bluuebunny/crossref_metadata_2025 huggingface dataset:
Socio-economic determinants of reproductive tract infections affecting the women (15-49 years): a cross sectional study in a tertiary care hospital of Chhattisgarh
Authors: Pandey Bhavana , Shukla Devesh Kumar
Published: June 2018

Background: RTIs/STIs are a common public health problem in developing countries, contributing to a huge economic burden among individuals and health systems. RTI's excluding HIV constitutes the second major cause of disease burden (after maternity related causes) in women of developing countries. This cross sectional study is carried out with objectives of, to study socio-economic profile of respondents and to determine socio-economic factors of RTI, affecting the women of reproductive age group attending CIMS, Hospital Bilaspur (C.G.).Methods: A descriptive cross sectional study conducted in a tertiary care hospital CIMS, Bilaspur (Chhattisgarh) from May 2015 to October 2016. Total 450 cases were studied. Predesigned and pretested questionnaire was used to collect information regarding the socio-demographic profile and clinical profile of women’s regarding RTI. Statistical analysis was done using SPSS and Chi-square test was applied.Results: 4.3% (450) patient attending Obstetrics and Gynecology OPD were found to be suffering from RTI. Out of the 450 women, 83.8% of the women had experienced at least one symptom suggestive of RTI previously. Abnormal vaginal discharge was reported by 88.9% followed by lower abdominal pain (78.9%), genital ulcer (34%) and menstrual irregularity 75.8% of women. Symptoms of RTI were higher in old age, illiterate, those with employed, rural residential, Schedule tribe category, poor socio-economic status, separated, divorce and widow and women their husband educated up to primary class.Conclusions: Generating community awareness, ensuring proper menstrual hygiene, and improving the socioeconomic status would help in reducing the cases of RTI.
The Notion of Sovereignty, According to the Contemporary Interpretation of Political Theology
Authors: Souza Maria Silveira , Barros Douglas Ferreira
Published: June 2018

Abstract: the Political Theology (2009) of Carl Schmitt encompasses the notion of sovereignty and maintains strict dialogue with Hobbes’ conception for this concept. Schmitt believes that his work would improve the concept that, modern, should incorporate to it the notion of State of Exception, restoring definitely its condition of summa potestas, conferred by the philosophers of the Middle Ages, but abandoned by modern thinkers. The aim of this study is to analyze the similarities between the theories of Hobbes and Schmitt, identifying the concepts that form the basis of hobbesian conception – State and sovereignty – afterwards used by Schmitt: sovereignty, state of exception, political theology.A Noção de Soberania, Segundo a Interpretação Contemporânea da Teologia PolíticaResumo: a obra Teologia Política, de Carl Schmitt, abrange a noção de soberania e mantém estrito diálogo com a formulação de Hobbes para este conceito. Schmitt crê que ao seu trabalho caberia aperfeiçoar o conceito que, moderno, deveria incorporar a noção de exceção para, definitivamente, restituir-lhe a condição de summa potestas, conferida pelos filósofos da Idade Média, mas abandonada pelos pensadores da modernidade. O objetivo desse trabalho é analisar as similaridades entre as teorias de Hobbes e Schmitt, identificando no primeiro os conceitos que servirão de base -Estado civil e soberania- àqueles utilizados por Schmitt: soberania, estado de exceção, teologia política.
A Road to Brazil
Authors: Monteiro Luciano Araujo
Published: June 2018

Abstract: this review is based on the study of Raimundo Magliano Filho, to show the importance of civil society participation Brazilian institutions in the public institutions, so that they are in fact, capable of serving the community. Magliano's work is well illustrates and brings great relevance to the current situation of our country, given the moment of discredit by which our regime passes democratic. UM CAMINHO PARA O BRASIL Esta resenha é baseada no estudo de Raimundo Magliano Filho, visando mostrar a importância da participação da sociedade civil brasileira nas instituições de caráter público, para que estas estejam de fato, aptas a atender a coletividade. O trabalho de Magliano é bem ilustrativo e trás grande relevância para a atual conjuntura de nosso país, dado o momento de descrédito pelo qual passa nosso regime democrático.
A Brief Analysis on Human Rights from Hannah Arendt’s Criticism
Authors: Praseres Janilce Silva , Saldanha Marcelo Ramos
Published: June 2018

Abstract: human rights are a set of ethical values whose purpose is to protect and enable the realization of human dignity in its various dimensions and also prevent the reduction of the individual to the condition of object or, above all, the reduction of his condition as subject of rights, such as the right to life, freedom, security, equality. The universal character of human rights protection demonstrates some weaknesses, especially in the transposition into concrete legal systems, so what we propose is a brief analysis of human rights from Hannah Arendt.Uma Breve Análise Acerca dos Direitos Humanos a partir da Crítica de Hannah ArendtResumo: os direitos humanos são um conjunto de valores éticos que têm por finalidade proteger e possibilitar a realização da dignidade humana em suas várias dimensões e, ainda, impedir a redução do indivíduo à condição de objeto ou, sobretudo, a diminuição da sua condição na qualidade de sujeito de direitos, a exemplo o direito à vida, à liberdade, à segurança, à igualdade. O caráter universal de proteção aos direitos humanos demonstra algumas fragilidades, principalmente, na transposição para ordenamentos jurídicos concretos, assim, o que propomos é uma breve análise acerca dos direitos humanos a partir de Hannah Arendt.
The Challenges of Education in Gender Issues and Sexuality in Times of Crisis
Authors: Cordeiro Ana Luisa Alves , Cordeiro Maria José De Jesus Alves , Medeiros Márcia Maria de
Published: June 2018

