Murine and human ETV6-RUNX1 pB-ALL revealed recurrent genomic alterations, with a relevant proportion affecting genes of the lysine demethylase (KDM) family. KDM5C loss-of-function resulted in increased levels of H3K4me3, which co-precipitated with RAG2 in a human cell line model, laying the molecular basis for recombination activity. We conclude that alterations of KDM family members represent a disease-driving mechanism and an explanation for RAG off-target cleavage observed in humans. Our results explain the genetic basis for clonal evolution of an ETV6-RUNX1 preleukemic clone to pB-ALL after infection exposure and offer the possibility of novel therapeutic approaches.
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Contesting Justice in Global Forest Governance: The Promises and Pitfalls of REDD+
Conservation and Society 2017 15(2):189-200
For more than 30 years, diverse actors in global forest governance have sought to address the justice concerns of forest peoples—concerns about displacement, marginalisation, and loss of identity—related to forest interventions. Despite the mainstreaming of justice obligations into the global forest governance architecture and the proliferation of justice practices across multiple scales of governance, claims of injustice persist. The growing prominence of Reduced Emissions from Deforestation and Degradation plus the enhancement of carbon stocks (REDD+) as a primary mechanism for addressing global forest loss and degradation has again directed attention to the justice effects of global forest policies on forest peoples across the Global South. While REDD+ proponents argue that safeguard procedures and participatory processes will promote justice, opponents argue REDD+ will exacerbate injustices. To generate new insights into the persistent justice debates in REDD+, this paper draws attention to the role of norms in constraining and shaping policy designs and outcomes. It asks: to what extent and how does REDD+ as articulated in UNFCCC decisions respond to the established justice trajectory in global forest governance? How do current approaches in REDD+ create and constrain opportunities for justice for forest peoples? An empirical analysis of justice norms in global forest governance, including REDD+, demonstrate that while justice possibilities under REDD+ could narrow, opportunities for norm contestation are expanding. These additional opportunities can create conditions conducive to broader norm shifts in global forest governance.
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What Does Conservation Mean for Women? the Case of the Cantanhez Forest National Park
Conservation and Society 2017 15(2):168-178
Community-based conservation programmes need to engage the support of all its members. Gender is a key component in shaping attitudes about conservation, and lack of attention to gender differences in perceptions can work against the aims of community-based conservation actions and initiatives. We present a study of the obstacles to women's participation in conservation strategies associated with Cantanhez Forest National Park (CFNP), in Guinea-Bissau, West Africa. Field-work took place in CFNP over two years, 2007-2008. Five women-only focus group interviews (N=47 participants) were conducted to understand the perceived effects of CFNP's establishment on women's daily activities, livelihoods and future expectations. The findings revealed that the women felt the Park was responsible for malnutrition in the communities due to damage of crops by wildlife. Although they were promised compensation, most of the farming households are still waiting for reimbursements for crop damage. Women expressed an unwillingness to directly participate in conservation efforts related to CFNP, but they believed that park researchers could help them to improve their lives.
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Intimate Exclusions from the REDD+ forests of Sungai Lamandau, Indonesia
Conservation and Society 2017 15(2):125-135
Due to land-use conversions for palm oil, mining and other extractive industries, Indonesia remains the largest contributor of greenhouse gases from primary forest loss in the world. Nowhere are solutions to large-scale forest loss more urgently required. To reverse the trend, the Government of Indonesia is banking on carbon market mechanisms like the Reducing Emissions from Deforestation and Degradation (REDD+) programme. REDD+ is designed to enable the provision of economic compensations to protect forests by making them more valuable standing than cut down. The Sungai Lamandau REDD+ demonstration activity is unique in Indonesia as the first REDD+ project officially proposed by a community group upon land they hope to manage autonomously. Despite the project's 'bottom-up' architecture, for some, access to Sungai Lamandau's REDD+ benefits remain exclusive. These exclusions are not only something imposed by powerful external actors, but has emerged endogenously, through the everyday functioning of gendered market relations, and community-based socio-environmental and ethno-territorial movements. This paper adopts a feminist-inspired intimacy-geopolitics to explore the nuanced powers of exclusion used by Sungai Lamandau's farmers to access the project's non-monetary REDD+ benefits. The paper focuses on 'intimate exclusions' – everyday processes of accumulation and dispossession among villagers and small-holders. In doing so, it highlights the hazards of developing REDD+ projects structured with limited sympathy for marginalised actors. Although the seemingly 'inclusive' benefits sharing structure attracted excellent ethical carbon credit ratings, the project still failed to address (and even exacerbated) existing inequalities – a root cause of Sungai Lamandau's forest degradation.
