Selection of epitopes from self-antigens for eliciting Th2 or Th1 activity in the treatment of autoimmune disease or cancer

Abstract

Vaccines have been valuable tools in the prevention of infectious diseases, and the rapid development of new vectors against constantly mutating foreign antigens in viruses such as influenza has become a regular, seasonal exercise. Harnessing the immune response against self-antigens is not necessarily analogous or as achievable by iterative processes, and since the desired outcome includes leaving the targeted organism intact, requires some precision engineering. In vaccine-based treatment of autoimmunity and cancer, the proper selection of antigens and generation of the desired antigen-specific therapeutic immunity has been challenging. Both cases involve a threshold of existing, undesired immunity that must be overcome, and despite considerable academic and industry efforts, this challenge has proven to be largely refractory to vaccine approaches leveraging enhanced vectors, adjuvants, and administration strategies. There are in silico approaches in development for predicting the immunogenicity of self-antigen epitopes, which are being validated slowly. One simple approach showing promise is the functional screening of self-antigen epitopes for selective Th1 antitumor immunogenicity, or inversely, selective Th2 immunogenicity for treatment of autoimmune inflammation. The approach reveals the importance of confirming both Th1 and Th2 components of a vaccine immunogen; the two can confound one another if not parsed but may be used individually to modulate antigen-specific inflammation in autoimmune disease or cancer.

http://ift.tt/2gNE3UG

Nachsorge des Endometriumkarzinoms

Zusammenfassung

Hintergrund

Obwohl die Prognose des Endometriumkarzinoms i. Allg. gut ist, kommt es bei ca. 15 % der im Stadium I und II erkrankten Patientinnen zu einem Rezidiv. Durch die im Einzelfall zugrunde liegende Primärtherapie resultieren unterschiedliche Nebenwirkungen und Langzeitfolgen.

Ziel

In der Übersichtsarbeit sollen die Ziele sowie die derzeit empfohlenen Maßnahmen und Untersuchungsintervalle für die Nachsorge des Endometriumkarzinoms dargestellt werden.

Material und Methoden

Eine selektive PubMed-Literaturrecherche zu Themen der Nachsorge des Endometriumkarzinoms wurde durchgeführt.

Ergebnisse

Das Ziel der Tumornachsorge ist es zum einen, zumeist erneut kurativ therapierbare Rezidive rechtzeitig zu entdecken, darüber hinaus aber auch Vorsorge vor Zweitmalignomen zu bieten. Ferner sollen Nebenwirkungen und Folgen der stattgehabten Behandlung erkannt, gelindert und behoben werden. Hierzu werden die spezifischen Empfehlungen und die vorliegende Datenlage vorgestellt.

Schlussfolgerung

Die Nachsorgeuntersuchung erfolgt im Wesentlichen klinisch und symptomorientiert in zunehmenden Zeitintervallen. Die Wertigkeit verschiedener Untersuchungsmaßnahmen wird diskutiert. Langfristiges Ziel der Nachsorge ist es, die Lebensqualität der Patientinnen zu erhalten.

http://ift.tt/2hyFWmb

A 45-Second Self-Test for Cardiorespiratory Fitness: Heart Rate-Based Estimation in Healthy Individuals

http://otorhinolarygology.blogspot.com/2016/12/a-45-second-self-test-for.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

A Priori Intrinsic PTM Size Parameters for Predicting the Ion Mobilities of Modified Peptides

Abstract

The rising profile of ion mobility spectrometry (IMS) in proteomics has driven the efforts to predict peptide cross-sections. In the simplest approach, these are derived by adding the contributions of all amino acid residues and post-translational modifications (PTMs) defined by their intrinsic size parameters (ISPs). We show that the ISPs for PTMs can be calculated from properties of constituent atoms, and introduce the "impact scores" that govern the shift of cross-sections from the central mass-dependent trend for unmodified peptides. The ISPs and scores tabulated for 100 more common PTMs enable predicting the domains for modified peptides in the IMS/MS space that would guide subproteome investigations.

Graphical Abstract

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http://ift.tt/2gDiHWC

Synthesis and Adsorption Properties of Ca-Al Layered Double Hydroxides for the Removal of Aqueous Fluoride

Abstract

Ca-Al layered double hydroxides (LDHs) with different Ca/Al molar ratios were composited at pH ranges, using a co-precipitation method, and were experimented to remove fluoride from wastewater and studied in terms of isotherm models such as Langmuir and Freundlich reactions. The composite LDHs were characterized with X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and Thermogravimetric analysis (TGA). The results showed that different synthesis conditions of Ca-Al LDHs had an influence on their morphology, layered structure, and particle size distribution, which substantially affected the uptake capacity for aqueous fluoride. LDHs with the Ca/Al molar ratio of 2 and synthesized at the pH of 12 had the highest capacity for the fluoride removal (e.g., 146.6 mg/g) and such reaction reached an equilibrium within 1 h. The Freundlich model was a better fit for this study. The high adsorption method of Ca-Al LDHs can be favorable to removing fluoride from wastewater streams.

http://ift.tt/2hyE4dI

Integrated Anaerobic-Aerobic Biodegradation of Multiple Contaminants Including Chlorinated Ethylenes, Benzene, Toluene, and Dichloromethane

Abstract

Complete bioremediation of soils containing multiple volatile organic compounds (VOCs) remains a challenge. To explore the possibility of complete bioremediation through integrated anaerobic-aerobic biodegradation, laboratory feasibility tests followed by alternate anaerobic-aerobic and aerobic-anaerobic biodegradation tests were performed. Chlorinated ethylenes, including tetrachloroethylene (PCE), trichloroethylene (TCE), cis-dichloroethylene (cis-DCE), and vinyl chloride (VC), and dichloromethane (DCM) were used for anaerobic biodegradation, whereas benzene, toluene, and DCM were used for aerobic biodegradation tests. Microbial communities involved in the biodegradation tests were analyzed to characterize the major bacteria that may contribute to biodegradation. The results demonstrated that integrated anaerobic-aerobic biodegradation was capable of completely degrading the seven VOCs with initial concentration of each VOC less than 30 mg/L. Benzene and toluene were degraded within 8 days, and DCM was degraded within 20 to 27 days under aerobic conditions when initial oxygen concentrations in the headspaces of test bottles were set to 5.3% and 21.0%. Dehalococcoides sp., generally considered sensitive to oxygen, survived aerobic conditions for 28 days and was activated during the subsequent anaerobic biodegradation. However, degradation of cis-DCE was suppressed after oxygen exposure for more than 201 days, suggesting the loss of viability of Dehalococcoides sp., as they are the only known anaerobic bacteria that can completely biodegrade chlorinated ethylenes to ethylene. Anaerobic degradation of DCM following previous aerobic degradation was complete, and yet-unknown microbes may be involved in the process. The findings may provide a scientific and practical basis for the complete bioremediation of multiple contaminants in situ and a subject for further exploration.

