bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of Iodine Content by Iodometric Titration and Spectrophotometric Evaluation Method in Commercially Available Salts
Authors: Bhausaheb Namekar Swapnil , Panjabrao Lokhande Sachin , Ramesh Jadhav Ganesh , Haridas Sonvane Rahul , Vinayak Lokhande Amar , Sayed Abdul Qadeer Farha Quadri
Published: February 2018

The iodine content of commercially available salts was determined quantitatively by iodometric titration and spectrophotometric measurement. The study was conducted at Aurangabad city during November 2016 to January 2017. A total of 15 samples of commonly utilized salts were selected. The samples were made available from local retail shops. The experimental measures were carried out based on iodometric titration and spectrohotometric analysis. Highly significant correlation between the two estimated methods was observed. The statistical analysis of titration indicated that mean of 39.85 with standard error 5.46, skewness 0.413, within range of 6.3 to 82.5 and p value of 0.0004. Packet mentioned values reveal mean of 15.6 with standard error 2.79, skewness 0.036, within range of 0 to 30 and p value 0.0004 UV-Vis spectral analysis put forth similar findings. The recommended daily iodine intake is 150μg for adults. Excess iodine results in iodine-induced hyperthyroidism. The study urges national and provisional authority from Department of Health to reconsider iodized salt quality as an urgent public health imperative.
Clinical Nutrition and Aging: Sarcopenia and Muscle Metabolism
Authors: Thirumani Devi A.
Published: February 2018

No Abstract.
Nutrition Support on Retroperitoneal Ganglioneuroblastoma - A Case Report
Authors: Manimegalai B.
Published: February 2018

Patients undergoing surgery face many metabolic and physiological challenges that may compromise nutritional status. Importance of Nutritional Support (NS) in improving the nutritional status of a patient is narrated in this case report.
Insects - An Innovative Source of Food
Authors: Pandey Sonika , Poonia Amrita
Published: February 2018

Edible insects are high in nutrition due to which they are eaten all around the world. Insect species that is used for human consumption should be selected, managed, and prepared by taking into account the required knowledge in countries where insect consumption is usual. Present evidence indicates that edible insects reared under controlled conditions are expected to cause no additional hazards compared with traditional animal products. They are also considered as a source of economy. Food safety research and regulatory issues should be considered by addressing the insect food chain, in view of species features, insect origins, farm management and environmental conditions.
Development and Quality Evaluation of Cereal Based Nutribars
Authors: Shahla K. , Suman K. T.
Published: February 2018

Nutribars were introduced in the last decade as a wholesome alternative product when consumers showed more interest in health and diets. The aim of this study was to develop nutribars using cereal flakes, dehydrated fruits, nuts and functional ingredients. Nutribars were prepared in 24 different combination based on jaggery honey mix and glucose syrup in which cereal flakes formed the main ingredient. Nutribars prepared using glucose syrup had comparatively better mean scores for different quality attributes than nutribars prepared with jaggery honey mix. The chemical and nutritional qualities were observed with moisture (10.20 to 12.50 %), protein (5.47 to 7.16%), fat (4.48 to 4.98), fibre (0.36 to 1.43%), starch (49.8 to 79.2%), total sugar (36.47 to 42.98), reducing sugar (21.61 to 31.22%), thiamine (0.376 to 0.668 mg/100g), calcium (48.06 to 74.50 mg/100g), iron (5.10 to 6.44 mg/100g), sodium (157.8 to 311.2 mg/100g), potassium (129.51 to 198.47 mg/100g) and zinc (0.815 to1.037 mg/100g). Microbial contamination and peroxides were not detected in the products. This study revealed the potential of nutribars as an energy dense nutrient rich wholesome food for different age groups.
An Appraisal on Ayurvedic Diet and Dietary Intake Considerations in View of Nutrition Science
Authors: Veena , , Verma Vandana
Published: February 2018

Now-a-days non-communicable diseases and metabolic disorders have become the major concern of health care providers and researchers. The major causes of these health problems are change in lifestyle and food behavior. Ayurveda has given great consideration to diet, dietary methods along with daily and seasonal regimens and code of conduct in health and disease. Acharya Charaka has quoted that human body and disease both are the product of nutrition. The state of health depends on diet and dietetic, faulty intake of diet results in diseased state. The person who wants to be free from different diseases should eat Hitakar Aahar (suitable diet) in adequate amount on appropriate time as per the status of digestive fire. Ayurveda has given an extensive description about Diet and Dietetics under the preview of Ashtha Aahar Vidhi Visheshayatana (eight specific factors related to method of food cooking, processing, food combinations and it’s intake) and Dwadasha Pravicharana (twelve rules related to method of intake of food), Viruddha Aahar (incompatible diet), Pathya (suitable), Apathya (unsuitable) diet.
All the ancient literatures related to different cultures including Ayurveda have focused on diet in maintenance of health and management of diseases. But the available dietetics literatures have not acknowledged the contribution of Ayurveda scholars. The dietetic concepts described in Ayurveda, may contribute a lot in maintenance of health and management of life style disorder. The aim of writing this article is to highlight the hidden concept of the diet and dietetics to the researchers in the field of dietetics and medicine.
Algunos aspectos de la relación entre Maimónides e Ibn Bayya
Authors: LOMBA FUENTES Joaquín
Published: February 2018

