Negative HER2/neu amplification using immunohistochemistry and chromogenic in situ hybridization techniques in skin melanoma cases

Background: This study was performed to evaluate the amplification of HER-2/neu in patients with melanoma. Materials and Methods: Amplification of HER-2/neu was evaluated in a group of patients with melanoma, referred to two referral centers in Tehran, using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) techniques. Results: Forty patients with mean age 57.9±19.5 years were enrolled in this study. The most frequent type of melanoma was acral, while lower limbs were the most frequent sites. The amplification of HER2/ neu was negative in 97.5 of patients with IHC and in 100 of patients with CISH technique. Only one case (2.5) shows weak positive staining (+2) in IHC method. Fifty five percent of melanoma was ulcerative, and the most common stages of tumors were stages 4b and 3b. More than 47 of cases were in Clark level III, while the mean of Breslow thickness was 3.56±2.87 mm. The stage of the case that showed weakly positive staining (2+) in IHC was 4b. Conclusions: The amplification of HER2/neu biomarker was negative in patients with melanoma, using both CISH and IHC techniques

The Immediate Effect of Lateral Wedge Insoles, With and Without a Subtalar Strap, on the Lateral Trunk Lean Motion in Patients With Knee Osteoarthritis

Background: Orthotic interventions for knee osteoarthritis (OA) aim to reduce mechanical loading on the medial compartment of the knee and may lessen the lateral trunk lean as the most important compensatory gait strategy. The lateral wedge insole is a known orthotic intervention for knee OA. However, the question whether the addition of a subtalar strap to the wedge improves its effect has not been addressed in the literature. Objective: To compare the effects of lateral wedge insoles, with and without a subtalar strap, on the lateral trunk lean in patients with knee OA. Methods: Twenty-three patients aged over 40 years, with grade I or II OA of the medial compartment of one knee, based on the American College of Rheumatology criteria, were included in this study. The patients were diagnosed with OA based on a clinical examination, and the diagnosis was confirmed with radiographs. A 3-dimensional motion measurement system was used to collect the gait data for 3 different conditions: (1) with no insole, (2) with a lateral wedge insole, and (3) with a lateral wedge insole and a subtalar strap. The immediate effect of the 3 test conditions on the lateral trunk lean was compared during a gait cycle a stance phase and at the point of midstance. Results: Based on the laboratory coordinate system, the 3 conditions had no significant effect on the lateral trunk lean during a gait cycle and a stance phase and at the point of midstance in patients with knee OA. Conclusion: The results of this study demonstrated that the lateral wedge insoles, with and without a subtalar strap, had no immediate effect on the lateral trunk lean in patients with knee OA. However, the long-term effect of lateral wedge insoles on the lateral trunk lean in these patients requires further investigation. © The Author(s) 2013

A comparative study on the equine and camelid antivenoms upon cardiovascular changes induced with Hemiscorpius lepturus venom in rats

Objective(s): In this study, the neutralizing abilities of the equine and the recently introduced camelid antivenoms on the hemodynamic parameters (inotropism, chronotropism, and arrhythmogenicity) were assessed following envenomation by Hemiscorpius lepturus venom in rats. Materials and Methods: At first, the electrophoretic profiles of both products were obtained by using the SDS-PAGE method (12.5%) and stained with Coomassie blue and silver nitrate. Secondly, different doses of the camelid antivenom (10, 50, and 100 μl) were given intravenously in 10 min before venom injection (400 μg/rat). The neutralizing potencies of camelid and equine antivenoms were measured by preincubation (100 μl) with H. lepturus venom for 30 min at room temperature. Finally, equal amounts of the antivenoms were injected intravenously to observe the hemodynamic changes. Results: Based on the electrophoretic profile, it was evident that undesired proteins significantly decreased in equine antivenom, owing to impurities. Pretreatment with the camelid antivenom (100 μl), neutralized the elevation of the mean arterial pressure evoked with scorpion venom injection (88.15±4.56 versus 10.2±1.23 percent at the 8th min). The Incubation of the venom and the camelid antivenom counteracted the hemodynamic changes, but the equine product had no effect. The intravascular injection of the equine antivenom transiently increased the mean arterial pressure as compared to the control (108.67±8.63 mmHg versus 52.67±1.93 mmHg at the 10th min). Conclusion: The most obvious finding emerging from this study was that the camelid antivenom neutralized the hemodynamic changes in rats significantly, but in comparison, the equine antivenom had just a minor ability

A comparative study of long interspersed element-1 protein immunoreactivity in cutaneous malignancies

Background: Skin cancer is the most common cancer worldwide and commonly classified into malignant melanoma (MM) and Nonmelanoma skin cancers (NMSCs), which mainly include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The extent to which Long Interspersed Element-1 (LINE-1, L1) ORF1p is expressed in cutaneous malignancies remains to be evaluated. This study aimed to assess LINE-1 ORF1p immunoreactivity in various skin cancer subtypes. Method: The expression level of LINE-1 ORF1p was evaluated in 95 skin cancer specimens comprising 36 (37.9) BCC, 28 (29.5) SCC, and 31 (32.6) melanoma using the tissue microarray (TMA) technique. Then the association between expression of LINE-1 encoded protein and clinicopathological parameters was analyzed. Results: We showed that LINE-1 ORF1p expression level was substantially higher in BCC and SCC patients compared with melanoma samples (p 0.05). Conclusions: According to our observation, LINE-1 ORF1p immunoreactivity in various skin tumor subtypes extends previous studies of LINE-1 expression in different cancers. LINE-1ORF1p overexpression in NMSCs compared with MM can be considered with caution as a tumor-specific antigen for NMSCs. © 2020 The Author(s)

