Πληροφορίες

Η φωτογραφία μου
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com, https://plus.google.com/communities/115462130054650919641?sqinv=VFJWaER0c2NCRl9ERzRjZWhxQmhzY09kVV84cjRn , ,https://plus.google.com/u/0/+AlexandrosGSfakianakis , https://www.youtube.com/channel/UCQH21WX8Qn5YSTKrlJ3OrmQ , https://www.youtube.com/channel/UCTREJHxB6yt4Gaqs4-mLzDA , https://twitter.com/g_orl?lang=el, https://www.instagram.com/alexandrossfakianakis/,

Δημοφιλείς αναρτήσεις

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Τρίτη, 5 Απριλίου 2016

IJERPH, Vol. 13, Pages 404: A Cascade of Champions: A Qualitative Study about the MA-CORD Media Competition Implementation

A media competition was part of the Massachusetts Childhood Obesity Research Demonstration (MA-CORD) Study. Criss et al., previously outlined the development and implementation of the competition, including variation in reach and adoption of the intervention across schools and afterschool programs. In this qualitative study, we examine community, provider, and organizational factors that explain the variation of media competition reach in school and afterschool programs, and describe the awareness of the media competition across other community sectors. Durlak and DuPre’s ecological framework for understanding effective implementation provided the theoretical underpinnings for this study. Fifty-four key informant interviews were conducted, transcribed, and analyzed. Organizational capacity of committed teachers/staff and adaptability of the media competition seemed to be drivers for higher reach within school and afterschool programs. Salient themes that emerged as facilitators of effective implementation were having a cascade of champions and providing opportunity to participate in the media competition outside traditional class time. Clinics and coalitions were identified as additional sectors aware of the media competition. Specifically, our findings offer a new perspective on intervention design and a recommended direction for further study.

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IJMS, Vol. 17, Pages 412: Comparative Analysis of Volatile Composition in Chinese Truffles via GC × GC/HR-TOF/MS and Electronic Nose

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To compare the volatile compounds of Chinese black truffle and white truffle from Yunnan province, this study presents the application of a direct solvent extraction/solvent-assisted flavor evaporation (DSE-SAFE) coupled with a comprehensive two-dimensional gas chromatography (GC × GC) high resolution time-of-flight mass spectrometry (HR-TOF/MS) and an electronic nose. Both of the analytical methods could distinguish the aroma profile of the two samples. In terms of the overall profile of truffle samples in this research, more kinds of acids were detected via the method of DSE-SAFE. Besides, compounds identified in black truffle (BT), but not in white truffle (WT), or vice versa, and those detected in both samples at different levels were considered to play an important role in differentiating the two samples. According to the analysis of electronic nose, the two samples could be separated, as well.

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IJMS, Vol. 17, Pages 500: Association between Pre-Transplant Serum Malondialdehyde Levels and Survival One Year after Liver Transplantation for Hepatocellular Carcinoma

Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT.

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Curcumin Downregulates Phosphate Carrier and Protects against Doxorubicin Induced Cardiomyocyte Apoptosis

Aim. To explore the effects of curcumin on phosphate carrier (PiC) and its role in protection against doxorubicin induced myocyte toxicity. Methods. Using H9c2 cell line, the cardiotoxic effect of doxorubicin and its mitigation by curcumin were studied. H9c2 cells were cultured with doxorubicin and/or curcumin at various concentrations. Analysis for apoptosis of H9c2 was done using flow cytometry. Confocal laser scanning microscopy was used to record the fluorescence intensity ratios and to determine the mitochondrial permeability transition pore (MPTP) opening state. Oxidative stress was measured using glutathione level, superoxide dismutase activities, and malondialdehyde content. The effect of doxorubicin and curcumin on PiC gene expression was measured by real-time PCR. Results. Curcumin decreased mRNA of PiC and was partly protective against oxidative stress, loss of mitochondrial transmembrane potential, and apoptosis induced by doxorubicin. Interestingly, the effect was not clearly dose dependent and the concentration of 12 mg/L was more efficient than 15 and 10 mg/L. Conclusion. Curcumin downregulates PiC and partly protects against doxorubicin induced oxidative stress and myocyte apoptosis.

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On a Generalization of the Hilbert Frame Generated by the Bilinear Mapping

The concept of -frame which is a generalization of the frame in Hilbert spaces generated by the bilinear mapping is considered. -frame operator is defined; analogues of some well-known results of frame theory are obtained in Hilbert spaces. Conditions for the existence of -frame in Hilbert spaces are obtained; the relationship between the definite bounded surjective operator and -frame is also studied. The concept of -orthonormal -basis is introduced.

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Measurement of Circulating 1,25-Dihydroxyvitamin D: Comparison of an Automated Method with a Liquid Chromatography Tandem Mass Spectrometry Method

Background. The clinical relevance of circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) is probably underappreciated, but variations in the measurement of this difficult analyte between different methods limit comparison of results. Methods. In 129 clinical samples, we compared a new automated assay with a commercially available liquid chromatography tandem mass spectrometry (LC-MS/MS) kit. Results. Median (interquartile range) 1,25(OH)2D concentrations with the automated assay and the LC-MS/MS method were 26.6 pg/mL (18.5–39.0 pg/mL) and 23.6 pg/mL (16.1–31.3 pg/mL), respectively (). Using the method-specific cut-offs for deficient 1,25(OH)2D levels (

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Hall Effect Devices with Three Terminals: Their Magnetic Sensitivity and Offset Cancellation Scheme

This paper discusses properties of Hall effect sensors with only three terminals and compares them to conventional four-terminal devices. It covers both Horizontal and Vertical Hall effect devices. Their Hall-geometry factor is computed analytically. Several modes of operation are proposed and their signal-to-noise ratio is compared. A six-phase offset cancellation scheme is developed. All theoretical results are checked by measurements. The residual offset of Vertical Hall effect devices with three contacts is found to be smaller than the offset of conventional Vertical Hall effect devices with five contacts.

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Organization Learning Oriented Approach with Application to Discrete Flight Control

In nature and society, there exist many learning modes; thus, in this paper the goal is to incorporate features from the social organizations to improve the learning of intelligent systems. Inspired by future prediction, in the high level, the discrete dynamics is further written into the equivalent prediction model which can provide the bridge from now to the future. In the low level, the efficiency could be improved in way of group learning. The philosophy is integrated into discrete neural flight control where the cascade dynamics is written into the prediction form and the minimal-learning-parameter technique is designed for parameter learning. The effectiveness of the proposed method is verified with simulation.