In this work we try to emphasise the relationship between Maimonides and Avempace. Both authors put man´s end in the theoretical life, the acquisition of the intellective virtues and the union with the Agent Intellect they consider as God’s gift. Also both insist in the necessity of acquiring the moral virtues, which are a way to get the intellective ones and the acquisition of the social life. Finally, both authors coincide in the values of the solitude for a wise man.
Modernidad hermenéutica en Maimónides a partir de una exégesis contenida en "Dalālat al-ḥa’irīn" (Morê nebuḵîm) I, 2
Authors: MONFERRER SALA Juan P.
Published: February 2018

One of the modern features in Maimonides’ exegesis is the interpretation of the figurative and symbolic concepts which can be found in the Biblical text. To this respect, the task developed by the Cordovan writer place the texts before new hermeneutic possibilities of analysis which offer original readings from his interpretation.
Santo Tomás de Aquino: "Del gobierno de los príncipes"
Authors: BEUCHOT Mauricio
Published: February 2018

In this article I intend to expose Thomas of Aquino’s main ideas written in his book De regimine principum (On princes’ regime) and to comment upon those related with the conteporary political philosophy. Among the ideas defended by Thomas of Aquino coming back to our culture, I appoint the following: the idea of Common Good, present in the communitaristic philosophy; the idea of Distributive Justice (John Rawls and Amartya Sen); and the idea of Just State, not only Legitimate one.
La crítica de Pedro Abelardo a otros nominalismos
Authors: GARCÍA-ENCINAS María J.
Published: February 2018

In writing this papes it is my purpose to recover, for the most contemporary discussion on universals, a part at least of the ideas of the medieval logician and philosopher Peter Abelard. More precisely, there are certain forms of nominalism, namely, mentalism, nominalism of sets, and nominalism of simmiliarity(ies), that have recenty reappeared with new strength in contemporary Analytic Metaphysics. Abelard, as a nominalist, did not only argued against realist philosophies, but also evaluated and criticized other forms of nominalism different from his own, like the ones I have just mentioned. My main object here is to confront Abelard’s arguments against them, showing how his arguments still prevail.
"De vita non sancta" en la Alta Edad Media
Authors: RAÑA DAFONTE César
Published: February 2018

This paper intends to show the relevance of penitential books in the High Middle Age to provide information about habits and every day life both in what is in agreement and in what trespasses the norms of conduct.
The Philosophical Roots of Lazarillo de Tormes in Sem Tob Carrión's Proverbs
Authors: ORTIZ DE LANDÁZURI Carlos
Published: February 2018

In this article the continuity between two types of late medieval and Renaissance narrative is approached, although they are separated by around 200 years and belong to different literary genres. The first part of the article analyses the genre of autobiography, the experience of shared environment in urban settings, and the difficulties of its survival in a Renaissance monarchy, as shown in Sem Tob de Carrión's Proverbs and in Lazarillo de Tormes. The second part analyses the ethical principles that, according to the Sem Tob Carrión's Proverbs, justified the formulation of a legal complaint against the monarch; and it analyses the degree of moral responsibility contracted by the characters of Lazarillo de Tormes in the genesis of the scandalous ethical case in which they are involved.
MEJORA DE LA REGULACIÓN EN LA ECONOMÍA COLABORATIVA. EL CASO DE LAS VIVIENDAS TURÍSTICAS EN ANDALUCÍA
Authors: RISCOS GÓMEZ JOSÉ FÉLIX , GARCÍA HIDALGO JOSÉ LUIS , PALMA MARTOS LUIS
Published: February 2018

El mercado del alojamiento colaborativo está experimentando un fuerte crecimiento en los últimos años. Esto supone, por un lado, una oportunidad para el estimular el crecimiento económico y el empleo en un sector estratégico como el turismo; pero, por otro, plantea importantes retos en materia de regulación, que se antojan claves para aprovechar los beneficios de esta nueva economía. El presente estudio reflexiona sobre esta cuestión para identificar los elementos propios de la buena regulación económica en el mercado del alojamiento turístico, a partir del estudio de las tentativas reguladoras de los órganos autonómicos, prestando especial atención al caso de Andalucía, por ser la experiencia de mayor éxito en este ámbito.
La herencia de Gustavo Giovannoni: estudio del "conservacionismo sincrético" de Leopoldo Torres Balbás a través de su faceta como historiador de la arquitectura
Authors: Calderón Roca Belén
Published: February 2018

Leopoldo Torres Balbás fue un importante artífice en el origen de una doctrina española sobre restauración arquitectónica. Del ámbito italiano y en concreto, de Gustavo Giovannoni, Torres Balbás heredó una particular forma de valorar la historia que le llevó a desarrollar un método sincrético para el estudio de la arquitectura, basado en el respeto de las singularidades de cada período y estilo que formaban parte de la fábrica histórica. En España, fue pionero en considerar el entorno de los monumentos como elemento digno de conservación, acometiendo intervenciones que perseguían la preservación del “carácter” del monumento, a la vez que su permanencia física en el tiempo.
El comercio de imágenes devocionales con América y la producción seriada de los talleres escultóricos sevillanos
Authors: Porres Benavides Jesús
Published: February 2018