http://ift.tt/2hnD5PG

Adsorption of Ni(II), Pb(II) and Zn(II) on Ca(NO 3 ) 2 -Neutralised Red Mud

Abstract

This study aimed to investigate a novel method of red mud neutralisation by Ca(NO₃)₂ (NRM), keeping its adsorption capacity in relation to natural red mud (RM) for Ni(II), Pb(II) and Zn(II). Results pointed out that the neutralisation process decreases the pH and electrical conductivity values on NRM due to reaction between the carbonate and bicarbonate alkalinity of red mud and calcium from calcium nitrate to form calcite (CaCO₃). The maximum adsorption capacity values of RM and NRM, respectively, were 1.78 and 1.79 mmol g⁻¹ for Ni(II), 2.13 and 2.23 mmol g⁻¹ for Pb(II) and 1.14 and 1.06 mmol g⁻¹ for Zn(II). Pseudo-second-order model is the main responsible for the adsorption of these metals on RM and NRM. The adsorption reaction is endothermic and these metals have affinity to RM and NRM. Thus, it is possible to neutralise the red mud with Ca(NO₃)₂ without adsorption capacity losses of Ni(II), Pb(II) and Zn(II).

http://ift.tt/2hyyV5n

Müssen intravasale venöse Fremdkörper immer entfernt werden?

http://ift.tt/2gDaYaX

Body mass does not impact the clinical response to intravenous abatacept in patients with rheumatoid arthritis. Analysis from the “pan-European registry collaboration for abatacept (PANABA)

Abstract

Some evidences suggest that obesity impairs the effectiveness of TNF inhibitors. We examined the impact of body mass index (BMI) on the clinical effectiveness of abatacept in rheumatoid arthritis (RA) patients. This is a pooled analysis of 10 prospective cohorts of RA patients. All patients with available BMI were included in this study. The primary endpoint was drug retention of abatacept in the different BMI categories. Multivariable Cox regression was used to estimate hazard ratios (HRs) for drug discontinuation. A secondary endpoint was EULAR/LUNDEX response rates at 6/12 months. Of the 2015 RA patients initiating therapy with IV abatacept, 380 (18.9%) were classified as obese. Obese patients had more functional disability, and were less often RF positive. The median abatacept retention time was 1.91 years for obese RA patients compared to 2.12 years for non-obese patients (p = 0.15). The risk of abatacept discontinuation was not significantly different for overweight (HR 1.03 (95% CI 0.89–1.19)), or for obese (HR 1.08 (95% CI 0.89–1.30)) compared to normal-weight patients. Rheumatoid factor positivity reduced the risk of abatacept discontinuation (HR 0.83 (95% CI 0.72–0.95)), while previous biologic therapy was positively associated with drug interruption (HRs increasing from 1.68 to 2.16 with the line of treatments). Obese and non-obese patients attained similar rates of EULAR/LUNDEX clinical response at 6/12 months. Drug retention and clinical response rates to abatacept do not seem to be decreased by obesity in RA patients.

http://ift.tt/2hxJDsm

Pharmacokinetics and derivation of an anticancer dosing regimen for the novel anti-cancer agent isobutyl-deoxynyboquinone (IB-DNQ), a NQO1 bioactivatable molecule, in the domestic felid species

Summary

Isobutyl-deoxynyboquinone (IB-DNQ) is a selective substrate for NAD(P)H:quinone oxidoreductase (NQO1), an enzyme overexpressed in many solid tumors. Following activation by NQO1, IB-DNQ participates in a catalytic futile reduction/reoxidation cycle with consequent toxic reactive oxygen species generation within the tumor microenvironment. To elucidate the potential of IB-DNQ to serve as a novel anticancer agent, in vitro studies coupled with in vivo pharmacokinetic and toxicologic investigations in the domestic felid species were conducted to investigate the tractability of IB-DNQ as a translationally applicable anticancer agent. First, using feline oral squamous cell carcinoma (OSCC) as a comparative cancer model, expressions of NQO1 were characterized in not only human, but also feline OSCC tissue microarrays. Second, IB-DNQ mediated cytotoxicity in three immortalized feline OSCC cell lines were studied under dose-dependent and sequential exposure conditions. Third, the feasibility of administering IB-DNQ at doses predicted to achieve cytotoxic plasma concentrations and biologically relevant durations of exposure were investigated through pharmacokinetic and tolerability studies in healthy research felines. Intravenous administration of IB-DNQ at 1.0–2.0 mg/kg achieved peak plasma concentrations and durations of exposure reaching or exceeding predicted in vitro cytotoxic concentrations. Clinical adverse side effects including ptyalism and tachypnea exhibited during and post-IV infusion of IB-DNQ were transient and tolerable. Additionally, IB-DNQ administration did not produce acute or delayed-onset unacceptable hematologic, non-hematologic, or off-target oxidative toxicities. Collectively, the findings reported here within provide important safety and pharmacokinetic data to support the continued development of IB-DNQ as a novel anticancer strategy for NQO1 expressing cancers.

http://ift.tt/2hw7VDa

Cathepsin B Improves ß-Amyloidosis and Learning and Memory in Models of Alzheimer’s Disease

Abstract

Amyloid-ß (Aß) precursor protein (APP) metabolism engages neuronal endolysosomal pathways for Aß processing and secretion. In Alzheimer's disease (AD), dysregulation of APP leads to excess Aß and neuronal dysfunction; suggesting that neuronal APP/Aß trafficking can be targeted for therapeutic gain. Cathepsin B (CatB) is a lysosomal cysteine protease that can lower Aß levels. However, whether CatB-modulation of Aß improves learning and memory function deficits in AD is not known. To this end, progenitor neurons were infected with recombinant adenovirus expressing CatB and recovered cell lysates subjected to proteomic analyses. The results demonstrated Lamp1 deregulation and linkages between CatB and the neuronal phagosome network. Hippocampal injections of adeno-associated virus expressing CatB reduced Aß levels, increased Lamp1 and improved learning and memory. The findings were associated with the emergence of c-fos + cells. The results support the idea that CatB can speed Aß metabolism through lysosomal pathways and as such reduce AD-associated memory deficits.

http://ift.tt/2hPDBCY

Diversity of mitochondrial DNA in three Arabian horse strains

Abstract

Arabian horse registries classify Arabian horses based on their dam lineages into five main strains. To test the maternal origin of Syrian Arabian horses, 192 horses representing the three major strains Saglawi, Kahlawi, and Hamdani were sequenced for 353 bp of their mitochondrial displacement loop (D-loop) region. Sequencing revealed 28 haplotypes comprising 38 sequence variations. The haplotype diversity values were 0.95, 0.91, and 0.90 in Kahlawi, Hamdani, and Saglawi strains, respectively. The pair-wise population differentiation estimates (Fst) between strains were low, ranging between 0.098 and 0.205. The haplotype diversity and the pair-wise population differentiation estimates (F_st) between strains showed high diversity within individuals of each strain and low variation between the three strains. Mitochondrial haplotypes scattered all over the neighbor-joining tree without clear separation of the three strains. In the median-joining network, the Syrian horses were grouped into seven major haplogroups. These results suggest that more than five ancestors exist that share common maternal haplotypes with other horse breeds.

http://ift.tt/2gMYrFv

A Review of 2255 Emergency Abdominal Operations Performed over 17 years (1996–2013) in a Gastrointestinal Surgery Unit in India

