Immuno-informatics based approaches to design a novel multi epitope-based vaccine for immune response reinforcement against Leptospirosis

Leptospirosis is known as a zoonotic disease of global importance originated from infection with the spirochete bacterium Leptospira. Although several leptospirosis vaccines have been tested, the vaccination is relatively unsuccessful in clinical application despite decades of research. Therefore, this study was conducted to construct a novel multi-epitope based vaccine against leptospirosis by using Hap1, LigA, LAg42, SphH and HSP58 antigens. T cell and IFN gamma epitopes were predicted from these antigens. In addition, to induce strong CD4+ helper T lymphocytes (HTLs) responses, Pan HLA DR-binding epitope (PADRE) and helper epitopes selected from Tetanus toxin fragment C (TTFrC) were applied. Moreover, for boosting immune response, Heparin-Binding Hemagglutinin (HBHA), a novel TLR4 agonist was added to the construct as an adjuvant. Finally, selected epitopes were linked together using EAAAK, GPGPG, AAY and HEYGAEALERAG linkers. Based on the predicted epitopes, a multi-epitope vaccine was construct with 490 amino acids. Physico-chemical properties, secondary and tertiary structures, stability, intrinsic protein disorder, solubility, and allergenicity of this vaccine construct were assessed by applying immunoinformatics analyses. A soluble, and non-allergic protein with a molecular weight of 53.476 kDa was obtained. Further analyses validated the stability of the chimeric protein and the predicted epitopes in the chimeric vaccine indicated strong potential to induce B-cell and T-cell mediated immune response. Therefore, immunoinformatics analysis showed that the modeled multi-epitope vaccine can properly stimulate the both T and B cells immune responses and could potentially be used for prophylactic or therapeutic usages

The prevalence of right to left shunt in chronic obstructive pulmonary disease patients with increased pulmonary hypertension

Background: One of the important etiologies for cryptogenic stroke is paradoxical embolization secondary to Patent Foramen Ovale (PFO). Foramen ovale can secondarily reopen due to Pulmonary Arterial Hypertension (PAH) which is common among the older age. PAH is known as a frequent and life threatening complication of COPD. The aim of this study was to determine the prevalence of PFO between COPD patients with PAH and compare it with the ratio of PFO in non PAH COPD patients by Valsalva Maneuver (VM) following the TCD test. Methods: This study was performed on 55 patients with COPD exacerbation who were admitted to Rasul-Akram Hospital in Tehran, Iran. The patients with high PAH were considered as the case group and the others without PAH were the control group. All patients underwent Trascranial Doppler (TCD) to detect intracardiac right-to-left shut (RLS) related by PFO. The data were collected and analyzed. Results: In the case group, among 45 patients 25 (55.5) males and 20 (44.5) females] with the mean age of 64.68±10.73 years, 31 (68.8) subjects had PFO. In 10 control patients whose PAP were normal during TTE, we detected PFO in 2 (20) patients during VM (p<0.001). There was a significant correlation with the number of microembolic signals (MES) and the increase in PAP (p=0.019). Conclusion: Right to left shunting was significantly more frequent in COPD patients with high PAP. High pulmonary pressure had a cardinal role in increasing the prevalence of RLS among these patients

Topical application of Semelil (ANGIPARS�) in treatment of pressure ulcers: A randomized clinical trial

Pressure ulcers are one of the major health care problems and results in a substantial amount of burden for both patients and health services. The aim of this study was to appraise effectiveness of topical Semelil (ANGIPARS�), a naive herbal extract, in pressure ulcers As a randomized controlled clinical trial, 18 patients with pressure ulcers were recruited from Vali-e-Asr hospital, Medical Sciences/ University of Tehran, Iran. Nine patients received topical Semelil (ANGIPARS�) during hospitalization and nine other patients received conventional treatment. Baseline characteristics of the topical and control groups did not differ across demographic, clinical and functional measures. The mean surface areas of the ulcers were reduced 48.2 ± 85.3 cm2 (78.3) and 2.8± 6.2 cm2 (6.3) in the treatment and control groups, respectively (p=0.000). From the results of this study it may be concluded that the use of topical Semelil (ANGIPARS�) with conventional treatment is more effective than those of only conventional treatment for patients with pressure ulcers