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Phytochemical Composition, Antifungal and Antioxidant Activity of Duguetia furfuracea A. St.-Hill

Background. Duguetia furfuracea is popular plant used in popular medicine. Hypothesis/Purpose. This claim evaluated the phytochemical composition of the hydroethanolic extract (HEDF), fractions of Duguetia furfuracea, and antioxidant and antifungal activity. Methods. The chemical profile was carried out by HPLC-DAD. The total phenolic contents and flavonoid components were determined by Folin-Ciocalteu and aluminium chloride reaction. The antioxidant activity was measured by scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and ferric reducing ability of plasma (FRAP) methods. The antifungal activity was determined by microdilution assay. Results. HPLC analysis revealed caffeic acid and rutin as major compounds (HEDF), caffeic acid and quercitrin (Mt-OH fraction), and quercitrin and isoquercitrin (Ac-OEt fraction). The highest levels of phenols and total flavonoids were found for Ac-OEt fraction, and the crude extract showed higher in vitro antioxidant potential. The antifungal activity showed synergic effect with fluconazole and EHDF against C. krusei, fluconazole and Mt-OH against C. krusei and C. tropicalis, and Ac-OE and fluconazole against C. albicans. Conclusion. The highest levels of phenols and total flavonoids were marked with antioxidant effect. This is the first report of bioactivity of the synergic effect of HEDF and fractions. More studies would be required to better clarify its mechanism of synergic action.

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Microwave-Assisted Solvent-Free Synthesis of Zeolitic Imidazolate Framework-67

A microporous metal-organic framework (MOF), cobalt-based zeolitic imidazolate framework-67 (ZIF-67), was synthesized by the combination of solvent-free hand-mill and microwave irradiation, without any organic solvent and within 30 minutes. The hand-milling process can mix the reactants well by the virtue of high moisture/water absorption capacity of reactants. In addition, the outstanding electromagnetic wave absorption capability of cobalt leads to efficient conversion to MOF structures before carbonization. The obtained ZIF-67 possesses high surface area and micropore volume.

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Fecal Microbiota Transplantation Using Upper Gastrointestinal Tract for the Treatment of Refractory or Severe Complicated Clostridium difficile Infection in Elderly Patients in Poor Medical Condition: The First Study in an Asian Country

Background and Aims. Fecal microbiota transplantation (FMT) is a highly effective treatment option for refractory Clostridium difficile infection (CDI). FMT may be challenging in patients with a low performance status, because of their poor medical condition. The aims of this study were to describe our experience treating patients in poor medical condition with refractory or severe complicated CDI using FMT via the upper GI tract route. Methods. This study was a retrospective review of seven elderly patients with refractory or severe complicated CDI and a poor medical condition who were treated with FMT through the upper GI tract route from May 2012 through August 2013. The outcomes studied included the cure rate of CDI and adverse events. Results. Of these seven patients who received FMT via the upper GI tract route, all patients were cured. During the 11-month follow-up period, CDI recurrence was observed in two patients; rescue FMT was performed in these patients, which led to a full cure. Vomiting was observed in two patients. Conclusions. FMT via the upper gastrointestinal tract route may be effective for the treatment of refractory or severe complicated CDI in patients with a low performance status. Physicians should be aware of adverse events, especially vomiting.

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Mathematical Model of Three Age-Structured Transmission Dynamics of Chikungunya Virus

We developed a new age-structured deterministic model for the transmission dynamics of chikungunya virus. The model is analyzed to gain insights into the qualitative features of its associated equilibria. Some of the theoretical and epidemiological findings indicate that the stable disease-free equilibrium is globally asymptotically stable when the associated reproduction number is less than unity. Furthermore, the model undergoes, in the presence of disease induced mortality, the phenomenon of backward bifurcation, where the stable disease-free equilibrium of the model coexists with a stable endemic equilibrium when the associated reproduction number is less than unity. Further analysis of the model indicates that the qualitative dynamics of the model are not altered by the inclusion of age structure. This is further emphasized by the sensitivity analysis results, which shows that the dominant parameters of the model are not altered by the inclusion of age structure. However, the numerical simulations show the flaw of the exclusion of age in the transmission dynamics of chikungunya with regard to control implementations. The exclusion of age structure fails to show the age distribution needed for an effective age based control strategy, leading to a one size fits all blanket control for the entire population.

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Oral immunotherapy with low allergenic hydrolysed egg in egg allergic children

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Abstract

Background

A major drawback of oral immunotherapy for food allergy, is the possibility of severe side effects. We assessed both safety and efficacy of a low allergenic hydrolysed egg (HydE) preparation used in a double-blind placebo controlled randomized study in egg allergic children.

Methods

In a pilot multicentre study, 29 egg allergic patients (aged 1-5.5 years) were administered daily for 6 months 9g HydE or placebo in a blinded, randomised manner. Safety was verified by oral food challenge to assess tolerance towards HydE at the start, and efficacy by an open oral food challenge (OFC, primary outcome) at the end. Additionally, changes in basophil activation and specific IgE and IgG4 were assessed.

Results

All egg allergic patients randomized to HydE (n=15) tolerated the full dose at day 1 and received the maintenance dose from the start at home. No statistically significant difference was observed on the final OFC (36% and 21% had a negative OFC in the treatment and placebo groups, respectively). Specific IgG4 levels increased, while both CD203c+ and CD63+ basophils decreased significantly more over time in the treatment than in the placebo group.

Conclusions

HydE can be regarded as a safe, low allergenic product to use in children allergic to egg. Although not significant, HydE given for 6 months increased numerically the proportion of patients becoming tolerant to egg. HydE induced a modulation of the immune response towards better tolerance. A longer treatment period and/or a higher dose may improve the clinical outcome and should be evaluated.

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Combined Blockade of the Histamine H1 and H4 Receptor Suppresses Peanut-Induced Intestinal Anaphylaxis by Regulating Dendritic Cell Function

Abstract

Background

Signaling through histamine receptors on dendritic cells (DCs) may be involved in the effector phase of peanut-induced intestinal anaphylaxis.

Objectives

To determine the role of histamine H1 (H1R) and H4 receptors (H4R) in intestinal allergic responses in a model of peanut allergy.

Methods

Balb/c mice were sensitized and challenged to peanut. During the challenge phase, mice were treated orally with the H1R antagonist, loratadine, and/or the H4R antagonist, JNJ7777120. Bone marrow-derived DCs (BMDCs) were adoptively transferred to non-sensitized WT mice. Symptoms, intestinal inflammation, mesenteric lymph node and intestine mucosal DCs were assessed. Effects of the drugs on DC chemotaxis, calcium mobilization, and antigen-presenting cell function were measured.

Results

Treatment with loratadine or JNJ7777120 individually partially suppressed development of diarrhea and intestinal inflammation and decreased the numbers of DCs in the mesenteric lymph nodes and lamina propria. Combined treatment with both drugs prevented development of diarrhea and intestinal inflammation. In vitro, the combination suppressed DC antigen presenting cell function to T helper cells and DC calcium mobilization and chemotaxis to histamine.

Conclusion

Blockade of both H1R and H4R in the challenge phase had additive effects in preventing the intestinal consequences of peanut sensitization and challenge. These effects were mediated through limitation of mesenteric lymph node and intestinal DC accumulation and function. Identification of this histamine-H1R/H4R-DC-CD4+ T cell axis provides new insights into the development of peanut-induced intestinal allergic responses and for prevention and treatment of peanut allergy.