Es bien conocida la relación comercial que tuvo Sevilla con América. Dicha relación se extrapoló también al ámbito artístico. Sevilla durante el siglo XVI tuvo numerosos talleres escultóricos que en gran medida surtieron de imágenes devocionales al nuevo mundo. Algunas de estas obras (esculturas, relieves y retablos) se tallaban ex profeso para encargos en dichas tierras, otras se realizaban para venderlas allí y otras se hicieron en serie mediante moldes y se reproducían en plomo o terracota.
Evaluation of Cover Crops Drill Interseeded into Corn Across the Mid‐Atlantic Region
Authors: Curran W.S. , Hoover R.J. , Mirsky S.B. , Roth G.W. , Ryan M.R. , Ackroyd V.J. , Wallace J. M. , Dempsey M.A. , Pelzer C.J.
Published: February 2018

Core Ideas

Cover crops were successfully established in corn with a drill interseeder.

Cover crop biomass production varied notably across the mid‐Atlantic region.

Spring cover crop biomass was often proportional to fall cover crop performance.

Interseeding cover crops at corn growth stages V2–V3 decreased corn grain yields.

Interseeding cover crops at or after corn V4 did not affect corn grain yield.

Cover crop adoption remains low in the mid‐Atlantic United States despite potential conservation and production benefits. The short growing season window after corn (Zea mays L.) is a primary limiting factor. A high‐clearance grain drill was recently developed to allow for cover crop interseeding into standing cash crops. Experiment 1 tested the viability of drill interseeding cover crops into corn at the V5 growth stage across multiple locations. Experiment 2 tested interseeding timing (V2–V6 corn growth stage) on corn yield in Pennsylvania. At 16 locations throughout Maryland, Pennsylvania, and New York, we evaluated cover crop fall and spring biomass and the effect on corn yield. Cover crop treatments included annual ryegrass [Lolium perenne L. ssp. multiflorum (Lam.) Husnot]), a mixture of legume species, and an annual ryegrass–legume mixture. Each cover crop treatment successfully established across locations yet was highly variable. Across locations, annual ryegrass–legume mixture produced the highest mean aboveground biomass in fall and spring. Spring biomass of interseeded cover crops generally increased compared with fall biomass. Interseeded cover crops did not affect grain yields of the host corn crop during the year of establishment across locations. Experiment 2 indicated that cover crops interseeded before the V3 growth stage reduced corn grain yields. We recommend interseeding at or after V4 to prevent competition with corn. Our results highlight the viability of drill‐interseeding as a strategy for increasing cover crop adoption.
Ambidexterity: a possible balance to manage complexity
Authors: Franco Massimo , Cerimele Alberto
Published: February 2018

The present article originates from the effort to answer the following question: is it possible for an organizational structure to steer between organizational routines and Black Swans? (Taleb, 2007). Unexpected, unique and low-frequency events are “unknown variable” that, despite the planning and precautions deployed, catch an organization off-guard, and might have catastrophic consequences. Unexpected events impact organizations, undermining the knowledge and redefining the list of competences that an organization needs in order to be competitive. The main goal of the present article is to shed light on the role and the challenges that firms undertake in their defining moments of adaptation of their organizational assets – the structure –. The rational pattern of adaptation is exemplified by the use of ambidextrous organizational structures, which focus on activities that can be defined as exploration and exploitation. Within the analysis of “the science of complexity”, parallels, paradoxes and metaphors representing a synthesis of a largely shared doctrine will be investigated: firms need to utilize known variables, or sometimes unknown ones, that are inevitably complex, in order to find the right fit, react swiftly to change, successfully compete, and obtain results.
A modernização do sistema educacional na França: a Nova Gestão Pública entre a afirmação do Estado e o governo descentralizado
Authors: Derouet Jean-Louis
Published: February 2018

O texto examina o processo de modernização do Sistema Educacional na França, buscando compreender a afirmação do Estado e o governo descentralizado no contexto de discussão da Nova Gestão Pública. Examinam-se os legados, narrativas e políticas de modernização, bem como os paradoxos da nova administração pública francesa na educação. Questiona-se se a Nova Gestão Pública foi, de fato, implementada no sistema educacional francês. Afirma-se que, na educação, apenas a responsabilidade administrativa e financeira adentrou nas instituições sem ter acarretado muitas consequências no trabalho dos professores. Os principais professores e fiscais estão desenvolvendo avaliações e auditorias, e assinando contratos, mas a estrutura burocrática predomina. Entende-se, todavia, que vem sendo buscada uma terceira via entre o Estado e o mercado, especialmente no tocante à descentralização, com ênfase nas responsabilidades locais mais compartilhadas e na possível mudança do estatuto dos funcionários públicos.
Podmiotowość moralna osoby w perspektywie olitycznego postulatu równej "wolności do"
Authors: Stoiński Andrzej
Published: February 2018