Abstract

There is little information regarding the clinical spectrum and outcome of emergency abdominal operations from specialized units in India. We examined these in our gastrointestinal surgery and liver transplantation unit from a prospective database maintained between July 1996 and April 2013. Out of 9966 operations performed, 2255 (26%) were emergency procedures (reoperations during the same admission, e.g., for necrotizing pancreatitis were excluded). The primary outcome was 30-day postoperative mortality. The mean age of the patients was 47 years (range 1–107) and included the following age groups: 0–18 years (n = 105, 4.7%); 19–64 years (n = 1766, 78.3%), and >65 years (n = 384, 17.0%). The majority were males (1609, 71%), and there were 646 females (29%). The most common indications were small bowel emergencies (598, 26.5%), followed by pancreatic (417, 18.5%) and colonic (281, 12.5%) emergencies. Pancreatic operations were the second commonest in the adult and middle aged group. Colorectal operations were the second commonest in the geriatric age group (>65 years). Emergency operations for other conditions were: postoperative complications following elective operations 171 (7.5%), gastroduodenal bleeding or perforation in 144 (6.3%), and liver surgery in 93 patients (4.1%) patients. In the small bowel emergencies, 223 patients (37.2%) had primary diagnosis of adhesive obstruction, gangrene in 135 patients (22.5%), perforation in 121 patients (20%), and fistula in 56 patients (9.3%). Mesenteric venous thrombosis was found to be the primary cause of small bowel emergencies, either as a primary cause in gangrene or as a secondary cause in perforations and adhesions. The postoperative mortality after emergencies was 12.6% compared to 2% in elective procedures. Mortality was significantly higher in males (14%) than females (9.6%), p < 0.005. Category wise mortality was as follows: pancreatic surgery (n = 86, 20.6%), surgery for postoperative complications (n = 33, 19.3%), duodenal surgery (n = 18, 12.5%), small intestinal surgery (n = 68, 11.4%), and colonic surgery (n = 35, 12.45%). Emergency operations comprise a significant proportion of a GI surgical unit's workload. The mortality is greatest after pancreatic operations followed by those done for postoperative complications. Despite advances in surgical and postoperative care, emergency operations for abdominal emergencies are associated with mortality which is six times higher compared to elective procedures.

http://ift.tt/2h2ePze

Erratum to: Microarray (phylochip) analysis of freshwater pathogens at several sites along the Northern German coast transecting both estuarine and freshwaters

http://ift.tt/2hPFsrj

Effects of initial moisture content of Korean traditional wheat-based fermentation starter nuruk on microbial abundance and diversity

Abstract

The brewing of makgeolli, one of Korea's most popular alcoholic beverages that is gaining popularity globally, is facilitated by nuruk, a traditional Korean cereal starter. The nuruk microbiome greatly influences the fermentation process as well as the nutritional, hygienic, and aromatic qualities of the product. This study is a continuation of our efforts to examine nuruk biodiversity at a depth previously unattainable. In this study, microfloral dynamics in wheat-based nuruk C, composed of traditional ingredients such as barley, green gram, and wheat and fermented under various internal moisture contents of 20% (C20), 26% (C26), and 30% (C30), was evaluated using 454 pyrosequencing during the 30-day fermentation process. Rarefaction analysis and alpha diversity parameters indicated adequate sampling. C20 showed the greatest fungal richness and diversity, C20 and C26 exhibited similar bacterial richness and diversity, while C30 had low fungal and bacterial richness. Fungal taxonomic assignments revealed that the initial moisture content caused selective enrichment of Aspergillus candidus with a decreasing trend during fermentation, whereas Saccharomycetales sp. exhibited increasing relative abundance with increasing moisture content from day 6 of the fermentation process. Depending on initial moisture level, changes in bacterial communities were also observed in the genera Streptomyces, Bacillus, and Staphylococcus, with decreasing trends whereas Saccharopolyspora exhibited a sigmoidal trend with the highest abundance in C26. These findings demonstrate the possible impact of initial moisture content of nuruk on microfloral richness, diversity, and dynamics; this study is thus a step toward our ultimate goal of enhancing the quality of nuruk.

http://ift.tt/2gMT60V

Expression and secretion of glycosylated heparin biosynthetic enzymes using Komagataella pastoris

Abstract

Heparin, an anticoagulant drug, is biosynthesized in selected animal cells. The heparin biosynthetic enzymes mainly consist of sulfotransferases and all are integral transmembrane glycoproteins. These enzymes are generally produced in engineered Escherichia coli as without their transmembrane domains as non-glycosylated fusion proteins. In this study, we used the yeast, Komagataella pastoris, to prepare four sulfotransferases involved in heparin biosynthesis as glycoproteins. While the yields of these yeast-expressed enzymes were considerably lower than E. coli-expressed enzymes, these enzymes were secreted into the fermentation media simplifying their purification and were endotoxin free. The activities of these sulfotransferases, expressed as glycoproteins in yeast, were compared to the bacterially expressed proteins. The yeast-expressed sulfotransferase glycoproteins showed improved kinetic properties than the bacterially expressed proteins.

http://ift.tt/2hPxMFl

On the Stability of the Quadruple Solutions of the Forward Kinematic Problem in Analytic Parallel Robots

Abstract

Many parallel robots can change between different assembly modes (solutions of the forward kinematic problem) without crossing singularities, either by enclosing cusps or alpha-curves of the planar sections of their singularity loci. Both the cusps and the alpha-curves are stable singularities, which do not disappear under small perturbations of the geometry of the robot. Recently, it has been shown that some analytic parallel robots can also perform these nonsingular changes of assembly mode by encircling isolated points of their singularity loci at which the forward kinematic problem admits solutions with multiplicity four. In this paper, we study the stability of these quadruple solutions when the design of the robot deviates from the analytic geometry, and we show that such quadruple solutions are not stable since the isolated singular points at which they occur degenerate into closed deltoid curves. However, we also demonstrate that, although the quadruple solutions are unstable, the behavior of the robot when moving around them is practically unaffected by the perturbations from the analytic geometry. This means that the robot preserves its ability to perform nonsingular transitions by enclosing the quadruple solutions, even when its geometry is not exactly analytic due to small manufacturing tolerances.

http://ift.tt/2hxqqaw

In ovo sexing of chicken eggs by fluorescence spectroscopy

Abstract

Culling of day-old male chicks in production of laying hen strains involves several millions of animals every year worldwide and is ethically controversial. In an attempt to provide an alternative, optical spectroscopy was investigated to determine nondestructively in ovo the sex of early embryos of the domestic chicken. The extraembryonic blood circulation system was accessed by producing a window in the egg shell and the flowing blood was illuminated with a near-infrared laser. The strong fluorescence and the weak Raman signals were acquired and spectroscopically analyzed between 800 and 1000 nm. The increase of fluorescence intensity between 3.5 and 11.5 days of incubation was found to be in agreement with the erythropoietic stages, thus enabling to identify hemoglobin as fluorescence source. Sex-related differences in the fluorescence spectrum were found at day 3.5, and principal component (PC) analysis showed that the blood of males was characterized by a specific fluorescence band located at ∼910 nm. Supervised classification of the PC scores enabled the determination of the sex of 380 eggs at day 3.5 of incubation with a correct rate up to 93% by combining the information derived from both fluorescence and Raman scattering.