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Increased microRNA-323-3p in IL-22/IL-17-producing T cells and asthma: a role in the regulation of the TGF-β pathway and IL-22 production

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Abstract

Background

IL-22- and IL-17-producing T cells have important roles in allergic diseases. microRNAs (miRNAs) are post-transcriptional regulators of gene expression and modulate numerous biological processes. Little is known about the functions of miRNAs in IL-22/IL-17-producing T cells.

Material and Methods

IL-22- and IL-17-positive T cells were sorted from human peripheral blood mononuclear cells (PBMCs) by intracellular staining and dual secretion assay. miRNA expression profiles were detected with TaqMan array microfluidic cards. T cells were transfected with miRNA mimics. Gene expression was analyzed using RT-qPCR and/or enzyme-linked immunosorbent assay in T cell subsets and PBMCs from patients with asthma and atopic dermatitis.

Results

The increased expression of miR-323-3p and non-coding RNA nc886 and reduced expression of miR-93, miR-181a, miR-26a and miR-874 were detected in IL-22-producing T cells. The pathway analysis of the putative targets suggested that these differentially expressed miRNAs could impact the proliferation, differentiation and effector functions of T cells. Further analyses showed the highest expression for miR-323-3p in IL-22- and IL-17-double-positive T cells and its capacity to suppress multiple genes from the transforming growth factor β pathway and the production of IL-22 in T cells. An increased expression of miR-323-3p in PBMCs from asthma patients and reverse correlation between miR-323-3p levels and IL-22 production in PBMCs cultured in T cell growth conditions was observed.

Conclusions

Our data suggest that miR-323-3p acts in a negative feedback loop to control the production of IL-22 in IL-22/IL-17-producing T cells and might thus impact the T cell responses in asthma.

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A chink in the armour of breast cancer cells

Working with human breast cancer cells, a team of scientists from Ann & Robert H. Lurie Children's Hospital of Chicago have successfully turned off a misbehaving protein that fuels the growth of a particularly aggressive, drug-resistant form of the...

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Three glycosyltransferases identified as significant mutational targets in colon cancer

Little is known about the molecular basis of aberrant protein glycosylation, a complex enzymatic process that is a hallmark of many human cancers including colorectal cancers (CRC), and how it may contribute to tumour progression. In a new study...

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Fra snus til rus

Ideen om at snus eller e-sigaretter er inngangsporter til røyking eller andre rusmidler er besnærende.

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Renormalized solutions of the 2D Euler equations

In this paper we prove that solutions of the 2D Euler equations in vorticity formulation obtained via vanishing viscosity approximation are renormalized.

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Renormalized solutions to the continuity equation with an integrable damping term

We consider the continuity equation with a nonsmooth vector field and a damping term. In their fundamental paper, DiPerna and Lions (Invent Math 98:511–547, 1989) proved that, when the damping term is bounded in space and time, the equation is well posed in the class of distributional solutions and the solution is transported by suitable characteristics of the vector field. In this paper, we prove existence and uniqueness of renormalized solutions in the case of an integrable damping term, employing a new logarithmic estimate inspired by analogous ideas of Ambrosio et al. (Rendiconti del Seminario Fisico Matematico di Padova 114:29–50, 2005), Crippa and De Lellis (J Reine Angew Math 616:15–46, 2008) in the Lagrangian case.

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Dextran based nanosized carrier for the controlled and targeted delivery of curcumin to liver cancer cells

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Thayyath Sreenivasan Anirudhan, Binusreejayan
Curcumin (Cur), a poly phenolic yellow colored compound present in Indian spice turmeric, has a wide variety of biological properties. Bioavailability of Cur is limited by its low water solubility, rapid metabolism and low stability. In the present study, we mainly focus on synthesis and characterization of dextran based nano-sized drug carrier (GHDx) for the delivery of Cur. A liver targeting moiety is incorporated in GHDx so as to improve the therapeutic efficiency and decrease adverse effects of conventional cancer therapy. The effect of different parameters on grafting variables was studied. GHDx was characterised by FTIR, 1H NMR XRD, TG/DTG, TEM, SEM, AFM, DLS and zeta potential analyses. Adsorption experiments were carried out for drug loading. Swelling of GHDx was studied as a function of pH and temperature. Three step release of Cur from GHDx was confirmed by analyzing in vitro release data in simulated intracellular pH using different kinetic models. In vitro cytotoxicity analysis on L929 and Hep G2 cells shows that GHDx is safe carrier while Cur loaded GHDx exhibits high toxicity with slow drug release towards hepatic cells. The results show that the GHDx can be customized as a stimuli sensitive potential carrier for the delivery of drugs.



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Molecular cloning and structural characterization of Ecdysis Triggering Hormone from Choristoneura fumiferana

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Bhagath Kumar P., Kasi Viswanath K., Tuleshwori Devi S., Sampath Kumar R., Daniel Doucet, Arthur Retnakaran, Peter J. Krell, Qili Feng, Dinakara Rao Ampasala
At the end of each stadium, insects undergo a precisely orchestrated process known as ecdysis which results in the replacement of the old cuticle with a new one. This physiological event is necessary to accommodate growth in arthropods since they have a rigid chitinous exoskeleton. Ecdysis is initiated by the direct action of Ecdysis Triggering Hormones on the central nervous system. Choristoneura fumiferana is a major defoliator of coniferous forests in Eastern North America. It is assumed that, studies on the ecdysis behavior of this pest might lead to the development of novel pest management strategies. Hence in this study, the cDNA of CfETH was cloned. The open reading frame of the cDNA sequence was found to encode three putative peptides viz., Pre-Ecdysis Triggering Hormone (PETH), Ecdysis Triggering Hormone (ETH), and Ecdysis Triggering Hormone Associated Peptide (ETH-AP). The CfETH transcript was detected in the epidermal tissue of larval and pupal stages, but not in eggs and adults. In order to explore the structural conformation of ETH, ab initio modelling and Molecular Dynamics (MD) Simulations were performed. Further, a library of insecticides was generated and virtual screening was performed to identify the compounds displaying high binding capacity to ETH.