Artykuł dotyczy zagadnienia wolności indywidualnej i problemu zagrożeń, jakie może pociągać za sobą hołdowanie niektórym jej odmianom. Klasycznie pojmowana wolność, zwana negatywną, utożsamiana z brakiem zewnętrznego przymusu, może stać w opozycji do tak zwanej wolności pozytywnej. To ostatnie pojęcie definiowane jest na ogół poprzez możność, co przywodzi na myśl jego związek z pojęciem władzy. Punktem wyjścia rozważań stała się analiza wybranych aspektów obu wolności. Rozróżnienie tych dwóch fenomenów jest istotne dla zrozumienia niektórych procesów zachodzących we współczesnej wspólnocie politycznej. Konsekwentne odwoływanie się do paradygmatu tzw. wolności pozytywnej może bowiem przynosić trudne do przewidzenia konsekwencje w postaci uzasadnianej ideologicznie ingerencji w wiele sfer ludzkiego działania. Za szczególnie brzemienne w skutki należy uważać konotacje tzw. wolności pozytywnej i równości. W istocie bowiem wolność pozytywna, a szczególnie jej postulat szerzenia równości, staje się pretekstem dla zwiększania zakresu politycznego panowania. Może to wyrażać się w dążności do urzeczywistniania aspiracji jednych grup społecznych kosztem innych. Takie podejście siłą rzeczy stoi w opozycji do poglądów upatrujących fundamentów społecznego porządku w prymacie wolności negatywnej i obowiązywaniu zasad sprawiedliwości. Wspomniana ingerencja instytucji państwa w ludzkie działanie, będąca skutkiem propagowania niektórych aspektów koncepcji „wolności do” może grozić redukcją podmiotowości moralnej osób.
Próba przezwyciężenia relatywizmu – przypadek Alasdaira MacIntyre’a
Authors: Andryszczak Piotr
Published: February 2018

MacIntyre jest przekonany, że nie istnieje racjonalność jako taka, a jedynie „racjonalność-tej-lub-owej-tradycji”. Wyróżnia on trzy tradycje intelektualne i moralne, które we współczesnym świece zmagają się o zwycięstwo. Pierwszą z nich nazywa „encyklopedyczną”, ponieważ jej kanoniczym tekstem jest IX wydanie encyklopedii Britannica. Druga z nich, zwana jest „genealogią”, wywodzi się od F. Nietzschego i w niej podobną rolę pełni jego dzieło "Z genealogii moralności". Trzecią zaś jest „tradycja”, której kluczowym przedstawicielem jest św. Tomasz z Akwinu. Zdaniem MacIntyre’a z konfrontacji pomiędzy nimi wychodzi zwycięsko tomizm, czego współczesnym wyrazem jest nauka moralna zawarta w encyklice "Veritatis Splendor". Z tego powodu najpierw ukazaliśmy sposób ujęcia i rozstrzygnięcia przez MacIntyre’a sporu pomiędzy trzema tradycjami. To doprowadziło go do przyjęcia absolutyzmu moralnego Jana Pawła II. Tekst zwieńczyliśmy uwagami krytycznymi odnoszącymi się do jego próby przezwyciężenia relatywizmu moralnego.
Role of ABC Transporters in Veterinary Medicine: Pharmaco- Toxicological Implications
Authors: Virkel Guillermo , Ballent Mariana , Lanusse Carlos , Lifschitz Adrián
Published: February 2018

Unlike physicians, veterinary practitioners must deal with a number of animal species with crucial differences in anatomy, physiology and metabolism. Accordingly, the pharmacokinetic behaviour, the clinical efficacy and the adverse or toxic effects of drugs may differ across domestic animals. Moreover, the use of drugs in food-producing species may impose a risk for humans due to the generation of chemical residues in edible products, a major concern for public health and consumer's safety. As is clearly known in human beings, the ATP binding cassette (ABC) of transport proteins may influence the bioavailability and elimination of numerous drugs and other xenobiotics in domestic animals as well. A number of drugs, currently available in the veterinary market, are substrates of one or more transporters. Therefore, significant drug-drug interactions among ABC substrates may have unpredictable pharmacotoxicological consequences in different species of veterinary interest. In this context, different investigations revealed the major relevance of P-gp and other transport proteins, like breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs), in both companion and livestock animals. Undoubtedly, the discovery of the ABC transporters and the deep understanding of their physiological role in the different species introduced a new paradigm into the veterinary pharmacology. This review focuses on the expression and function of the major transport proteins expressed in species of veterinary interest, and their impact on drug disposition, efficacy and toxicity.
New Drugs, Therapeutic Strategies, and Future Direction for the Treatment of Pulmonary Arterial Hypertension
Authors: Mercurio Valentina , Bianco Anna , Campi Giacomo , Cuomo Alessandra , Diab Nermin , Mancini Angela , Parrella Paolo , Petretta Mario , Hassoun Paul M. , Bonaduce Domenico
Published: February 2018

Despite recent advances in Pulmonary Arterial Hypertension (PAH) treatment, this condition is still characterized by an extremely poor prognosis. In this review, we discuss the use of newly-approved drugs for PAH treatment with already known mechanisms of action (macitentan), innovative targets (riociguat and selexipag), and novel therapeutic approaches with initial up-front combination therapy. Secondly, we describe new potential signaling pathways and investigational drugs with promising role in the treatment of PAH.
DNA Double Strand Break Repair - Related Synthetic Lethality
Authors: Toma Monika , Skorski Tomasz , Sliwinski Tomasz
Published: February 2018