Graphical abstract

The fluorescence of blood obtained in ovo by illumination of embryonic vessels with a IR laser displays spectral differences that can be employed for sexing of eggs in early stage of incubation, before onset of embryo sensitivity and without hindering its development into a healthy chick

http://ift.tt/2hxQQtb

A comparison of sample preparation strategies for biological tissues and subsequent trace element analysis using LA-ICP-MS

Abstract

Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is one of the most commonly applied methods for lateral trace element distribution analysis in medical studies. Many improvements of the technique regarding quantification and achievable lateral resolution have been achieved in the last years. Nevertheless, sample preparation is also of major importance and the optimal sample preparation strategy still has not been defined. While conventional histology knows a number of sample pre-treatment strategies, little is known about the effect of these approaches on the lateral distributions of elements and/or their quantities in tissues. The technique of formalin fixation and paraffin embedding (FFPE) has emerged as the gold standard in tissue preparation. However, the potential use for elemental distribution studies is questionable due to a large number of sample preparation steps. In this work, LA-ICP-MS was used to examine the applicability of the FFPE sample preparation approach for elemental distribution studies. Qualitative elemental distributions as well as quantitative concentrations in cryo-cut tissues as well as FFPE samples were compared. Results showed that some metals (especially Na and K) are severely affected by the FFPE process, whereas others (e.g., Mn, Ni) are less influenced. Based on these results, a general recommendation can be given: FFPE samples are completely unsuitable for the analysis of alkaline metals. When analyzing transition metals, FFPE samples can give comparable results to snap-frozen tissues.

Graphical abstract

Sample preparation strategies for biological tissues are compared with regard to the elemental distributions and average trace element concentrations.

http://ift.tt/2hxKmKQ

Detection of lead nanoparticles in game meat by single particle ICP-MS following use of lead-containing bullets

Abstract

This study investigated whether game meat may contain nanoparticles of lead from ammunition. Lead nanoparticles in the range 40 to 750 nm were detected by ICP-MS in single particle mode in game shot with lead-containing bullets. The median diameter of the detected nanoparticles was around 60 nm. The particle mass concentration ranged from 290 to 340 ng/g meat and the particle number concentrations from 27 to 50 million particles/g meat. The size limit of detection strongly depended on the level of dissolved lead and was in the range of 40 to 80 nm. In game meat sampled more than 10 cm away from the wound channel, no lead particles with a diameter larger than 40 nm were detected. In addition to dissolved lead in meat that originated from particulates, the presence of lead nano particles in game meat represents a hitherto unattended source of lead with a largely unknown toxicological impact to humans.

Graphical Abstract

Detection of lead nanoparticles in game meat by single particle ICP-MS following use of leadcontaining bullets

http://ift.tt/2hxMdz5

Extraction, selenylation modification and antitumor activity of the glucan from Castanea mollissima Blume

Abstract

The present study aimed to characterize the glucan from C. mollissima Blume fruits and its selenium derivative, then investigate their antitumor activity in vitro. A glucan, designated as CPA, was firstly isolated from the fruits of C. mollissima Blume. Structure analysis indicated that CPA was a linear 1,6-α-D-glucan with the average molecular weight about 2.0 × 10³ kDa. The selenylation modification derivative of CPA (sCPA), exhibited a stronger antiproliferative effect on tumor cells than CPA in vitro. CPA and sCPA could induce HeLa cells apoptosis and decrease mitochondrial membrane potential. sCPA could also arrest HeLa cells in S phase, promote reactive oxygen species generation and activate caspase-3 activity in HeLa cells. These results manifest that CPA and sCPA inhibit the proliferation of HeLa cells via different mechanisms, which is meaningful for their potential use as antitumor drugs.

http://ift.tt/2gKoXk8

Glycosylation: a hallmark of cancer?

Abstract

The hallmarks of cancer are characterized by functional capabilities that allow cancer cells to survive, proliferate and disseminate during the multistep tumorigenesis. Cancer being a cellular disease, changes in cellular glycoproteins play an important role in malignant transformation and cancer progression. The present review summarizes various studies that depicted correlation of glycosylation with tumor initiation, progression and metastasis, which are helpful in early diagnosis, disease monitoring and prognosis. The results are further strengthened by our reports, which depicted alterations in sialylation and fucosylation in different cancers. Alterations in glycosyltransferases are also involved in formation of various tumor antigens (e.g. Sialyl Lewis x) which serves as ligand for the cell adhesion molecule, selectin which is involved in adhesion of cancer cells to vascular endothelium and thus contributes to hematogenous metastasis. Increased glycosylation accompanied by alterations in glycosyltranferases, glycosidases, glycans and mucins (MUC)s are also involved in loss of E-cadherin, a key molecule implicated in metastatic dissemination of cells. The present review also summarizes the correlation of glycosylation with all the hallmarks of cancer. The enormous progress in the design of novel inhibitors of pathway intermediates of sialylation and fucosylation can prove wonders in combating the dreadful disease. The results provide the evidence that altered glycosylation is linked to tumor initiation, progression and metastasis. Hence, it can be considered as a new hallmark of cancer development and strategies to develop novel glycosylation targeted molecules should be strengthened.

http://ift.tt/2h1NQUv

Pharmacokinetics and derivation of an anticancer dosing regimen for the novel anti-cancer agent isobutyl-deoxynyboquinone (IB-DNQ), a NQO1 bioactivatable molecule, in the domestic felid species

Summary

Isobutyl-deoxynyboquinone (IB-DNQ) is a selective substrate for NAD(P)H:quinone oxidoreductase (NQO1), an enzyme overexpressed in many solid tumors. Following activation by NQO1, IB-DNQ participates in a catalytic futile reduction/reoxidation cycle with consequent toxic reactive oxygen species generation within the tumor microenvironment. To elucidate the potential of IB-DNQ to serve as a novel anticancer agent, in vitro studies coupled with in vivo pharmacokinetic and toxicologic investigations in the domestic felid species were conducted to investigate the tractability of IB-DNQ as a translationally applicable anticancer agent. First, using feline oral squamous cell carcinoma (OSCC) as a comparative cancer model, expressions of NQO1 were characterized in not only human, but also feline OSCC tissue microarrays. Second, IB-DNQ mediated cytotoxicity in three immortalized feline OSCC cell lines were studied under dose-dependent and sequential exposure conditions. Third, the feasibility of administering IB-DNQ at doses predicted to achieve cytotoxic plasma concentrations and biologically relevant durations of exposure were investigated through pharmacokinetic and tolerability studies in healthy research felines. Intravenous administration of IB-DNQ at 1.0–2.0 mg/kg achieved peak plasma concentrations and durations of exposure reaching or exceeding predicted in vitro cytotoxic concentrations. Clinical adverse side effects including ptyalism and tachypnea exhibited during and post-IV infusion of IB-DNQ were transient and tolerable. Additionally, IB-DNQ administration did not produce acute or delayed-onset unacceptable hematologic, non-hematologic, or off-target oxidative toxicities. Collectively, the findings reported here within provide important safety and pharmacokinetic data to support the continued development of IB-DNQ as a novel anticancer strategy for NQO1 expressing cancers.

http://ift.tt/2hw7VDa

Neuroimaging of neuropathic pain: review of current status and future directions

Abstract

The goal of this review is to discuss the various imaging modalities to study neuropathic pain and its future implication in understanding pain network, for the diagnosis and management of patients with chronic neuropathic pain. Neuropathic pain is characterized by pain secondary to lesions or dysfunction of the central nervous system (CNS) or the peripheral nervous system. Neuropathic pain is generally chronic and disabling, and responds poorly to conventional treatment. Although our understanding of the imaging changes in chronic pain state is evolving, we still face practical challenges in implementing these finding to objectively diagnose and follow treatment response in patients with chronic pain and to guide targeted and individualized treatment to each chronic pain condition.

http://ift.tt/2hOLAQO

Characteristics of Gastric Cancer in Lebanon: a Descriptive Study from a Single Institutional Experience

Abstract

Background

The epidemiology of gastric cancer in the Middle East has never been described. Therefore, the characteristics of gastric cancer in the Lebanese population will be reported in this study.