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IFC: Editorial Board

Publication date: June 2016
Source:International Journal of Biological Macromolecules, Volume 87





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Dextran-PLGA-loaded docetaxel micelles with enhanced cytotoxicity and better pharmacokinetic profile

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Kaisar Raza, Nitesh Kumar, Charu Misra, Lokesh Kaushik, Santosh Kumar Guru, Pramod Kumar, Ruchi Malik, Shashi Bhushan, O.P. Katare
Docetaxel is one of the promising drugs and employed for the management of variety of cancers. However, challenges like poor-bioavailability, low tissue-permeability, compromised aqueous solubility and dose-dependent side-effects limit its clinical applications. Whereas, PLGA–based polymeric micelles possess the ability to enhance the tissue permeability of drugs and increase their biocompatibility. Henceforth, it was aimed to fabricate the dextran-PLGA-based polymeric-micelles loaded with docetaxel to explore the potential benefits in drug delivery. Dextran was chemically linked to PLGA and the linkage was confirmed by FT-IR, UV and NMR-spectroscopy. Critical-micelle-concentration of amphiphilic polymer was determined and drug was encapsulated by diffusion technique and erythrocyte compatibility. The system was evaluated for drug release profile and in vitro cytotoxicity studies. The pharmacokinetic profile was studied in rats. The micelles obtained were of 96.5±2.5nm and offered drug encapsulation of order of 54.85±1.21%.The cytotoxicity of drug against MCF-7 and MDA-MB-231 cell lines was enhanced by approx. 100%. The pharmacokinetic profile was substantially modified and about 16-folds enhancement in bioavailability was observed vis-à-vis plain drug. The approach was not only able to control the drug release, but also offered promise to enhance the pharmacokinetic and pharmacodynamic potential of docetaxel and similar anticancer agents.



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Comments on “Prevalence of contact allergy in the general population in different European regions” and “Prevalence of fragrance contact allergy in the general population of five European countries”

Abstract

We read with interest the two articles by Diepgen TL et al.1,2 on the prevalence of contact allergy, and the prevalence of fragrance contact allergy in the general population. The possibility to draw conclusions about the occurrence of disease in the general population from prevalence studies depends on the representativeness of the studied sample. In Materials and Methods is stated “A random sample was selected from the general population, based on electoral precincts…” and “The study followed a stratified, proportional, sampling-with-replacement design.”

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Rescue therapy with anti-programmed cell death protein 1 inhibitors (PD-1) of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in 5 cases

Abstract

Locally unresectable and metastatic cutaneous squamous cell carcinomas pose a therapeutic challenge. Their overall response to chemotherapy, radiation and/or EGFR inhibitors is poor. Five consecutive heavily pretreated advanced patients with progressive cutaneous squamous cell carcinoma (four cases) or basosquamous carcinoma (one case) received an immune checkpoint inhibitor, either nivolumab or pembrolizumab, directed at PD-1 receptor. Two patients with large necrotic lesions obtained partial responses and three cases experienced stabilization of their disease. Responses were observed within three months and persisted beyond 6 months. Tolerance to treatment was good with no significant toxicity. Two patients died after 5.5 and 6 months due to complications unrelated to anti-PD1 therapy. Limited genomic profiling showed all tumors had a high overall mutation burden. Our observations suggest that anti-PD-1 inhibitors may have a clinically meaningful activity in aggressive advanced cutaneous squamous cell cancers refractory to standard therapy. The value of PD-1 blocking agents in aggressive non-melanoma skin cancers needs to be confirmed in prospective trials.

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VIP, whose receptor-mediated signalling may be defective in alopecia areata, provides protection from hair follicle immune privilege collapse

Summary

Background

Alopecia areata (AA) is an autoimmune disorder whose pathogenesis involves the collapse of the relative immune privilege (IP) of the hair follicle (HF). Given that vasoactive intestinal peptide (VIP) is an immunoinhibitory neuropeptide released by perifollicular sensory nerve fibres, which plays a role in IP maintenance, it may modulate human HF-IP and thus therapeutically relevant for AA.

Objectives

Do human HFs express VIP receptors, and does their stimulation protect from or restore experimentally induced HF-IP collapse? Is VIP signalling defective in AA HFs?

Methods

First, VIP and VIP receptors (VPAC1, VPAC2) expression in human scalp HFs and AA skin was assessed. In HF organ culture, we then explored whether VIP treatment can restore and/or protect from interferonγ-induced HF-IP collapse, assessing the expression of the key IP markers by quantitative (immuno-)histomorphometry.

Results

Here, we provide the first evidence that VIP receptors are expressed in the epithelium of healthy human HFs at the gene and protein level and that VIP receptor protein expression, but not VIP+ nerve fibres, is significantly down-regulated in lesional hair bulbs of AA patients, suggesting defects in VIP receptor-mediated signalling. Moreover, we show that VIP protects the HF from experimentally induced IP collapse in vitro, but does not fully restore it once collapsed.

Conclusions

These pilot data suggest that insufficient VIP receptor-mediated signalling may contribute to impairing HF-IP in AA patients and that VIP is a promising candidate “HF-IP guardian” that may be therapeutically exploited to inhibit the progression of AA lesions

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Ichthyosis as the dermatological phenotype associated to TTC7A mutations

Abstract

The phenotype associated to spontaneous mutation in the Tetratricopeptide Repeat Domain 7A (TTC7A) in the flaky skin (fsn) mice1 combines gastric hyperplasia, hyperproliferative immune disorder and skin anomalies. All fsn mice progressively develop thick white scales and patchy alopecia that turns into papulo-squamous lesions, marked hyperkeratosis and hypergranulosis associated to a dermal mixed inflammatory infiltrate on skin biopsy2,3. To date, the fsn mouse constitutes a model for human psoriasis vulgaris3.

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Free Transverse Vibration Analysis of Axially Functionally Graded Tapered Euler-Bernoulli Beams through Spline Finite Point Method

A new model for the free transverse vibration of axially functionally graded (FG) tapered Euler-Bernoulli beams is developed through the spline finite point method (SFPM) by investigating the effects of the variation of cross-sectional and material properties along the longitudinal directions. In the proposed method, the beam is discretized with a set of uniformly scattered spline nodes along the beam axis instead of meshes, and the displacement field is approximated by the particularly constructed cubic B-spline interpolation functions with good adaptability for various boundary conditions. Unlike traditional discretization and modeling methods, the global structural stiffness and mass matrices for beams of the proposed model are directly generated after spline discretization without needing element meshes, generation, and assembling. The proposed method shows the distinguished features of high modeling efficiency, low computational cost, and convenience for boundary condition treatment. The performance of the proposed method is verified through numerical examples available in the published literature. All results demonstrate that the proposed method can analyze the free vibration of axially FG tapered Euler-Bernoulli beams with various boundary conditions. Moreover, high accuracy and efficiency can be achieved.

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Effect of Opioid on Adult Hippocampal Neurogenesis

During the past decade, the study of the mechanisms and functional implications of adult neurogenesis has significantly progressed. Many studies focus on the factors that regulate proliferation and fate determination of adult neural stem/progenitor cells, including addictive drugs such as opioid. Here, we review the most recent works on opiate drugs’ effect on different developmental stages of adult hippocampal neurogenesis, as well as the possible underlying mechanisms. We conclude that opiate drugs in general cause a loss of newly born neural progenitors in the subgranular zone of dentate gyrus, by either modulating proliferation or interfering with differentiation and maturation. We also discuss the consequent impact of regulation of adult neurogenesis in animal’s opioid addiction behavior. We further look into the future directions in studying the convergence between the adult neurogenesis field and opioid addiction field, since the adult-born granular cells were shown to play a role in neuroplasticity and may help to reduce the vulnerability to drug craving and relapse.