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

BACKGROUND: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. METHODS: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. FINDINGS: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. INTERPRETATION: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

In vitro anthelmintic effect of Tobacco (Nicotiana tabacum) extract on parasitic nematode, Marshallagia marshalli

Because of developing resistance to the existing anthelmintic drugs, there is a need for new anthelmintic agents. Tobacco plant has alkaloid materials that have antiparasitic effect. We investigated the in vitro anthelminthic effect of aqueous and alcoholic extract of Tobacco (Nicotiana tabacum) against M. marshalli. For investigating this effect, we prepared three dilutions of aqueous and alcoholic extract of Tobacco (25, 50 and 75 mg/ml). The worms exposed to extracts for 10 h at 25�30 °C. The buffer PBS used as negative control and 50 mg/ml dilution of Levamisole used as standard reference. In each group, 50 worms were examined. We used an inhibition mobility test for our study. Survival analysis with Cox proportional hazard model was used for data analysis. The result showed that compared with Levamisole 50 mg/ml, dilution of 25 and 50 mg/ml of the aqueous extract had the same anthelminthic effects (P > 0.05), but 75 mg/ml dilution of the aqueous extract and dilution of 25, 50 and 75 mg/ml of alcoholic extract had more anthelminthic effect (P < 0.05). Overall, extracts of Tobacco possess considerable anthelminthic activity and more potent effects were observed with the highest concentrations. Therefore, the in vivo study on Tobocco in animal models is recommended. © 2014, Indian Society for Parasitology

Typical laryngeal carcinoid tumor: A case report

Neuroendocrine tumors of the larynx comprise a rare group of tumors categorized as typical carcinoid, atypical carcinoid, small-cell neuroendocrine carcinomas, and paragangliomas. Atypical carcinoid type occasionally denotes carcinoid syndrome. Typical carcinoid is extremely rare. The primary diagnosis is based on light histochemical studies that should be confirmed by immunocytological and/or ultrastuctural investigation. The different biological behaviors of these tumors lead to a specific diagnosis of paramount importance. © Iranian Red Crescent Medical Journal

Supplementary Material for: Immunotherapy with a Recombinant Hybrid Molecule Alleviates Allergic Responses More Efficiently than an Allergenic Cocktail or Pollen Extract in a Model of <b><i>Chenopodium album</i></b> Allergy

<b><i>Background:</i></b> The aim of this study is to assess the therapeutic potential of a recombinant hybrid molecule (rHM) alongside an allergenic cocktail from recombinant wild-type allergens as well as pollen extract on <i>Chenopodium album</i> allergy, using a BALB/c mouse model. <b><i>Methods:</i></b> The BALB/c mice had already been sensitized to <i>C. album</i> via intraperitoneal injections of alum-adsorbed allergenic cocktail and immunotherapy procedure was followed by subcutaneous injections of the rHM, allergenic cocktail and pollen extract at weekly intervals. Humoral immune responses were determined via measurement of specific antibodies in serum. Splenocytes of immunized mice were stimulated in vitro and then proliferation responses, cytokine secretion and mRNA expression of genes involved in immunotherapy were examined by ELISA and real-time PCR. <b><i>Results:</i></b> Sensitized mice were identified with high specific IgE against allergenic cocktail when compared with healthy mice. Immunotherapy with the rHM induced the highest ratio of the IgG2a/IgG1 levels compared to allergenic cocktail or <i>C. album</i> pollen extract. The rHM was able to induce proliferative responses as well as the allergenic cocktail in cultured splenocytes. Immunotherapy with the rHM significantly improved secretion of IFN-γ and IL-10, while secretion of IL-13 rapidly diminished. Interestingly, mRNA expression of GATA3 was strongly decreased in rHM-treated mice whereas mRNA expression of T-bet and Foxp3 was significantly increased. <b><i>Conclusion:</i></b> Our results prove that immunotherapy with the rHM effectively controlled allergic responses by shifting from a Th2-like immune response to a Th1-dominated immune response