Patients and Methods

A retrospective study that included all patients diagnosed with gastric cancer at Hotel Dieu de France University Hospital in Beirut, Lebanon between 2010 and 2016 was conducted. All eligible patients were reviewed for demographic and epidemiologic analysis.

Results

The study included 123 patients diagnosed with gastric cancer. The median age at diagnosis was 59 years (range 15–72 years), and the median ECOG performance status was 2 (range 1–4). Most patients were metastatic at diagnosis (52.8%), and diffuse pathology type was predominant (39%). HER2 was positive in 16.2% and correlated with the occurrence of hepatic metastasis (p = 0.048). The HER2 status did not differ significantly between the histological subtypes, the site of the tumor, the stage of the gastric cancer at diagnosis, and the recurrence of cancer (p > 0.05).

Conclusion

Gastric cancer in the Lebanese population is characterized by aggressive features such as advanced stage at diagnosis, high prevalence of diffuse type histology, and HER2 positivity.

http://ift.tt/2gBL7A4

Evaluating the Correlation Between the Survival Rate of Patients with Esophageal Squamous Cell Carcinoma and Expression of p53 and Cyclin D1 Biomarkers Along with Other Prognostic Factors

Abstract

Objective

In the present study, we aimed to evaluate the relationship between the survival rate of patients with esophageal squamous cell carcinoma (SCC) and expression of two biomarkers along with age, gender, tumor margin, depth of invasion, site of tumor, tumor diameter, tumor grade, number of involved nodes, and vascular invasion.

Materials and Methods

In this retrospective survey, medical records of patients referred to the Shohada-e Tajrish hospital during 2001 to 2005 were reviewed and subjects with definite diagnosis of SCC were included. Required data were extracted from the patients' records, and their prepared paraffin-embedded tissue blocks were collected under supervision of two pathologists. Immunohistochemistry (IHC) analysis was performed at the Firoozgar hospital in Tehran, Iran.

Results

The studied population included 20 men (74%) and 7 women (26%). The mean age at diagnosis was 58 ± 22. Results showed significantly higher survival rates in women compared to men (85.7 vs. 40%) (p = 0.001) and in patients with well-differentiated tumors compared to poor-differentiated cases (20 vs. 5%) (p = 0.004). No significant relationship was found between p53 expression and prognostic factors like age, gender, the site, grade, and size of the tumor, depth of invasion, involvement of lymph nodes, and vascular invasion.

Conclusion

Positivity of p53 and cyclin D1 was not found to be predictive of survival in patients with esophageal SCC which might be due to the small sample size of the present survey. Further investigations with larger sample populations and longer follow-ups are required to evaluate this correlation.

http://ift.tt/2hG4JIB

Patient Experience After Receiving a Diagnosis of Gastric Cancer in the USA

Abstract

Purpose

This study investigated the patient perspective during cancer treatment and throughout the survivorship period and to understand how the patient experience may be related to choices for the treatment of gastric cancer.

Methods

Eligible patients in the Vector Oncology electronic medical records database were ≥18 years of age, diagnosed with gastric cancer, and received active treatment. Quality of life (QOL) was collected using the Patient Care Monitor (PCM). Time to deterioration in QOL and overall survival were measured, adjusting for demographic and baseline clinical characteristics. Logistic regression model and classification and regression trees (CART) were used to identify factors associated with treatment choice.

Results

There were 776 patients in this study, of whom 301 (38.8%) reported QOL data. Most patients reported problems on all PCM subscales; problems were more common during the treatment period. Median time to deterioration of PCM subscales ranged from 42 days for treatment side effects to 331 days for impaired performance. Median survival was low: 6.9 and 5.5 months from the start of first- and second-line therapy, respectively. The choices made between therapeutic options were primarily associated with the site at which the oncologist practiced.

Conclusions

Patients with gastric cancer report a considerable number of concerns on all subscales of the PCM, particularly during active treatment periods. The treatment heterogeneity and relative lack of clinical and symptom- or QOL-related factors associated with treatment choice suggest a gap in evidence that must be filled.

http://ift.tt/2gBGwOD

A Rare Case of Metastatic Colorectal Carcinoma in the Testicle

http://ift.tt/2hG8D49

An integrated microfluidic PCR system with immunomagnetic nanoparticles for the detection of bacterial pathogens

Abstract

There is growing interest in rapid microbial pre-concentration methods to lower the detection limit of bacterial pathogens of low abundance in samples. Here, we report an integrated microfluidic PCR system that enables bacterial cells of interest in samples to be concentrated prior to PCR. It consists of two major compartments: a preconcentration chamber for the immunomagnetic separation of bacterial cells, and a PCR chamber for the DNA amplification of the concentrated cells. We demonstrate the feasibility of the system for the detection of microbial pathogens by preconcentrating the human pathogen Escherichia coli O157:H7, and also amplifying its DNA. The detection limit of E. coli O157:H7 in the PCR system is 1 × 10³ CFU (colony forming unit)/mL. On-chip processing steps, including preconcentration and PCR steps, take less than two hours. Our system can serve as a rapid, specific, and quantitative platform for the detection of microbial pathogens in samples of large volume.

http://ift.tt/2gM1JJ3

Foramina parietalia permagna: familial and radiological evaluation of two cases and review of literature

Abstract

Purpose

Foramina parietalia permagna is a variable intramembranous ossification defect of the parietal bones. Foramina parietalia permagna have an autosomal dominant inheritance, and it is showed that mutations in chromosome 5 and 11 are causing this anomaly. Enlarged parietal foramina occurs extremely rare. They are usually asymptomatic, but occasional headache, vomiting, pain over unprotected cerebral cortex, and seizures may be experienced by the patients. In the literature, some associated congenital bony defects, soft tissue pathologies, underlying neuronal deficits, and vascular variations have been described.

Methods

We report two cases of foramina parietal permagna with their pedigrees and genetic analysis.

Results

In case 1, cytogenetic analysis revealed a mutation of the ALX4 gene and all of the members of the family diagnosed with FPP. MRI revealed inferior vermian cerebellar hypoplasia. Surgery was not considered. In case 2, cytogenetic analysis could not be obtained because of financial reasons. Cranial MRI revealed hypoplastic right transverse sinus and sigmoid sinus, with a persistent parafalcine sinus. Surgery was not considered.

Conclusion

Despite of its rarity, genetic background and some important associated anomalies make foramina parietalia permagna more than an uncommon insignificant genetic disorder.

http://ift.tt/2hxhbY3

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn’s Disease in Remission: A Pilot Randomized Double-Blind Controlled Study

Abstract

Aim

To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD).