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Venovenous Extracorporeal Membrane Oxygenation in Intractable Pulmonary Insufficiency: Practical Issues and Future Directions

Venovenous extracorporeal membrane oxygenation (vv-ECMO) is a highly invasive method for organ support that is gaining in popularity due to recent technical advances and its successful application in the recent H1N1 epidemic. Although running a vv-ECMO program is potentially feasible for many hospitals, there are many theoretical concepts and practical issues that merit attention and require expertise. In this review, we focus on indications for vv-ECMO, components of the circuit, and management of patients on vv-ECMO. Concepts regarding oxygenation and decarboxylation and how they can be influenced are discussed. Day-to-day management, weaning, and most frequent complications are covered in light of the recent literature.

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Study of Tribological Behavior of Silicon Carbide Based Aluminum Metal Matrix Composites under Dry and Lubricated Environment

Friction and wear behavior of silicon carbide based aluminum metal matrix composite and aluminum matrix alloy have been studied for sliding speeds of 3.14 m/s and 3.77 m/s and load range from 10 N to 30 N under dry and lubricated environment, respectively. The experiments were performed on pin on disk tribometer (Make: DUCOM). The composite was fabricated by stir casting process and has several challenges like inferior bonds and interfacial reaction products which will deteriorate the mechanical and tribological properties. Therefore, addition of reactive metal like magnesium (Mg) should be done which will lead to reduced solidification shrinkage, lower tendency towards hot tearing, and faster process cycles. Results have revealed that the developed composites have lower coefficient of friction and wear rates when compared with aluminum matrix alloy under dry and lubricated environment. Experimental results show that under dry condition coefficient of friction of both the matrix alloy and the composite decreases with increase in load, whereas it increases with increase in sliding speeds; on the other hand wear rates of both aluminum matrix alloy and the composites increase with increase in load as well as with sliding speeds. FESEM of worn surfaces are also used to understand the wear mechanisms.

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ROS-Mediated NLRP3 Inflammasome Activation in Brain, Heart, Kidney, and Testis Ischemia/Reperfusion Injury

Ischemia and reperfusion (I/R) causes a reduction in arterial blood supply to tissues, followed by the restoration of perfusion and consequent reoxygenation. The reestablishment of blood flow triggers further damage to the ischemic tissue through reactive oxygen species (ROS) accumulation, interference with cellular ion homeostasis, and inflammatory responses to cell death. In normal conditions, ROS mediate important beneficial responses. When their production is prolonged or elevated, harmful events are observed with peculiar cellular changes. In particular, during I/R, ROS stimulate tissue inflammation and induce NLRP3 inflammasome activation. The mechanisms underlying the activation of NLRP3 are several and not completely elucidated. It was recently shown that NLRP3 might sense directly the presence of ROS produced by normal or malfunctioning mitochondria or indirectly by other activators of NLRP3. Aim of the present review is to describe the current knowledge on the role of NLRP3 in some organs (brain, heart, kidney, and testis) after I/R injury, with particular regard to the role played by ROS in its activation. Furthermore, as no specific therapy for the prevention or treatment of the high mortality and morbidity associated with I/R is available, the state of the art of the development of novel therapeutic approaches is illustrated.

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Capsular hook-assisted implantation of modified capsular tension ring

A 16-year-old boy presented with decrease of vision over a period of 2 years. On examination, he was diagnosed to have microspherophakia with lenticular myopia with secondary glaucoma in both eyes. He was treated by lens aspiration and two-point capsular support using a modified capsular tension ring (M-CTR) and capsular tension segment (CTS) sutured to the sclera along with implantation of a foldable intraocular lens inside the bag. Lens aspiration was performed without artificial capsular hook support of the bag, as the lens was soft and vitreous was formed. However, M-CTR rotation into the bag was fraught with repeated adherence of the advancing end of the M-CTR into the loose bag causing simultaneous rotation of the bag with the rotation of the ring resulting in transient increase in bag subluxation. Capsular hooks provided appropriate countertraction to the unsupported bag, thus facilitating easy insertion and rotation of the ring into the bag.



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Choir singing boosts immune system activity in cancer patients and carers

Singing in a choir for just one hour boosts levels of immune proteins in people affected by cancer, reduces stress and improves mood, which in turn could have a positive impact on overall health, a new study by Tenovus Cancer Care and the Royal College of...

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Association between ECE1 gene polymorphisms and risk of intracerebral haemorrhage

Objective

To determine whether endothelin converting enzyme-1 (ECE1) gene polymorphisms contribute to susceptibility to intracerebral haemorrhage (ICH) by influencing blood pressure.

Methods

This case–control study enrolled patients with ICH and healthy control subjects from a Southern Han Chinese population. The ECE1 gene polymorphisms rs212528 and rs213045 were genotyped. The association between the genotypes and the risk of ICH was assessed. The effects of these two ECE1 gene polymorphisms on blood pressure were also analysed.

Results

A total of 389 patients with ICH and 404 healthy control subjects participated in the study. There was no significant association between the ECE1 rs212528 and rs213045 polymorphisms and ICH even after adjusting for different confounding variables. In patients with ICH, the systolic blood pressure of patients with the rs212528 AA genotype was significantly lower than that of patients with the AG/GG genotypes.

Conclusions

These results indicated that the ECE1 rs212528 and rs213045 polymorphisms had no major role to play in the genetic susceptibility to ICH, although rs212528 might influence blood pressure in patients with ICH.



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A 5-year analysis of semen parameters in Saudi Arabian men attending infertility clinics

Objective

To evaluate semen parameters in infertile Saudi Arabian men.

Methods

In this retrospective study, semen analysis and other clinical data were extracted from medical records of men attending an infertility clinic. Patients were stratified according to smoking status and presence or absence of varicocele.

Results

The study included 425 patients. Nonsmokers (n = 322) had significantly higher serum testosterone and sperm motility than smokers (n = 194). Serum testosterone, semen volume, motility, morphology, sperm/ejaculation and sperm count were significantly higher in patients without varicocele (n = 328) than in those with varicocele (n = 188).

Conclusions

In this study, smoking and the presence of varicocele had negative effects on semen parameters in infertile men.



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Study of the relationship between male erectile dysfunction and type 2 diabetes mellitus/metabolic syndrome and its components

Aim

To study the relationship between erectile dysfunction and type 2 diabetes mellitus (T2DM)/metabolic syndrome (MetS).

Methods

This prospective study invited male patients with T2DM attending for a routine outpatient check-up to complete two questionnaires. A general questionnaire was used to collect demographic and clinical characteristics, while sexual function was assessed using the International Index of Erectile Function scoring system. The prevalence of MetS in this patient population was determined using information from the general questionnaire. Risk factors for erectile dysfunction were identified using univariate and multivariate logistic regression analyses.