Abstract: the impeachment process of the elected President Dilma Rousseff (2011-2016/Interrupted) in Brazil, besides its political and economic dimension, national and international, is characterized by macho, racist and heteronormative delineations, directly affecting identity groups, among them those of women, peasants, ethnic-racial and LGBTs. The aim of this article is to analyze some (ultra)conservative trends in educational policies in the treatment of gender and sexuality issues without disregarding other intersectionalities. The analysis has as theoretical reference referential that interface education, gender and ethnic-racial relations. It is a qualitative approach, constituting two axes: bibliographical and documentary. The expressive advance, especially in the political sphere, of the aforementioned tendencies, works in the dismantling of rights related to gender issues in the sphere of education, articulating the ethnic-racial and sexual orientation issues, thus characterizing the setbacks that operate intersectionally.Os Desafios da Educação nas Questões de Gênero e Sexualidade em Tempos de CriseResumo: o processo de impeachment da presidenta eleita Dilma Rousseff (2011-2016/Interrompido), no Brasil, além de sua dimensão política e econômica, nacional e internacional, se caracteriza com delineamentos machistas, racistas e heteronormativos, afetando diretamente grupos identitários, entre os quais os de mulheres, campesinos, étnico-raciais e LGBTs. O objetivo deste artigo é analisar algumas implicações de tendências (ultra)conservadoras nas políticas educacionais no trato das questões de gênero e sexualidade sem desconsiderar outras interseccionalidades. A análise tem como aporte teórico referenciais que fazem a interface educação, gênero e relações étnico-raciais. É de abordagem qualitativa, constituindo-se de dois eixos: bibliográfico e documental. O avanço expressivo, em especial na esfera política, de tendências supra citadas atua no desmonte de direitos relacionados às questões de gênero na esfera da educação, articulando-se às questões étnico-raciais e de orientação sexual, caracterizando-se assim em retrocessos que operam interseccionalmente.
ÉTICA E POLÍTICA: UMA ESTREITA RELAÇÃO
Authors: Neves Silva Rosemary Francisca
Published: June 2018

Apresentação do Dossiê.
El Gran Impulso y el crecimiento balanceado y desbalanceado
Authors: Currie Lauchlin
Published: June 2018

Este artículo, que es a la vez una contribución a la historia del pensamiento económico y una aclaración de la teoría del desarrollo económico en la que se basó el Plan de Desarrollo colombiano de 1970-1974, Las cuatro estrategias, discute la propuesta de Paul Rosenstein-Rodan para acelerar el crecimiento en los países en desarrollo, y critica los puntos de vista de Albert Hirschman sobre el falso problema crecimiento balanceado-crecimiento desbalanceado que, en opinión del autor, dilapidó mucho tiempo y muchos esfuerzos, y, desvió la atención de los problemas verdaderos que debían ser tema de la teoría del desarrollo y de las políticas para acelerar el crecimiento económico y salir del subdesarrollo.
La dinámica de la construcción en Bogotá 1995-2013
Authors: Araque Solano Alex Smith , Silva Yuly Paola
Published: June 2018

Los precios de la vivienda en Bogotá en el periodo 1995-2013 generaron un debate sobre la existencia de una burbuja inmobiliaria. Este artículo analiza los determinantes de la oferta y la demanda del sector, de los mercados asociados y de la velocidad de crecimiento de la tasa de interés y de los precios del suelo. Los resultados muestran que en el mercado no hubo una burbuja en 2012 y que las condiciones económicas de la década de 2010 provocaron el aumento de los precios de la vivienda. El aumento de estos precios en todo el país exige evaluar los efectos territoriales de la política nacional de vivienda, el papel de las administraciones locales, el uso de los instrumentos de gestión del suelo y los efectos de estas presiones de precios sobre la calidad y habitabilidad de las viviendas.
Street Law, Inc.: Context, History and Future
Authors: Arbetman Lee
Published: June 2018

In 1972, a small group of Georgetown University law students developed a series of practical law lessons for use with public high school students in Washington, D.C. These visionaries recognized that ordinary citizens—not just lawyers—needed a basic understanding of practical law in order to take on civic responsibilities. The lessons were popular with the high school students and with their law student teachers. Responding to their practical nature, the high school students called these lessons “Street Law.” The name stuck.

A pilot program in two local high schools in 1972–73 launched a movement—first in the United States but eventually around the world—to teach the public about law and public policy using learner-centered, interactive teaching methods. Today, Street Law programs can be found in every state in the U.S. and in more than 40 countries around the world.