Cancer is a heterogeneous disease with a high degree of diversity between and within tumors. Our limited knowledge of their biology results in ineffective treatment. However, personalized approach may represent a milestone in the field of anticancer therapy. It can increase specificity of treatment against tumor initiating cancer stem cells (CSCs) and cancer progenitor cells (CPCs) with minimal effect on normal cells and tissues. Cancerous cells carry multiple genetic and epigenetic aberrations which may disrupt pathways essential for cell survival. Discovery of synthetic lethality has led a new hope of creating effective and personalized antitumor treatment. Synthetic lethality occurs when simultaneous inactivation of two genes or their products causes cell death whereas individual inactivation of either gene is not lethal. The effectiveness of numerous anti-tumor therapies depends on induction of DNA damage therefore tumor cells expressing abnormalities in genes whose products are crucial for DNA repair pathways are promising targets for synthetic lethality. Here, we discuss mechanistic aspects of synthetic lethality in the context of deficiencies in DNA double strand break repair pathways. In addition, we review clinical trials utilizing synthetic lethality interactions and discuss the mechanisms of resistance.
The Use of Immunotherapy to Treat Metastatic Breast Cancer
Authors: Nicolini Andrea , Barak Vivian , Biava Piermario , Ferrari Paola , Rossi Giuseppe , Carpi Angelo
Published: February 2018

This article reviews the principal attempts of immune-modulation or immune therapy in metastatic breast cancer. It considers their rationale and reports on results from the relevant key clinical trials. Immune-modulatory or immune-stimulating cytokines used alone or combined with conventional therapies is among the principal approaches of immune manipulation in breast cancer. As this issue has recently been reviewed by us, the aim of the current article is to discuss our updated and unpublished data on this topic. Overall survival in luminal (28 patients) and non-luminal (9 patients) molecular subtypes is 91 and 59 months respectively that is about two and half or three times longer than expected. Thereafter, we focus on monoclonal antibodies (mAb) based-therapies including novel strategies to overcome resistance to anti-HER2 mAb. The main vaccine platforms in different molecular subtypes and immune therapies in triple negative metastatic breast cancer (m-TNBC) are discussed in the last sections. Some phase III investigations have already changed the current clinical practice. In fact, pertuzumab plus trastuzumab and docetaxel is the recommended first line regimen in HER2 positive locally recurrent or metastatic breast cancer and bevacizumab plus paclitaxel or docetaxel is a reasonable option for m-TNBC. In some other observational or phase I/II studies on first-line trastuzumab plus chemotherapy and hormonal therapy and in that on HER2 peptide/protein vaccines promising although preliminary findings have been reported to be further validated. In the remaining studies, results were disappointing. In the future, finding new predictive biomarkers and exploring more suitable synergizing combinations, time and dose-dependent-scheduled sequences of currently and further investigated immunological approaches are main challenges.
Flavonoids in the Treatment of Alzheimer’s and Other Neurodegenerative Diseases
Authors: Airoldi Cristina , La Ferla Barbara , D`Orazio Giuseppe , Ciaramelli Carlotta , Palmioli Alessandro
Published: February 2018

Flavonoids are phytochemicals present in almost all terrestrial plants and, as a
consequence, in plant-based foods, and thus consumed by humans through diet. Recent evidences
suggest that several flavonoids have positive effects against dementia and Alzheimer’s
disease, reversing age-related declines in neurocognitive performances. In this review,
we provide a general classification of natural and synthetic flavonoids, a description
of their physico-chemical properties, in particular their redox properties and stability, and an
extensive overview about their biological activities and structure-activity relationship in the
field of neurodegenerative diseases. In addition, a section will be dedicated to the synthetic
strategies for the preparation of bioactive derivatives. This information will be essential for
the design and development of new drugs that can improve brain functions.
The Role of 5-HT1A Receptor in Cancer as a New Opportunity in Medicinal Chemistry
Authors: Corvino Angela , Fiorino Ferdinando , Severino Beatrice , Saccone Irene , Frecentese Francesco , Perissutti Elisa , Di Vaio Paola , Santagada Vincenzo , Caliendo Giuseppe , Magli Elisa
Published: February 2018

The 5-HT1A receptor is a pharmacologically well characterized serotonin receptor
subtype and it has long been investigated because of its involvement in several physiopathological
mechanisms and treatment of neurological diseases like ansia and depression.
Serotonin (5-HT) also shows many non-neural functions such as essential hypertension, embryogenesis,
follicle maturation and behavior. Moreover, it exerts a growth factor function on
different types of non-tumoral cells, and it was also found to be related to oncogenes. In fact,
growth-stimulatory activity of serotonin in different human tumor cells has been reported. Recently,
new chemical molecules binding the 5-HT1A receptor have been described as novel
therapeutic entities useful in neuroprotection, cognitive impairment, Parkinson’s Disease, pain
treatment, malignant carcinoid syndrome and cancer. It was widely demonstrated that 5-HT1A
receptor is involved in the carcinogenesis and consequently in many human tumor types, such
as prostate, bladder, small cell lung, colonrectal and cholangiocarcinoma. Furthermore, depending
on the tumor type, 5-HT1A receptor antagonists were shown to be capable of blocking
the 5HT-induced increase in tumor growth. In this review, we have focused our attention on
each tumor type where the 5-HT1A receptor is involved, investigating the role of this molecular
target and the different classes of compounds that have shown the capability to modulate it.
The analyzed aspects could represent a hint for the medical chemists to develop novel molecules
as selective 5-HT1A agents are useful in further elucidating the role of this therapeutic
target.
Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors
Authors: Rivellese Felice , Lobasso Antonio , Barbieri Letizia , Liccardo Bianca , de Paulis Amato , Rossi Francesca Wanda
Published: February 2018

:

Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by synovial
inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several
systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the
main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis.