Results

A total of 175 patients provided valid questionnaires; of these, 148 (84.6%) had MetS. The prevalence of erectile dysfunction was 90.9% (159/175) in the entire survey population compared with 89.2% (132/148) in patients with MetS. Multivariate logistic regression analysis identified the following risk factors for erectile dysfunction in patients with T2DM and/or MetS: age, blood pressure and duration of diabetes.

Conclusion

These current findings suggest that the MetS and its components have a negative impact on male erectile function.



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Polymorphism 2184A/G in the AGER gene is not associated with diabetic retinopathy in Han Chinese patients with type 2 diabetes

Objective

To assess the association between the 2184A/G polymorphism in the advanced glycosylation end product-specific receptor (AGER) gene and the susceptibility to diabetic retinopathy (DR) in Han Chinese patients with type 2 diabetes mellitus (T2DM).

Methods

This cross-sectional genotyping study included patients with T2DM with and without DR. Genotype and allele frequencies of the 2184A/G polymorphism were detected using polymerase chain reaction–restriction fragment-length polymorphism analysis.

Results

This study included 943 patients with T2DM (285 with DR [DR group] and 658 without DR [NDR group]). There were no significant differences in age, sex, body mass index, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, diastolic blood pressure, glycosylated haemoglobin, fasting blood glucose, postprandial 2-hour blood glucose, and triglycerides between the two groups. The duration of T2DM and systolic blood pressure were significantly increased in the DR group compared with the NDR group. No significant differences were found in allele (A and G) and genotype (AA, AG and GG) frequencies of the 2184A/G polymorphism between the two groups.

Conclusion

The 2184A/G polymorphism in the AGER gene is not associated with DR in Han Chinese patients with T2DM.



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Intra-aortic balloon pump combined with mechanical ventilation for treating patients aged > 60 years in cardiogenic shock: Retrospective analysis

Objective

To examine if mechanical ventilation with positive end-expiratory pressure (PEEP) combined with intra-aortic balloon pump (IABP) provided a better outcome than IABP alone for the treatment of cardiogenic shock after acute myocardial infarction in patients aged > 60 years.

Methods

This was a retrospective analysis of data from patients in cardiogenic shock, refractory to pharmacological therapy and treated at a geriatric coronary care unit.

Results

Sixty-two patients were eligible for study inclusion: 33 received IABP alone; 29 received IABP combined with mechanical ventilation. Patients in the IABP + mechanical ventilation group had lower mean arterial blood pressure (BP), systolic BP and partial pressure of oxygen compared with the IABP group, indicating worse cardiac and pulmonary function. In addition, higher rates of pulmonary infection and renal insufficiency were observed in the IABP + mechanical ventilation group than in the IABP group. A statistically significant improvement of left ventricular function before and after treatment was observed in the IABP + mechanical ventilation group, but not in the IABP group. Pulmonary infection and renal insufficiency were risk factors for all-cause in-hospital mortality; successful revascularization was a negative risk factor. There was no between-group difference in survival.

Conclusion

Mechanical ventilation with an appropriate level of PEEP appears to enhance the beneficial effects of IABP on left ventricular function for patients in cardiogenic shock.



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Assessment of associations between ischaemic attacks in patients with type 2 diabetes mellitus and air concentrations of particulate matter

Objective

To investigate the relationship between air concentrations of fine particulate matter <2.5 µm in diameter (PM2.5) and ischaemic attacks in high-risk elderly patients (aged ≥60 years).

Methods

This retrospective data analysis study extracted clinical data from an electronic medical chart system and environmental air quality data from the Ministry of the Environment Atmospheric Environmental Regional Observation System. Patients were stratified into four groups according to whether or not they had type 2 diabetes mellitus (T2DM) and/or an ischaemic attack (i.e. cerebral infarctions and myocardial infarctions) during the 2-year study period. Analysis of the combined clinical and environmental data produced the odds ratio for the likelihood of experiencing an ischaemic attack.

Results

Clinical data were collected from 94 647 patients. On days when the air temperature was ≥25℃ and PM2.5 concentration was ≥20µg/m3, an ischaemic attack was more likely to occur in the T2DM group than in the group without T2DM. An ischaemic attack was more likely to occur 2 days after an increase in the PM2.5 concentration compared with the same day as and 3–6 days after the increase.

Conclusion

The results of this study confirmed an association between PM2.5 and ischaemic attacks in high-risk patients.



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Effects of different anaesthetics on cytokine levels in children with community-acquired pneumonia undergoing flexible fibreoptic bronchoscopy

Objective

To determine the effects of propofol and sevoflurane on cytokine levels in children with community-acquired pneumonia undergoing flexible fibreoptic bronchoscopy (FFB).

Method

Children with community-acquired pneumonia were randomly assigned to receive 3–5 mg/kg propofol i.v. or 8% inhaled sevoflurane. Haemodynamic variables, stress hormone responses and serum cytokines were compared between the two groups.

Results

Out of 50 children aged 2–12 years (propofol, n = 25; sevoflurane, n = 25), there were no significant between-group differences in haemodynamic variables and stress hormones. Interleukin (IL)-6 and IL-10 decreased significantly following FFB in both groups. IL-6 levels were significantly lower in the sevoflurane group than propofol group at 4 h and 1 d following FFB (61.3 ± 11.9 versus 82.6 ± 19.7 pg/ml; 52.8 ± 9.7 versus 75.4 ± 13.6 pg/ml, respectively). IL-10 levels in the sevoflurane group were significantly lower than in the propofol group at 1 d following FFB.

Conclusions

In children with community-acquired pneumonia, use of sevoflurane was associated with lower circulating IL-6 and IL-10 levels compared with propofol, following FFB. Pneumonia severity is reflected by higher blood cytokine levels, thus, sevoflurane may be more beneficial to recovery from community-acquired pneumonia than propofol, however further studies are required to test this hypothesis.



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Differential expression of circulating microRNAs in blood and haematoma samples from patients with intracerebral haemorrhage

Objective

To measure the differential expression of microRNAs (miRNAs) in peripheral blood samples from patients with intracerebral haemorrhage (ICH) and to measure the levels of hsa-miR-21-5p in peripheral blood and haematoma samples from patients with ICH.

Methods

This case–control study enrolled individuals with ICH in the putamen treated by craniotomy and age- and sex-matched healthy control subjects. Serum miRNA expression profiles were determined in the patient and control groups using miRNA polymerase chain reaction (PCR) arrays. The ICH-related miRNA hsa-miR-21-5p was selected and its differential expression was assessed in peripheral blood and haematoma specimens from patients with ICH compared with peripheral blood samples controls using real-time PCR.

Results

Seven patients and five control subjects were included in the miRNA expression profile analysis; and 31 patients and 22 control subjects provided samples for the real-time PCR of hsa-miR-21-5p expression. A total of 59 miRNAs were significantly downregulated in patients with ICH. Relative hsa-miR-21-5p levels of 0.43 and 0.31 for peripheral blood and haematoma samples, respectively, were obtained in the patient group compared with the control subjects.