Propelling this global movement to advance justice through practical education about law and democracy is Street Law, Inc., a Washington, D.C. area non-profit organization that is an outgrowth of the early Street Law program at Georgetown University Law Center. That pilot effort has also grown into a full-fledged, credit-bearing experiential education program at Georgetown that has served as a model program for more than 120 law schools across the country and around the world. Nearly 1,000 upper division Georgetown Law students have participated in this program since its inception. Many have gone on to positions as law firm partners, corporate counsel, government officials in the U.S. and abroad, and even members of the federal court bench. They have taken from their law school experience a commitment to public education about law and democracy.
Blogs as a teaching tool and method of Public Legal Education: a case study
Authors: Roper Victoria
Published: June 2018

Social media, and blogs specifically, can potentially have a dual raison d'être: enriching a law student’s educational experience whilst simultaneously educating the general public. Through a case study analysis of a blog project employed in a clinical legal education module at Northumbria University, the opportunities, challenges and limitations of using blogs in this way will be explored from both a pedagogical and public legal education perspective.
REPARASI DAN KARAKTERISASI ALFA-Fe2O3 /ZEOLIT Y UNTUK REAKSI PERENGKAHAN ASAM PALMITAT
Authors: Abdulloh Abdulloh , Purkan Purkan , Hardiansyah Nizar
Published: June 2018

Telah dilakukan preparasi dan karakterisasi a-Fe2O3/zeolite Y sebagai katalis uji reaksi perengkahan asam palmitat. Zeolit A disintesis dari NaOH, NaAlO2 dan TEOS dengan metode kristalisasi bertahap. Katalis alfa-Fe2O3/zeolite Y disiapkan melalui metode impregnasi menggunakan larutan Fe(NO3)3 1 M dan proses kalsinasi pada suhu 500 oC dengan dialiri gas N2 selama 5 jam. Katalis dikarakterisasi dengan XRD, FTIR dan surface area analyzer menggunakan metode BET. Uji aktivitas katalis dilakukan pada suhu 380 – 400 oC. Analisis GC-MS terhadap hasil reaksi perengkahan menunjukkan terbentuknya senyawa-senyawa hidrokarbon seperti alkana dan alkena yang memiliki rantai karbon lebih pendek dari asam palmitat atau biogasoline
Gambaran Histopatologi Hepar Tikus Putih (Rattus Novergicus) yang Diinduksi dengan Parasetamol dosis Toksik Pasca Pemberian Ekstrak Etanol Daun Kelor (Moringa Oleifera)
Authors: Kumala I Noer
Published: June 2018

Hepar tempat utama metabolisme obat yang disebut juga sebagai biotransformasi dan hasil akhir dari reaksi ini berupa substansi yang tidak aktif dan lebih larut dalam air, sehingga cepat diekskresi melalui empedu dan urin. Setiap gangguan hati dapat menghambat fungsi normal tubuh. Kerusakan sel-sel hepar dapat disebabkan antara lain oleh obat, virus, dan berbagai senyawa kimia lain mempunyai daya hepatotoksik, antara lain adalah parasetamol.Penelitian ini menggunakan 5 kelompok Tikus Putih (masing-masing kelompok 5 ekor tikus) yang diinduksi parasetamol dosis toksik kemudian diberikan ekstrak Etanol Daun Kelor (Moringa Oleifera) dengan dosis 250mg/200BB, 500mg/200 BB, dan 1000mg/200BB selama 7 hari untuk kelompok P1, P2 dan P3 sedangkan kelompok Kontrol positif hanya diberi pakan dan minum biasa, serta kelompok control negatif hanya diberikan parasetamol dosis toksik saja. Hasil penelitian menunjukkan bahwa kelompok perlakuan P3 dengan pemberian ekstrk etanol dosis tinggi yaitu 1000 mg/200 BB dapat melindungi hepar tikus yang telah diinduksi dengan parasetamol dosis toksik, hal ini dapat dibuktikan dengan melihat gambaran histopatologi hepar tikus yang mengalami pengurangan baik dari sisi peradangan, nekrosis maupun degenerasi.
HEKİM ATAMA PROBLEMİNİN GENETİK ALGORİTMA İLE OPTİMİZASYONU - THE OPTIMIZATION OF MEDICUS ASSIGNMENT PROBLEM THROUGH GENETIC ALGORITHM
Authors: İLKUÇAR Muhammer , GÜNGÖR İbrahim
Published: June 2018

u çalışmada, sağlık bakanlığı
bünyesinde çalışan belirli branşlardaki hekimlerin, hizmet puanı, kıdem ve
tercihlerine göre, bakanlığa bağlı sağlık kurumlarının mevcut personel durumu
ve ihtiyaçları da göz önüne alınarak, kurumlara rotasyon işleminin optimizasyonu
yapılmıştır. Hekimler; hizmet puanı, kıdemi, görev süresi, halen çalıştığı
kurum ve çalışmak istediği kurum tercihleri dikkate alınarak, öncelikli tercihi
olmak şartıyla, tercih ettiği kurumlardan birine atanmaya çalışılır. Atama
sırasında; kurumlardaki çalışması gereken personel sayısı, halen çalışan
personel sayısı, istenen personel sayısı, kurumdan atanarak ayrılacak personel
sayısı, kurumda halen çalışan personelin belirli bir oranının atanarak
ayrılabileceği gibi durumlar dikkate alınarak, kurumların personel ihtiyaçları
karşılanmaya çalışılmalı ve hekimlerin kurumlar arasında mümkün olduğu kadar
dengeli dağıtımı yapılmalıdır. Bu çalışmada aday ve kurum istekleri ve
kısıtları dikkate alınarak hem adayları, hem de kurumları azami memnun edecek bir
aday-kurum atamasının optimizasyonu yapılmıştır. Problemde çözüm yöntemi olarak
genetik algoritma kullanılmıştır. Kullanılan genetik algoritmada, kromozom
seçme işlemi, geliştirilen yazılım ile otomatik hale getirilerek, problemin
çözümü sırasında kromozom seçme yönteminde dolayı oluşabilecek monotonluk
önlenmiştir. Kromozomlar üzerinde yapılan çaprazlama veya mutasyon işleminden
sonra adayların tercih etmediği kurumlara atanması söz konusu olabilmektedir.
Bu sorun, kromozom düzeltme algoritması yardımıyla adayların tercih ettiği
kurumlardan birine (öncelikli tercihine) atanmasıyla giderilmiştir. Problemde,
gerçek verileri simule eden bir veri seti oluşturma fonksiyonu yardımıyla
farklı veri setleri oluşturularak, geliştirilen yöntem test edilmiştir. Problemin
çözümü için; C#.NET Express programlama dili ve MS SQL 2005 Express veri tabanı
kullanılmıştır.
A Novel Digital Approach to Predict Production Rates from PCP Wells
Authors: Álvarez Julieta , Espinola Oswaldo , Ramírez Christian , Torres Adelfo
Published: June 2018