Methods

This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores.

Results

High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3.

Conclusions

Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted.

Clinicaltrials.gov registration no

NCT02615288.

http://ift.tt/2hFXSi9

Inflammatory Bowel Disease-Related Abstracts Presented at National Conferences in the USA Are Frequently Unpublished as Full Manuscripts

Abstract

Background

Numerous abstracts related to inflammatory bowel disease (IBD) are presented at national conferences in the USA. The overall rate of publication of these abstracts as complete manuscripts is unknown .

Methods

Abstracts submitted to the 2010 American College of Gastroenterology (ACG), Advances in Inflammatory Bowel Diseases (AIBD), and the American Gastroenterological Association abstracts at Digestive Disease Week (DDW) were reviewed. Each abstract was reviewed manually by two authors for type of research, study design, patient population, and outcome. Both PubMed and Google were then searched to determine whether the abstract was published as a full manuscript within five years of the conference. Univariate and multivariate logistic regression analysis was carried out using Stata 14.1.

Results

In total, 872 abstracts were reviewed. 49% (426/872) were published as complete manuscripts within five years of the conference. The average length of time to publication was 1.87 years (range 0–5). 42% of abstracts from ACG, 58% from AIBD, and 23% from DDW were eventually published (p < 0.0001). However, abstracts presented at DDW had the shortest time to publication compared to the other conferences (p = 0.002). Factors predictive of eventual publication include: number of authors (mean 7.5 for published vs 6.4 for unpublished p = 0.0001), clinical research compared to basic and translational (p = 0.026), and studies assessing drug safety with no adverse effects reported (p = 0.006).

Conclusion

Nearly 50% of the abstracts presented at major gastroenterology conferences in the USA are published as full manuscripts 5 years after the conference. Further studies are needed to assess why so many abstracts are not published.

http://ift.tt/2gBwu00

Failure of the Obesity Surgery Mortality Risk Score (OS-MRS) to Predict Postoperative Complications After Bariatric Surgery. A Single-Center Series and Systematic Review

Abstract

Background

The obesity surgery mortality risk score (OS-MRS) was developed to determine the risk of postoperative mortality in patients undergoing bariatric surgery. The aim of the present study is to assess the utility of this score for preventing the risk of postoperative complications from bariatric surgery.

Methods

Prospective study of 321 patients undergoing bariatric surgery to whom the OS-MRS was applied. Postoperative complications were classified according to the Clavien-Dindo system. The relation between the OS-MRS and the appearance of complications and mortality was analyzed. A Medline/Embase search was conducted using bariatric surgery, mortality, and complications as key words. Studies using the OS-MRS to predict morbidity and mortality were included.

Results

Of the 321 patients, 303 (94.3%) underwent gastric bypass and the remaining 18 (5.6%) a sleeve gastrectomy. The OS-MRS classified 178 patients as class A (55.5%), 129 as class B (40.2%), and 14 as class C (4.4%). According to the Clavien-Dindo system, 10.4% of the complications were ≥III. There was one death (class B). No significant association was found between the OS-MRS and the rate of complications.

Conclusions

In our study, the OS-MRS is not correlated with the appearance of early complications or mortality. Future studies must focus on systems for predicting the appearance and severity of postoperative complications classified according to the Clavien-Dindo system, and not only on mortality.

http://ift.tt/2hmaYjM

Temporal Query Processing in Social Network

Abstract

With the increasing of requirements from many aspects, various queries and analyses arise focusing on social network. Queries like finding users, friends or social activities satisfying a certain period gives temporal insights into retrieval or statistics, hence augmenting temporal query capability in such context, namely, temporal social network (TSN), is meaningful. In this paper, we mainly study three kinds of temporal queries in social network, which explore temporal attribute in user's online duration, friendship duration and participation in social activities. To address the problems, first we formally give problem descriptions, and propose 6 primitive query definitions, which are helpful for accomplishing the three queries through combining them. Next, we design a storage model to store the data of our context, and propose implementation of primitive queries based on the model. After that, we argue indexing techniques are able to accelerate the query procedure and then propose two index structures, TUR-tree, indexing temporal data of users and friendship, and TUA-tree, indexing temporal data of participations. Then we address implementation of primitive queries based on indexes, and design query algorithms to solve the three queries. We believe the algorithms could be improved and optimizations are presented. We evaluate our idea on a dataset which is synthetically generated from real dataset, and experimental results show that our indexes and query processing are effective and scalable.

http://ift.tt/2gEpqV5

Responsiveness of a Brief Measure of Lung Cancer Screening Knowledge

Abstract

Our aim was to examine the responsiveness of a lung cancer screening brief knowledge measure (LCS-12). Eligible participants were aged 55–80 years, current smokers or had quit within 15 years, and English speaking. They completed a baseline pretest survey, viewed a lung cancer screening video-based patient decision aid, and then filled out a follow-up posttest survey. We performed a paired samples t-test, calculated effect size, and calculated absolute and relative percent improvement for each item. Participants (n = 30) were primarily White (63%) with less than a college degree (63%), and half were female (50%). Mean age was 61.5 years (standard deviation [SD] = 4.67) and average smoking history was 30.4 pack-years (range = 4.6–90.0). Mean score on the 12-item measure increased from 47.3% correct on the pretest to 80.3% correct on the posttest (mean pretest score = 5.67 vs. mean posttest score = 9.63; mean score difference = 3.97, SD = 2.87, 95% CI = 2.90, 5.04). Total knowledge scores improved significantly and were responsive to the decision aid intervention (paired samples t-test = 7.57, p < .001; Cohen's effect size = 1.59; standard response mean [SRM] = 1.38). All individual items were responsive, yet two items had lower absolute responsiveness than the others (item 8: "Without screening, is lung cancer often found at a later stage when cure is less likely?" pretest correct = 83.3% vs. posttest = 96.7%, responsiveness = 13.4%; and item 10: "Can a CT scan find lung disease that is not cancer?" pretest correct = 80.0% vs. posttest = 93.3%, responsiveness = 13.3%). The LCS-12 knowledge measure may be a useful outcome measure of shared decision making for lung cancer screening.

http://ift.tt/2hlaWJ4

Optimization of Methods Verifying Volunteers’ Ability to Provide Hospice Care

Abstract

The subject of the presented work was an attempt at optimization of the methods used for verification of the candidates for medical voluntary workers in a hospice and decreasing the danger of a negative influence of an incompetent volunteer on a person in a terminal stage of a disease and his or her relatives. The study was carried out in St. Lazarus Hospice in Krakow, Poland, and included 154 adult participants in four consecutive editions of "A course for volunteers – a guardian of the sick" organized by the hospice. In order to improve the recruitment of these workers, the hitherto methods of selection (an interview with the coordinator of volunteering and no less than 50% of attendance in classes of a preparatory course for volunteers") were expanded by additional instruments—the tests whose usefulness was examined in practice. Knowledge of candidates was tested with the use of a written examination which consisted of four open questions and an MCQ test comprising 31 questions. Practical abilities were checked by the Objective Structured Clinical Examination (OSCE). A reference point for the results of these tests was a hidden standardized long-term observation carried out during the subsequent work of the volunteers in the stationary ward in the hospice using the Amsterdam Attitude and Communication Scale (AACS). Among the tests used, the greatest value (confirmed by a quantitative and qualitative analysis) in predicting how a given person would cope with practical tasks and in contact with the sick and their relatives had a practical test of the OSCE type.