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Ju/'hoansi Lodging in a Namibian Conservancy: CBNRM, Tourism and Increasing Domination
Conservation and Society 2017 15(2):136-146
Following Ingold's dwelling perspective, the world comes into being because an organism/person is continuously interacting with his/her environment through bodily activity. Ingold contrasts dwelling with building; in the latter, people construct the world cognitively before they can live in it. In this paper, we add the concept of 'lodging' to refer to a situation in which people live in an environment that contains increasing dominating powers. Under the influence of conservation and the implementation of a Community Based Natural Resource Management (CBNRM) programme, with a strong focus on tourism, the environment of the Ju/'hoansi Bushmen of the Nyae Nyae Conservancy in Namibia has changed dramatically. In this paper, we use various examples to show how the environment has become more dominant, often in very subtle ways. We argue that the Ju/'hoansi do not dwell as they used to, but lodge instead in an environment that is increasingly influenced by CBNRM and tourism activities. Some of the Ju/'hoansi's agency has become limited to acquiescing; they passively adapt to and cope with the changes in their environment, while others have shown a more active adaptation strategy.
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Indicators for Ecosystem Conservation and Protected Area Designation in the Mediterranean Context
Conservation and Society 2017 15(2):217-231
Protected areas constitute a key foundation for national and international strategies of effective biodiversity and ecosystems conservation. Yet, they are not islands; they are components of their surrounding social and ecological contexts. Reconciling biodiversity conservation, people, protected areas and sustainable livelihoods requires a focused strategic planning for conservation and development. The designation of new reserves must be thus based on sound indicators within ecological, socioeconomic, institutional, and financial contexts. Many of the ecological and socioeconomic indicators have been designed for this purpose by practitioners and conservation planners around the world. Although these indicators are crucial to orient conservation priorities and protected areas' designation patterns, their identification remains a big challenge, largely due to the fact that an indicator is a simplification of a system (whether natural or social) which is characterized by high structural complexity, considerable spatial heterogeneity and temporal fluctuations. This paper presents a review of ecological and socioeconomic indicators globally used to orient conservation planning on the global and national levels. It also suggests a set of suitable, relevant, and practical set of indicators, adapted to Mediterranean-type continental environments.
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Persistent Neoliberalisation in PES: Taxes, Tariffs, and the World Bank in Costa Rica
Conservation and Society 2017 15(2):147-156
Recent critiques of 'payments for ecosystem services' (PES) and other market-based instruments for environmental conservation have noted that such mechanisms rarely (if ever) operate according to idealised market rules. The characterisation of PES as a form of 'neoliberal conservation', therefore, has been questioned and even deemed to be misguided. While close examination of local context and micropolitics often reveals a nuanced view of contested and hybrid implementation, similar analysis can also reveal the way that officials continue to steer programs towards market ideals. In this paper, I consider the case of Costa Rica's national Pagos por Servicios Ambientales (PSA) program, to suggest that–in spite of its imperfect correspondence to an idealised neoliberal model–it is undergoing a continual process of neoliberalisation. I explore, in particular, the evolution of PSA financing, which has shifted (under the influence of two World Bank projects) towards direct financialised transactions between 'users' and 'providers' of ecosystem services. The paper provides a historical account of the complex (and sometimes contradictory) processes that have produced the program's current hybrid neoliberal form. It explores World Bank / Costa Rica relations and market-oriented interventions to the financing of ecosystem service payments, and it explains that (despite inherent contradictions inhibiting market formation) neoliberal actors within the state can still implement mechanisms designed to approximate markets.
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Mapping Scenario Narratives: A Technique to Enhance Landscape-scale Biodiversity Planning
Conservation and Society 2017 15(2):179-188
Developing regional scenarios enables planners to engage land managers in discussions about the future, especially in contexts that are complex, uncertain and difficult to control. Richly-crafted qualitative narratives are an effective way to document future scenarios that integrate social, economic and biophysical attributes. Converting such narratives into spatial representations of future landscapes often relies on computational modelling. This paper presents an alternative technique. Key themes from scenario narratives are translated into spatial representations using simple rule sets within a Geographic Information System (GIS). The technique was applied to a case study exploring future scenarios for biodiversity in a predominantly privately-owned agricultural landscape. Iterative analysis of scenarios and their spatial implications enables land managers to explore outcomes from potential interventions and identify strategies that might mitigate the impact of future issues of environmental concern.