:

Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In
addition, the widespread adoption of treat to target and tight control strategies has led to a substantial
improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the
treatment of RA. However, despite the availability of multiple therapeutic options, up to 40% of
patients do not respond to current treatments, including biologics. Small-molecule therapies offer
an alternative to biological therapies for the treatment of inflammatory diseases. In the past 5
years, a number of small-molecule compounds targeting Janus Kinases (JAKs) have been developed.
Since JAKs are essential for cell signaling in immune cells, in particular controlling the response
to many cytokines, their inhibitors quickly became a promising class of oral therapeutics
that proved effective in the treatment of RA.

:

ofacitinib is the first Janus Kinase (JAK) inhibitor approved for the treatment of RA, followed
more recently by baricitinib. Several other JAK inhibitors, are currently being tested in phase II
and III trials for the treatment of a different autoimmune diseases. Most of these compounds exhibit
an overall acceptable safety profile similar to that of biologic agents, with infections being the
most frequent adverse event. Apart from tofacitinib, safety data on other JAK inhibitors are still
limited. Long-term follow-up and further research are needed to evaluate the general safety profile
and the global risk of malignancy of these small molecules, although no clear association with malignancy
has been reported to date.

:

Here, we will review the main characteristics of JAK inhibitors, including details on their
molecular targets and on the clinical evidences obtained so far in the treatment of RA.
Numeric, Agent-based or System Dynamics Model? Which Modeling Approach is the Best for Vast Population Simulation?
Authors: Cimler Richard , Tomaskova Hana , Kuhnova Jitka , Dolezal Ondrej , Pscheidl Pavel , Kuca Kamil
Published: February 2018

Background:

Alzheimer’s disease is one of the most common mental illnesses. It is posited
that more than 25% of the population is affected by some mental disease during their lifetime. Treatment
of each patient draws resources from the economy concerned. Therefore, it is important to quantify
the potential economic impact.

Methods:

Agent-based, system dynamics and numerical approaches to dynamic modeling of the population
of the European Union and its patients with Alzheimer’s disease are presented in this article.
Simulations, their characteristics, and the results from different modeling tools are compared.

Results:

The results of these approaches are compared with EU population growth predictions from the
statistical office of the EU by Eurostat. The methodology of a creation of the models is described and
all three modeling approaches are compared. The suitability of each modeling approach for the population
modeling is discussed.

Conclusion:

In this case study, all three approaches gave us the results corresponding with the EU
population prediction. Moreover, we were able to predict the number of patients with AD and, based on
the modeling method, we were also able to monitor different characteristics of the population.
Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants
Authors: Pontes Daniela Santos , de Araujo Rodrigo Santos Aquino , Dantas Natalina , Scotti Luciana , Scotti Marcus Tullius , de Moura Ricardo Olimpio , Mendonca-Junior Francisco Jaime Bezerra
Published: February 2018

The ever increasing number of multidrug-resistant microorganism pathogens has become a
great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms
of resistance are intimately associated, but comprehension of the biochemical and molecular functions
of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to
alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the
emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how
bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing
propositions to fight against these superbugs, and to search for new drugs. In this review, we present
and discuss both general information and examples of common genetic and molecular mechanisms
related to antibiotic resistance, as well as how the expression and interactions of ARGs are important
to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic
adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of
action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux
pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion
systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the
problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics.
Learning from Nature: Bioinspired Strategies Towards Antimicrobial Nanostructured Systems
Authors: Vitiello Giuseppe , Silvestri Brigida , Luciani Giuseppina
Published: February 2018

Microbial contamination still remains a major issue of the modern era, due to the widespread
of drug-resistant pathogens. This has prompted researchers to come up with novel antimicrobial
systems that could overcome antibiotic-resistance. In this context, nature can provide inestimable
source of inspiration to design high-performance multifunctional materials with potent activity
against drug-resistant pathogens. Actually, integrating the bio-inspired-approach with nanotechnology
can provide cutting-edge solutions for drug-resistant infections. In this context, this review will
examine recent advances in the development of bio-inspired antimicrobial nanostructures. Advantages
of bioinspired approach to nanomaterials over conventional routes have been highlighted. Generally,
bionspired synthesis can be carried out either by mimicking the functions of natural materials/
structures or by mimicking the biological processes employed to produce substances or materials.
The review provides an overview of both strategies as applied to the synthesis of inorganic, organic
as well as hybrid nanostructures. Antimicrobial efficacy and biological properties of these systems
have been highlighted. Antimicrobial and antibiofouling nanostructured surfaces are also discussed.
The Sesamum indicum Rhizosphere Associated Bacterium: A Source of Antifungal Compound
Authors: Chaudhary Renu , Balhara Meenakshi , Jangir Deepak , Dangi Mrridula , Dangi Mehak , Khatri Savita , Chhillar Anil K.
Published: February 2018

Background:

The impact of fungal infections on human health has increased considerably
within a past few decades. Although drugs with antifungal properties are available, but they are less effective
and are associated with side effects.