Conclusion

Hsa-miR-21-5p levels were significantly reduced in both peripheral blood and haematoma samples in patients with ICH.



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Detecting Gene Rearrangements in Patient Populations Through a 2-Step Diagnostic Test Comprised of Rapid IHC Enrichment Followed by Sensitive Next-Generation Sequencing.

Targeted therapy combined with companion diagnostics has led to the advancement of next-generation sequencing (NGS) for detection of molecular alterations. However, using a diagnostic test to identify patient populations with low prevalence molecular alterations, such as gene rearrangements, poses efficiency, and cost challenges. To address this, we have developed a 2-step diagnostic test to identify NTRK1, NTRK2, NTRK3, ROS1, and ALK rearrangements in formalin-fixed paraffin-embedded clinical specimens. This test is comprised of immunohistochemistry screening using a pan-receptor tyrosine kinase cocktail of antibodies to identify samples expressing TrkA (encoded by NTRK1), TrkB (encoded by NTRK2), TrkC (encoded by NTRK3), ROS1, and ALK followed by an RNA-based anchored multiplex polymerase chain reaction NGS assay. We demonstrate that the NGS assay is accurate and reproducible in identification of gene rearrangements. Furthermore, implementation of an RNA quality control metric to assess the presence of amplifiable nucleic acid input material enables a measure of confidence when an NGS result is negative for gene rearrangements. Finally, we demonstrate that performing a pan-receptor tyrosine kinase immunohistochemistry staining enriches detection of the patient population for gene rearrangements from 4% to 9% and has a 100% negative predictive value. Together, this 2-step assay is an efficient method for detection of gene rearrangements in both clinical testing and studies of archival formalin-fixed paraffin-embedded specimens. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://ift.tt/1hexVwJ Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Renal Splenosis: Renal Mass Biopsy Diagnosis of a Tumor Clinically Mimicking Renal Cell Carcinoma.

Renal mass biopsy is increasingly used to guide conservative tumor management, placing increasing importance on pathologists' ability to diagnose small tumor samples. A 66-year-old man with a history of prior splenectomy for trauma presented for urologic evaluation after identification of a left 5.8 cm renal mass. Partial envelopment of the mass by renal parenchyma and equivocal enhancement on computed tomography raised concern for renal cell carcinoma. Needle-core biopsy revealed blood, subtle vasculature, few aggregates of lymphocytes, and rare renal tubules. Immunohistochemical staining revealed CD8-positive sinusoids but negative reactivity for epithelial antigens (PAX8, keratin, epithelial membrane antigen, carbonic anhydrase IX), supporting diagnosis of renal splenosis. Renal splenosis is a rare phenomenon that can form a sizeable intrarenal mass, mimicking renal cell carcinoma. Pathologists' awareness of this uncommon occurrence may avoid unnecessary surgery. CD8-positive sinusoids and negative epithelial markers are helpful confirmatory features in the biopsy setting. Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.

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The Diagnostic Role of SPINK1 in Differentiating Hepatocellular Carcinoma From Nonmalignant Lesions.

Background and Aim: Distinction of small-sized hepatocellular carcinoma (HCC) from dysplastic nodules may be difficult. In addition, distinction of well-differentiated HCC (WD-HCC) from high-grade dysplastic nodule (HGDN) is also difficult in small needle biopsy. We aimed to study serine peptidase inhibitor, Kazal type 1 (SPINK1) immunohistochemical expression in HCC to differentiate it from nonmalignant lesions. Methods: This study included 179 specimens from the archival material of Pathology Department, National Liver Institute, Menoufia University, between 2007 and 2014, divided as 93 HCC and 86 nonmalignant lesions. All cases were stained for SPINK1 antibody. Results: SPINK1 was expressed in 76.3% of HCC cases with a diagnostic accuracy of 79.3%. There was a significant difference between focal nodular hyperplasia and WD-HCC cases regarding mean value of SPINK1 expression (P=0.015). In addition, there was low SPINK1 score in cirrhosis cases compared with WD-HCC. Moreover, there was a high significant difference between WD-HCC and HGDN regarding SPINK1 expression (P=0.001), with 83.3% sensitivity and 84.6% specificity. Conclusions: SPINK1 can be used to differentiate between a WD-HCC and a HGDN with high diagnostic validity. Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Application of MDM2 Fluorescence In Situ Hybridization and Immunohistochemistry in Distinguishing Dedifferentiated Liposarcoma From Other High-grade Sarcomas.

Distinguishing dedifferentiated liposarcoma (DDLPS) from other high-grade spindle and pleomorphic sarcomas is important because of better prognosis in case of DDLPS. MDM2 amplification, a genetic abnormality of well-differentiated liposarcoma, is known to be present not only in DDLPS, but also in some other sarcomas. To differentiate DDLPS, we investigated MDM2 amplification and expression in high-grade spindle sarcomas. Eighty-five cases of nonlipogenic high-grade sarcomas, diagnosed between 2008 and 2011, were investigated. Tissue microarray, immunohistochemistry, and fluorescence in situ hybridization for MDM2 were performed. Forty-one of 85 cases (48.2%) showed MDM2 amplification and expression. Cases of MDM2 amplification were reclassified based on histology, immunophenotype, and clinical data. Thirty-nine of 41 cases, including those originally diagnosed as DDLPS (n=30), undifferentiated pleomorphic sarcoma (n=7), myxofibrosarcoma (n=1), and pleomorphic liposarcoma (n=1) could be reclassified as DDLPS. In addition, MDM2 immunohistochemistry and MDM2 fluorescence in situ hybridization showed an excellent correlation (P

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Interleukin 18 -607 A/C Gene Polymorphism is Associated With Susceptibility to IgA Nephropathy in a Chinese Han Population.

The association between a single-nucleotide polymorphism (SNP; -607A/C) in the promoter region of the IL-18 gene with IL-18 promoter transcription activity and the level of IL-18 protein production has been observed repeatedly. However, the association between the IL-18-607A/C (rs1946518) promoter polymorphism and IgA nephropathy (IgAN) in a Chinese Han population is still unclear. A total of 166 patients with renal biopsy-proven IgAN and 198 healthy controls were recruited for this study. The SNP was genotyped by the polymerase chain reaction and the high-resolution melting method. Clinical characteristics and pathology grading of patients with IgAN were recorded at the time of the kidney biopsy. There was a significant difference in the distribution between the AA genotype and the AC/CC genotype [P=0.007, OR (95% CI)=1.885 (1.183-3.003)]. However, no significant differences were observed between the rs1946518 SNP and quantitative traits (all P>0.05) or different pathology grades (Lee's grading system and tubular atrophy/interstitial fibrosis according to the Oxford classification) (P=0.769 and P=0.7) of the patients. We first demonstrated that the AA genotype of the IL-18-607A/C was associated with an increased susceptibility to IgAN in this population. Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Effect of Hydrochloric Acid Decalcification on Expression Pattern of Prognostic Markers in Invasive Breast Carcinomas.