Progressive cavity pumps (PCP) have been used as artificial lift system for heavy oil lifting, low productivity wells and other challenging conditions which are common characteristics of brownfields. In addition to those conditions, there is the current complicated economic environment in which operating companies seek to reduce investments while enhancing field production operations with low-cost solutions aiming to increase the overall's field recovery factor.

The initial step when trying to enhance field production operations in wells operating with PCPs as artificial lift system is performing a well-level analysis. During this analysis, the existing operational conditions and its corresponding production are evaluated. The continuity and accuracy of this analysis is highly dependent on the data input for analysis purposes. For instance, the rate of production is required as input and due to the nature of operation in brownfields, this value is not measured with the required frequency needed for performing a proper production enhancement analysis.

This paper aims to provide a simple, automated, and accurate way to perform a calculated rate of production that is cost effective and easy to maintain, capable of being used during field production operations enhancement analysis, and applicable to wells operating with PCPs as artificial lift in heavy oil conditions, using regression and analytical methods.

Both methods are being used part of a digital oilfield solution implemented in a heavy oil brownfield with telemetry-instrumented PCP wells. This solution is working inside a production operations platform that validates input data, manages different frequencies and types of data, and automatically calculates a production rate, which is then pushed to a visualization dashboard.

Results provide an accurate production rate estimate suitable for reservoir engineering analyses while providing insight for the production operations enhancement.
Estimation of the marketing potential of industrial enterprises in the period of re-engineering of business processes
Authors: M. Taraniuk Leonid , S. Kobyzskyi Denys , Thomson Mark
Published: June 2018

Activity of business entities requires a constant increase in the level of their economic potential and the level of competitiveness of the products on the market. This task can be fulfilled provided the concept of constant economic growth is formed in the activity of enterprises, which can be implemented through the management of changes in the economic activity of enterprises. One of the components is the marketing activity, which plays one of the leading roles in shaping the sustainable development of an industrial enterprise when carrying out transformational changes in its activity. These changes, which are the re-engineering of business processes, help the company management adapt to the changing market (marketing) environment and optimize the internal business processes. The relevance of the research is undeniable. The article presents the main directions of transition to the effective marketing activity in the period of re-engineering of industrial enterprises’ business processes based on the analysis of the main trends of marketing and innovation activities of economic entities from different countries. The authors developed the indices that characterize the marketing potential of the company during the business processes’ re-engineering. They proposed to use an integral index of the company’s marketing potential during radical transformations and to take effective management decisions based on the prevailing range of its criteria values when carrying out an economic estimation of the company’s marketing potential in the period of business processes’ re-engineering. The results obtained from the calculations demonstrate the final estimation of the industrial enterprise’s marketing potential during the business processes’ re-engineering, which allows the top management of the industrial company to determine the level of performance of the company marketing activity and make sound managerial decisions for its further development.
ACANTA MAĞARALARI: BUDDHİST GELENEK VE ÇAİTYALAR
Authors: Kayalı Yalçın
Published: June 2018

Buddhist kültüre ait oldukça önemli
unsurları içerisinde barındıran Acanta mağaralarının tarihi, MÖ 2. yüzyıla
kadar gitmektedir. Bu mağaralar, oluşturuldukları dönem itibarıyla ikiye
ayrılmaktadır. Birinci grup, MÖ 2-1. yüzyıllar arasında oluşturulmuşken; ikinci
grup ise yaklaşık olarak dört yüz yıl süren bir aranın ardından, MS 4-6.
yüzyıllar arasında oluşturulmuştur. Tarihsel süreçte birinci grup olarak
adlandırılan mağaralar, Buddhizm’in Hīnayāna mezhebi inanırları tarafından
kullanılmış, ikinci grup ise Mahāyāna mezhebinin manastırları olarak hizmet
vermiştir. Yapısal ve şekilsel özellikleri bakımından da ikiye ayrılan Acanta
mağaralarının, yirmi beşi vihāra, beşi ise çaitya formunda inşa edilmiştir.
Çalışmamıza konu olan çaitya-grihaların içerisinde birer küçük stūpa
bulunmaktadır. Stūpalar, Buddhist kültüre ait oldukça kıymetli ipuçlarını
günümüze taşımaktadır. Bu sebeple çalışmamızda, Acanta’daki çaityaların yapısal
ve kültürel özellikleri incelenerek, Hint kültüründeki yeri ve önemi konusuna
vurgu yapılmak istenmiştir.
Hydrologic processes of groundwater in a small monsoon-influenced mountainous watershed
Authors: Yuan Ruiqiang , Wang Shiqin , Yang Lihu , Liu Jianrong , Wang Peng , Song Xianfang
Published: June 2018