http://ift.tt/2hw3msN

Erratum to: Picosecond lasers for tattoo removal: a systematic review

http://ift.tt/2hNqstX

The efficacy and safety of 2-μm continuous laser in the treatment of high-risk patients with benign prostatic hyperplasia

Abstract

Two-micrometer laser resection of prostate-tangerine technique dissects whole prostatic lobes off the surgical capsular, similar to peeling a tangerine. The present study aimed to evaluate the safety and efficacy of 2-μm continuous laser vaporization in the treatment of high-risk patients with benign prostatic hyperplasia (BPH) during the 24-month follow-up. The study included 248 patients with moderate to severe lower urinary tract symptoms who underwent 2-μm continuous laser vaporization of the prostate. All patients were accompanied with different degree comorbidities and 94 patients were taking oral anticoagulants. BPH was successfully treated with 2-μm continuous laser vaporization in all patients. Mean pre-operative prostate volume was 76 ± 25.3 ml and mean operative time was 49.8 ± 16.5 min. There were no major complications intra-operatively or postoperatively, and no blood transfusions were needed. About 20 patients (8.1%) needed bladder irrigation postoperatively. Average catheterization time was 2.0 ± 1.8 days (range 1–5 days). Four patients required reoperation due to enlarged prostates from residual adenoma. At 3-, 6-, 12-, and 24-month follow-ups, maximum urinary flow rates (Qmax) increased from 6.9 ± 1.7 to 19.1 ± 4.2, 19.5 ± 4.6, 19.4 ± 4.6, and 19.5 ± 4.1 ml/s, respectively. Mean International Prostate Symptom Scores (IPSS) decreased from 27.6 ± 5.1 (pre-operation) to 9.2 ± 2.6, 7.12 ± 1.42, 6.18 ± 1.32, and 6.25 ± 1.30 at 3-, 6-, 12-, and 24-month post-operation, respectively. Two-micrometer continuous laser vaporization is a safe and effective surgical endoscopic technique associated with low complication rate in BPH patients at high risk and those on anticoagulation therapy who have severe LUTS caused by BPH.

http://ift.tt/2gWO9QE

Network meta-analysis as a tool for improving the effectiveness assessment of biosimilars based on both direct and indirect evidence: application to infliximab in rheumatoid arthritis

http://ift.tt/2gzxJgd

Face-to-face interaction of multisolitons in spin-1/2 quantum plasma

Abstract

We investigate the face-to-face collision between multisolitons in spin-1/2 quantum plasma. It is studied in the framework of the model proposed by Marklund et al in Phys. Rev. E 76, 067401 (2007). This study is done with the help of the extended Poincare–Lighthill–Kno (PLK) method. The extended PLK method is also used to obtain two Korteweg–de Vries (KdV) equations and the phase shifts and trajectories during the head-on collision of multisolitons. The collision-induced phase shifts (trajectory changes) are also obtained. The effects of the Zeeman energy, total mass density of the charged plasma particles, speed of the wave and the ratio of the sound speed to Alfvén speed on the phase shifts are studied. It is observed that the phase shifts are significantly affected by all these parameters.

http://ift.tt/2ht0xLw

Indian Journal of Medical and Paediatric Oncology (Indian J Med Paediatr Oncol)

EDITORIAL COMMENTARY

Classical or pylorus-preserving pancreatoduodenectomy in pancreatic and periampullary cancer: "The jury is still out!" [pg. 209]
Savio George Barreto
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

REVIEW ARTICLES

Should every patient with pancreatic cancer receive perioperative/neoadjuvant therapy? [pg. 211]
Ulrich Nitsche, Bo Kong, Alexander Balmert, Helmut Friess, Jörg Kleeff
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Skin: A mirror of internal malignancy [pg. 214]
Rita V Vora, RahulKrishna S Kota, Nilofar G Diwan, Nidhi B Jivani, Shailee S Gandhi
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Status of barium studies in the present era of oncology: Are they a history? [pg. 223]
Abhishek Mahajan, Subash Desai, Nilesh Pandurang Sable, Meenakshi Haresh Thakur
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

ORIGINAL ARTICLES

Protection behaviors for cytotoxic drugs in oncology nurses of chemotherapy centers in Shiraz hospitals, South of Iran [pg. 227]
Khadijeh Abbasi, Maryam Hazrati, Abolfazl Mohammadbeigi, Jasem Ansari, Mahboubeh Sajadi, Azam Hosseinnazzhad, Esmail Moshiri
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Outcomes, cost comparison, and patient satisfaction during long-term central venous access in cancer patients: Experience from a Tertiary Care Cancer Institute in South India [pg. 232]
K Govind Babu, MC Suresh Babu, D Lokanatha, Gita R Bhat
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Effect of areca nut chewing and maximal mouth opening in schoolgoing children in Ahmedabad [pg. 239]
Azizfatema Munawer Khan, Megha S Sheth, Romsha R Purohit
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Clinicopathological features and outcomes in advanced nonsmall cell lung cancer with tailored therapy [pg. 242]
Stalin Bala, Sadashivudu Gundeti, Vijay Gandhi Linga, Lakshmi Srinivas Maddali, Raghunadha Rao Digumarti, Shantveer G Uppin
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Clinicopathological profile of gastrointestinal lymphomas in Kashmir [pg. 251]
Mehnaaz Sultan Khuroo, Summyia Farooq Khwaja, Ajaz Rather, Zhahid Hassan, Ruby Reshi, Naira Sultan Khuroo
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Metabolic toxicities in patients undergoing treatment for nonhematological malignancy: A cross-sectional study [pg. 256]
Subhash Gupta, Kunhi Parambath Haresh, Soumyajit Roy, Lakhan Kashyap, Narayan Adhikari, Rambha Pandey, Dayanand Sharma, Pramod Kumar Julka, Goura Kishor Rath
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Managing metastatic renal cell carcinoma-challenges, pitfalls, and outcomes in the real world [pg. 260]
Karnam Ashok Kumar, Gundeti Sadashivudu, KV Krishnamani, Vijay Gandhi Linga, Lakshmi Srinivas Maddali, Raghunadha Rao Digumarti
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Evaluation of thyroid lesions by fine-needle aspiration cytology based on Bethesda system for reporting thyroid cytopathology classification among the population of South Bihar [pg. 265]
Richa Bhartiya, Mahasweta Mallik, Nawanita Kumari, Brijendra Narayan Prasad
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Oxaliplatin-related neuropathy in Indian patients – no difference between generic and original molecules [pg. 271]
Bhawna Sirohi, Vikas Ostwal, Shaheenah Dawood, Gilberto Lopes, Sanjay Talole, Chaitali Nashikkar, Shailesh Shrikhande
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Burden of cervical cancer and role of screening in India [pg. 278]
Saurabh Bobdey, Jignasa Sathwara, Aanchal Jain, Ganesh Balasubramaniam
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Cognizance and utilization about breast cancer screening among the health professional female students and staffs of University Kuala Lumpur, Royal College of Medicine Perak, Malaysia [pg. 286]
ATM Emdadul Haque, Muhammad Afif Bin Mohd Hisham, Noor Azwa Laili Binti Ahmad Adzman, Nur Atiqah Binti Azudin, Nursakinah Binti Shafri, Mainul Haque
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