Objective and Method:

To screen the bacterial isolates from Sesamum indicum and to investigate the
antifungal activity of the screened bacterial isolates against Aspergillus sp. Co-culture assay and agar
overlay were used to scrutinize the anti-Aspergillus activity. Furthermore, optimization of media and
growth conditions to enhance the production of anti-Aspergillus compound.

Results:

Several bacterial cultures were isolated from Sesamum indicum rhizosphere collected from
Mandi (H.P.) India. These bacterial cultures were assayed for antifungal activity against Aspergillus species
i.e. A. fumigatus and A. niger. Two most potent strains were chosen for more detailed analyses. The
biochemical characterization and 16S ribosomal RNA sequencing revealed that Burkholderia sp. strain
RC1 and Acinetobacter pittii strain RC2 exhibit strong similarity (100%) with Burkholderia sp. SR2-07
and Acinetobacter sp. strain 3-59. Additionally, it was also validated that RC1 and RC2 showed
significant difference in the production of anti-Aspergillusactivity under altered growth conditions.

Conclusion:

Results from this study recommend that plant rhizosphere remains a rich hotspot for delivering
a novel antifungal compounds.
Efficacy of P2Y12 Receptor Blockers After Myocardial Infarction and Genetic Variability of their Metabolic Pathways
Authors: Máchal Jan , Hlinomaz Ota
Published: February 2018

Background: Various antiplatelet drugs are used following Acute Coronary Syndromes (ACS). Of them, adenosine diphosphate receptor P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor are currently used for post-ACS long-term treatment. Although they act on the same receptor, they differ in pharmacodynamics and pharmacokinetics. Several enzymes and transporters involved in the metabolism of P2Y12 inhibitors show genetic variability with functional impact. This includes Pglycoprotein, carboxylesterase 1 and, most notably, CYP2C19 that is important in clopidogrel activation. Common gain-of-function or loss-of-function alleles of CYP2C19 gene are associated with lower or higher platelet reactivity that may impact clinical outcomes of clopidogrel treatment. Prasugrel is considered to be less dependent on CYP2C19 variability as it is also metabolized by other CYP450 isoforms. Some studies, however, showed the relevance of CYP2C19 variants for platelet reactivity during prasugrel treatment as well. Ticagrelor is metabolized mainly by CYP3A4, which does not show functionally relevant genetic variability. Its concentrations may be modified by the variants of Pglycoprotein gene ABCB1. While no substantial difference between the clinical efficacy of prasugrel and ticagrelor has been documented, both of them have been shown to be superior to clopidogrel in post-ACS treatment. This can be partially explained by lower variability at each step of their metabolism. It is probable that factors influencing the pharmacokinetics of both drugs, including genetic factors, may predict the clinical efficacy of antiplatelet treatment in personalized medicine.  Conclusion: We summarize the pharmacokinetics and pharmacogenetics of P2Y12 inhibitors with respect to their clinical effects in post-myocardial infarction treatment.
Screening for Rare Genetic Variants Associated with Atherosclerosis: Opportunity for Personalized Medicine
Authors: Peterlin Ana , Petrovič Daniel , Peterlin Borut
Published: February 2018

Atherosclerosis and its clinical manifestations is a leading cause of disease burden worldwide.
Currently, most of the individuals carrying a strong predisposition to complications of atherosclerosis
because of monogenic dyslipidaemias remain undiagnosed and consequently are not given an opportunity
for prevention. Therefore, one of the main public health challenges remains the identification
of individuals with significantly increased risk for atherosclerosis due to monogenic predisposition.
Next-Generation Sequencing (NGS) has revolutionized genetic testing in symptomatic patients. Although
new genomic technologies are still developing, and evidence on the use of this methodology for
screening purposes is still lacking, genome testing might provide a powerful tool for the identification of
individuals at risk. This may pave the way for the implementation of personalized medicine in the field
of atherosclerosis prevention.

In this review, we discuss the potential of genetic screening for atherosclerosis prevention and present
the potential target of 17 genes responsible for monogenic dyslipidaemias associated with atherosclerosis.
Design, Synthesis and Biological Evaluation of Novel Urea and Thiourea Bearing thieno[3,2-d]-pyrimidines as PI3 Kinase Inhibitors
Authors: Bodige Srinu , Ravula Parameshwar , Gulipalli Kali Charan , Endoori Srinivas , Chandra J.N. Narendra Sharath , Cherukumalli Purna Koteswara Rao , Vanaja G.R , Seelam Nareshvarma
Published: February 2018

Background:

Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly
involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore,
inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer.

Methods:

The present research work involves molecular docking studies performed to screen derivatives of urea
and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The
designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their
anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme.

Results:

Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2-
d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines
with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent
PI3Kα inhibitory activity with IC50 value of 1.26 µM.