Mountain block recharge is the least well quantified owing to the lack of a thorough understanding of mountain block hydrological processes. Observations of spatio-temporal variations of groundwater were employed to clarify hydrologic processes in a semi-arid mountainous watershed of northern China. Results showed that the annual feeding rate of precipitation changed between 21% and 40%. However, infiltration of precipitation was mainly drained as interflow on slopes and recharged into the mountain valley as focused recharge. As a result, the mean correlation coefficient between precipitation and groundwater level was only 0.20 and seasonal variations were reduced. Mountain slope is essentially impermeable with no bedrock percolation under arid circumstances. Only a bedrock percolation event occurred after multiple closely-spaced heavy rains during the four-year observation, which induced a local rapid ascending of the water table and an enhanced lateral recharge from upgradient watersheds. The influence of the enhanced lateral recharge lasted three years, suggesting a huge groundwater catchment overcoming local watershed divides in mountain blocks. The average of the gradual recession of the water table was 5.1 mm/d with a maximum of 11.4 mm/d in the beginning stage. Both interflow and bedrock percolation are important. Our results highlight the changeability of hydrologic processes in mountain watersheds.
Multi-date trends in groundwater pollution from pit latrines
Authors: Dzwairo Bloodless
Published: June 2018

This paper provides a multi-date review of trends in groundwater pollution from pit latrine sanitation structures using global, regional and South African cases. The paper focuses on three parameters which are microorganisms, nitrate and phosphorus, which are aligned with the challenge of waterborne diseases, and generally linked to poor water quality, and inadequate sanitation and hygiene. Poor sanitation and hygiene open up transmission routes for ingestion of faecal matter, which as at 2018 continue to pose risks of diarrhoea, opportunistic infections, and consequent malnutrition. These challenges currently account for approximately 1.7 million deaths annually, of which more than 90% are in developing countries, which have low sanitation coverage. While pit toilets are the generally preferred form of sanitation technology for developing countries, most provide evidence of the interconnectedness between the structures and groundwater pollution. The mechanism of pollution is generally indicated to be seepage of polluted pit latrine leachate into groundwater. This specific type of microbial and chemical routing from toilets into the environment increases the prevalence of diseases. These diseases usually result in high mortality for developing countries. Therefore, this review has highlighted the need to minimize pollution of groundwater from pit latrines, thereby contributing towards sustainable water quality management.
Enhanced biosorption of Cr(VI) using cotton fibers coated with chitosan – role of ester bonds
Authors: Rojas Sergio I. , Duarte Diana C. , Mosquera Sergio D. , Salcedo Felipe , Hinestroza Juan P. , Husserl Johana
Published: June 2018

We report on the role of ester bonds in the enhanced removal of hexavalent chromium from water using cotton fibers coated with chitosan. Adsorption capacities up to five times higher than those of the unmodified fibers were observed when the cotton fibers were exposed to an NaOH, followed by citric acid (0.97 M), and a chitosan solution (2%). We found that the use of NaOH favors the formation of ester bonds over amide bonds on the surface of the cotton fibers. This increase in the surface density of ester bonds generates an increase in the amount of exposed amino groups from the chitosan, hence increasing the removal capacity of the modified fibers. Experimental results also reveal that the adsorption is induced by the electrostatic attraction between the protonated amino groups on the surface and the negatively charged chromium ions in the water. Adsorption isotherms and kinetic studies indicated that the adsorption process fits the Langmuir and the Freundlich isotherm models as well as the pseudo-first and pseudo-second order kinetic models. These results can open a new avenue for the manufacturing of fibers with enhanced removal capacities for hexavalent chromium.
Circulating Biomarkers in Migraine: New Opportunities for Precision Medicine
Authors: Ferroni Patrizia , Barbanti Piero , Spila Antonella , Fratangeli Federica , Aurilia Cinzia , Fofi Luisa , Egeo Gabriella , Guadagni Fiorella
Published: June 2018

Background:

Migraine is the most common neurological disorder and the second
most disabling human condition, whose pathogenesis is favored by a combination of genetic,
epigenetic, and environmental factors. In recent years, several efforts have been made to identify
reliable biomarker(s) useful to monitor disease activity and/or ascertain the response to a
specific treatment.

Objective:

To review the current evidence on the potential biological markers associated with
migraine.

Methods:

A structured search of peer-reviewed research literature was performed by searching
major publications databases up to December 2017.

Results:

Several circulating biomarkers have been proposed as diagnostic or therapeutic tools
in migraine, mostly related to migraine’s inflammatory pathophysiological aspects. Nonetheless,
their detection is still a challenge for the scientific community, reflecting, at least in part,
disease complexity and clinical diagnostic limitations. At the present time, calcitonin generelated
peptide (CGRP) represents probably the most promising candidate as a diagnostic
and/or therapeutic biomarker, as its plasma levels are elevated during migraine attack and decrease
during successful treatment. Other molecules (including some neuropeptides, cytokines,
adipokines, or vascular activation markers) despite promising, do not possess the sufficient
prerequisites to be considered as migraine biomarkers.