CASE REPORTS

Juvenile granulosa cell tumor associated with Ollier disease [pg. 293]
Abhilasha Ashok Sampagar, Rahul R Jahagirdar, Vibha Sanjay Bafna, Sandip P Bartakke
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Thymoma masquerading as transfusion dependent anemia [pg. 296]
Javvid Muzamil, Aejaz Aziz Shiekh, Gull Mohammad Bhat, Abdul Rashid Lone, Shuaeb Bhat, Firdousa Nabi
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

PRACTITIONER SECTION

A rare case of lung cancer presenting as an ischioanal fossa mass [pg. 300]
Nishitha Shetty, Ranvijay Singh, Maryam Naveed, Ashwini M Ronghe, Falguni Shashikant Barot
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Multiple solitary extramedullary anaplastic plasmacytomas [pg. 303]
Sandesh Madi, Vishnu Senthil, Monappa Naik, Sandeep Vijayan
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

LETTERS TO EDITOR

Folate supplementation in transfusion-dependent thalassemia: Do we really need such high doses? [pg. 305]
Gaurav Tripathi, Manas Kalra, Amita Mahajan
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Early tumor shrinkage as an "on-treatment" clinical predictor of long-term outcome in solid organ cancers [pg. 306]
Pratishtha Banga Chaudhari
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Cancer risk of general people due to using joss stick for religious worshiping [pg. 307]
Beuy Joob, Viroj Wiwanitkit
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

A rare case of hepatoid carcinoma of the ovary with pancytopenia and hypocellular marrow [pg. 307]
Manoj Lakhotia, Hans Raj Pahadiya, Akanksha Choudhary, Ronak Gandhi, Ramesh Chand Purohit
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Multiple cutaneous malignancies in a child with xeroderma pigmentosum: A case report [pg. 309]
Rita V Vora, RahulKrishna SureshKumar Kota, Nilofar G Diwan
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

The masquerading splenic lesion [pg. 311]
Mansoor C Abdulla, Jemshad Alungal, Ram Naryan, Neena Mampilly
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

ASCO 2016 GI CANCER UPDATE

Focused update on Gastrointestinal (GI) Oncology from ASCO 2016 [pg. 314]
Ravi Kumar Paluri
[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

ERRATUM

Erratum: Evaluation of myeloid cells (tumor associated tissue eosinophils and mast cells) infiltration in different grades of oral squamous cell carcinoma [pg. 319]

[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Erratum: Isolated humeral recurrence in endometrial carcinoma [pg. 320]

[ABSTRACT]   [HTML FULL TEXT]   [PDF]   [Mobile HTML Full text ]   [EPub]

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

High Mass Ion Detection with Charge Detector Coupled to Rectilinear Ion Trap Mass Spectrometer

Abstract

Conventional linear ion trap mass analyzers (LIT-MS) provide high ion capacity and show their MSⁿ ability; however, the detection of high mass ions is still challenging because LIT-MS with secondary electron detectors (SED) cannot detect high mass ions. To detect high mass ions, we coupled a charge detector (CD) to a rectilinear ion trap mass spectrometer (RIT-MS). Immunoglobulin G ions (m/z ~150,000) are measured successfully with controlled ion kinetic energy. In addition, when mass-to-charge (m/z) ratios of singly charged ions exceed 10 kTh, the detection efficiency of CD is found to be greater than that of SED. The CD can be coupled to LIT-MS to extend the detection mass range and provide the potential to perform MSⁿ of high mass ions inside the ion trap.

Graphical Abstract

ᅟ

http://ift.tt/2hMs5rW

Characterization of Lipid A Variants by Energy-Resolved Mass Spectrometry: Impact of Acyl Chains

Abstract

Lipid A molecules consist of a diglucosamine sugar core with a number of appended acyl chains that vary in their length and connectivity. Because of the challenging nature of characterizing these molecules and differentiating between isomeric species, an energy-resolved MS/MS strategy was undertaken to track the fragmentation trends and map genealogies of product ions originating from consecutive cleavages of acyl chains. Generalizations were developed based on the number and locations of the primary and secondary acyl chains as well as variations in preferential cleavages arising from the location of the phosphate groups. Secondary acyl chain cleavage occurs most readily for lipid A species at the 3′ position, followed by primary acyl chain fragmentation at both the 3′ and 3 positions. In the instances of bisphosphorylated lipid A variants, phosphate loss occurs readily in conjunction with the most favorable primary and secondary acyl chain cleavages.

Graphical Abstract

ᅟ

http://ift.tt/2hMtheQ

Development of a Magnetic Microbead Affinity Selection Screen (MagMASS) Using Mass Spectrometry for Ligands to the Retinoid X Receptor-α

Abstract

To overcome limiting factors in mass spectrometry-based screening methods such as automation while still facilitating the screening of complex mixtures such as botanical extracts, magnetic microbead affinity selection screening (MagMASS) was developed. The screening process involves immobilization of a target protein on a magnetic microbead using a variety of possible chemistries, incubation with mixtures of molecules containing possible ligands, a washing step that removes non-bound compounds while a magnetic field retains the beads in the microtiter well, and an organic solvent release step followed by LC-MS analysis. Using retinoid X receptor-α (RXRα) as an example, which is a nuclear receptor and target for anti-inflammation therapy as well as cancer treatment and prevention, a MagMASS assay was developed and compared with an existing screening assay, pulsed ultrafiltration (PUF)-MS. Optimization of MagMASS involved evaluation of multiple protein constructs and several magnetic bead immobilization chemistries. The full-length RXRα construct immobilized with amylose beads provided optimum results. Additional enhancements of MagMASS were the application of 96-well plates to enable automation, use of UHPLC instead of HPLC for faster MS analyses, and application of metabolomics software for faster, automated data analysis. Performance of MagMASS was demonstrated using mixtures of synthetic compounds and known ligands spiked into botanical extracts.

Graphical Abstract

ᅟ

http://ift.tt/2hMotGs

pH Effects on Electrospray Ionization Efficiency

Abstract

Electrospray ionization efficiency is known to be affected by mobile phase composition. In this paper, a detailed study of analyte ionization efficiency dependence on mobile phase pH is presented. The pH effect was studied on 28 compounds with different chemical properties. Neither pK _a nor solution phase ionization degree by itself was observed to be sufficient at describing how aqueous phase pH affects the ionization efficiency of the analyte. Therefore, the analyte behavior was related to various physicochemical properties via linear discriminant analyses. Distinction between pH-dependent and pH-independent compounds was achieved using two parameters: number of potential charge centers and hydrogen bonding acceptor capacity (in the case of 80% acetonitrile) or polarity of neutral form of analyte and pK _a (in the case of 20% acetonitrile). It was also observed that decreasing pH may increase ionization efficiency of a compound by more than two orders of magnitude.

Graphical Abstract

ᅟ

http://ift.tt/2hMq92G

Thank You

--

Αλέξανδρος Γ. Σφακιανάκης

Αναπαύσεως 5 Άγιος Νικόλαος Λασιθίου 72100

2841026182

6948891480