Context: In the United States, it is estimated that 100,000 people are living with metastatic breast cancer (BC) with bone representing the most common site of involvement. However, patients with isolated bone metastasis at presentation may have a longer survival. Therapeutic options for BC bone metastases often include systemic anticancer therapy (endocrine, chemotherapy, monoclonal antibodies, and/or other targeted therapies), which is largely dependent on the immunohistochemical (IHC) repertoire of the cancer for the prognostic markers [estrogen (ER) and progesterone receptors (PR), Ki-67, p53, and Her-2/neu] at its osseous metastatic site. Traditionally, specimens obtained from the bone metastasis require decalcification, which may affect the immunoreactivity of these prognostic markers. To the best of our knowledge, limited studies describe the effect of decalcification on immunoexpression of the above-mentioned markers. A detailed illustration of the effect of decalcification on BC specimens in a real-time manner is lacking in the literature. Objective: Herein, we sought to determine the impact of decalcification on the IHC expression pattern of the above listed markers on BC tissue following decalcification. Design: After Institutional Review Board approval, sections from the residual tumor specimens were collected prospectively from 15 BC excision specimens and 1 curetting from a BC bone metastasis. The sections (3 to 6 sections/case) for decalcification were collected following routine submission for pathologic evaluation. The sections were subjected to hydrochloric acid (HCl)-based Decal Stat decalcifying solution for 2, 12, 18, and 24 hours in each case. IHC studies for ER, PR, Ki-67, p53, and Her-2/neu were performed on 1 representative section of the regularly processed tumor block and 1 decalcified tumor block from each time point. Scoring of ER and PR were performed according to the Allred scoring system. Scoring of Her-2/neu was performed according to CAP/ASCO guidelines. Results: The tumors comprised 11 grade 3 invasive ductal carcinomas, 2 grade 2 invasive ductal carcinomas, 2 grade 3 invasive lobular carcinoma, and 1 metastatic BC to bone. Nine cases showed Allred score 8 for ER, 1 case showed Allred score 4, 1 case showed Allred score 2, and the remaining 5 were ER negative. For PR, 1 showed Allred score 8, 2 Allred score 7, 4 Allred score 6, 1 each Allred score 5 and score 2 with the remainder negative for PR. Ki-67 ranged from 5% to 95%. Five cases showed p53 overexpression ranging from 35% to 95%. Five cases each showed 3+, 6 cases showed 2+ Her-2/neu, 3 cases showed 1+ Her-2/neu, and the remaining 2 were negative. All specimens demonstrated decline in ER, PR, Ki-67, and p53 immunoreactivity after 2 hours of decalcification, with additional decline up to 24 hours. The most significant declines in immunoreactivity occurred with Ki-67 and p53. Most of the Her-2/neu cases with an equivocal score declined to zero after 24 hours of decalcification. However, 3 out of 11 cases showing Her-2/neu overexpression remained at the baseline scoring even after extended (24 h) decalcification. Conclusions: Our results demonstrated that the decalcification process affects the immunoreactivity of the prognostic BC markers. There is progressive loss of reactivity at 2 hours and beyond for markers with lower degrees of expression. In addition, heterogeneity in marker distribution progressed from diffuse to more focal beyond 1 hour. Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.

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New STAT!Ref Editions: Dentistry and Patient Safety & Quality Improvement

We are excited to share with you the newest dentistry and patient safety editions recently added to STAT!Ref. As a reminder, all STAT!Ref content is full-text, cross-searchable and every single resource is available on the STAT!Ref Mobile App.

Already have these resources? When STAT!Ref gets a new edition to a resource subscribers already purchase, they get that new edition in their online subscription automatically. It's a hassle-free, value-added convenience to ensure that our customers receive the newest and best content available.

Quintessence of Dental Technology  Environment of Care® Crosswalk  Infection Prevention and Control Issues in the Environment of Care  Pickard's Manual of Operative Dentistry

New Dentistry Editions:

Volume 39 (2016) has recently been added to Quintessence of Dental Technology. A selection of the newest materials and best fabrication techniques for esthetic restorative results are elegantly presented in QDT 2016. Original articles on minimally invasive procedures, CAD/CAM, difficult cases, and the ever-challenging transition zone take center stage this year. The State of the Art article features full-mouth esthetic rehabilitation of the severely worn and compromised dentition, and the Biomaterials Update focuses on self-etching primer as an alternative to strong hydrofluoric and porcelain etching. Rounding out the issue is a special feature on achieving excellence in portrait photography, courtesy of Naoki Aiba. Bundle this resource with Esthetic and Restorative Dentistry: Material Selection and Technique and Fundamentals of Fixed Prosthodontics.

An ideal introduction to the theory and practical aspects of conservative dentistry, the tenth edition of Pickards' Guide to Minimally Invasive Operative Dentistry is a must-have text for all dental students, new graduates and oral healthcare professionals alike. Written in an easy to understand and concise style, the authors introduce the essentials of dental disease before outlining how to collect patient information clinically in order to detect, diagnose, plan and deliver care. Bundle this resource with Fundamentals of Operative Dentistry: A Contemporary Approach and Esthetic and Restorative Dentistry: Material Selection and Technique.

New Patient Safety and Quality Improvement Editions:

The 2016 Environment of Care Crosswalk is a one-stop-shop e-book for all 2016 Joint Commission Environment of Care (EC), Emergency Management (EM), and Life Safety (LS) standards and elements of performance (EPs) for hospitals and the industry standards and regulations that align with them. Easy-to-read crosswalk listings include links to applicable standards, regulations, and reference material. This crosswalk represents an essential time- and labor-saving tool to hospital facility and emergency management staff as well as the vendors they work with to keep facilities safe. Key Topics include: Joint Commission EC, EM, and LS standards and EPs as of January 1, 2016, CMS, OSHA, NFPA, EPA, and other regulations and Standards and regulations compliance. Bundle this resource with Joint Commission and CMS Crosswalk, Joint Commission: The Source and Joint Commission: Environment of Care News.

Infection Prevention and Control Issues in the Environment of Care, Third Edition has been completely revised with current domestic and international standards, as well as new case studies and tools. This new edition addresses unique infection control issues for all health care settings. Infection Prevention and Control Issues in the Environment of Care provides guidelines and strategies to help you organize, improve, and benchmark your IC efforts. Case studies offer examples of plans or projects that have proven effective in a range of health care facilities. Useful resources and websites will help you further examine key issues. Bundle this resource with Bennett & Brachman's Hospital Infections and Best Practices in Infection Prevention and Control: An International Perspective.

To talk to a STAT!Ref Team Member about these new editions, or others within the disciplines of Dentistry or Patient Safety and Quality Improvement please feel free to call 800-901-5494 or fill out this form today.

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