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Turbulent Terrains: The Contradictions and Politics of Decentralised Conservation
Conservation and Society 2017 15(2):157-167
The most salient feature of conservation today is contradiction. Conservation is simultaneously characterized by decentralisation and recentralisation, deterritorialisation and reterritorialisation, deregulation and reregulation. At the heart of these contradictions are reconfigurations of state-society relations, provoking unprecedented risk but also opportunity for rural communities. Paramount to these processes is the threat of 'recentralizing while decentralizing' (Ribot et al. 2006). Governments decentralise authority while simultaneously finding ways to retain central control and maintain their political and/or economic interests. Recentralising while decentralising especially defines Tanzania's most recent decentralisation scheme, Wildlife Management Areas (WMAs). This paper contributes to the debate about WMAs and the nature of decentralisation. The WMAs, I argue, represent risk but also opportunity for rural communities. Amidst the contradictions and conundrum of decentralising and recentralising, new political spaces invariably emerge, wherein novel alliances, political community, and resistance unfold. In cases like Enduimet and Lake Natron WMAs, this has translated into appropriating and redeploying WMAs in ways that privilege community interests. Notwithstanding the significant constraints that continue jeopardizing most WMAs, the cases reviewed in this paper offer some hope for WMAs' turbulent terrains.
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Human Niche Construction: Noongar Evidence in Pre-colonial Southwestern Australia
Conservation and Society 2017 15(2):201-216
Through a lens of Human Niche Construction theory, we examine Noongar (an indigenous people of south western Australia) relationships with southwestern Australian flora and suggest influences of these relationships on contemporary botanical patterns in this global biodiversity hotspot. By conducting a review of historical and contemporary literature and drawing upon the contemporary knowledge of Noongar Elders, we examine the merits of five key hypotheses of human niche construction theory in relation to this large cultural group. We find compelling evidence that supports Noongar niche construction, but caution that further research is required to test its likely ecological and evolutionary outcomes. We suggest that further collaborative, multi-disciplinary research that applies Noongar and Western science will lead to a greater understanding of the biological assets of southwestern Australia.
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The Cultural Politics of Sacred Groves: A Case Study of Devithans in Sikkim, India
Conservation and Society 2017 15(2):232-242
Sacred groves are areas that are conserved by communities for spiritual or cultural beliefs. They often have associated limitations on activities within the forest. India is believed to have the highest concentration of sacred groves in the world. However, in our research of devithan s – Nepali sacred groves – in the eastern Himalayan state of Sikkim, India, we reveal that their very existence in India has long remained unacknowledged in sacred natural site research. By researching the proliferation of devithan s in the village of Biring, East Sikkim, we not only foreground their existence, but also unpack their cultural politics to reveal the contestations and appropriations around the symbolic value of sacred sites. Given that historically the Buddhist Lepcha-Bhutias' cultural association with Sikkim's sacred landscape has been celebrated, while that of Nepali ethnic groups has been largely invisibilised, we argue that devithan s have emerged as a potential political instrument for the latter to validate political and cultural claims to Sikkim's sacred landscape. The predominant tone in sacred grove scholarship in India has largely been anchored in the language of ecology, and tends to understand sacred groves as communal sites without exploring the associated constitutive politics. By using a cultural politics lens to understand devithan s, this research expands beyond simplistic narratives to focus on present day cultural politics that are internal to communities that often not only sustain groves, but also help them to proliferate.
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Cyclooxygenase-2 inhibitors and free flap complications after autologous breast reconstruction, a retrospective cohort study
A key component of modern analgesics is the use of multimodal opioid sparing analgesia (MOSA). In the past, our analgesic regime after autologous breast reconstruction (ABR) included either NSAID or a selective cyclooxygenase-2 inhibitor (COX-2). COX-2 inhibitors could be superior to NSAID due to the well-known side effects from NSAID (bleeding/gastrointestinal ulcers). However, COX-2 inhibitors have been suggested to increase flap failure rates. We report our experience with using COX-2 inhibitors as part of our postoperative MOSA after ABR using free flaps.
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Analysis of complex protein interactions - Science Daily
| Analysis of complex protein interactions Science Daily "In comparison with conventional methods, the novel 'split-BioID' provides outstanding spatio-temporal resolution that enables easy analysis of context-dependent protein complexes," emphasises Isabel Schopp, a PhD candidate in the Béthune research ... |
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lncRNA DANCR promotes tumor progression and cancer stemness features in osteosarcoma by upregulating AXL via miR-33a-5p inhibition
lncRNAs regulate the initiation and progression of osteosarcoma, although the mechanism by which this occurs remains unknown. The present study shows that over-expression of the lncRNA DANCR increased osteosarcoma cell proliferation, migration, and invasion in vitro, as well as promoted xenograft tumor growth and lung metastasis in vivo. Mechanistically, DANCR promoted osteosarcoma progression by mediating cancer stem cells (CSC) features. Moreover, pull-down assays and luciferase reporter assays indicated that DANCR upregulated expression of the receptor tyrosine kinase AXL by competitively binding to miR-33a-5p.
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Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
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The device, cleared in Europe a couple of years ago, is used to ablate cardiac tissue as part of treatment for atrial fibrillation. It featu...
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Overdue: a US advisory board for research integrity Overdue: a US advisory board for research integrity, Published online: 11 February 201...