Conclusion:

Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction
at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory
agents for cancer therapy.
Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia
Authors: Maugeri Grazia , D'Amico Agata G. , Rasà Daniela M. , Saccone Salvatore , Federico Concetta , Magro Gaetano , Cavallaro Sebastiano , D'Agata Velia
Published: February 2018

Background:

Caffeine represents the most used psychoactive drug in the world acting through different
mechanisms of action and on several molecular targets. It exerts an anti-cancer role in glioblastoma multiforme
(GBM). This neoplasia is characterized by extensive hypoxic foci triggering hypoxia-inducible factors
(HIFs) expression. Among these factors, HIF-1α performs a crucial role in the induction of vascular endothelium
growth factor (VEGF), a key player in angiogenesis and cell migration.

Methods:

In this work, we have investigated whether caffeine counteracts GBM progression by modulating
hypoxic event. Moreover, we analyzed the activation of phosphoinositide three kinase (PI3K)/Akt and mammalian
mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling cascades.

Results:

Our results have indicated that this psychostimulant drug significantly reduced HIF-1α and VEGF
expression in GBM cells exposed to hypoxia. This effect is mediated through inhibition of PI3K/Akt and
MAPK/ERK signaling pathways both implied in HIFs regulation.

Conclusion:

The present data give new insight into antitumor activity of caffeine during GBM progression.
Lysosomal Potassium Channels: Potential Roles in Lysosomal Function and Neurodegenerative Diseases
Authors: Feng Xinghua , Zhao Zhuangzhuang , Li Qian , Tan Zhiyong
Published: February 2018

Background & Objective: The lysosome is a membrane-enclosed organelle widely found in
every eukaryotic cell. It has been deemed as the stomach of the cells. Recent studies revealed that it
also functions as an intracellular calcium store and is a platform for nutrient-dependent signal transduction.
Similar with the plasma membrane, the lysosome membrane is furnished with various proteins,
including pumps, ion channels and transporters. So far, two types of lysosomal potassium channels
have been identified: large-conductance and Ca2+-activated potassium channel (BK) and
TMEM175. TMEM175 has been linked to several neurodegeneration diseases, such as the Alzheimer
and Parkinson disease. Recent studies showed that TMEM175 is a lysosomal potassium channel with
novel architecture and plays important roles in setting the lysosomal membrane potential and maintaining
pH stability. TMEM175 deficiency leads to compromised lysosomal function, which might be
responsible for the pathogenesis of related diseases. BK is a well-known potassium channel for its
function on the plasma membrane. Studies from two independent groups revealed that functional BK
channels are also expressed on the lysosomal plasma membrane. Dysfunction of BK causes impaired
lysosomal calcium signaling and abnormal lipid accumulation, a featured phenotype of most lysosomal
storage diseases (LSDs). Boosting BK activity could rescue the lipid accumulation in several LSD
cell models. Overall, the lysosomal potassium channels are essential for the lysosome physiological
function, including lysosomal calcium signaling and autophagy. The dysfunction of lysosomal potassium
channels is related to some neurodegeneration disorders.

Conclusion:

Therefore, lysosomal potassium channels are suggested as potential targets for the intervention
of lysosomal disorders.
Post-embryonic development stages of Tityus columbianus (Thorell, 1846), (Scorpiones, Buthidae): morphometric estimation approach
Authors: Gómez C. Matías , Flórez Eduardo , Hernández Linda , Fajardo Medina Gonzalo E.
Published: February 2018

Poca información existe sobre el ciclo de vida y número de mudas por los cuales pasa Tityus columbianus (Thorell, 1846) para alcanzar la madurez. En este studio, el número de estados de desarrollo posembriónico fue determimnado usando herramientas de morfometría geométrica y a través de las ecuaciones clàsicas de Pzibram & Megusâr (1984). Los análisis incluyeron digitalización de imagenes, definición de puntos de referencia homólogos (o “landmarks”) y derivación de matrices basadas en distancias Euclidianas. Los análisis permiten esatablecer que T. columbianus pasa por seis a siete estados (mudas) en su desarrollo post-embrionario.
The Utilization of Mobile Phones with medical related apps among foreign medical students in WMU, China (Preprint)
Authors: Chen Laite , Jiang Chen-Yang
Published: February 2018

BACKGROUND

Smart phones containing medical related apps have been applied to medical practice and proved to be helpful by previous studies. However, no attention has been paid to the use of mobile phone and medical related apps among foreign medical students(FMSs) in China.

OBJECTIVE

The objective of the study was to investigate the utilization of mobile phones with medical apps among FMSs in WMU.

METHODS

A survey of FMSs was conducted in Wenzhou Medical University (WMU). Data from questionnaire include the major obstacles FMSs face in China; the acceptance and preference of medical related apps in FMSs; the patterns of medical related app usage within FMSs.

RESULTS

This study included ninety-three FMSs, all of whom owned at least one mobile phone. Most owners had more than one medical related app. No difference on gender or operating system was found in utilization of apps. 55% of FMSs reported using medical related apps on a daily basis, among which, 65% of them spent more than 20 minutes on medical related apps everyday.

CONCLUSIONS

Mobile phones were highly applied among FMSs in WMU. With more effort in app designing, smart phones could be a possible solution for necessary aid in learning medicine overseas.