Experimental Evaluation of Mouse Hind Paw Edema Induced by Iranian Naja oxiana Venom

Iranian Naja oxiana (the Elapidae family) known as cobra snake inhabits in the northwestern part of Iran. This study aimed to evaluate the edematogenic potency of the crude venom with intraplantar injection into mice. Additionally, the inhibitory effects of three different drugs (i.e., promethazine, dexamethasone, and piroxicam) on paw edema were examined. Moreover, the gelatinase activity of this venom was assessed using the zymography method. Paw edema was induced by the intraplantar injection of different concentrations of the venom (0.5-5 μg dissolved in 50 μl of normal saline) into the mice (six in each group). It was estimated through the measurement of the increase in the paw thickness (%) with a digital caliper. The paws were pretreated and the rate of changes was measured after the venom injection. Pathological findings in the treated paws were evaluated with hematoxylin and eosin staining. Paw thickness reached its maximum amount within 5 min and resolved after 1 h. This venom had no gelatinase activity using the zymography method ruling out its role in edema. It caused non-hemorrhagic diffuse edema with the infiltration of inflammatory cells (i.e., leukocytes and lymphocytes) in the dermis. Intraperitoneal pretreatment with drugs significantly inhibited the venom-induced (1 μg/paw) edema; however, all the mice died unexpectedly a day after piroxicam injection. This in vitro and in vivo preliminary study demonstrated for the first time that N. oxiana venom-induced non-hemorrhagic edema in a short time. Dexamethasone (phospholipase A2 inhibitor; 1 mg/kg) and promethazine (H1 inhibitor; 5 mg/kg) decreased the venom-induced edema (p <0.001). It is suggested to carry out further studies to identify different mediators in venom-induced edema formation

DNA plasmid coding for Phlebotomus sergenti salivary protein PsSP9, a member of the SP15 family of proteins, protects against Leishmania tropica

Background: The vector-borne disease leishmaniasis is transmitted to humans by infected female sand flies, which transmits Leishmania parasites together with saliva during blood feeding. In Iran, cutaneous leishmaniasis (CL) is caused by Leishmania (L.) major and L. tropica, and their main vectors are Phlebotomus (Ph.) papatasi and Ph. sergenti, respectively. Previous studies have demonstrated that mice immunized with the salivary gland homogenate (SGH) of Ph. papatasi or subjected to bites from uninfected sand flies are protected against L. major infection. Methods and results: In this work we tested the immune response in BALB/c mice to 14 different plasmids coding for the most abundant salivary proteins of Ph. sergenti. The plasmid coding for the salivary protein PsSP9 induced a DTH response in the presence of a significant increase of IFN-γ expression in draining lymph nodes (dLN) as compared to control plasmid and no detectable PsSP9 antibody response. Animals immunized with whole Ph. sergenti SGH developed only a saliva-specific antibody response and no DTH response. Mice immunized with whole Ph. sergenti saliva and challenged intradermally with L. tropica plus Ph. sergenti SGH in their ears, exhibited no protective effect. In contrast, PsSP9-immunized mice showed protection against L. tropica infection resulting in a reduction in nodule size, disease burden and parasite burden compared to controls. Two months post infection, protection was associated with a significant increase in the ratio of IFN-γ to IL-5 expression in the dLN compared to controls. Conclusion: This study demonstrates that while immunity to the whole Ph. sergenti saliva does not induce a protective response against cutaneous leishmaniasis in BALB/c mice, PsSP9, a member of the PpSP15 family of Ph. sergenti salivary proteins, provides protection against L. tropica infection. These results suggest that this family of proteins in Ph. sergenti, Ph. duboscqi and Ph. papatasi may have similar immunogenic and protective properties against different Leishmania species. Indeed, this anti-saliva immunity may act as an adjuvant to accelerate the cell-mediated immune response to co-administered Leishmania antigens, or even cause the activation of infected macrophages to remove parasites more efficiently. These findings highlight the idea of applying arthropod saliva components in vaccination approaches for diseases caused by vector-borne pathogens. © 2019, Public Library of Science. All rights reserved

Metaheuristics for Transmission Network Expansion Planning

This chapter presents the characteristics of the metaheuristic algorithms used to solve the transmission network expansion planning (TNEP) problem. The algorithms used to handle single or multiple objectives are discussed on the basis of selected literature contributions. Besides the main objective given by the costs of the transmission system infrastructure, various other objectives are taken into account, representing generation, demand, reliability and environmental aspects. In the single-objective case, many metaheuristics have been proposed, in general without making strong comparisons with other solution methods and without providing superior results with respect to classical mathematical programming. In the multi-objective case, there is a better convenience of using metaheuristics able to handle conflicting objectives, in particular with a Pareto front-based approach. In all cases, improvements are still expected in the definition of benchmark functions, benchmark networks and robust comparison criteria

Millennials in the Workplace: A Communication Perspective on Millennials’ Organizational Relationships and Performance

Stereotypes about Millennials, born between 1979 and 1994, depict them as self-centered, unmotivated, disrespectful, and disloyal, contributing to widespread concern about how communication with Millennials will affect organizations and how they will develop relationships with other organizational members. We review these purported characteristics, as well as Millennials’ more positive qualities—they work well in teams, are motivated to have an impact on their organizations, favor open and frequent communication with their supervisors, and are at ease with communication technologies. We discuss Millennials’ communicated values and expectations and their potential effect on coworkers, as well as how workplace interaction may change Millennials