Conclusion:

The characterization of migraine-specific biomarkers would be fundamental in a
perspective of precision medicine, enabling risk assessment and tailored treatments. However,
speculating on the clinical validity of migraine biomarkers may be premature and controlled
clinical trials are presently needed to investigate both the diagnostic and therapeutic value of
these biomarkers in migraine.
Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity
Authors: Hahn Roberta Zilles , Antunes Marina Venzon , Verza Simone Gasparin , Perassolo Magda Susana , Suyenaga Edna Sayuri , Schwartsmann Gilberto , Linden Rafael
Published: June 2018

Background:

Irinotecan (IRI) is a widely used chemotherapeutic drug, mostly used
for first-line treatment of colorectal and pancreatic cancer. IRI doses are usually established
based on patient’s body surface area, an approach associated with large inter-individual variability
in drug exposure and high incidence of severe toxicity. Toxic and therapeutic effects of
IRI are also due to its active metabolite SN-38, reported to be up to 100 times more cytotoxic
than IRI. SN-38 is detoxified by the formation of SN-38 glucuronide, through UGT1A1. Genetic
polymorphisms in the UGT1A1 gene are associated to higher exposures to SN-38 and
severe toxicity. Pharmacokinetic models to describe IRI and SN-38 kinetic profiles are available,
with few studies exploring pharmacokinetic and pharmacogenetic-based dose individualization.
The aim of this manuscript is to review the available evidence supporting pharmacogenetic
and pharmacokinetic dose individualization of IRI in order to reduce the occurrence
of severe toxicity during cancer treatment.

Methods:

The PubMed database was searched, considering papers published in the period
from 1995-2017, using the keywords irinotecan, pharmacogenetics, metabolic genotyping,
dose individualization, therapeutic drug monitoring, pharmacokinetics and pharmacodynamics,
either alone or in combination, with original papers being selected based on the presence
of relevant data.

Conclusion:

The findings of this review confirm the importance of considering individual patient
characteristics to select IRI doses. Currently, the most straightforward approach for IRI
dose individualization is UGT1A1 genotyping. However, this strategy is sub-optimal due to
several other genetic and environmental contributions to the variable pharmacokinetics of IRI
and its active metabolite. The use of dried blood spot sampling could allow the clinical application
of limited sampling and population pharmacokinetic models for IRI doses individualization.
Rational Drug Design Approach of Receptor Tyrosine Kinase Type III Inhibitors
Authors: Kim Cheolhee , Kim Eunae
Published: June 2018

:

Rational drug design is accomplished through the complementary use of structural biology and computational biology of biological macromolecules involved in disease pathology. Most of the known theoretical approaches for drug design are based on knowledge of the biological targets to which the drug binds. This approach can be used to design drug molecules that restore the balance of the signaling pathway by inhibiting or stimulating biological targets by molecular modeling procedures as well as by molecular dynamics simulations. Type III receptor tyrosine kinase affects most of the fundamental cellular processes including cell cycle, cell migration, cell metabolism, and survival, as well as cell proliferation and differentiation. Many inhibitors of successful rational drug design show that some computational techniques can be combined to achieve synergistic effects.
Energy Metabolism Impairment in Migraine
Authors: Cevoli Sabina , Favoni Valentina , Cortelli Pietro
Published: June 2018

Migraine is a common disabling neurological disorder which is characterised by a
recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology
of migraine remains not entirely understood, although many mechanisms involving
the central and peripheral nervous system are now becoming clear. In particular, it is
widely accepted that migraine is associated with energy metabolic impairment of the brain.
The purpose of this review is to present an updated overview of the energy metabolism involvement
in the migraine pathophysiology. Several biochemical, morphological and magnetic
resonance spectroscopy studies have confirmed the presence of energy production deficiency
together with an increment of energy consumption in migraine patients. An increment
of energy demand over a certain threshold creates metabolic and biochemical preconditions
for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is
generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or
secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial
respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis
that improving brain energy metabolism may reduce the susceptibility to migraine.
Research and Development of Proteins and Peptides with Therapeutic Potential from Yam Tubers
Authors: Zhang Liang , Ng Tzi Bun , Lam Jenny Ka Wing , Wang Shi Wei , Lao Lixing , Zhang Kalin Yanbo , Sze Stephen Cho Wing
Published: June 2018

We discuss the diverse biological activities, therapeutic potential, and clinical applications of peptides and proteins isolated from various yams species including Dioscorea opposita Thunb (Chinese yam), D alata, D japonica (Japanese yam), D pseudojaponica, D batatas (Korea yam), and D cayenensis. Yam peptides and proteins have many pharmacological activities including immunomodulatory, antioxidant, estrogen-stimulating, osteogenic, angiotensin I-converting enzyme inhibiting, carbonic anhydrase and trypsin inhibiting, chitinase, anti-insect, anti-dust mite, lectin, and anti-proliferative activities. Yam peptides and proteins have therapeutic potential for treating cardiovascular diseases, inflammatory diseases, cancers, aging disorders, menopause, and osteoporosis.
Emerging Antitumor Activities of the Bitter Melon (Momordica charantia)
Authors: Fang Evandro Fei , Froetscher Lynn , Scheibye-Knudsen Morten , Bohr Vilhelm A. , Wong Jack Ho , Ng Tzi Bun
Published: June 2018

Bitter melon or bitter gourd (Momordica charantia) is a common vegetable in Asia and it is
distinctive for its bitter taste. As an ingredient in folk medicine, research from different laboratories in
recent years supports its potential medicinal applications with anti-tumor, anti-diabetic, anti-HIV activities
in both in vitro and animal studies. In this short review, we summarize herein the recent progress in
the antitumor aspect of bitter melon with a focus on the underlying molecular mechanisms. Further
mechanistic studies as well as clinical trials are necessary to further verify its medicinal applications.
Clinical Use of Toxic Proteins and Peptides from Tian Hua Fen and Scorpion Venom
Authors: Ling Chen , Zhang Yuanhui , Li Jun , Chen Wenli , Ling Changquan
Published: June 2018

Traditional Chinese Medicine (TCM) has been practiced in China for thousands of years. As a complementary and alternative treatment, herbal medicines that are frequently used in the TCM are the most accepted in the Western world. However, animal materials, which are equally important in the TCM practice, are not well-known in other countries. On the other hand, the Chinese doctors had documented the toxic profiles of hundreds of animals and plants thousand years ago. Furthermore, they saw the potential benefits of these materials and used their toxic properties to treat a wide variety of diseases, such as heavy pain and cancer. Since the 50s of the last century, efforts of the Chinese government and societies to modernize TCM have achieved tremendous scientific results in both laboratory and clinic. A number of toxic proteins have been isolated and their functions identified. Although most of the literature was written in Chinese, this review provide a summary, in English, regarding our knowledge of the clinical use of the toxic proteins isolated from a plant, Tian Hua Fen, and an animal, scorpion, both of which are famous toxic prescriptions in TCM.
Design, Synthesis and Pharmacological Evaluation of Novel Antiinflammatory and Analgesic O-Benzyloxime Compounds Derived From Natural Eugenol
Authors: César da Silva Rodrigo , Veiga Fabiano , Vilela Fabiana Cardoso , Pereira André Victor , Tavares da Silva Cunha Thayssa , Tesch Roberta , Viegas Claudio , Dias Danielle Ferreira , Giusti-Paiva Alexandre , Veloso Marcia Paranho , Fraga Carlos Alberto Manssour
Published: June 2018

Background: :

A new series of O-benzyloximes derived from eugenol was synthesized
and was evaluated for its antinociceptive and anti-inflammatory properties.

Methods: :

The target compounds were obtained in good global 25-28% yields over 6 steps, which
led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4-
(methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4-
bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4-
(methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes.

Results::

These compounds have significant analgesic and anti-inflammatory effects, as evidenced
by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin
test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities
and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory
effects, exceeding the standard drugs indomethacin and celecoxib.

Conclusion: :

Molecular docking studies have provided additional evidence that the pharmacological
profile of these compounds may be related to inhibition of COX enzymes, with slight preference for
COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive
prototypes, with a novel structural pattern capable of being explored in further studies aiming at
their optimization and development as drug candidates.
Anti-Microbial and Free Radical Scavenging Activities of Nigella Sativa Colloidal-Emulgel
Authors: Eid Ahmad M. , Jaradat Nidal A. , Elmarzugi Nagib A. , Alkowni Raed , Hussen Fatima , Ayyash Laila A. , Sawafta Maher , Danaa Hadeel
Published: June 2018

Background:

Nigella sativa L. (N. sativa) has been reported to have biological activities
such as anti-bacterial, anti-inflammatory, anti-oxidant and anti-fungal activities.

Objective:

This study aims to develop N. Sativa colloidal-emulgel with the evaluation of its antibacterial,
anti-oxidant and in-vivo irritation and sensation testing.

Method:

Colloidal-emulgel formulations were prepared for N. sativa using different surfactants
(Sodium Lauryl Sulphate (S.L.S) and sucrose ester). N. sativa emulsion formulations were prepared
using heat inversion technique. After that, the optimum formulation was mixed with Carbopol to
produce the colloidal-emulgel. The droplet size, size distribution, and rheological behavior were
measured for emulgel formulations. Anti-bacterial and anti-oxidant activities were also reported in
the in vivo studies for sensitivity, irritancy and spreadability.

Results:

It was found that the sucrose ester was able to produce the optimum emulsion formulation
with droplets size of less than 1 μm. In the anti-bacterial test for Staphylococcus aureus, it was
found that emulgel has an inhibition zone of 2.5 cm in diameter, but the oil alone being 1.3 cm.
According to MRSA, the inhibition zone for emulgel was 1.1 cm, but for oil, it was 0.5 cm in diameter.
Emulgel does not show any irritation or sensitivity. Also it has a homogeneous appearance
with a smooth texture. In addition, it shows fair mechanical properties, and easy spreadability with
acceptable bio-adhesion.

Conclusion:

It is concluded that N. sativa emulgel has been prepared with dermatological and cosmeceutical
benefits.
A One-pot Multicomponent ‘Click’ Approach to the Synthesis of Novel Tamoxifen-triazole Conjugates using Nano Iron Oxide Catalyst and their Preliminary Antiproliferative Activity Studies
Authors: Katiki Mohana Rao , Kommula Dileep , Polepalli Sowjanya , Jain Nishant , Murty Madugula Sree Rama
Published: June 2018

Background:

In an effort to establish new drug candidates with improved antiproliferative
activity, we report here a novel class of compounds designed rationally by the replacement of
an ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) and the introduction of 1,4-
substituted 1,2,3-triazoles in the basic side chain.

Methods:

Magnetically separable iron oxide nanoparticles have been found to effectively catalyze
the one-pot multicomponent click synthesis of 1,4-disubstituted 1,2,3-triazole conjugates in water.
IR, 1HNMR, 13CNMR and HRMS experiments have been implemented for the unmistakable determination
of the regiochemistry of the process. The novel compounds were evaluated for their antiproliferative
activity against four human tumor cell lines, namely, MCF-7, MDA-MB-231, HeLa,
and A549. Cell growth inhibition was assessed according to the standard Sulforhodamine B (SRB)
cell proliferation method.

Results:

The most active compounds 4h, 4n and 5a have been identified with superior GI50 values
in the range of 0.13–0.31 µM as compared with the reference drug, tamoxifen (0.25-0.72 µM).

Conclusion:

Additionally, taking the stereochemistry into consideration, E isomers seem slightly
more active towards the tested cancer cell lines with respect to Z isomers.
Recent Developments in Azole Compounds as Antitubercular Agent
Authors: Das Rina , Asthana Gyati S. , Suri Krishan A. , Mehta Dinesh , Asthana Abhay
Published: June 2018

Tuberculosis (TB) is a global health disaster and is a wide-reaching hitch. The improper use of antibiotics in chemotherapy of TB patients led to the current problem of tuberculosis therapy which gives rise to Multi-Drug Resistant (MDR) strains. Nitrogen heterocycles including azole compounds are an important class of therapeutic agent with electron-rich property. Azole-based derivatives easily bind with the enzymes and receptors in organisms through noncovalent interactions, thereby possessing various applications in medicinal chemistry. Research on azoles derivatives have been expansively carried out and have become one of the extremely active area in recent years and the progress is quite rapid. A genuine attempt to review chemistry of azoles and to describe various azole-based compounds synthesized in the last two decades having promising antitubercular potential is described in the present article. It is hopeful that azole compounds may continue to serve as an important direction for the exploitation of azole-based antitubercular drugs with better curative effect, lower toxicity, less side effects, especially fewer resistances and so on.
Innovative Approaches for the Degradation of Biogenic Amines in Foods
Authors: Ebrahimi Behzad , Farshidi Maryam
Published: June 2018

Biogenic Amines (BA) are low molecular weight organic bases that have biological activity, they can be formed and degraded as a result of normal metabolic activity in animals, plants and microorganisms, and are usually produced by the decarboxylation of amino acids. The most common biogenic amines which can be found in foods are aliphatic (putrescine, cadaverine, spermine, spermidine), aromatic (tyramine, phenylethyl amine) or heterocyclic (histamine, tryptamine) structures.
Hypotensive Effect of Hydroalcoholic Ziziphus jujuba Extract on Normotensive Rats
Authors: Mohebbati Reza , Rahimi Maryam , Bavarsad Kosar , Beheshti Farimah , KhajaviRad Abolfazl , Shafei Mohammad N.
Published: June 2018

Objective:

Ziziphus jujuba (Z.J) is a medicinal plant with several properties such as antioxidant,
antibacterial, hypnotic and wound healing activity. It also has lowering blood pressure effect
and people use it to treat hypertension. In the present study, the effect of hydroalcoholic extract of Z.J
on cardiovascular parameters in the normotensive rats was investigated.

Methods:

Animal groups include: 1) Sham, only cannulation of artery 2) saline, received saline for
four weeks 3-5) Z.J groups (100, 200 and 400 mg/kg) that treated with Z.J via gavage for four weeks.
In the experiment day (28th Day) femoral artery of all rats cannulated and Systolic Blood Pressure
(SBP), Mean Atrial Pressure (MAP) and Heart Rate (HR) recorded by a power lab system. The weight
of animal in all groups also was recorded in the beginning and the last day of experiment.

Results:

There was no significant difference in HR, SBP and MAP parameters between sham and control
groups. The SBP and MAP in higher doses of Z.J (200 and 400 mg) significantly decreased compared
to control group. The HR only in dose 200 mg of Z.J significantly decreased than the control
group.

Conclusion:

The results of present study show that hydroalcoholic extract of Z.J has an inhibitory effect
on basal cardiovascular parameters and its best effects have been shown in dose 200 mg/kg.
Current Perspectives for Diabetes and Allostatic Load: The Role of Nutrition
Authors: Macit Melahat S. , Acar-Tek Nilüfer
Published: June 2018

Allostasis and allostatic load are new concepts explaining the changes in body stemming
from chronic stress. These concepts are explained with the assessment of metabolic, cardiovascular,
inflammatory, and neuroendocrine systems. Type 2 Diabetes Mellitus (DM) is a chronic disease with
the fluctuations in fasting plasma glucose, and also in other various biomarkers and poses a risk
forother chronic diseases. The course and duration of the disease, genetic factors, and environmental
factors, including nutrition, aggravate these complications. Allostatic load is a multi-system assessment.
Individuals’ compliance with the medical nutrition therapy in the short and long-term, changes
in anthropometric and biochemical biomarkers that are used to measure the nutritional status. In the
monitoring of patients with diabetes, it’s important to assess metabolic, cardiovascular, neuroendocrine,
and immune system biomarkers as well as fasting blood glucose. There exist studies in the literature,
investigating the relationship of the allostatic load with socio-economic status, chronic diseases
such as diabetes and cardiovascular diseases, gender, and ethnicity. In these studies, chronic stress, nutritional
status, stress, and allostasis are briefly described. In the present literature review, it was aimed
to evaluate different aspects of the relationships among diabetes, nutrition, allostatic load, and stress.